Public Health Service Food and Drug Administration
Seattle District Pacific Region 2201 23rd Drive SE Bothell, WA 98021-4421
Telephone: 425-486-8788 FAX: 425-483-4996
June 25, 2008
CERTIFIED MAIL RETURN RECEIPT REQUESTED
Gregory R. Page, President and CEO Cargill, Inc. 15407 McGinty Road West Wayzata, Minnesota 55391
In reply refer to Warning Letter SEA 08-22
WARNING LETTER
Dear Mr. Page:
An inspection of your licensed medicated feed mill, Cargill, Inc., located at 1406 Industrial Avenue, Billings, Montana, conducted by the U.S. Food and Drug Administration (FDA) on February 25, 26, and 27, 2008, found significant deviations from current Good Manufacturing Practice (cGMP) regulations for Medicated Feeds (Title 21, Code of Federal Regulations, Part 225 (21 C.F.R. 225)). These deviations cause feeds being manufactured at this facility to be adulterated within the meaning of section 501 (a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 351(a)(2)(B)]. In addition, your llama feed, Llama Mineral, was found to contain the new animal drug [redacted] (chlortetracycline), which is not approved for use in llama feed. The use of the new animal drug, Type A, medicated article [redacted] (chlortetracycline), contrary to its approved labeling causes the drug to be deemed unsafe within the meaning of section 512(a)(1) of the Act [21 U.S.C. § 360b(a)(1)] and adulterated with in the meaning of section 501 (a)(5) of the Act [21 U.S.C. § 351(a)(5)]. In addition, the llama feed containing [redacted] (chlortetracycline) is deemed to be unsafe within the meaning of section 512(a)(2) of the Act [21 U.S.C. § 360b(a)(2)] and adulterated within the meaning of section 501 (a)(6) of the Act [21 U.S.C. § 351(a)(6)].
We reviewed your firm's response, dated March 13, 2008, to the FDA-483. We found that the response lacks sufficient detail, explanation, documentation, or substantive corrective action plans to adequately address the deviations noted during the February 2008 inspection of your licensed medicated feed mill in Billings, Montana.
We acknowledge your firm has made some changes and corrections in response to Agency findings and requests. However, we have found that, while some individual cGMP deficiencies may have been corrected, your firm has failed to institute sufficient corrections for your firm's manufacturing processes to conform to the following cGMP requirements in 21 C.F.R. 225:
1. When results of laboratory assays of drug components indicated that medicated feeds were not within permissible assay limits, your facility did not implement investigations and corrective actions, as required by 21 C.F.R. 225.58(d). For example:
a. An assay of the cattle feed "NB TRANS PL 5LB [redacted]" manufactured on March 29, 2007, and submitted for sulfamethazine analysis on or about April 12, 2007, determined a sulfamethazine level 26% above the claimed potency. No investigation or corrective action was undertaken at that time.
b. An assay of the cattle feed "NB TRANS PL 10LB [redacted] manufactured on May 15, 2007, and submitted for sulfamethazine analysis on or about June 12, 2007, determined a sulfamethazine level 24.4% above the claimed potency. No investigation or corrective action was undertaken at that time.
We acknowledge your firm's response that the importance of performing an immediate investigation into the reason for an out-of-tolerance assay result and implementing corrective action has been reviewed with appropriate personnel to ensure compliance with regard to any future out-of-tolerance assays. We further acknowledge your firm's action of completing investigations into these two assays at the time of the February 2008 inspection. However, the results. of the assays were reported to your Billings, Montana feed mill seven to ten months prior to the February 2008 inspection. FDA does not consider an investigation occurring after a seven to ten month delay to be sufficient. Further, your response states that with respect to the February 2008 investigation, "no manufacturing errors were noted." However, FDA was informed by your firm at the time of inspection that the assay of the feed manufactured on March 29, 2007, failed because [redacted] mixer was not functioning properly. The malfunction of [redacted] mixer constitutes a manufacturing error.
2. When results of laboratory assays indicated that medicated feeds failed to meet the labeled drug potency, your facility did not take corrective actions that included discontinuing distribution of the feeds, as required by 21 C.F.R. 225.58(e). For example:
a. An assay of the cattle feed "NB TRANS PL 5LB [redacted]" manufactured on March 29, 2007, and submitted for sulfamethazine analysis on or about April 12, 2007, determined a sulfamethazine level 26% above the claimed potency. No investigation or corrective action was undertaken at that time, including discontinuing distribution of the affected feed products.
b. An assay of the cattle feed "NB TRANS PL 10LB [redacted]" manufactured on May 15, 2007, and submitted for sulfamethazine analysis on or about June 12, 2007, determined a sulfamethazine level 24.4% above the claimed potency. No corrective action was undertaken at that time, including discontinuing distribution of the affected feed products.
We acknowledge your firm's response that the importance of withholding such feed from distribution has been reviewed with appropriate personnel to ensure compliance with regard to any future out-of-tolerance assays. Your response also notes that there was no product available for recovery. This is understandable as the investigation into the assays that showed the feeds not to be in accord with permissible limits did not occur for seven to ten months after the assay results were reported. However, as discussed above, FDA does not consider corrective action taken seven to ten months after the reported assay results to be sufficient.
3. Laboratory analysis results demonstrate that the cleanout procedures established and used in the production of your facility's medicated feeds are not adequate to prevent unsafe contamination of feed, as required by 21 C.F.R. 225.65(b). For example:
a. Laboratory analysis by the Montana State Department of Agriculture found chlorotetracycline in Nutrena Naturewise Lamb and Sheep Feed, manufactured on February 4, 2008, at 550 grams per ton, which is 10 times higher than the level of 50 grams per ton indicated on the product's label. FDA analysis of a sample collected from a different portion of the same lot of lamb and sheep feed found levels of chlorotetracycline at 160 grams per ton (320 % of formula).
b. FDA analysis of a retain sample collected from a lot of medicated cattle feed manufactured at your facility, identified as "Nutrabeef Cattle Grower Feed," found levels of chlortetracycline at 4.8 parts per million (ppm). This product is formulated to contain no chlortetracycline.
c. FDA analysis of a retain sample collected from a lot of medicated cattle feed manufactured at your facility, identified as "Miller FDLT 45/27," found levels of chlortetracycline at 88.0 ppm. This product is formulated to contain no chlortetracycline.
d. FDA analysis of a retain sample collected from a lot of non-medicated llama feed manufactured at your facility, identified as "Llama Mineral," found levels of chlortetracycline at 96.0 ppm. This product is formulated to contain no chlortetracycline.
We acknowledge your firm's response that the incident described above regarding Nutrena Naturewise Lamb and Sheep Feed represents an isolated incident.
However, this response is inadequate in light of analytical sample results confirming cross contamination in several additional products (i.e., "Nutrabeef Cattle Grower Feed," "Miller FDLT 45/27," and "Llama Mineral"). As these analytical results indicate that this is not an isolated incident, FDA continues to have concerns regarding the adequacy of the cleanout procedures at your Billings, Montana facility.
4. Your facility does hot utilize proper sequential production of medicated feeds on a predetermined basis designed to prevent unsafe contamination of feeds with residual drugs in the manufacture of medicated and non-medicated feeds, as required by 21 C.F.R. 225.65(b)(3). For example:
a. On February 4, 2008, your facility produced a medicated feed, identified as "Nutrena Naturewise Lamb and Sheep Feed," which is formulated to contain relatively low levels (0.55 lbs per ton) of the Type A, medicated article [redacted] (chlortetracycline), following the production of a medicated feed, identified as "Nutrena CTC 10 Gram," which is formulated to contain relatively high levels (222 lbs per ton) of the Type A, medicated article [redacted]. This resulted in levels of chlortetracycline in the lamb and sheep feed up to 1000% higher than the levels indicated on the product's label.
b. On January 8, 2008, your facility produced a lot of non-medicated feed, identified as "Llama Mineral," which is formulated to contain no chlortetracycline, following the production of a medicated feed, identified as "Nutrena CTC 10 Gram," which is formulated to contain relatively high levels (222 lbs per ton) of the Type A, medicated article [redacted] (chlortetracycline). This resulted in cross contamination of the "Llam a Mineral" with levels of chlortetracycline at 96.0 ppm.
c. On November 19, 2007, your facility produced a lot of, medicated feed, identified as "Miller FDLT 45/27," which is formulated to contain no chlortetracycline, following the production of a medicated feed, identified as "Nutrena CTC 10 Gram," which is formulated to contain relatively high levels (222 lbs per ton) of the Type A, medicated article [redacted] (chlortetracycline). This resulted in cross contamination of the "Miller FDLT 45/27" with levels of chlortetracycline at 88.0 ppm.
d. On November 5, 2007, your facility produced a lot of medicated feed, identified as "Nutrabeef Cattle Grower Feed," which is formulated to contain no chlortetracycline, following the production of a medicated feed, identified as "Nutrena CTC 10 Gram," which is formulated to contain relatively high levels (222 lbs per ton) of the Type A, medicated article [redacted] (chlortetracycline). This resulted in cross contamination of the "Nutrabeef Cattle Grower Feed" with levels of chlortetracycline at 4.8 ppm.
We acknowledge your firm's response that: (1) the incident described above regarding Nutrena Naturewise Lamb and Sheep Feed represents an isolated incident; (2) the Billings, Montana facility has reviewed its sequencing and flushing procedures and has determined that the procedures for sequencing feeds are adequate and substantiated with appropriate residue testing analysis; and (3) the importance of proper sequencing and flushing has been reviewed with appropriate personnel. We further acknowledge your firm's decision to no longer manufacture the medicated feed identified as "Nutrena CTC 10 Gram" at the Billings, Montana facility. Though the firm has suspended its production of the Nutrena CTC 10 Gram, this response fails to detail any changes in the firm's sequencing procedures to prevent future cross-contamination of products.
As a manufacturer of medicated feeds you are required to use all Type A, medicated articles and Type B medicated feeds in accordance with their labeled mixing directions. However, you did not use the Type A, medicated article [redacted] in accordance with its labeled mixing directions when you added it directly into feed ration mixes rather than following the product's labeled mixing direction, which indicates to [redacted] and then [redacted] therefore, the use of the new animal drug, Type A, medicated article [redacted] (chlortetracycline), contrary to its approved labeling causes the drug to be deemed unsafe within the meaning of section 512(a)(1) of the Act [21 U.S.C. § 360b(a)(1)] and adulterated within the meaning of section 501(a)(5) of the Act [21 U.S.C. § 351(a)(5)].
We acknowledge your firm's response stating that adding this drug directly from the bag to the mixer "is a long-time standard industry practice" and that "[d]rug reconciliation records, mixer efficiency tests and laboratory assays have all substantiated this practice...." However, this response is inadequate as it fails to indicate what efforts the firm will undertake to bring its manufacturing processes into compliance with the [redacted](chlortetracycline) labeled mixing directions.
The above is not intended to be an all-inclusive list of violations. As a manufacturer of medicated and non-medicated feeds, you are responsible for assuring that your overall operation and the products you manufacture and distribute are in compliance with the law.
You should take prompt action to correct these violations and you should establish procedures whereby such violations do not recur. Failure to promptly correct these violations may result in regulatory and/or administrative sanctions. These sanctions include, but are not limited to, seizure, injunction, and/or notice of opportunity for a hearing on a proposal to withdraw approval of your Medicated Feed Mill License under section 512(m)(4)(B)(ii) of the Act [21 U.S.C. § 360b(m)(4)(B)(ii)] and 21 C.F.R. 515.22(c)(2).
Based on the results of the February 2008 inspection, evaluated together with the evidence before FDA when the Medicated Feed License was approved, the methods used in, or the facilities and controls used for, the manufacture, processing, and packing of medicated feeds are inadequate to assure and preserve the identity, strength, quality, and purity of the new animal drug therein. This letter notifies you of our findings and provides you an opportunity to correct the above deficiencies in your operations.
You should notify this office in writing, within fifteen (15) working days of receipt of this letter, of the specific steps you have taken to correct the noted violations. Your, response should include an explanation of each step being taken to correct the cGMP violations and prevent their recurrence. If corrective action cannot be completed within fifteen (15) working days, state the reason for the delay and the date by which the corrections will be completed. Include copies of any available documentation demonstrating that corrections have been made.
Please send your written response to the Food and Drug Administration, Attention: Michael J. Donovan, Compliance Officer, 22201 23rd Drive SE, Bothell, Washington 98021. If you have questions regarding any issue in this letter, please contact Mr. Donovan at (425) 483-4906.
Sincerely,
/S/
Charles M. Breen District Director
Enclosure:
Form FDA 483
cc: Terry Wright, Plant Manager Cargill, Inc., 1406 Industrial Avenue, Billings, Montana 59101-3127
Sue Carson, Quality Assurance and Regulatory Manager Cargill Animal Nutrition, P.O. Box 5614, Minneapolis, Minnesota 55440-5614
Bob Church, Agricultural Specialist Montana Department of Agriculture, Feed and Fertilizer Division 303 North Roberts, Helena, Montana 59620-0201
http://www.fda.gov/foi/warning_letters/s6856c.htm
> This resulted in levels of chlortetracycline in the lamb and sheep feed up to 1000% higher than the levels indicated on the product's label. ...
holy smokes! no wonder many of us are becoming resistant to antibiotics. ...
http://staphmrsa.blogspot.com/
Chlortetracycline plus lasalocid sodium
http://www.fda.gov/cvm/FOI/141-250033106.pdf
Chlortetracycline review history and regulatory outcomes
snip...
Final review and outcomes
The APVMA completed the Chlortetracycline Review Final Report* in May 1999 but did not publish a final report because only a small number of registrants were involved. The APVMA found that the registration and approvals of the products containing chlortetracycline could be varied to meet the current requirements for continued registration.
In the final review the APVMA recommended:
cancelling approval for the use of chlortetracycline in sheep, lambs and lactating animals
ancelling approval for the use of chlortetracycline in animals producing milk for human consumption. Product labels must carry the statement, ‘Do not use in lactating cows where milk or milk products may be used for human consumption.’
increasing withholding periods for pigs, poultry, and cattle for some use patterns
withdrawing MRLs for milk, sheep, lambs and lactating animals
establishing new MRLs for pig offal (liver and kidney)
establishing MRLs for cattle, eggs and poultry.
Chlortetracycline as a topical application is currently listed in Table 5 of the MRL Standard; Table 5 applies to ‘Uses of substances where maximum residue limits are not necessary‘.
For more information please contact the Chemical Review Program on (02) 6210 4749 or by email to chemrev@apvma.gov.au
* Contact the APVMA for copies of this document
http://www.apvma.gov.au/chemrev/chlortetracyclineHistory.shtml
TSS
Wednesday, July 23, 2008
Thursday, March 27, 2008
Community-associated methicillin-resistant Staphylococcus aureus ST8 ("USA300") in an HIV-positive patient in Cologne, Germany, February 2008
Euro Surveill 2008;13(13) Published online March 2008
Community-associated methicillin-resistant Staphylococcus aureus ST8 ("USA300") in an HIV-positive patient in Cologne, Germany, February 2008
W Witte (wittew@rki.de), C Braulke, B Strommenger
Robert Koch Institut, Wernigerode, Germany
--------------------------------------------------------------------------------
The first cases of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) were reported in 1996 in Minnesota, United States (US) and were deep-seated skin and soft tissue infections and a few cases of necrotising pneumonia, mainly in children and among the Native American population [1]. A few years later, a large outbreak of CA-MRSA infections was reported in the men who have sex with men (MSM) community in California, predominantly among human immunodeficiency virus (HIV)-positive patients; data on sexual transmission was not available [2]. A recent report on the spread of CA-MRSA, mainly due to the widely disseminated strain "USA300", in numerous MSM in San Francisco and in one patient in Boston suggested sexual transmission [3], but initiated critical reviews concerning the transmission route and the corresponding public health message [4,5].
CA-MRSA "USA300", the most widely spread CA-MRSA strain in the US [6], has been detected in Germany since 2005 [7]. This clonal lineage is characterised by multilocus sequence type (MLST) ST8, spa-sequence type t008, SCCmec IVa, the presence of an additional arginine decomposition pathway (arginine catabolic mobile element (ACME) on a staphylococcal cassette chromosome (SCC)-element) with arcA as marker gene, and macrolide-resistance coded by the msrA (efflux pump) and mphB (phosphorylation) genes [7,8]. The contribution of ACME to virulence has been shown in a rabbit model [9]. The capacity of CA-MRSA "USA300" to cause invasive infections seems not to be due to production of the Panton-Valentine leukocidin cytotoxin, but rather to the synthesis of a large number of small phenol-soluble peptides, which are able to recruit and lyse neutrophilic granulocytes [10].
Here we report a case of infection with CA-MRSA ST8 ("USA300") in an HIV-positive 35-year-old MSM patient in Cologne, Germany. The isolate originated from an infected cyst in the upper abdominal area, which opened spontaneously. The patient suffered from acquired immunodeficiency syndrome (AIDS). His CD4+ T-cell count was 200/microlitre with a fully suppressed virus load due to HIV treatment. A specimen from the cyst was taken for microbiological diagnostics. Primary topical treatment was performed by instillation of Leukase beads containing trypsin, framycetin sulphate and lidocaine hydrochloride (Merck, Vienna). After obtaining the microbiology results, oral doxycyclin (200 mg per day) was included in the treatment. The infection had healed completely after 14 days. Nasal swabs were negative for MRSA.
The isolate exhibited the typical characteristics of CA-MRSA ST8 ("USA300", see above). It was resistant to oxacillin, erythromycin, ciprofloxacin, moxifloxacin and susceptible to gentamicin, oxytetracycline, clindamycin, rifampicin, cotrimoxazole, fusidic acid, linezolid, fosfomycin, tigecycline and daptomycin.
As shown in the US, CA-MRSA ST8 ("USA300") may spread rapidly in MSM communities [3]. European doctors caring for HIV-positive patients and MSM with skin and soft tissue infections should be aware of the possibility of CA-MRSA in order to provide proper care and prevent further spread.
Targeted measures include proper bacteriological diagnosis of skin and soft tissue infections in patients attending dermatological and surgical practises, as well as in HIV-positive patients. When MRSA is detected, it is likely that the infection is caused by a CA-MRSA strain. Early recognition of CA-MRSA ST8 ("USA300") is possible by PCR detection of the lukS-lukF and arcA genes [11]. Confirmation is obtained by additional typing such as spa-typing, MLST, and SCCmec [7]. Further spread can be prevented by personal, environmental and health care hygienic measures [12,13].
--------------------------------------------------------------------------------
References
Naimi TS, LeDell KH, Boxrud DJ, Groom AV, Steward CD, Johnson SK, et al. Epidemiology and clonality of community-acquired methicillin-resistant Staphylococcus aureus in Minnesota. Clin Infect Dis. 2001 Oct 1;33(7):990-6.
Centers for Disease Control and Prevention (CDC). Outbreaks of community-associated methicillin-resistant Staphylococcus aureus skin infection - Los Angeles County California, 2002-2003. MMWR Morb Mortal Wkly Rep. 2003;52(5):88. Available from: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5205a4.htm
Diep BA, Chambers HF, Graber CJ, Szumowski JD, Miller LG, Han LL, et al. Emergence of multidrug-resistant, community-associated, methicillin-resistant Staphylococcus aureus clone USA300 in men who have sex with men. Ann Intern Med. 2008;148(4):249-57.
Skiest D, Brown K, Cooper TW, Hoffman-Roberts H, Mussa HR, Elliott AC. Prospective comparison of methicillin-susceptible and methicillin-resistant community associated Staphylococcus aureus infections in hospitalized patients. J Infect. 2007;54(5):427-34.
Centers for Disease Control and Prevention (CDC). CDC statement on MRSA in men who have sex with men. 2008 Jan 16. Available from: http://www.cdc.gov/od/oc/media/pressrel/2008/t080116.htm
Van de Laar MJW, Monnet DL, Herida M. Multidrug-resistant methicillin-resistant Staphylococcus aureus (MRSA) strain in a men-who-have-sex-with-men (MSM) community in the United States: comment. Euro Surveill. 2008;13(3). Available from: http://www.eurosurveillance.org/edition/v13n03/080117_1.asp
Witte W, Strommenger B, Cuny C, Heuck D, Nuebel U. Methicillin-resistant Staphylococcus aureus containing the Panton-Valentine leucocidin gene in Germany in 2005 and 2006. J Antimicrob Chemother. 2007;60(6):1258-63.
Tenover F, McDougal L, Goering RV, Killgore G, Projan SJ, Patel JB, et al. Characterization of a strain of community-associated methicillin-resistant Staphylococcus aureus widely disseminated in the United States. J Clin Microbiol. 2006;44(1):108-18.
Chambers HF. Deconstructing virulence of the community MRSA clone USA300. in NARSA 8th Annual Meeting. 2007. Reston, VA, USA, March 5-6. Available from: http://www3.niaid.nih.gov/topics/antimicrobialResistance/PDF/futureMedicineMRSAeditorial.pdf
Wang R, Braughton KR, Kretschmer D, Bach TH, Queck SY, Li M, et al. Identification of novel cytolytic peptides as key virulence determinants. Nature Med. 2007;13(12):1510-4.
Strommenger B, Braulke C, Pasemann B, Schmidt C, Witte W. Multiplex PCR for rapid detection of Staphylococcus aureus isolates suspected to represent community-acquired strains. J Clin Microbiol. 2008;46(2):582-7.
Cohen PR. Community-acquired methicillin-resistant Staphylococcus aureus skin infections: implications for patients and practitioners. Am J Clin Dermatol. 2007;8(5):259-70.
Wiese-Posselt M, Heuck D, Draeger A, Mielke M, Witte W, Ammon A et al. Successful termination of a furunculosis outbreak due to lukS-lukF-positive, methicillin-susceptible Staphylococcus aureus in a German village by stringent decolonization, 2002 - 2005. Clin Infect Dis. 2007;44(11):88-95.
Citation style for this article: . Community-associated methicillin-resistant Staphylococcus aureus ST8 ("USA300") in an HIV-positive patient in Cologne, Germany, February 2008. Euro Surveill 2008;13(13). Available online: http://www.eurosurveillance.org/edition/v13n13/080327_3.asp
http://www.eurosurveillance.org/edition/v13n13/080327_3.asp
tss
Community-associated methicillin-resistant Staphylococcus aureus ST8 ("USA300") in an HIV-positive patient in Cologne, Germany, February 2008
W Witte (wittew@rki.de), C Braulke, B Strommenger
Robert Koch Institut, Wernigerode, Germany
--------------------------------------------------------------------------------
The first cases of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) were reported in 1996 in Minnesota, United States (US) and were deep-seated skin and soft tissue infections and a few cases of necrotising pneumonia, mainly in children and among the Native American population [1]. A few years later, a large outbreak of CA-MRSA infections was reported in the men who have sex with men (MSM) community in California, predominantly among human immunodeficiency virus (HIV)-positive patients; data on sexual transmission was not available [2]. A recent report on the spread of CA-MRSA, mainly due to the widely disseminated strain "USA300", in numerous MSM in San Francisco and in one patient in Boston suggested sexual transmission [3], but initiated critical reviews concerning the transmission route and the corresponding public health message [4,5].
CA-MRSA "USA300", the most widely spread CA-MRSA strain in the US [6], has been detected in Germany since 2005 [7]. This clonal lineage is characterised by multilocus sequence type (MLST) ST8, spa-sequence type t008, SCCmec IVa, the presence of an additional arginine decomposition pathway (arginine catabolic mobile element (ACME) on a staphylococcal cassette chromosome (SCC)-element) with arcA as marker gene, and macrolide-resistance coded by the msrA (efflux pump) and mphB (phosphorylation) genes [7,8]. The contribution of ACME to virulence has been shown in a rabbit model [9]. The capacity of CA-MRSA "USA300" to cause invasive infections seems not to be due to production of the Panton-Valentine leukocidin cytotoxin, but rather to the synthesis of a large number of small phenol-soluble peptides, which are able to recruit and lyse neutrophilic granulocytes [10].
Here we report a case of infection with CA-MRSA ST8 ("USA300") in an HIV-positive 35-year-old MSM patient in Cologne, Germany. The isolate originated from an infected cyst in the upper abdominal area, which opened spontaneously. The patient suffered from acquired immunodeficiency syndrome (AIDS). His CD4+ T-cell count was 200/microlitre with a fully suppressed virus load due to HIV treatment. A specimen from the cyst was taken for microbiological diagnostics. Primary topical treatment was performed by instillation of Leukase beads containing trypsin, framycetin sulphate and lidocaine hydrochloride (Merck, Vienna). After obtaining the microbiology results, oral doxycyclin (200 mg per day) was included in the treatment. The infection had healed completely after 14 days. Nasal swabs were negative for MRSA.
The isolate exhibited the typical characteristics of CA-MRSA ST8 ("USA300", see above). It was resistant to oxacillin, erythromycin, ciprofloxacin, moxifloxacin and susceptible to gentamicin, oxytetracycline, clindamycin, rifampicin, cotrimoxazole, fusidic acid, linezolid, fosfomycin, tigecycline and daptomycin.
As shown in the US, CA-MRSA ST8 ("USA300") may spread rapidly in MSM communities [3]. European doctors caring for HIV-positive patients and MSM with skin and soft tissue infections should be aware of the possibility of CA-MRSA in order to provide proper care and prevent further spread.
Targeted measures include proper bacteriological diagnosis of skin and soft tissue infections in patients attending dermatological and surgical practises, as well as in HIV-positive patients. When MRSA is detected, it is likely that the infection is caused by a CA-MRSA strain. Early recognition of CA-MRSA ST8 ("USA300") is possible by PCR detection of the lukS-lukF and arcA genes [11]. Confirmation is obtained by additional typing such as spa-typing, MLST, and SCCmec [7]. Further spread can be prevented by personal, environmental and health care hygienic measures [12,13].
--------------------------------------------------------------------------------
References
Naimi TS, LeDell KH, Boxrud DJ, Groom AV, Steward CD, Johnson SK, et al. Epidemiology and clonality of community-acquired methicillin-resistant Staphylococcus aureus in Minnesota. Clin Infect Dis. 2001 Oct 1;33(7):990-6.
Centers for Disease Control and Prevention (CDC). Outbreaks of community-associated methicillin-resistant Staphylococcus aureus skin infection - Los Angeles County California, 2002-2003. MMWR Morb Mortal Wkly Rep. 2003;52(5):88. Available from: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5205a4.htm
Diep BA, Chambers HF, Graber CJ, Szumowski JD, Miller LG, Han LL, et al. Emergence of multidrug-resistant, community-associated, methicillin-resistant Staphylococcus aureus clone USA300 in men who have sex with men. Ann Intern Med. 2008;148(4):249-57.
Skiest D, Brown K, Cooper TW, Hoffman-Roberts H, Mussa HR, Elliott AC. Prospective comparison of methicillin-susceptible and methicillin-resistant community associated Staphylococcus aureus infections in hospitalized patients. J Infect. 2007;54(5):427-34.
Centers for Disease Control and Prevention (CDC). CDC statement on MRSA in men who have sex with men. 2008 Jan 16. Available from: http://www.cdc.gov/od/oc/media/pressrel/2008/t080116.htm
Van de Laar MJW, Monnet DL, Herida M. Multidrug-resistant methicillin-resistant Staphylococcus aureus (MRSA) strain in a men-who-have-sex-with-men (MSM) community in the United States: comment. Euro Surveill. 2008;13(3). Available from: http://www.eurosurveillance.org/edition/v13n03/080117_1.asp
Witte W, Strommenger B, Cuny C, Heuck D, Nuebel U. Methicillin-resistant Staphylococcus aureus containing the Panton-Valentine leucocidin gene in Germany in 2005 and 2006. J Antimicrob Chemother. 2007;60(6):1258-63.
Tenover F, McDougal L, Goering RV, Killgore G, Projan SJ, Patel JB, et al. Characterization of a strain of community-associated methicillin-resistant Staphylococcus aureus widely disseminated in the United States. J Clin Microbiol. 2006;44(1):108-18.
Chambers HF. Deconstructing virulence of the community MRSA clone USA300. in NARSA 8th Annual Meeting. 2007. Reston, VA, USA, March 5-6. Available from: http://www3.niaid.nih.gov/topics/antimicrobialResistance/PDF/futureMedicineMRSAeditorial.pdf
Wang R, Braughton KR, Kretschmer D, Bach TH, Queck SY, Li M, et al. Identification of novel cytolytic peptides as key virulence determinants. Nature Med. 2007;13(12):1510-4.
Strommenger B, Braulke C, Pasemann B, Schmidt C, Witte W. Multiplex PCR for rapid detection of Staphylococcus aureus isolates suspected to represent community-acquired strains. J Clin Microbiol. 2008;46(2):582-7.
Cohen PR. Community-acquired methicillin-resistant Staphylococcus aureus skin infections: implications for patients and practitioners. Am J Clin Dermatol. 2007;8(5):259-70.
Wiese-Posselt M, Heuck D, Draeger A, Mielke M, Witte W, Ammon A et al. Successful termination of a furunculosis outbreak due to lukS-lukF-positive, methicillin-susceptible Staphylococcus aureus in a German village by stringent decolonization, 2002 - 2005. Clin Infect Dis. 2007;44(11):88-95.
Citation style for this article: . Community-associated methicillin-resistant Staphylococcus aureus ST8 ("USA300") in an HIV-positive patient in Cologne, Germany, February 2008. Euro Surveill 2008;13(13). Available online: http://www.eurosurveillance.org/edition/v13n13/080327_3.asp
http://www.eurosurveillance.org/edition/v13n13/080327_3.asp
tss
Thursday, March 20, 2008
Methicillin-Resistant and -Susceptible Staphylococcus aureus Sequence Type 398 in Pigs and Humans
Volume 14, Number 3–March 2008
Dispatch
Methicillin-Resistant and -Susceptible Staphylococcus aureus Sequence Type 398 in Pigs and Humans
Alex van Belkum,* Damian C. Melles,* Justine K. Peeters,* Willem B. van Leeuwen,* Engeline van Duijkeren,† Xander W. Huijsdens,‡ Emile Spalburg,‡ Albert J. de Neeling,‡ and Henri A. Verbrugh,* on behalf of the Dutch Working Party on Surveillance and Research of MRSA (SOM)1
*University Medical Center Rotterdam, Rotterdam, the Netherlands; †University of Utrecht, Utrecht, the Netherlands; and ‡National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
Suggested citation for this article
Abstract
Methicillin-resistant Staphylococcus aureus sequence type 398 (ST398 MRSA) was identified in Dutch pigs and pig farmers. ST398 methicillin-susceptible S. aureus circulates among humans at low frequency (0.2%) but was isolated in 3 human cases of bacteremia (2.1%; p = 0.026). Although its natural host is probably porcine, ST398 MRSA likely causes infections in humans.
snip...
Conclusions
The massive colonization of Dutch pigs with a single sequence type of MRSA was unexpected (12). Molecular strain typing was initially compromised because PFGE failed (14). Spa gene sequencing (13) showed heterogeneity in the ST398 MRSA lineage with types t011 and t108, which are closely related, covering >75% of all isolates. Hence, 1 or 2 new MRSA lineages had been discovered. We found a degree of genetic association between spa types and the presence of certain SCCmec cassettes, which suggests bacterial evolution and horizontal DNA exchange in the zoonotic reservoir.
We found that ST398 is rare among Dutch MSSA strains colonizing healthy persons (2 [0.2%] of 829 strains). However, a relatively high number of MSSA isolates homologous to the ST398 MRSA were derived from bacteremic patients (3 [2.1%] of 146; p = 0.026). These 3 bacteremia isolates were not related epidemiologically; they were isolated from different patients in different medical departments over an extended period. This finding suggests that these MSSA strains are quite virulent. The strict segregation of ST398 strains (Figure 1, panel A; Figure 2) corroborates that the strains belong to a separate biotype associated with pigs (15).
Our findings pose a warning to public health surveillance: if the ST398 MSSA virulence toward humans would be maintained within the ST398 MRSA lineage from pigs, care should be taken not to introduce this strain into humans. We consider it to be likely that ST398 MRSA from pigs is capable of causing serious infection in humans even though its primary host seems to be pigs.
Dr van Belkum is with the Department of Medical Microbiology and Infectious Diseases, University Medical Center Rotterdam, Rotterdam, the Netherlands. His research interests include MRSA.
References
snip...full text ;
http://www.cdc.gov/eid/content/14/3/479.htm
Methicillin-resistant Staphylococcus aureus (MRSA)
http://staphmrsa.blogspot.com/2008/03/iceid-2008-methicillin-resistant.html
ICEID 2008 Foodborne Disease Outbreaks Leafy Greens and Meats
International Conference on Emerging Infectious Diseases 2008
Slide Sessions and Poster Abstracts
http://staphmrsa.blogspot.com/2008/03/iceid-2008-foodborne-disease-outbreaks.html
TSS
Dispatch
Methicillin-Resistant and -Susceptible Staphylococcus aureus Sequence Type 398 in Pigs and Humans
Alex van Belkum,* Damian C. Melles,* Justine K. Peeters,* Willem B. van Leeuwen,* Engeline van Duijkeren,† Xander W. Huijsdens,‡ Emile Spalburg,‡ Albert J. de Neeling,‡ and Henri A. Verbrugh,* on behalf of the Dutch Working Party on Surveillance and Research of MRSA (SOM)1
*University Medical Center Rotterdam, Rotterdam, the Netherlands; †University of Utrecht, Utrecht, the Netherlands; and ‡National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
Suggested citation for this article
Abstract
Methicillin-resistant Staphylococcus aureus sequence type 398 (ST398 MRSA) was identified in Dutch pigs and pig farmers. ST398 methicillin-susceptible S. aureus circulates among humans at low frequency (0.2%) but was isolated in 3 human cases of bacteremia (2.1%; p = 0.026). Although its natural host is probably porcine, ST398 MRSA likely causes infections in humans.
snip...
Conclusions
The massive colonization of Dutch pigs with a single sequence type of MRSA was unexpected (12). Molecular strain typing was initially compromised because PFGE failed (14). Spa gene sequencing (13) showed heterogeneity in the ST398 MRSA lineage with types t011 and t108, which are closely related, covering >75% of all isolates. Hence, 1 or 2 new MRSA lineages had been discovered. We found a degree of genetic association between spa types and the presence of certain SCCmec cassettes, which suggests bacterial evolution and horizontal DNA exchange in the zoonotic reservoir.
We found that ST398 is rare among Dutch MSSA strains colonizing healthy persons (2 [0.2%] of 829 strains). However, a relatively high number of MSSA isolates homologous to the ST398 MRSA were derived from bacteremic patients (3 [2.1%] of 146; p = 0.026). These 3 bacteremia isolates were not related epidemiologically; they were isolated from different patients in different medical departments over an extended period. This finding suggests that these MSSA strains are quite virulent. The strict segregation of ST398 strains (Figure 1, panel A; Figure 2) corroborates that the strains belong to a separate biotype associated with pigs (15).
Our findings pose a warning to public health surveillance: if the ST398 MSSA virulence toward humans would be maintained within the ST398 MRSA lineage from pigs, care should be taken not to introduce this strain into humans. We consider it to be likely that ST398 MRSA from pigs is capable of causing serious infection in humans even though its primary host seems to be pigs.
Dr van Belkum is with the Department of Medical Microbiology and Infectious Diseases, University Medical Center Rotterdam, Rotterdam, the Netherlands. His research interests include MRSA.
References
snip...full text ;
http://www.cdc.gov/eid/content/14/3/479.htm
Methicillin-resistant Staphylococcus aureus (MRSA)
http://staphmrsa.blogspot.com/2008/03/iceid-2008-methicillin-resistant.html
ICEID 2008 Foodborne Disease Outbreaks Leafy Greens and Meats
International Conference on Emerging Infectious Diseases 2008
Slide Sessions and Poster Abstracts
http://staphmrsa.blogspot.com/2008/03/iceid-2008-foodborne-disease-outbreaks.html
TSS
Wednesday, March 19, 2008
ICEID 2008 Foodborne Disease Outbreaks Leafy Greens and Meats
Page 1 of 262
International Conference on Emerging Infectious Diseases 2008
Slide Sessions and Poster Abstracts
Foodborne Disease Outbreaks Associated with Leafy Greens, 1973–2006
K. M. Herman, T. L. Ayers, M. Lynch; Centers for Disease Control and
Prevention, Atlanta, GA.
Background: Several recent large outbreaks have been associated with leafy
green foods in the United States, such as Escherichia coli O157:H7 infections due to spinach;
however, the characteristics of all reported outbreaks due to leafy greens have not been described. The Centers for Disease Control and Prevention conducts surveillance for foodborne disease outbreaks (FBDO) investigated by local and state health departments in the United States. Methods: We reviewed data from the FBDO surveillance system for 1973-2006. A leafy green-associated FBDO is defined as two or more illnesses due to the consumption of a single leafy green food item (lettuce, cabbage, mesclun mix, spinach) or a salad item containing one or more leafy greens. These data were compared with U.S. leafy greens per capita availability, a proxy for leafy green consumption. Results: Among 10,421 FBDO reported during 1973-
2006, 502 (4.8%) outbreaks, 18,242 (6.5%) illnesses, and 15 (4.0%) deaths were associated with leafy greens. Among leafy green-associated FBDO with a confirmed etiology, Norovirus was responsible for 196 (58.3%) outbreaks, followed by Salmonella, 35 (10.4%) outbreaks, and
Escherichia coli O157:H7, 30 (8.9%). The median size of leafy green-associated outbreaks (18 illnesses) was twice the median size of non-leafy green-associated outbreaks (9). During 1986-1995, U.S. leafy green consumption increased 17.2% from the previous decade. During the same period, the proportion of all FBDO due to leafy greens increased 59.6%. Likewise, during 1996-2005 leafy green consumption increased 9.0% and leafy greenassociated outbreaks increased 38.6%. In 296 (69.4%) outbreaks, leafy greens were served at a restaurant; 11 (2.2%) involved cases in multiple states. Conclusions: Leafy greens are an important cause of FBDO and may transmit pathogens with human or animal reservoirs. The proportion of FBDO due to leafy greens has increased, and cannot be accounted for completely by an increase in leafy green
consumption. Contaminated leafy greens may cause restaurant-associated or widespread outbreaks. Efforts by local, state, and federal agencies to control leafy green outbreaks should span from the point of harvest to the point of preparation.
Board 21. Fresh produce outbreaks in Australia, 2001-2006
M. D. Kirk1, K. Fullerton1, J. Gregory2; 1OzFoodNet, Canberra, AUSTRALIA,
2OzFoodNet, Department Human
Services, Victoria, AUSTRALIA.
Background: Recent outbreaks in Australia and abroad have highlighted the role of fresh produce in foodborne disease outbreaks. Since fresh produce is often eaten without
cooking, its outbreak potential can be significant. Methods: Data from the OzFoodNet Outbreak Register from January 2001 to June 2005 were reviewed. OzFoodNet Quarterly and Annual Reports (published and unpublished) from July 2005 through December 2006 were also reviewed. Produce-related outbreaks were defined as outbreaks of foodborne or suspected foodborne transmission where the confirmed or suspected vehicle included fresh, uncooked produce. Results: From January 2001 through June 2005 there were 1767 reported gastroenteritis outbreaks recorded. Of these outbreaks, 426 (24%) were either foodborne (157, 37%) or suspected foodborne (269, 63%). Sixteen (4%) of these outbreaks were identified as produce-related. An additional 9 produce-related outbreaks were identified in the review of quarterly and annual reports. These 25 outbreaks affected at least 686 people, with 51 people hospitalized and no fatalities. The mean number of people affected in these outbreaks was 30 people, with a range from 2 to 125 people. These outbreaks occurred in association with food served at restaurants (44%), primary produce (20%), and fastfood/ takeaway food (20%). These outbreaks were caused by Salmonella (60%), followed by unknown aetiology (20%), norovirus (12%), and Campylobacter (8%). Conclusions: Fresh produce causes considerable foodborne
disease in Australia. Fresh produce is particularly vulnerable to causing outbreaks due to the lack of an adequate killstep for pathogens.
Board 95. Tomato Handling Policies and Practices in Restaurants
E. G. Kirkland, V. J. Radke, C. A. Selman; CDC, EHS-Net, Atlanta, GA.
Background: Recently, several foodborne illness outbreaks have been associated with tomatoes served in restaurants. Prevention of foodborne illness outbreaks requires proper food storage and preparation practices; these tomato outbreaks suggest that tomatoes are being stored and prepared improperly in restaurants. Yet relatively little data exists on tomato storage and preparation policies and practices in restaurants. Thus, the purpose of this study is to gain a better understanding of how tomatoes are stored and prepared in restaurants. Methods: Data were collected in 450 restaurants through interviews with restaurant managers and observations of tomato storage, washing and cutting in restaurant kitchen environments. This study was conducted by the Environmental Health
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Specialists Network (EHS-Net). EHS-Net is a collaboration involving the Centers for Disease Control and Prevention (CDC), the U.S. Food and Drug Administration (FDA), and nine Emerging Infections Program sites (California, Connecticut, Georgia, Iowa, Minnesota, New York, Rhode Island and Tennessee); these partners have come together in an effort to better understand the environmental causes of foodborne illness. Results: The median temperature of prepared tomatoes in storage and holding was 44°F degrees; the median temperature of cut tomatoes in storage and holding was 43°F degrees. In 94% of restaurants, managers reported that tomatoes were washed; in 83% of washing observations, tomatoes were rinsed or held under running water and in 18% of washing observations, tomatoes were soaked or immersed in water. Produce-only cutting boards were used in 51% of tomatocutting
observations, and gloves were used in 64% of observations. Conclusions: Some good tomato handling practices were observed. For example, most restaurants reported washing their tomatoes, and gloves were used in the majority of tomato-cutting observations. However, some practices did not meet FDA recommendations for preventing pathogen contamination and proliferation on tomatoes- cut tomatoes were stored above 41 degrees, tomatoes were washed by soaking in water rather than by placing under running water, and produce only cutting
boards were not always used. These data indicate that education concerning safe tomato handling practices is needed in restaurants.
Foodborne & Waterborne Infections
Board 87. Foodborne Disease Outbreak Trends, and Sources and Timeliness of
Detection in Connecticut, 2004-2007
D. Mlynarski, Q. Phan, T. Rabatsky-Ehr, K. Purviance, J. Brockmeyer, J. Krasnitski, A. Nepaul, L. LoBianco, K. Frenette, P. Mshar, J. L. Hadler; Connecticut Department of Public Health,
Hartford, CT.
Background: It is critical to public health preparedness (PHP) to understand the epidemiology of outbreaks, and means and timeliness of their detection. In Connecticut (CT), foodborne
disease outbreaks (FOs) are considered public health emergencies reportable by telephone to state and local public health authorities. We examined 3.5 years of FO surveillance in CT as part of a broader effort at enhancing PHP-related surveillance. Methods:CT data reported to CDC by the electronic Foodborne Outbreak Reporting System was reviewed for January 2004-June 2007. The number, causative agents, settings and food vehicles implicated were
examined. Methods of detection were summarized; median time delay from first illness onset to public health notification was calculated. Results: From 1/1/04-6/30/07, 58 FOs were reported. The number increased annually from 13 to 19 between 2004 and 2006 with 10
FOs in the first 6 months of 2007. Causative agents included norovirus (62%), bacterial pathogens (28%), toxins (3%) and parasites (2%). The increase from 2004 to 2006 was mainly due to norovirus (7 to 12). Overall, 64% of FOs were associated with contamination or mishandling of food at food service establishments and 19% with widely distributed contaminated food items. Private citizens reported 62% (median 3-day delay) and clinicians reported 12% (median 1-day delay) of FOs. Public health surveillance, including routine Pulsed Field Gel Electrophoresis (PFGE) of selected bacterial pathogens, detected 21% (median 26-day delay). Most (71%) PFGE-identified outbreaks were associated with widely distributed food items. Conclusions: Reported FOs have been increasing, in part driven by an increase in those due to norovirus. Astute citizens and clinicians are the most important sources of rapid detection and
reporting. Clinicians have a responsibility to report suspected outbreaks and assist in their detection by ordering appropriate diagnostic testing on persons with acute gastrointestinal
illness. Active public health surveillance, including routine PFGE typing, is important to detection of outbreaks caused by widely distributed contaminated food items; however, it is not very timely. Efforts are needed to improve timeliness of detection of outbreaks, particularly those using molecular subtyping methods such as PFGE.
Board 88. Indiana Outbreak of Salmonella I 4,[5],12:i:- monophasic at a
Supermarket Deli – 2006
L. Granzow1, S. Gorsuch1, B. Swearingen2; 1Indiana State Department of
Health, Indpls, IN, 2Johnson County Health
Department, Greenwood, IN.
Background: On July 11, 2006, the Indiana State Department of Health (ISDH) initiated an investigation in response to an increase in salmonellosis in two adjacent counties.
Geographic information system (GIS) mapping confirmed the clustering of cases at the respective north-south borders of the two counties. The most common exposure (76.2%) among cases was a supermarket (SM) location, with 78.9% of cases having purchased items from
the deli. Pulse-field gel electrophoresis (PFGE) confirmed 199 cases in a 2-enzyme matched outbreak of Salmonella I 4,[5],12:i:- monophasic, an emerging serotype. The PFGE pattern was unique during the outbreak period on the national PulseNet database with a rare Bln I pattern (0.35%). The multiple-locus variable-number tandem repeat analysis (MLVA) pattern was also unique (N of I 4,[5],12:i:- database = 450). The outbreak ended after a near 4-month period, including 15 counties and 2 out-of state residents. A knife block at the SM was a 2-enzyme match for the outbreak strain. Methods: The ISDH conducted a case-control study (1:1, N=32), matched by zip code, using a reverse digit dialing system. The study case definition included those with onset dates in July and met the clinical definition of salmonellosis. The Fisher’s exact test (SAS 9.1) was used to evaluate the association between illness and exposure. Results: Of the five supermarkets reported, a statistically significant relationship (a = 0.05) was found
between illness and shopping at the SM deli (OR=21.21, p<0.0001).> 4 µg/mL) increased significantly (p=0.0158) from 2002 (13.8%) to 2005 (19.6%), and dropped slightly in 2006 (18.9%)
following the ban of fluoroquinolone use in poultry production. In C. jejuni from chicken breast, however, CipR was present in 15.1% of isolates from 2005 and 16.9% in 2006. During the five year testing, TetR increased from 27.6% to 47.8% overall. EryR each year was present
in <1%> 5 antimicrobials was AZI-CLI-ERY-TEL-TET. C. coli showed higher proportion of
MDR than C. jejuni. The PFGE results showed that Campylobacter genetically were very diverse, however certain clones were widely dispersed in different meat brands from different store chains in all five years. Conclusions: Campylobacter, including antimicrobial resistant strains, persist in retail chicken meats and provide a reservoir of resistant strains in the food supply.
Antimicrobial Resistance
Board 6. Salmonella enterica serovar Heidelberg from Retail Meats: Results:
of the National Antimicrobial Resistance Monitoring System (NARMS): 2002-2006.
S. Zhao, E. Hall-Robinson, A. Glenn, S. Friedman, J. Abbott, S. Ayers, P.
McDermott; Food & Drug Administration, Laurel, MD.
Background: Salmonella enterica serovar Heidelberg is frequently associated with foodborne illness in humans, and is commonly isolated from poultry and their derived meats. A recent upsurge in antimicrobial resistance in this serovar has been recognized. There are few data on the prevalence, antimicrobial susceptibility, and genetic diversity of S. Heidelberg isolates in retail meats. Methods: We compared the prevalence of S. Heidelberg in a sampling of 20,294 meats, including chicken breast, ground turkey, ground beef and pork chops collected during
2002-2006 for the National Antimicrobial Resistance Monitoring System (NARMS). Isolates were analyzed for
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antimicrobial susceptibility and compared genetically using pulsed-field gel electrophoresis (PFGE). Results: A total of 297 S. Heidelberg isolates were recovered, representing 22%(297/1372) of all Salmonella serovars from retail meats. Among the 297 isolates, 178 (60%) from ground turkey, 109 (37%) from chicken breast and 10 (2%) from pork chop; no S. Heidelberg was found in ground beef. A total of 197 (66%) of the isolates were resistant to at least one of
the 15 antimicrobial agents tested and 49 (16%) of the isolates were resistant to >5 antimicrobials. Five isolates (1.7%) were resistant to >9 antimicrobials, all of which were recovered form ground turkey. The proportion of resistance to different antimicrobials were: tetracycline (40%), streptomycin (38%), sulfamethoxazole (30%), gentamicin (27%), and kanamycin (21%), ampicillin (19%), amoxicillin-clavulanic acid (10%), cefoxitin (9%), ceftiofur
(9%), chloramphenicol (1%), and nalidixic acid (1%). Resistance was consistently more prevalent in S. Heidelberg from ground turkey than from chicken breast. All isolates were susceptible
to amikacin, ceftriaxone, ciprofloxacin and trimethoprim/ sulfamethoxazole. PFGE using XbaI and BlnI generated 107 patterns. Certain clones were widely dispersed in different types of meats and meat brands from different store chains in all three sampling years. Conclusions: These date indicate that S. Heidelberg is a common serovar in retail poultry meats, and includes clones of multidrug-resistant strains.
Board 18. Human Health Burden of Acute Diarrheal Illness in the United
States, FoodNet Population Survey, 2006-2007
L. B. Moyer1, P. Clogher2, C. Fuller3, T. F. Jones4, A. Lasher5, D. M.
Norton6, S. Solghan7, M. Tobin-D'Angelo8, O.
Henao9; 1CDC and VA Medical Center, Atlanta, GA, 2CT EIP, New Haven, CT, 3MN
Dept of Health, St Paul, MN, 4TN
Dept of Health, Nashville, TN, 5FDA, College Park, MD, 6CA EIP, Oakland, CA,
7NY Dept of Health, Albany, NY, 8GA
Div of Publ Health, Atlanta, GA, 9CDC, Atlanta, GA.
Background: Foodborne pathogens cause an estimated 76 million illnesses each year. Although most illnesses are self-limiting, the human health burden is substantial and includes healthcare provider visits, medications, laboratory tests, hospitalizations, and time missed from work. We describe the human health burden of acute diarrheal illness using data from the 2006-2007 FoodNet Population Survey. Methods: During 2006-2007, FoodNet conducted a 12-month population-based survey in 10 sites using a standard random-digit dialing methodology.
Demographic information was collected and respondents were asked about illness and activities in the month beforethe interview. Acute diarrheal illness was defined as >3 loose stools in 24-hours lasting >1 day or resulting in impairment of daily activities. Persons with a chronic illness in which diarrhea was a major symptom were excluded. Weighted proportions were calculated to adjust for study design and age and sex. Results: The weighted prevalence
of acute diarrheal illness in the month prior to interview was 6.9% (95% CI 6.6-7.2). Acute diarrheal illness prevalence was greatest among those <5>65 years old (4.4%, 95%
CI 3.5-5.3). The mean duration of diarrhea was 4 days (median 2) and 1.7% reported bloody diarrhea. Of the 20.0% who visited a medical care provider, 26.7% went to a doctor’s office or
clinic more than once, 13.0% went to an emergency department, 1.0% were admitted to a hospital overnight and an additional 2.3% spent more than one night in the hospital. Stool specimens were submitted from 4.0% of persons reporting acute diarrheal illness, 32.9%
took anti-diarrheal medications and 10.6% used antibiotics. Of those who had a job during this time period (52.0%), 33.2% missed time from work because of their or their child’s illness
(median 2 days). Of those attending school (7.2%), 66.3% missed time from school because of the illness (median 2 days). Conclusion: Acute diarrheal illness remains an important human health burden causing substantial personal and societal costs from multiple healthcare contacts and days missed from work or school. Continued efforts are needed to identify the causes and risk factors for illness; thus, helping to direct intervention and prevention efforts to reduce the burden of illness.
Board 19. Salmonella Bacteriuria in New York State FoodNet Counties,
2002-2006
G. L. Smith1, S. M. Zansky2, D. L. Hoefer2, J. B. Karr3, N. L. Spina2, S. M.
Solghan2, T. P. Root4; 1NYSDOH, Geneva,
NY, 2NYSDOH, Albany, NY, 3NYSDOH, Rochester, NY, 4Wadsworth Center
Laboratories-NYSDOH, Albany, NY.
Background: Salmonellosis is a major cause of foodborne illness in the U.S. Commonly associated with gastrointestinal illness, it can also cause extra-intestinal illness including urinary tract infections. Recent national trends indicate Salmonella bacteriuria increasing in incidence and as a proportion of all Salmonella, especially among elderly women. Analysis of Salmonella bacteriuria in 34 New York State (NYS) Emerging Infections Program (EIP)
FoodNet counties was conducted to look for similar trends. Methods: The NYS FoodNet program has conducted population-based active surveillance for laboratory-confirmed cases of
infection of Salmonella. Using the NYS Department of Health (NYSDOH) Communicable Disease Electronic Surveillance System (CDESS) and the Clinical Laboratory Information System (CLIMS), confirmed cases of Salmonella identified between 2002-2006 were included
in this analysis. The most invasive source for each case is recorded. Data was examined to compare incidence rates of Salmonella isolated from urine and proportion of urine isolates by gender and age group. Results: 2337 confirmed cases of Salmonella were identified between 2002-2006. Of 2333 cases with a known specimen source, 189 cases were isolated from urine (8.1%). The annual proportion of urine isolates ranged from 5.1% (2002) to 11.1% (2005).
The incidence rate of Salmonella bacteriuria increased from 0.8 cases per 100,000 persons in 2002 to 1.1/100,000 in 2006 with the highest rate of 1.3/100,000 in 2005. Most cases isolated from urine occurred among women (88.4%). For both sexes, incidence from urine increased with age, beginning around 50 years of age with the greatest percentage of cases attributable to those >70 years. Conclusions: Salmonella bacteriuria has long been identified in
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NYS residents but recently represent a greater proportion of the total cases. The majority of cases occur in elderly females similar to national reports. Collecting and reporting specimen
source is an important component of foodborne disease surveillance, helping to identify changes in the epidemiology of those illnesses. Possible change in test practices, role of urine catheters, and urine predilection of some Salmonella serotypes may contribute to the
increased incidence of Salmonella bacteriuria in NYS and warrant further study.
Board 239. Antimicrobial Resistant Salmonella from Retail Chicken in
Pennsylvania 2006-2007
S. C. Rankin1, N. M. Mikanatha2, D. Tewari3, A. Russo3, R. Localio1, S.
Altekruse4, C. Sandt5, E. Lautenbach1, J.
Tait2, M. Hydock3, S. Reynolds5, N. G. Warren5, T. M. Chiller6, D. G.
White7; 1University of Pennsylvania,
Philadelphia, PA, 2Pennsylvania Department of Health, Harrisburg, PA,
3Pennsylvania Department of Agriculture,
Harrisburg, PA, 4National Institutes of Health, Bethesda, MD, 5Pennsylvania
Department of Health, Lionville, PA,
6Centers for Disease Control and Prevention, Atlanta, GA, 7Food and Drug
Administration, Laurel, MD.
Background: Infections caused by antibiotic-resistant Salmonella strains are
associated with more severe
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illnesse, and higher mortality than those due to susceptible strains. Consumption of chicken is a known risk factor for salmonellosis. However, the prevalence of resistant Salmonella in poultry meat and their relationship to human Salmonella isolates has not been well-characterized. Methods: Chicken was purchased from a stratified random sample of retail outlets in a three county region of Central Pennsylvania for 12 months during 2006-2007. Each month 30 samples were purchased from retail outlets. The samples included prepackaged and open display poultry. Information was obtained on USDA establishment numbers and
organic/antibiotic-free status from package labels, where available. Isolates were characterized by serotyping, antibiotic susceptibility testing and pulsed-field gel electrophoresis (PFGE). Antibiotic resistant strains were analyzed for the presence of resistance genes by PCR. PFGE profiles of antibiotic resistant isolates were compared with human Salmonella isolates from the state public health laboratory during the study period. Results: Salmonella was isolated
from 84 (22%) of 378 samples. The most common serotypes were Typhimurium 28 (33%), Kentucky 24 (29%), and Enteritidis 22 (26%). 45 isolates showed resistance to one or more drugs; 40% demonstrated resistance to at least five drugs. 8/45 (18%) resistant isolates had a blaCMY ß-lactamase gene. The packaged chicken originated from 20 different establishments. Salmonella isolation was associated with poultry from particular establishments (p=0.007, chi sq=37.6, df=19). In one establishment that processed only organic poultry, 10 (53%) of 19 samples were positive. PFGE patterns of Typhimurium and Kentucky isolates from chicken matched patterns in the human database. Conclusion: The occurrence of drug-resistant Salmonella in retail chicken is a public health concern. This study identified strains with
reduced susceptibility to expanded-spectrum cephalosporins and isolates from humans and chickens with the same PFGE profiles. The study also identified an association of Salmonella
contamination with poultry from specific establishments. These results indicate the need for enhanced inter-agency surveillance.
Board 225. Longitudinal Study of Antimicrobial Resistance among Escherichia
coli Isolated from Integrated Multi-site Cohorts of Humans and Swine
W. Alali1, H. M. Scott1, R. Harvey2, B. Norby1, B. Lawhorn1, S. Pillai1;
1Texas A&M University, College Station, TX,
2USDA-ARS-SPARC, College Station, TX.
Background: Many studies have attempted to link antimicrobial use in food animal agriculture with an increased risk of antimicrobial-resistant (AR) bacterial levels in humans. Methods: We examined the relationship between the prevalence of AR E. coli isolated from human wastewater and swine fecal samples and the risk factors: (host species, production type (swine), vocation (human swine workers, non-workers, and slaughter-plant workers), and season) in a multi-site housing, vertically integrated swine and human population agri-food system. Human and swine E. coli (N = 4048 and 3485, respectively) isolated from wastewater and
fecal samples were tested for antimicrobial susceptibility using the SensititreTM broth microdilution system. Results: There were significant (P < 0.05) differences in AR isolates: 1) between host-species with swine at higher risk for tetracycline, kanamycin, ceftiofur, gentamicin, streptomycin, chloramphenicol, sulfisoxazole, and ampicillin, 2) swine production group was significantly associated with AR with purchased boars, nursery piglets, and breeding boars at a higher risk of Page 190 of 262 resistance to streptomycin and tetracycline, and 3) human swine worker cohorts exhibited lowered sulfisoxazole and cefoxitin prevalence compared to non-workers, while slaughter-plant workers exhibited elevated cefoxitin prevalence compared to non-workers. High variability among seasonal samples over the 3-year period was observed. There were significant differences in multiple resistance isolates between host species, with swine at higher risk than humans of carrying multi-resistant strains, slaughter-plant workers at higher risk than swine non-workers; however, there were no significant differences in multiple resistance isolates within swine by production group. Conclusions: Occupational exposure to slaughter facilities appeared to be associated with an increased relative odds for the prevalence of cefoxitin resistance and multiple resistance compared to swine non-workers.
A Veterinary Curriculum in the Appropriate Use of Antibiotics
P. C. Bartlett; Michigan State University, E. Lansing, MI. Background:
Debate still continues regarding the relative importance of agricultural antibiotic usage in fostering antimicrobial resistance (AR) among human pathogens. This debate may have delayed the development of educational materials aimed at promoting the prudent and judicious use of antibiotics in veterinary medicine. However, a consensus exists that unnecessary or wasteful usage should be curtailed whenever possible. Methods: The U.S. Centers for Disease Control and Prevention (CDC) funded the development of an interactive and multi-media educational web site to aid in teaching veterinary students about their responsibilities and obligations to curtail the unnecessary use of antibiotics. The overall purpose is to preserve antibiotic efficacy for both humans and animals. Audio, video, interactive questions and animation are used to make the presentation varied and entertaining. Written for veterinary students, the site also has applicability to others in the food animal industries. Results: The web site is designed to supplement existing courses in public health, epidemiology, pharmacology and species-specific veterinary medicine. The introductory module emphasizes the interconnectedness of animal and human health as it follows an outbreak investigation scenario to teach basic microbiologic and epidemiologic principles of AR. Also taught are methods for determining AR and the importance of AR to public health. Species-specific modules regard international issues and multiple clinical situations for dairy cattle, beef cattle, exotic animals and swine. Future modules will address
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companion animals and poultry. Emphasis is on therapeutic situations when antimicrobial agents are often used unnecessarily when alternative treatment methods are available, when the use of antibiograms (susceptibility profiles) is possible or when antibiotic treatment may be less efficacious and economical than are available preventive medicine procedures. Conclusions: This web site is being written for training veterinary students throughout the USA, but it will be freely available to the international public. The web site is due for release in 2008. Search: CDC Get Smart on the Farm or find the link at the CDC web site:
http://www.cdc.gov/narms/get_smart.htm
or
www.cvm.msu.edu
Antimicrobial Resistance
Board 79. Antimicrobial Resistance in Salmonella Isolates Recovered from Cattle at Slaughter
P. J. Fedorka-Cray1, J. G. Frye1, M. Rose2, N. Anandaraman3, J. Haro1; 1USDA-ARS, Athens, GA, 2Intervet Innovation GmbH, Schwabenheim, GERMANY, 3USDA-FSIS, Washington, DC.
Background: Since 1997, the animal arm of the National Antimicrobial Resistance Monitoring System (NARMS) has monitored changes in antimicrobial susceptibilities of Salmonella isolates from animal origin. Additionally, since 2000, susceptibility of bovine Salmonella isolates collected in the US has been monitored against the 4th generation cephalosporins (4-GC) cefquinome, exclusively developed for veterinary medicine, and cefepime. Cephalosporins are used extensively to treat human and cattle diseases. To identify emerging resistance patterns, resistance trends to the cephalosporins (ceftriaxone, ceftiofur, cefoxitin and cefquinome) in Salmonella isolates collected from cattle at slaughter were analyzed. Methods: Salmonella enterica isolates (n=7,199) obtained from cattle at federally inspected slaughter/processing plants during 1997 - 2006 and submitted to NARMS were tested for minimum inhibitory concentrations (MICs) using a custom panel of antimicrobials. Isolates collected during 2000-2006 (n=4,685) were also tested on a second panel with cefquinome and cefepime. Results: Resistance to ceftriaxone remained below 1%, except in 2005 when resistance increased to 2.1%. From 1997 to 2005, resistance to ceftiofur increased from 0% to 21.6%, with the exception of 2004 when it decreased to 13.3%. Resistance decreased again in 2006 to 18.9%. A similar pattern was observed for cefoxitin (testing started in 2000). Cefoxitin resistance increased from 2000 to 2005 from 9.1% to 19.8%, except in 2004 when it decreased to 13.2%. As with ceftiofur, a decrease was observed in 2006 when resistance was 17.9%. From 2000 to 2006 the MIC50 of cefquinome remained at 0.06 µg/ml, except in 2002 when the MIC50 increased by one dilution to 0.12 µg/ml. The highest MIC90 for cefquinome was 1.0 µg/ml in 2002 and 2005. MICs of cefepime were generally about one dilution step below those of cefquinome. Changes in resistance for all drugs were in large part driven by serotype, particularly S. Newport, Reading, Typhimurium and Agona. Conclusions: Salmonella enterica isolates remained highly susceptible to the human 3-GC ceftriaxone and the 4-GCs cefquinome and cefepime. Overall, an increase in both veterinary 3-GC ceftiofur and human 2-GC cefoxitin has been observed at similar levels and appears to be serotype dependent.
Board 80. Prevalence of Antibiotic Use, Knowledge and Attitudes Toward Antibiotic-free Meat
S. C. Rankin1, N. M'ikanatha2, R. Dewar2, E. Lautenbach1; 1University of Pennsylvania, Philadelphia, PA, 2Pennsylvania Department of Health, Harrisburg, PA.
Background: Inappropriate use of antibiotics is a major public health concern as it contributes to antimicrobial resistance. Understanding consumers’ knowledge and attitudes can inform multifaceted actions to achieve judicious use of antibiotics. Methods: In 2006 questions regarding antibiotic prescriptions and attitudes toward antibiotic-free meat were asked as part of Pennsylvania Behavioral Risk Factor Surveillance System (BRFSS). Results: Among Pennsylvania adults, 38.1% (95% CI, 36.4-39.8%) responded they had been prescribed antibiotics in the previous 12 months and 43.9% (95%CI, 41.1-46.7%) of these had received at least two prescriptions. Among adults taking antibiotics in the past year, 11.4% (95%CI, 9.6-13.6%) had not completed the course of treatment. Prescriptions for self-identified diagnoses usually not caused by bacteria (e.g., cough or cold) were reported by 30.3% (95%CI, 27.7-33.1%). Knowledge about use of antibiotics in animal husbandry varied by demographic characteristics (Figure): 53.6% (95% CI, 52.8%-55.4%) of non-Hispanic whites were aware of antibiotics in feed, whereas 42% (95% CI, 34.8-50.1%) of African Americans and 39.8% (95%CI, 29.0-51.7%) of Hispanics were aware. Knowledge also increased with age, education, and income. Overall 26.2% (95% CI, 24.6- 31.9%) of the survey participants reported that that they try to purchase antibiotics-free meat. Conclusion: Inappropriate prescriptions and noncompliance with treatment regimens call for simultaneous interventions among clinicians and patients. To promote judicious use of antibiotics in food animals, additional measures to engage consumers are needed.
see full text of these abstracts 262 pages ;
http://www.cdc.gov/eid/content/14/3/ICEID2008.pdf
TSS
International Conference on Emerging Infectious Diseases 2008
Slide Sessions and Poster Abstracts
Foodborne Disease Outbreaks Associated with Leafy Greens, 1973–2006
K. M. Herman, T. L. Ayers, M. Lynch; Centers for Disease Control and
Prevention, Atlanta, GA.
Background: Several recent large outbreaks have been associated with leafy
green foods in the United States, such as Escherichia coli O157:H7 infections due to spinach;
however, the characteristics of all reported outbreaks due to leafy greens have not been described. The Centers for Disease Control and Prevention conducts surveillance for foodborne disease outbreaks (FBDO) investigated by local and state health departments in the United States. Methods: We reviewed data from the FBDO surveillance system for 1973-2006. A leafy green-associated FBDO is defined as two or more illnesses due to the consumption of a single leafy green food item (lettuce, cabbage, mesclun mix, spinach) or a salad item containing one or more leafy greens. These data were compared with U.S. leafy greens per capita availability, a proxy for leafy green consumption. Results: Among 10,421 FBDO reported during 1973-
2006, 502 (4.8%) outbreaks, 18,242 (6.5%) illnesses, and 15 (4.0%) deaths were associated with leafy greens. Among leafy green-associated FBDO with a confirmed etiology, Norovirus was responsible for 196 (58.3%) outbreaks, followed by Salmonella, 35 (10.4%) outbreaks, and
Escherichia coli O157:H7, 30 (8.9%). The median size of leafy green-associated outbreaks (18 illnesses) was twice the median size of non-leafy green-associated outbreaks (9). During 1986-1995, U.S. leafy green consumption increased 17.2% from the previous decade. During the same period, the proportion of all FBDO due to leafy greens increased 59.6%. Likewise, during 1996-2005 leafy green consumption increased 9.0% and leafy greenassociated outbreaks increased 38.6%. In 296 (69.4%) outbreaks, leafy greens were served at a restaurant; 11 (2.2%) involved cases in multiple states. Conclusions: Leafy greens are an important cause of FBDO and may transmit pathogens with human or animal reservoirs. The proportion of FBDO due to leafy greens has increased, and cannot be accounted for completely by an increase in leafy green
consumption. Contaminated leafy greens may cause restaurant-associated or widespread outbreaks. Efforts by local, state, and federal agencies to control leafy green outbreaks should span from the point of harvest to the point of preparation.
Board 21. Fresh produce outbreaks in Australia, 2001-2006
M. D. Kirk1, K. Fullerton1, J. Gregory2; 1OzFoodNet, Canberra, AUSTRALIA,
2OzFoodNet, Department Human
Services, Victoria, AUSTRALIA.
Background: Recent outbreaks in Australia and abroad have highlighted the role of fresh produce in foodborne disease outbreaks. Since fresh produce is often eaten without
cooking, its outbreak potential can be significant. Methods: Data from the OzFoodNet Outbreak Register from January 2001 to June 2005 were reviewed. OzFoodNet Quarterly and Annual Reports (published and unpublished) from July 2005 through December 2006 were also reviewed. Produce-related outbreaks were defined as outbreaks of foodborne or suspected foodborne transmission where the confirmed or suspected vehicle included fresh, uncooked produce. Results: From January 2001 through June 2005 there were 1767 reported gastroenteritis outbreaks recorded. Of these outbreaks, 426 (24%) were either foodborne (157, 37%) or suspected foodborne (269, 63%). Sixteen (4%) of these outbreaks were identified as produce-related. An additional 9 produce-related outbreaks were identified in the review of quarterly and annual reports. These 25 outbreaks affected at least 686 people, with 51 people hospitalized and no fatalities. The mean number of people affected in these outbreaks was 30 people, with a range from 2 to 125 people. These outbreaks occurred in association with food served at restaurants (44%), primary produce (20%), and fastfood/ takeaway food (20%). These outbreaks were caused by Salmonella (60%), followed by unknown aetiology (20%), norovirus (12%), and Campylobacter (8%). Conclusions: Fresh produce causes considerable foodborne
disease in Australia. Fresh produce is particularly vulnerable to causing outbreaks due to the lack of an adequate killstep for pathogens.
Board 95. Tomato Handling Policies and Practices in Restaurants
E. G. Kirkland, V. J. Radke, C. A. Selman; CDC, EHS-Net, Atlanta, GA.
Background: Recently, several foodborne illness outbreaks have been associated with tomatoes served in restaurants. Prevention of foodborne illness outbreaks requires proper food storage and preparation practices; these tomato outbreaks suggest that tomatoes are being stored and prepared improperly in restaurants. Yet relatively little data exists on tomato storage and preparation policies and practices in restaurants. Thus, the purpose of this study is to gain a better understanding of how tomatoes are stored and prepared in restaurants. Methods: Data were collected in 450 restaurants through interviews with restaurant managers and observations of tomato storage, washing and cutting in restaurant kitchen environments. This study was conducted by the Environmental Health
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Specialists Network (EHS-Net). EHS-Net is a collaboration involving the Centers for Disease Control and Prevention (CDC), the U.S. Food and Drug Administration (FDA), and nine Emerging Infections Program sites (California, Connecticut, Georgia, Iowa, Minnesota, New York, Rhode Island and Tennessee); these partners have come together in an effort to better understand the environmental causes of foodborne illness. Results: The median temperature of prepared tomatoes in storage and holding was 44°F degrees; the median temperature of cut tomatoes in storage and holding was 43°F degrees. In 94% of restaurants, managers reported that tomatoes were washed; in 83% of washing observations, tomatoes were rinsed or held under running water and in 18% of washing observations, tomatoes were soaked or immersed in water. Produce-only cutting boards were used in 51% of tomatocutting
observations, and gloves were used in 64% of observations. Conclusions: Some good tomato handling practices were observed. For example, most restaurants reported washing their tomatoes, and gloves were used in the majority of tomato-cutting observations. However, some practices did not meet FDA recommendations for preventing pathogen contamination and proliferation on tomatoes- cut tomatoes were stored above 41 degrees, tomatoes were washed by soaking in water rather than by placing under running water, and produce only cutting
boards were not always used. These data indicate that education concerning safe tomato handling practices is needed in restaurants.
Foodborne & Waterborne Infections
Board 87. Foodborne Disease Outbreak Trends, and Sources and Timeliness of
Detection in Connecticut, 2004-2007
D. Mlynarski, Q. Phan, T. Rabatsky-Ehr, K. Purviance, J. Brockmeyer, J. Krasnitski, A. Nepaul, L. LoBianco, K. Frenette, P. Mshar, J. L. Hadler; Connecticut Department of Public Health,
Hartford, CT.
Background: It is critical to public health preparedness (PHP) to understand the epidemiology of outbreaks, and means and timeliness of their detection. In Connecticut (CT), foodborne
disease outbreaks (FOs) are considered public health emergencies reportable by telephone to state and local public health authorities. We examined 3.5 years of FO surveillance in CT as part of a broader effort at enhancing PHP-related surveillance. Methods:CT data reported to CDC by the electronic Foodborne Outbreak Reporting System was reviewed for January 2004-June 2007. The number, causative agents, settings and food vehicles implicated were
examined. Methods of detection were summarized; median time delay from first illness onset to public health notification was calculated. Results: From 1/1/04-6/30/07, 58 FOs were reported. The number increased annually from 13 to 19 between 2004 and 2006 with 10
FOs in the first 6 months of 2007. Causative agents included norovirus (62%), bacterial pathogens (28%), toxins (3%) and parasites (2%). The increase from 2004 to 2006 was mainly due to norovirus (7 to 12). Overall, 64% of FOs were associated with contamination or mishandling of food at food service establishments and 19% with widely distributed contaminated food items. Private citizens reported 62% (median 3-day delay) and clinicians reported 12% (median 1-day delay) of FOs. Public health surveillance, including routine Pulsed Field Gel Electrophoresis (PFGE) of selected bacterial pathogens, detected 21% (median 26-day delay). Most (71%) PFGE-identified outbreaks were associated with widely distributed food items. Conclusions: Reported FOs have been increasing, in part driven by an increase in those due to norovirus. Astute citizens and clinicians are the most important sources of rapid detection and
reporting. Clinicians have a responsibility to report suspected outbreaks and assist in their detection by ordering appropriate diagnostic testing on persons with acute gastrointestinal
illness. Active public health surveillance, including routine PFGE typing, is important to detection of outbreaks caused by widely distributed contaminated food items; however, it is not very timely. Efforts are needed to improve timeliness of detection of outbreaks, particularly those using molecular subtyping methods such as PFGE.
Board 88. Indiana Outbreak of Salmonella I 4,[5],12:i:- monophasic at a
Supermarket Deli – 2006
L. Granzow1, S. Gorsuch1, B. Swearingen2; 1Indiana State Department of
Health, Indpls, IN, 2Johnson County Health
Department, Greenwood, IN.
Background: On July 11, 2006, the Indiana State Department of Health (ISDH) initiated an investigation in response to an increase in salmonellosis in two adjacent counties.
Geographic information system (GIS) mapping confirmed the clustering of cases at the respective north-south borders of the two counties. The most common exposure (76.2%) among cases was a supermarket (SM) location, with 78.9% of cases having purchased items from
the deli. Pulse-field gel electrophoresis (PFGE) confirmed 199 cases in a 2-enzyme matched outbreak of Salmonella I 4,[5],12:i:- monophasic, an emerging serotype. The PFGE pattern was unique during the outbreak period on the national PulseNet database with a rare Bln I pattern (0.35%). The multiple-locus variable-number tandem repeat analysis (MLVA) pattern was also unique (N of I 4,[5],12:i:- database = 450). The outbreak ended after a near 4-month period, including 15 counties and 2 out-of state residents. A knife block at the SM was a 2-enzyme match for the outbreak strain. Methods: The ISDH conducted a case-control study (1:1, N=32), matched by zip code, using a reverse digit dialing system. The study case definition included those with onset dates in July and met the clinical definition of salmonellosis. The Fisher’s exact test (SAS 9.1) was used to evaluate the association between illness and exposure. Results: Of the five supermarkets reported, a statistically significant relationship (a = 0.05) was found
between illness and shopping at the SM deli (OR=21.21, p<0.0001).> 4 µg/mL) increased significantly (p=0.0158) from 2002 (13.8%) to 2005 (19.6%), and dropped slightly in 2006 (18.9%)
following the ban of fluoroquinolone use in poultry production. In C. jejuni from chicken breast, however, CipR was present in 15.1% of isolates from 2005 and 16.9% in 2006. During the five year testing, TetR increased from 27.6% to 47.8% overall. EryR each year was present
in <1%> 5 antimicrobials was AZI-CLI-ERY-TEL-TET. C. coli showed higher proportion of
MDR than C. jejuni. The PFGE results showed that Campylobacter genetically were very diverse, however certain clones were widely dispersed in different meat brands from different store chains in all five years. Conclusions: Campylobacter, including antimicrobial resistant strains, persist in retail chicken meats and provide a reservoir of resistant strains in the food supply.
Antimicrobial Resistance
Board 6. Salmonella enterica serovar Heidelberg from Retail Meats: Results:
of the National Antimicrobial Resistance Monitoring System (NARMS): 2002-2006.
S. Zhao, E. Hall-Robinson, A. Glenn, S. Friedman, J. Abbott, S. Ayers, P.
McDermott; Food & Drug Administration, Laurel, MD.
Background: Salmonella enterica serovar Heidelberg is frequently associated with foodborne illness in humans, and is commonly isolated from poultry and their derived meats. A recent upsurge in antimicrobial resistance in this serovar has been recognized. There are few data on the prevalence, antimicrobial susceptibility, and genetic diversity of S. Heidelberg isolates in retail meats. Methods: We compared the prevalence of S. Heidelberg in a sampling of 20,294 meats, including chicken breast, ground turkey, ground beef and pork chops collected during
2002-2006 for the National Antimicrobial Resistance Monitoring System (NARMS). Isolates were analyzed for
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antimicrobial susceptibility and compared genetically using pulsed-field gel electrophoresis (PFGE). Results: A total of 297 S. Heidelberg isolates were recovered, representing 22%(297/1372) of all Salmonella serovars from retail meats. Among the 297 isolates, 178 (60%) from ground turkey, 109 (37%) from chicken breast and 10 (2%) from pork chop; no S. Heidelberg was found in ground beef. A total of 197 (66%) of the isolates were resistant to at least one of
the 15 antimicrobial agents tested and 49 (16%) of the isolates were resistant to >5 antimicrobials. Five isolates (1.7%) were resistant to >9 antimicrobials, all of which were recovered form ground turkey. The proportion of resistance to different antimicrobials were: tetracycline (40%), streptomycin (38%), sulfamethoxazole (30%), gentamicin (27%), and kanamycin (21%), ampicillin (19%), amoxicillin-clavulanic acid (10%), cefoxitin (9%), ceftiofur
(9%), chloramphenicol (1%), and nalidixic acid (1%). Resistance was consistently more prevalent in S. Heidelberg from ground turkey than from chicken breast. All isolates were susceptible
to amikacin, ceftriaxone, ciprofloxacin and trimethoprim/ sulfamethoxazole. PFGE using XbaI and BlnI generated 107 patterns. Certain clones were widely dispersed in different types of meats and meat brands from different store chains in all three sampling years. Conclusions: These date indicate that S. Heidelberg is a common serovar in retail poultry meats, and includes clones of multidrug-resistant strains.
Board 18. Human Health Burden of Acute Diarrheal Illness in the United
States, FoodNet Population Survey, 2006-2007
L. B. Moyer1, P. Clogher2, C. Fuller3, T. F. Jones4, A. Lasher5, D. M.
Norton6, S. Solghan7, M. Tobin-D'Angelo8, O.
Henao9; 1CDC and VA Medical Center, Atlanta, GA, 2CT EIP, New Haven, CT, 3MN
Dept of Health, St Paul, MN, 4TN
Dept of Health, Nashville, TN, 5FDA, College Park, MD, 6CA EIP, Oakland, CA,
7NY Dept of Health, Albany, NY, 8GA
Div of Publ Health, Atlanta, GA, 9CDC, Atlanta, GA.
Background: Foodborne pathogens cause an estimated 76 million illnesses each year. Although most illnesses are self-limiting, the human health burden is substantial and includes healthcare provider visits, medications, laboratory tests, hospitalizations, and time missed from work. We describe the human health burden of acute diarrheal illness using data from the 2006-2007 FoodNet Population Survey. Methods: During 2006-2007, FoodNet conducted a 12-month population-based survey in 10 sites using a standard random-digit dialing methodology.
Demographic information was collected and respondents were asked about illness and activities in the month beforethe interview. Acute diarrheal illness was defined as >3 loose stools in 24-hours lasting >1 day or resulting in impairment of daily activities. Persons with a chronic illness in which diarrhea was a major symptom were excluded. Weighted proportions were calculated to adjust for study design and age and sex. Results: The weighted prevalence
of acute diarrheal illness in the month prior to interview was 6.9% (95% CI 6.6-7.2). Acute diarrheal illness prevalence was greatest among those <5>65 years old (4.4%, 95%
CI 3.5-5.3). The mean duration of diarrhea was 4 days (median 2) and 1.7% reported bloody diarrhea. Of the 20.0% who visited a medical care provider, 26.7% went to a doctor’s office or
clinic more than once, 13.0% went to an emergency department, 1.0% were admitted to a hospital overnight and an additional 2.3% spent more than one night in the hospital. Stool specimens were submitted from 4.0% of persons reporting acute diarrheal illness, 32.9%
took anti-diarrheal medications and 10.6% used antibiotics. Of those who had a job during this time period (52.0%), 33.2% missed time from work because of their or their child’s illness
(median 2 days). Of those attending school (7.2%), 66.3% missed time from school because of the illness (median 2 days). Conclusion: Acute diarrheal illness remains an important human health burden causing substantial personal and societal costs from multiple healthcare contacts and days missed from work or school. Continued efforts are needed to identify the causes and risk factors for illness; thus, helping to direct intervention and prevention efforts to reduce the burden of illness.
Board 19. Salmonella Bacteriuria in New York State FoodNet Counties,
2002-2006
G. L. Smith1, S. M. Zansky2, D. L. Hoefer2, J. B. Karr3, N. L. Spina2, S. M.
Solghan2, T. P. Root4; 1NYSDOH, Geneva,
NY, 2NYSDOH, Albany, NY, 3NYSDOH, Rochester, NY, 4Wadsworth Center
Laboratories-NYSDOH, Albany, NY.
Background: Salmonellosis is a major cause of foodborne illness in the U.S. Commonly associated with gastrointestinal illness, it can also cause extra-intestinal illness including urinary tract infections. Recent national trends indicate Salmonella bacteriuria increasing in incidence and as a proportion of all Salmonella, especially among elderly women. Analysis of Salmonella bacteriuria in 34 New York State (NYS) Emerging Infections Program (EIP)
FoodNet counties was conducted to look for similar trends. Methods: The NYS FoodNet program has conducted population-based active surveillance for laboratory-confirmed cases of
infection of Salmonella. Using the NYS Department of Health (NYSDOH) Communicable Disease Electronic Surveillance System (CDESS) and the Clinical Laboratory Information System (CLIMS), confirmed cases of Salmonella identified between 2002-2006 were included
in this analysis. The most invasive source for each case is recorded. Data was examined to compare incidence rates of Salmonella isolated from urine and proportion of urine isolates by gender and age group. Results: 2337 confirmed cases of Salmonella were identified between 2002-2006. Of 2333 cases with a known specimen source, 189 cases were isolated from urine (8.1%). The annual proportion of urine isolates ranged from 5.1% (2002) to 11.1% (2005).
The incidence rate of Salmonella bacteriuria increased from 0.8 cases per 100,000 persons in 2002 to 1.1/100,000 in 2006 with the highest rate of 1.3/100,000 in 2005. Most cases isolated from urine occurred among women (88.4%). For both sexes, incidence from urine increased with age, beginning around 50 years of age with the greatest percentage of cases attributable to those >70 years. Conclusions: Salmonella bacteriuria has long been identified in
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NYS residents but recently represent a greater proportion of the total cases. The majority of cases occur in elderly females similar to national reports. Collecting and reporting specimen
source is an important component of foodborne disease surveillance, helping to identify changes in the epidemiology of those illnesses. Possible change in test practices, role of urine catheters, and urine predilection of some Salmonella serotypes may contribute to the
increased incidence of Salmonella bacteriuria in NYS and warrant further study.
Board 239. Antimicrobial Resistant Salmonella from Retail Chicken in
Pennsylvania 2006-2007
S. C. Rankin1, N. M. Mikanatha2, D. Tewari3, A. Russo3, R. Localio1, S.
Altekruse4, C. Sandt5, E. Lautenbach1, J.
Tait2, M. Hydock3, S. Reynolds5, N. G. Warren5, T. M. Chiller6, D. G.
White7; 1University of Pennsylvania,
Philadelphia, PA, 2Pennsylvania Department of Health, Harrisburg, PA,
3Pennsylvania Department of Agriculture,
Harrisburg, PA, 4National Institutes of Health, Bethesda, MD, 5Pennsylvania
Department of Health, Lionville, PA,
6Centers for Disease Control and Prevention, Atlanta, GA, 7Food and Drug
Administration, Laurel, MD.
Background: Infections caused by antibiotic-resistant Salmonella strains are
associated with more severe
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illnesse, and higher mortality than those due to susceptible strains. Consumption of chicken is a known risk factor for salmonellosis. However, the prevalence of resistant Salmonella in poultry meat and their relationship to human Salmonella isolates has not been well-characterized. Methods: Chicken was purchased from a stratified random sample of retail outlets in a three county region of Central Pennsylvania for 12 months during 2006-2007. Each month 30 samples were purchased from retail outlets. The samples included prepackaged and open display poultry. Information was obtained on USDA establishment numbers and
organic/antibiotic-free status from package labels, where available. Isolates were characterized by serotyping, antibiotic susceptibility testing and pulsed-field gel electrophoresis (PFGE). Antibiotic resistant strains were analyzed for the presence of resistance genes by PCR. PFGE profiles of antibiotic resistant isolates were compared with human Salmonella isolates from the state public health laboratory during the study period. Results: Salmonella was isolated
from 84 (22%) of 378 samples. The most common serotypes were Typhimurium 28 (33%), Kentucky 24 (29%), and Enteritidis 22 (26%). 45 isolates showed resistance to one or more drugs; 40% demonstrated resistance to at least five drugs. 8/45 (18%) resistant isolates had a blaCMY ß-lactamase gene. The packaged chicken originated from 20 different establishments. Salmonella isolation was associated with poultry from particular establishments (p=0.007, chi sq=37.6, df=19). In one establishment that processed only organic poultry, 10 (53%) of 19 samples were positive. PFGE patterns of Typhimurium and Kentucky isolates from chicken matched patterns in the human database. Conclusion: The occurrence of drug-resistant Salmonella in retail chicken is a public health concern. This study identified strains with
reduced susceptibility to expanded-spectrum cephalosporins and isolates from humans and chickens with the same PFGE profiles. The study also identified an association of Salmonella
contamination with poultry from specific establishments. These results indicate the need for enhanced inter-agency surveillance.
Board 225. Longitudinal Study of Antimicrobial Resistance among Escherichia
coli Isolated from Integrated Multi-site Cohorts of Humans and Swine
W. Alali1, H. M. Scott1, R. Harvey2, B. Norby1, B. Lawhorn1, S. Pillai1;
1Texas A&M University, College Station, TX,
2USDA-ARS-SPARC, College Station, TX.
Background: Many studies have attempted to link antimicrobial use in food animal agriculture with an increased risk of antimicrobial-resistant (AR) bacterial levels in humans. Methods: We examined the relationship between the prevalence of AR E. coli isolated from human wastewater and swine fecal samples and the risk factors: (host species, production type (swine), vocation (human swine workers, non-workers, and slaughter-plant workers), and season) in a multi-site housing, vertically integrated swine and human population agri-food system. Human and swine E. coli (N = 4048 and 3485, respectively) isolated from wastewater and
fecal samples were tested for antimicrobial susceptibility using the SensititreTM broth microdilution system. Results: There were significant (P < 0.05) differences in AR isolates: 1) between host-species with swine at higher risk for tetracycline, kanamycin, ceftiofur, gentamicin, streptomycin, chloramphenicol, sulfisoxazole, and ampicillin, 2) swine production group was significantly associated with AR with purchased boars, nursery piglets, and breeding boars at a higher risk of Page 190 of 262 resistance to streptomycin and tetracycline, and 3) human swine worker cohorts exhibited lowered sulfisoxazole and cefoxitin prevalence compared to non-workers, while slaughter-plant workers exhibited elevated cefoxitin prevalence compared to non-workers. High variability among seasonal samples over the 3-year period was observed. There were significant differences in multiple resistance isolates between host species, with swine at higher risk than humans of carrying multi-resistant strains, slaughter-plant workers at higher risk than swine non-workers; however, there were no significant differences in multiple resistance isolates within swine by production group. Conclusions: Occupational exposure to slaughter facilities appeared to be associated with an increased relative odds for the prevalence of cefoxitin resistance and multiple resistance compared to swine non-workers.
A Veterinary Curriculum in the Appropriate Use of Antibiotics
P. C. Bartlett; Michigan State University, E. Lansing, MI. Background:
Debate still continues regarding the relative importance of agricultural antibiotic usage in fostering antimicrobial resistance (AR) among human pathogens. This debate may have delayed the development of educational materials aimed at promoting the prudent and judicious use of antibiotics in veterinary medicine. However, a consensus exists that unnecessary or wasteful usage should be curtailed whenever possible. Methods: The U.S. Centers for Disease Control and Prevention (CDC) funded the development of an interactive and multi-media educational web site to aid in teaching veterinary students about their responsibilities and obligations to curtail the unnecessary use of antibiotics. The overall purpose is to preserve antibiotic efficacy for both humans and animals. Audio, video, interactive questions and animation are used to make the presentation varied and entertaining. Written for veterinary students, the site also has applicability to others in the food animal industries. Results: The web site is designed to supplement existing courses in public health, epidemiology, pharmacology and species-specific veterinary medicine. The introductory module emphasizes the interconnectedness of animal and human health as it follows an outbreak investigation scenario to teach basic microbiologic and epidemiologic principles of AR. Also taught are methods for determining AR and the importance of AR to public health. Species-specific modules regard international issues and multiple clinical situations for dairy cattle, beef cattle, exotic animals and swine. Future modules will address
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companion animals and poultry. Emphasis is on therapeutic situations when antimicrobial agents are often used unnecessarily when alternative treatment methods are available, when the use of antibiograms (susceptibility profiles) is possible or when antibiotic treatment may be less efficacious and economical than are available preventive medicine procedures. Conclusions: This web site is being written for training veterinary students throughout the USA, but it will be freely available to the international public. The web site is due for release in 2008. Search: CDC Get Smart on the Farm or find the link at the CDC web site:
http://www.cdc.gov/narms/get_smart.htm
or
www.cvm.msu.edu
Antimicrobial Resistance
Board 79. Antimicrobial Resistance in Salmonella Isolates Recovered from Cattle at Slaughter
P. J. Fedorka-Cray1, J. G. Frye1, M. Rose2, N. Anandaraman3, J. Haro1; 1USDA-ARS, Athens, GA, 2Intervet Innovation GmbH, Schwabenheim, GERMANY, 3USDA-FSIS, Washington, DC.
Background: Since 1997, the animal arm of the National Antimicrobial Resistance Monitoring System (NARMS) has monitored changes in antimicrobial susceptibilities of Salmonella isolates from animal origin. Additionally, since 2000, susceptibility of bovine Salmonella isolates collected in the US has been monitored against the 4th generation cephalosporins (4-GC) cefquinome, exclusively developed for veterinary medicine, and cefepime. Cephalosporins are used extensively to treat human and cattle diseases. To identify emerging resistance patterns, resistance trends to the cephalosporins (ceftriaxone, ceftiofur, cefoxitin and cefquinome) in Salmonella isolates collected from cattle at slaughter were analyzed. Methods: Salmonella enterica isolates (n=7,199) obtained from cattle at federally inspected slaughter/processing plants during 1997 - 2006 and submitted to NARMS were tested for minimum inhibitory concentrations (MICs) using a custom panel of antimicrobials. Isolates collected during 2000-2006 (n=4,685) were also tested on a second panel with cefquinome and cefepime. Results: Resistance to ceftriaxone remained below 1%, except in 2005 when resistance increased to 2.1%. From 1997 to 2005, resistance to ceftiofur increased from 0% to 21.6%, with the exception of 2004 when it decreased to 13.3%. Resistance decreased again in 2006 to 18.9%. A similar pattern was observed for cefoxitin (testing started in 2000). Cefoxitin resistance increased from 2000 to 2005 from 9.1% to 19.8%, except in 2004 when it decreased to 13.2%. As with ceftiofur, a decrease was observed in 2006 when resistance was 17.9%. From 2000 to 2006 the MIC50 of cefquinome remained at 0.06 µg/ml, except in 2002 when the MIC50 increased by one dilution to 0.12 µg/ml. The highest MIC90 for cefquinome was 1.0 µg/ml in 2002 and 2005. MICs of cefepime were generally about one dilution step below those of cefquinome. Changes in resistance for all drugs were in large part driven by serotype, particularly S. Newport, Reading, Typhimurium and Agona. Conclusions: Salmonella enterica isolates remained highly susceptible to the human 3-GC ceftriaxone and the 4-GCs cefquinome and cefepime. Overall, an increase in both veterinary 3-GC ceftiofur and human 2-GC cefoxitin has been observed at similar levels and appears to be serotype dependent.
Board 80. Prevalence of Antibiotic Use, Knowledge and Attitudes Toward Antibiotic-free Meat
S. C. Rankin1, N. M'ikanatha2, R. Dewar2, E. Lautenbach1; 1University of Pennsylvania, Philadelphia, PA, 2Pennsylvania Department of Health, Harrisburg, PA.
Background: Inappropriate use of antibiotics is a major public health concern as it contributes to antimicrobial resistance. Understanding consumers’ knowledge and attitudes can inform multifaceted actions to achieve judicious use of antibiotics. Methods: In 2006 questions regarding antibiotic prescriptions and attitudes toward antibiotic-free meat were asked as part of Pennsylvania Behavioral Risk Factor Surveillance System (BRFSS). Results: Among Pennsylvania adults, 38.1% (95% CI, 36.4-39.8%) responded they had been prescribed antibiotics in the previous 12 months and 43.9% (95%CI, 41.1-46.7%) of these had received at least two prescriptions. Among adults taking antibiotics in the past year, 11.4% (95%CI, 9.6-13.6%) had not completed the course of treatment. Prescriptions for self-identified diagnoses usually not caused by bacteria (e.g., cough or cold) were reported by 30.3% (95%CI, 27.7-33.1%). Knowledge about use of antibiotics in animal husbandry varied by demographic characteristics (Figure): 53.6% (95% CI, 52.8%-55.4%) of non-Hispanic whites were aware of antibiotics in feed, whereas 42% (95% CI, 34.8-50.1%) of African Americans and 39.8% (95%CI, 29.0-51.7%) of Hispanics were aware. Knowledge also increased with age, education, and income. Overall 26.2% (95% CI, 24.6- 31.9%) of the survey participants reported that that they try to purchase antibiotics-free meat. Conclusion: Inappropriate prescriptions and noncompliance with treatment regimens call for simultaneous interventions among clinicians and patients. To promote judicious use of antibiotics in food animals, additional measures to engage consumers are needed.
see full text of these abstracts 262 pages ;
http://www.cdc.gov/eid/content/14/3/ICEID2008.pdf
TSS
ICEID 2008 Methicillin-Resistant Staphylococcus aureus MRSA
Methicillin-Resistant Stapylococcal Infections
Trends in Invasive Infection with Methicillin-resistant Staphylococcus
aureus (MRSA) in Connecticut, 2001-2006
S. Petit1, Z. Fraser1, M. Mandour2, J. L. Hadler1; 1Connecticut Department
of Public Health, Hartford, CT,
2Connecticut Department of Public Health Laboratory, Hartford, CT.
Background: In 2007, CDC published an article that described the epidemiology of invasive
MRSA infections in 2004-05 in 9 sentinel sites, including Connecticut (CT). The CT system has been in place since 2001 and provides an opportunity to examine trends in the 3 major groupings of MRSA by place of onset and relationship to healthcare: hospital-onset (HO) vs. community-onset but healthcareassociated (HA) or community-associated (CA) MRSA. Methods: Cases identified from laboratory reporting of MRSA isolates from normally sterile body sites were classified after medical record review as HO (isolate >2 days after hospital admission), HA (hospital admission, surgery, dialysis, or long-term care facility stay in the past year, a history of MRSA, or an indwelling device); or CA (by exclusion). A systematic sample of blood isolates were typed by pulsed-field gel electrophoresis (PFGE). Results: In
2001-2006, 5464 cases of invasive MRSA were reported; 34.5% HO, 58.9% HA and 6.6% CA. Annual incidence overall (26.2 per 100,000) and of HA-MRSA (15.4) was stable. However, incidence of HOMRSA decreased (10.0 to 7.6) while CA incidence increased (1.1 to 2.8, p<0.01 p="0.02)." p =".049,"> 1 hospitalization (80%, [268/335] vs. 63% [245/390], P <.0001) and had > 2 infections (33%, [110/335]) vs. 23% [88/390], P =.002) respectively. There were twice as many deaths during the 6-month follow up period among patients with MRSA infection (24%,
79/335) as among patients with MSSA infection (12% 45/390, OR 2.4, 95% CI 1.6-3.5, P < .0001). After adjustment for age and CH-IND, this difference remained significant (OR 1.9, 95% CI 1.2-2.9, P =.005). There was clinical evidence that SA infection caused or clearly contributed to death in 28% (35/124) of all deaths; 7% (25/335) among those with MRSA infection and 3% (10/390) among those with MSSA infection. After adjustment for age, those with MRSA infection were almost 3 times more likely than those with MSSA infection to die of SA disease (OR 2.8, 95% CI 1.3-6.0, P =.007). Conclusions: In this patient population, methicillin resistance was associated with a greater risk of death attributable to SA disease and to death from any cause. MRSA infections were more common among those with chronic illnesses. Optimal methods of prevention and treatment of healthcare-associated SA, particularly MRSA infections, are urgently needed. Community-Associated (CA) Methicillin-Resistant Staphylococcus aureus (MRSA) in Affected Households: Prevalence of Colonization and Incidence of Subsequent Infections J. M. Buck1, R. Gorwitz2, R. Lynfield1, K. Harriman3; 1Minnesota Department of Health, Saint Paul, MN, 2Centers for Disease Control and Prevention, Atlanta, GA, 3California Department of Public Health, Richmond, CA. Background: MRSA has emerged as a community pathogen over the last decade. Several reports indicate that CA-MRSA infections can occur among multiple household members (HHMs). We describe MRSA colonization prevalence and subsequent infection incidence among children with CAMRSA infections and their HHMs. Methods: MRSA infections in children <18 p =" 0.03)," p =" 0.03)."> 0.05). Conclusions: The prevalence of MRSA colonization in affected HHs did not decrease during the study period; over 20% of HHs had at least one colonized HHM one year after initial CP infection. Use of mupirocin did not appear to affect long term MRSA colonization or infection in HHs. Behavior modifications (e.g. not sharing personal items) may be more important in reducing MRSA transmission. Additional strategies to prevent CA-MRSA infection and transmission in HHs should be evaluated.
Detection of Community Acquired Methicillin Resistant Staphylococcus aureus
Associated with Nosocomial Infections
S. M. Tallent, D. M. Toney; Virginia Division of Consolidated Laboratory
Services, Richmond, VA.
Background: Staphylococcus aureus is a human commensal that has emerged as a significant
pathogen due to the production of a variety of virulence factors and acquisition of numerous antimicrobial resistant genes. Methicillin resistant S. aureus (MRSA) is an antimicrobial resistant strain traditionally associated with hospital infections, but is now increasingly associated with illness in typically healthy individuals outside healthcare facilities. Pulsed-field gel electrophoresis (PFGE) genotyping of staphylococcal isolates by the CDC categorized MRSA strains into two groups, community-acquired methicillin resistant S. aureus (CA-MRSA) and hospital-acquired methicillin resistant S. aureus (HAMRSA). The two groups clustered into ten lineages which were designated as pulsetypes USA100- USA1100. More recently, distinctions between HA-MRSA and CA-MRSA have become less apparent, presumably due to recombination events giving rise to new MRSA strains that differ from the USA pulsetypes. Methods: S. aureus isolates from previous hospital and community outbreaks occurring in
Virginia as early as 1997 were subjected to PFGE genotyping, generating a DNA fingerprint database at the Division of Consolidated Laboratory Services (DCLS), the Virginia state laboratory. Archived isolates from 2005-2007 (N=258) were compared to the prototype USA fingerprint patterns and classified based on pattern similarities. Clusters of isolates possessing >80% similarity to the USA pulsetypes were further evaluated. Results: Forty percent of the 258 MRSA isolates examined clustered with USA100, the most common HA-MRSA pulsetype. Of these strains, 23% were associated with community outbreaks not hospital infections based on epidemiologic investigations. In contrast, 22% of the 258 isolates clustered with USA300, the most common CA-MRSA pulsetype. Of these, 88% were previously determined to be
associated with nosocomial infections. Conclusions: This study has identified a subset of MRSA strains designated as outliers based on PFGE pulsetype patterns and epidemiology. Additional molecular characterization is ongoing to understand these findings, determine if this is a representative trend in Virginia and whether the most invasive form of MRSA has become endemic to Virginia’s healthcare facilities.
Board 7. Community-Associated Methicillin-Resistant Staphylococcus aureus
Infection Risk Factor Study
K. Como-Sabetti1, K. Harriman2, S. Fridkin3, R. Lynfield4; 1Minnesota Department of Health, Minneapolis, MN, 2California Department of Public Health, Richmond, CA, 3Centers for Disease Control and Prevention, Atlanta, GA, 4Minnesota Department of Health, Saint Paul, MN.
Background: Little is known about risk factors for methicillin-resistant Staphylococcus aureus (CA-MRSA) infection in non-outbreak settings. Methods: MN Department of Health initiated a hypothesis-generating CA-MRSA case control study in 2003. 150 patients with S. aureus infections, including both CA-MRSA and CA methicillinsensitive SA (MSSA), were identified by 3 sentinel labs. 2-3 age-group matched healthy community controls (CC) were identified by sequential digit dialing. Participants were interviewed about possible risk factors and an antibiotic history was obtained from healthcare providers. Univariate and multivariate conditional logistic regression were conducted using SAS for 3 separate analyses to avoid biased estimates: CA-MRSA cases vs. CA-MSSA cases, CAMRSA cases vs. CA-MRSA CCs, and CA-MSSA cases vs. CA-MSSA CCs.Results: 75 CA-MRSA and CA-MSSA cases and 438 CCs were enrolled. Antibiotic use in the prior 1-6 months (recent ABX) was more frequent among CAMRSA cases than CA-MSSA cases or CCs (33% vs. 17% vs. 14%). History of boils was infrequent (10% CA-MSSA, 1% CA-MSSA, 1% CCs). Race, education, income, household members per room, dog in the home, history of boils, and towel sharing were associated with CA-MRSA when compared to CA-MSSA or CA-MRSA CCs. Recent ABX and number of recent ABX courses were associated with CA-MRSA when compared to CA-MSSA cases (p=0.03;
OR=2.5, and p<0.01; OR=2.2 respectively) and persisted when compared to CA-MRSA CCs (p=0.05; OR=2.3, and p=0.02; OR=1.9 respectively), but were not associated with CA-MSSA cases compared to CA-MSSA CCs. After adjusting for socioeconomic factors, history of boils was associated with CA-MRSA compared to CA-MSSA (p=0.002; AOR=76.8) but not when compared to CA-MRSA CCs. Recent ABX and ABX courses were associated with CAMRSA compared to CA-MSSA (p=0.02, AOR=1.9, and p=0.01, AOR=2.2 respectively) and compared to CA-MRSA CCs (p=0.05, AOR=2.4, and p=0.02 and AOR = 1.9 respectively). Conclusions: In non-outbreak settings, antibiotic use and history of boils (which may be a proxy for prior CA-MRSA skin disease) appear to be risk factors for CAMRSA. Further investigation of antibiotic use and specific antibiotic classes is needed. Although not definitive, this study reinforces the importance of careful antibiotic stewardship.
Board 83. Critical or Fatal Illness Due to Community-associated Staphylococcus aureus (CA-SA) Infection, Minnesota (MN), 2005-2007
Page 121 of 262 L. Lesher1, J. Buck1, J. Bartkus1, S. Jawahir1, D. Boxrud1, K. Harriman2, R. Lynfield1; 1Minnesota Department of Health, Saint Paul, MN, 2California Department of Public Health, Richmond, CA.
Background: CA-SA infections have been associated with critical illness and death. Methods: Reporting for rapidly fatal or critical illness due to CA-SA infection, including isolate collection, was instituted statewide in MN in 2005. Cases were defined as previously healthy people who had fatal illness or ICU admission and no healthcareassociated (HA) MRSA risk factors per CDC definition, excluding hospitalization for birth. Isolates were characterized by pulsed-field gel electrophoresis (PFGE) and PCR for toxic shock syndrome toxin 1 (TSST1), Panton-Valentine leukocidin (PVL), and staphylococcal enterotoxin (SE) genes A, B, C, D. Results: 32 cases were reported January 2005 through October 2007; 21 (66%) methicillin-resistant SA (MRSA) and 11 (34%) methicillin-susceptible SA (MSSA) cases. 14 (67%) MRSA cases were male; median age, 17 years (12 days-88 years), and 5 (45%) MSSA cases were male; median age, 18 years (1 day-59 years). Two cases had multifocal infections; MRSA with pneumonia and septic arthritis; MSSA with meningitis, lumbar wound, pneumonia (fatal). Of MRSA cases, 11 (52%) had pneumonia (3 fatal), 5 (24%) had skin infections (4 bacteremic - 1 fatal; 1 necrotizing fasciitis - fatal), 2 (9%) had sepsis (1 fatal), 1 (5%) had meningitis, 1 (5%) had osteomyelitis. Of MSSA cases, 4 (36%) had pneumonia (2 fatal), 2 (18%) had skin infections with bacteremia, 2 (18%) had TSS, 1 (9%) had meningitis (fatal), 1 (9%) had sepsis. The median age of fatal cases was 58 years for MRSA, 27 years for MSSA. PFGE typing and toxin PCR were performed on 17 MRSA and 7 MSSA isolates. All MRSA isolates belonged to clonal groups associated with CAMRSA; USA300 (15), USA400 (1), USA1000 (1). MSSA isolates were found in groups associated with CA and HAMRSA; USA200 (1), USA400 (1), USA600 (2), USA700 (1), USA1000 (2). Among MRSA, toxin PCR found PVL in 14 USA300 isolates (2 fatal) and 1 USA400 (fatal), which also had SEA and SEC. Among MSSA, SEB was found in 1 USA1000 isolate (fatal) and TSST1 in 1 USA200 (clinical TSS), and 2 MSSA isolates from fatal cases were negative for all toxins tested. Conclusions: Most critical/fatal CA-SA reported cases were MRSA. A high fatality rate was observed in cases with meningitis or pneumonia. Fatal MRSA cases were older than MSSA cases. Most isolates contained toxins previously implicated in severe disease. Molecular
Epidemiology Board 109. Staphylococcal Cassette Chromosome mec (SCCmec) Characterization and Panton-Valentine Leukocidin Gene Occurrence for Methicillin-Resistant Staphylococcus aureus in Turkey, from 2003 to 2006
A. Kilic, A. Uskudar Guclu, Z. Senses, H. Aydogan, A. C. Basustaoglu; Gulhane Military Medical Academy, Ankara, TURKEY.
Background: Methicillin-resistant Staphylococcus aureus (MRSA) cause serious community-acquired and nosocomial diseases all over the world. Methods: We determined the SCCmec types and occurrence of the PVL gene by using TaqMan real-time PCR method, and correlated these with phenotypic antibiotic susceptibility patterns for MRSA strains collected from Gulhane Military Medical Academy Hospital (GMMAH) during four years study period. To our knowledge, this is the first report from Turkey of molecular SCCmec typing analysis of MRSA stains. From 2003 through 2006, a total of 385 clinical MRSA strains were collected in the Clinical Microbiology Laboratory at GMMAH were included in the study. Results: Overall, SCCmec types-I, II, II, IV, V, nontypeable and PVL occurrence were detected in 11 (2.8%), 3 (0.8%), 316 (82.1%), 20 (5.1%), 20 (5.1%), 15 (3.9%) and 5 (1.3%) isolates, respectively. A total of 330 (85.5%) were SCCmec-I/II/III, and of 40 (10.3%) were SCCmec-IV/V. SCCmec-I/II/III isolates were recovered more from serious infections in surgical departments especially having intensive care units than the SCCmec-IV/V isolates (?2=13.560, p<0.001). SCCmec-I/II/III MRSA strains were predominantly recovered from the blood stream as 53.0% (?2=6.016, p=0.014), while SCCmec-IV/V strains were predominantly isolated from skin, soft tissue and abscess as 55.0% (?2= 11.025, p<0.001). The PVL gene was detected in 10.0% of SCCmec- IV/V isolates in contrast to 0.3% in SCCmec-I/II/III (?2= 25.164, p<0.001). SCCmec-I/II/III MRSA strains were more resistant to clindamycin (?2=5.078, p=0.024), amoxicillin-clavulanate (?2=84.912, p<0.001), erythromycin (?2=4.651, p=0.031), gentamicin (?2=24.869, p<0.001), and rifampin (?2=18.878, p<0.001) than SCCmec-IV/V MRSA strains. Conclusions: These data indicate that SCCmec-III MRSA strains not to carrying PVL gene are the predominant MRSA strains in our hospital settings in Ankara, capital of Turkey. SCCmec-I/II/III MRSA strains may cause serious infections in surgical department especially having intensive care units.
Board 227. Staphylococcus aureus and Methicillin Resistant Staphylococcus aureus on surfaces in a University and a Jail Setting
M. Felkner1, K. Bartlett2, K. Andrews2, L. Field2, J. Taylor1, T. Baldwin1, J. Presley2, J. Duncan2, S. Newsome1; 1Texas Department of State Health Services, Austin, TX, 2The University of Texas at Austin, Austin, TX.
Background: Longtime pathogen Staphylococcus aureus has become more threatening with its evolution of antibiotic resistance, particularly the emergence of methicillin resistance outside health care settings. Commonly touched surfaces may harbor methicillin resistant S. aureus (MRSA) and be possible reservoirs of organisms facilitating disease transmission in the community. This study provides information regarding the presence of MRSA on commonly touched objects in both a university and a jail setting. Methods: University surface samples were obtained from bathrooms, common use areas, and recreational and sports facilities. Samples were collected at the jail from bathrooms, cells, common use areas, the clinic, laundry, and vehicles. Samples were collected using sterile, cotton-tipped swabs. Specimens were screened for S. aureus and MRSA using standard media. Susceptibility was determined using the ETest strip. Percentages of contaminated surfaces were calculated and chi-square comparisons were made between university and jail settings. Results: Seventeen (7.0%) of 244 university samples and 10 (7.5%) of 132 jail samples grew S. aureus. MRSA was recovered from 3 (1.2%) university samples, constituting 17.6% of S. aureus samples. Eight (6.1%) jail samples were MRSA, comprising 80% of jail S. aureus samples. The proportion of MRSA-contaminated surfaces and the ratio of MRSA to methicillin susceptible S. aureus were significantly greater at the jail that at the university (p<0.05). Conclusions: Our results indicate that environmental contamination with MRSA may be positively correlated with the carriage rate within the population. Page 191 of 262 Implementation of environmental sanitation should be of particular concern in populations with high MRSA nasal carriage rates.
Board 264. 30-Day and 180-Day Case Fatality Rates among Invasive Methicillin-Resistant Staphylococcus aureus Patients (Tennessee, 2004–2007)
K. R. Glenn, M. A. Kainer; Tennessee Department of Health, Nashville, TN.
Background: Tennessee had the second highest incidence of invasive MRSA (I-MRSA) of 10 EIP study sites in 2005, with an incidence of 53 per 100,000. The national in-hospital case-fatality was 17.8%. U.S. in-hospital mortality rate from I-MRSA was 6.3 per 100,000. We wanted to assess the 30-day and 180-day crude case-fatality (CFR) and mortality rates of I-MRSA and determine factors associated with death. Methods: Vital statistics data was available up to Oct. 31, 2007. We used data from the Active Bacterial Core (ABC) surveillance component of the Emerging Infections Program in Davidson County. Cases from Oct. 2004-Jul. 2007 were included for 30-day CFR/mortality rates. Cases from Oct. 2004-Apr. 2007 were included to determine 180-day CFR/mortality rates. We reviewed Tennessee vital statistic data to determine patient outcomes; we matched by name and birthdate. We
Page 208 of 262
calculated the number of days between the initial MRSA-positive culture and date of death recorded on death certificates for each matched case to determine the numerator for the 30- and 180-day CFR/mortality rates. Results: I-MRSA rates for 2004-2007 were 59.1 per 100,000. The 30-day I-MRSA mortality rate was 7.3; 180-day I-MRSA mortality rate was 9.9 per 100,000. Fifty-four of 192 deaths (28%) were identified from vital statistic records alone (i.e., occurred following discharge). The overall 30- and 180-day CFRs were 13.2% and 19.1%, respectively. Blood stream infections (BSI) accounted for 85% of I-MRSA. Patients with MRSA BSI had higher 30- and 180-day crude CFRs compared to patients with non-BSI I-MRSA (14.7% vs. 4.5% [relative risk {RR}= 3.3, 95% CI: 1.5-7.3] and 21.4% vs. 5.7%, [RR= 3.8, 95% CI: 1.8-7.9], respectively). 30-day CFRs were not statistically significant among Blacks and Whites (12.6% vs. 14.3%, respectively). Healthcare-associated I-MRSA had a higher 30- and 180-day CFR compared to community-associated MRSA (14.4% vs. 9% [RR= 1.7, 95% CI: 1.0-2.9] and 21.0% vs. 12.7%, [RR= 1.7, 95% CI: 1.1- 2.8] respectively). Conclusions: MRSA BSI is associated with much higher CFR than other IMRSA. Policy and practices aimed toward the reduction of I-MRSA rates in Tennessee are necessary to decrease the number of deaths annually associated with I-MRSA.
Board 268. Dissemination of Community-Associated Methicillin-Resistant Staphylococcus aureus CMRSA7 (USA400) in Northern Saskatchewan, Canada
J. Irvine1, B. Quinn1, D. Stockdale1, S. Woods2, M. Nsugngu2, P. Levett3, R. McDonald3, G. Golding4, G. Horsman3, M. Mulvey4, the Northern Antibiotic Resistance Partnership; 1Population Health Unit, LaRonge, SK, CANADA, 2Northern Inter-tribal Health Authority, Prince Albert, SK, CANADA, 3Saskatchewan Disease Control Laboratory, Regina, SK, CANADA, 4National Microbiology Laboratory, Winnipeg, MB, CANADA.
Background: Although the USA300 (CMRSA10) strain of community-associated methicillin-resistance (CAMRSA) is rapidly disseminating across North America, some reports have described the emergence of CA-MRSA in northern Canadian communities. This study examines the incidence and molecular epidemiology of CA-MRSA in Page 210 of 262 three of the most northerly Saskatchewan health regions. Methods: Surveillance was conducted over six years beginning in 2001 in three of the most northerly Saskatchewan health regions for all communities (on and offreserve). Specimens from clinical indications were collected from remote community health centers and small rural hospitals (<35 beds) and MRSA positive cases were reported to the respective health authorities. Cases with asymptomatic carriage were excluded. In order to calculate total CA-MRSA rates of recurrence, cases occurring more than 2 months of the preceding episode and / or at a different site, were considered a recurrent episode. Pulsed-field gel electrophoresis (PFGE) of SmaI digested genomic DNA and RT-PCR for the mecA, nuc, and PVL-encoding genes was used to characterize a subset of the isolates. Results: A total of 1,927 MRSA events in 1,409 individuals were reported over the study period with 99% being community-associated. Fifty-six percent (N=783) of the individuals were < 20 years of age, while the majority of their cases (80.8%) were skin and soft tissue infections. The annual rate of CA-MRSA distinct individuals reported in these health regions increased from 9 per 10,000 population in 2001 (range to 4-10 per 10,000) to 169 per 10,000 in 2006 (range 43-233 per 10,000). An annual periodicity was observed with the highest number of cases being reported during the third quarter (July-September). Of the CAMRSA cases, 15.1% of the individuals had at least one recurrent episode after 2 months. A subset of strains (N=192) were typed and 97.4% (N=187) were found to be Canadian PFGE epidemic type CMRSA7 (USA400) with 3 strains being CMRSA2 (USA100/800) and 2 strains being CMRSA10 (USA300). Conclusions: This report describes the rapid emergence of CA-MRSA in Northern Saskatchewan. The molecular epidemiology appears to be different from urban centers in southern Canada with the majority of cases being caused by CMRSA7 (USA400). Antimicrobial Resistance
Board 294. Daptomycin Resistance and hVISA Development in MRSA Endocarditis
M. Pastagia1, N. Casau-Schulhof1, S. G. Jenkins2, J. Jao2; 1Mount Sinai Hospital, New York, New York, NY, 2Mount Sinai Medical Center, New York, NY.
Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a common etiology of endocarditis in hemodialysis patients. We present a patient without any prior hospitalizations or vancomycin usage within the past ten years who developed MRSA endocarditis with persistent bacteremia while on daptomycin therapy. She then became resistant to daptomycin while on therapy, and ultimately cleared her bacteremia only after valve replacement. We performed microbiological tests on her blood and valve isolates. Methods: We performed E-strip testing of the four blood isolates with MRSA bacteremia as well as the tissue heart valve after replacement with vancomycin, daptomycin, linezolid, and tigecycline E-strips to establish the MIC. These specimens were also tested for
Page 222 of 262
heterogeneously vancomycin intermediate Staphylococcus aureus (hVISA) via teicoplanin E-strips of 0.5 and 2 McFarland standards. Results: The initial positive blood culture with MRSA was shown to have a MIC to vancomycin of 6 and 3 for daptomycin. These numbers remained similar for the subsequent two positive blood cultures a few days later while she remained on daptomycin, renally dosed. The fourth positive blood culture nearly one week later while on daptomycin was found to have a vancomycin MIC of 6 and a daptomycin MIC of 4. The heart valve was subsequently replaced, and the MICs of the tissue valve to vancomycin was 3, and to daptomycin was 6. All of these isolates were then tested for hVISA via teicoplanin E-strip testing at 0.5 and 2 McFarland standards. This testing revealed MICs of 3 and 4 at 0.5 and 2 McFarland, respectively for the initial blood culture. The subsequent two blood cultures showed MICs of 6 and 8 respectively. By the fourth blood culture, the MICs were 12 and 8 respectively. Ultimately the tissue valve’s MICs to teicoplanin were tested, and found to be 12 and 16, respectively. Conclusions: It is quite uncommon for patients who have not been on prior vancomycin therapy extensively to develop resistance to daptomycin so quickly. Here, we present such a case and were able to demonstrate that this isolate became a heterogeneously vancomyin intermediate Staphylococcus aureus after nearly one week of daptomycin therapy. This transformation from a non-hVISA to an hVISA strain may be predictive of antibiotic failure in this case.
Board 295. Laboratory Analysis of Staphylococcus aureus in Florida: January 1, 2003 to December 31, 2005 with an Emphasis on Methicillin Resistance
S. K. Kolar1, R. Sanderson2, A. Sanchez-Anguiano1; 1University of South Florida, Tampa, FL, 2Florida Department of Health, Tampa, FL. Background: Methicillin resistance among S. aureus has been a concern in the healthcare setting. Recently, MRSA has emerged in the community setting. Methods: This cross-sectional study examines methicillin resistance among S. aureus laboratory isolates in an outpatient population in the state of Florida. The database included all S. aureus laboratory results from a large commercial laboratory from January 1, 2003 to December 31, 2005 provided to the Florida Department of Health. Results: There was a total of 61,596 isolates in the database with the number of isolates doubling each year. The percent of isolates that were methicillin resistant significantly increased each year from 35.1% in 2003 to 49.7% in 2005. Isolates from skin and soft tissue comprised 79.6% of the reported site of infections, of which 52.7% were methicillin resistant in 2005. Methicillin resistance varied by year, age group, gender, county, and region. There was little difference in methicillin resistance between males and females (49.0% and 50.2% in 2005). There was some variation between the age groups, the 21- 30 age group had the highest percentage of MRSA (51% in 2005) and the <1 age group the lowest (40.2% in 2005). Variation by region and county was noted with the western panhandle having the highest percentage of MRSA (62.5% in 2005) and the southwest region the lowest (41.7% in 2005). The percentage of MRSA isolates that were resistant to trimethoprim-sulfamethoxazole, gentamycin, and rifampin was less than three percent. Discussion: The percent of isolates that were methiclillin resistant significantly increased during the study period. The differences by age group and region of the state were larger and may be important to consider when evaluating a potential S. aureus infection. Resistance to non beta-lactam antibiotics remains low and these could be alternative for empiric antimicrobial therapy in the outpatient setting.
New or Rapid
Diagnostics Board 38.
Novel Method and Medium for Detecting and Identifying both Methicillin Susceptible (MSSA) and Methicillin resistant(MRSA) Staphylococcus aureus
S. C. Edberg; Yale-New Haven Hospital, New Haven, CT.
Background: Currently, to detect MSSA or MRSA two pathways are available. The first uses semi-selective culture media; incubation 18-24h, then a series of tests for identification; subculture to a mec A inducing medium for an additional 18 to 24h. Accordingly, considerable skilled labor and time are required. The second pathway utilizes specific genetic amplification of the mecA gene for MRSA, and another amplification for MSSA. Each is quite costly in materials and equipment, thus precluding its use from all but the largest hospitals. A novel specific method and medium for detection of (MSSA) and (MRSA) [AureusAlert®, Pilots Point LLC] (AA) is presented. It requires no skilled labor, determines the presence of S. aureus (SA) within 4h, and differentiates MSSA and MRSA in an additional 12- 16h, and costs 25% of PCR. Methods: The testing procedure first utilizes an enhanced plasma substrate. The specimen (e.g., nasal swab) is inoculated into this plasma substrate and incubated at 35C. If SA is present, in from 2 to 6 hours on average, a clot forms because of the detection of coagulase. Hence, the observation of the clot is Page 99 of 262 specific for the presence of SA.. The clot is then dissolved, freeing the SA. An aliquot from the liquefied clot is added to a culture medium that promotes the growth of SA and also has cefoxitin to ascertain methicillin resistance. After incubation (8-18 h), growth, as evidenced by a color change, is specific for MRSA; no color change indicates the presence of MSSA. A total of 60 MSSA and 60 MRSA from patient nasal cultures were constructed to determine minimum SA sensitivity. In addition, 50 ICU patient samples were tested and compared to the mannitol salt agar (MSA) procedure. Results: From the 60 MSSA constructed, all were positive in 5 h; 49 in 4 h; 38 in 3 h; and 26 in 2. From the 60 MRSA constructed, all were positive in 6 h; 54 in 5h; 49 in 4h; 36 in 3h, and 24 in 2h. Detection limit in all were 102-3. From the 50 patients, there were no false positives. MSA and AA both detected MSSA in 9; AA alone in 2. For MRSA, both MSA and MRSA detected 13, MSA alone detected 1, and AA alone detected 2. Conclusions: AureusAlert® offers the prospect for all sized institutions at risk for SA a low cost, rapid means to detect both MSSA and MRSA utilizing unskilled labor. Widespread clinical evaluation is warranted.
Transmission of Methicillin-Resistant Staphylococcus intermedius between Animals and Humans
E. van Duijkeren1, D. Houwers1, A. Schoormans1, M. Broekhuizen-Stins1, R. Ikawaty2, A. Fluit2, J. Wagenaar1; 1Faculty of Veterinary Medicine, Utrecht University, Utrecht, THE NETHERLANDS, Page 19 of 262 2Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, THE NETHERLANDS.
Background: Staphylococcus intermedius is a commensal and a pathogen in dogs and cats, but is rarely isolated from humans. However, S. intermedius in humans has been associated with dog bite wounds, bacteraemia, pneumonia and ear infections. In the Netherlands, the prevalence of canine and feline infections with methicillin-resistant S. intermedius (MRSI) is increasing and therefore also the risk of their zoonotic transmission. Methods: At Utrecht University MRSI were cultured from infected surgical wounds of five dogs and one cat which had undergone surgery at the same veterinary clinic (clinic A). Samples were taken from the nose of the surgeon, from six technicians and from the nose and coat of two healthy dogs living at the clinic in order to identify the source. In addition, 22 environmental samples were taken from several sites at the clinic. S. intermedius was identified in these samples using standard techniques. Antimicrobial susceptibilities were determined by an agar diffusion method. The mecA gene was detected by PCR. The isolates were genotyped by PFGE using SmaI as restriction enzyme. Four epidemiologically unrelated MRSI isolates from patients at other veterinary clinics were also included. Results: MRSI was cultured from the nose of the surgeon, three technicians, one healthy dog and four environmental samples. The isolates were resistant against ampicillin, amoxicillin with clavulanic acid, cephalexin, ceftiofur, ceftazidime, enrofloxacin, gentamicin, kanamycin, chloramphenicol, lincomycin, clindamycin, tetracycline and trimethoprim/sulphamethoxazole and susceptible to fusidic acid and rifampicin. This was the same resistance pattern as the initial isolates from the six patients. All isolates were mecA positive by PCR. The PFGE profiles from the MRSI isolates from clinic A were all indistinguishable and differed from the profiles of the isolates from other clinics. Conclusions: Together, these data suggest transmission of MRSI between animals and humans. To our knowledge, this is the first report on the transmission of MRSI between humans and animals. People working at veterinary clinics should be aware of this risk for their own and their patients’ sake.
Methicillin-resistant Staphylococcus aureus (MRSA) Infections among Pets in Minnesota
J. B. Bender1, K. Coughlan1, K. Waters1, D. Boxrud2, K. Peterson3, J. Buck4; 1University of Minnesota, Veterinary Public Health, St. Paul, MN, 2Minnesota Department of Health, Public Health Laboratory, St. Paul, MN, 3University of Minnesota, Veterinary Medical Center, St. Paul, MN, 4Minnesota Department of Health, St. Paul, MN.
Background: Methicillin-resistant Staphylococcus aureus (MRSA) infections are increasingly being reported in dogs, horses, pigs, and cats. The zoonotic potential from these infections is unknown and requires further assessment. To document the occurrence among select animal populations, samples were collected from animals residing in a long-term care facility, pets of patients recently diagnosed with MRSA infection, and clinically ill animals presenting to a veterinary hospital. Methods: Nasal and rectal swabs were collected from asymptomatic animals in a long-term care facility and pets of patients recently diagnosed with MRSA. Culture-confirmed MRSA recovered from ill animals were identified through surveillance in a veterinary hospital. Collected isolates were sent to the Minnesota Department of Health for confirmation, antimicrobial susceptibility testing, and molecular subtyping. Results: Two of 11 resident Page 39 of 262 cats from the long-term care facility were identified with MRSA. All isolates were genotype USA100. MRSA was isolated from 2 of 28 asymptomatic pets of pet owners diagnosed with community-associated MRSA. Isolates from the 2 animals were genotype USA300. Since October 2003, MRSA has been identified in 18 refractory cases presented to the veterinary medical clinic. Isolates were obtained from 12 dogs, 5 cats, and 1 horse. Thirteen of 16 available isolates were genotype USA100 and the remaining 3 were genotype USA300. Nine of 12 interviewed family members of the infected pet were recently hospitalized or had on-going severe illnesses (i.e. chemotherapy), or were healthcare providers. Spread within the veterinary clinic was suspected from several case clusters supported by isolation of indistinguishable strains among case isolates. Conclusions: Pets with MRSA likely acquire their infection from their owners as demonstrated by the presence of common genotypes among the various populations. There is a need to re-enforce precautionary measures and hand hygiene to pet owners diagnosed with MRSA infection. Owner education should describe the potential risk of transmission from and/or to pets. Further research to quantify this household risk, the length of carriage in pets, and the potential treatment options is needed.
http://www.cdc.gov/eid/content/14/3/ICEID2008.pdf
TSS
Trends in Invasive Infection with Methicillin-resistant Staphylococcus
aureus (MRSA) in Connecticut, 2001-2006
S. Petit1, Z. Fraser1, M. Mandour2, J. L. Hadler1; 1Connecticut Department
of Public Health, Hartford, CT,
2Connecticut Department of Public Health Laboratory, Hartford, CT.
Background: In 2007, CDC published an article that described the epidemiology of invasive
MRSA infections in 2004-05 in 9 sentinel sites, including Connecticut (CT). The CT system has been in place since 2001 and provides an opportunity to examine trends in the 3 major groupings of MRSA by place of onset and relationship to healthcare: hospital-onset (HO) vs. community-onset but healthcareassociated (HA) or community-associated (CA) MRSA. Methods: Cases identified from laboratory reporting of MRSA isolates from normally sterile body sites were classified after medical record review as HO (isolate >2 days after hospital admission), HA (hospital admission, surgery, dialysis, or long-term care facility stay in the past year, a history of MRSA, or an indwelling device); or CA (by exclusion). A systematic sample of blood isolates were typed by pulsed-field gel electrophoresis (PFGE). Results: In
2001-2006, 5464 cases of invasive MRSA were reported; 34.5% HO, 58.9% HA and 6.6% CA. Annual incidence overall (26.2 per 100,000) and of HA-MRSA (15.4) was stable. However, incidence of HOMRSA decreased (10.0 to 7.6) while CA incidence increased (1.1 to 2.8, p<0.01 p="0.02)." p =".049,"> 1 hospitalization (80%, [268/335] vs. 63% [245/390], P <.0001) and had > 2 infections (33%, [110/335]) vs. 23% [88/390], P =.002) respectively. There were twice as many deaths during the 6-month follow up period among patients with MRSA infection (24%,
79/335) as among patients with MSSA infection (12% 45/390, OR 2.4, 95% CI 1.6-3.5, P < .0001). After adjustment for age and CH-IND, this difference remained significant (OR 1.9, 95% CI 1.2-2.9, P =.005). There was clinical evidence that SA infection caused or clearly contributed to death in 28% (35/124) of all deaths; 7% (25/335) among those with MRSA infection and 3% (10/390) among those with MSSA infection. After adjustment for age, those with MRSA infection were almost 3 times more likely than those with MSSA infection to die of SA disease (OR 2.8, 95% CI 1.3-6.0, P =.007). Conclusions: In this patient population, methicillin resistance was associated with a greater risk of death attributable to SA disease and to death from any cause. MRSA infections were more common among those with chronic illnesses. Optimal methods of prevention and treatment of healthcare-associated SA, particularly MRSA infections, are urgently needed. Community-Associated (CA) Methicillin-Resistant Staphylococcus aureus (MRSA) in Affected Households: Prevalence of Colonization and Incidence of Subsequent Infections J. M. Buck1, R. Gorwitz2, R. Lynfield1, K. Harriman3; 1Minnesota Department of Health, Saint Paul, MN, 2Centers for Disease Control and Prevention, Atlanta, GA, 3California Department of Public Health, Richmond, CA. Background: MRSA has emerged as a community pathogen over the last decade. Several reports indicate that CA-MRSA infections can occur among multiple household members (HHMs). We describe MRSA colonization prevalence and subsequent infection incidence among children with CAMRSA infections and their HHMs. Methods: MRSA infections in children <18 p =" 0.03)," p =" 0.03)."> 0.05). Conclusions: The prevalence of MRSA colonization in affected HHs did not decrease during the study period; over 20% of HHs had at least one colonized HHM one year after initial CP infection. Use of mupirocin did not appear to affect long term MRSA colonization or infection in HHs. Behavior modifications (e.g. not sharing personal items) may be more important in reducing MRSA transmission. Additional strategies to prevent CA-MRSA infection and transmission in HHs should be evaluated.
Detection of Community Acquired Methicillin Resistant Staphylococcus aureus
Associated with Nosocomial Infections
S. M. Tallent, D. M. Toney; Virginia Division of Consolidated Laboratory
Services, Richmond, VA.
Background: Staphylococcus aureus is a human commensal that has emerged as a significant
pathogen due to the production of a variety of virulence factors and acquisition of numerous antimicrobial resistant genes. Methicillin resistant S. aureus (MRSA) is an antimicrobial resistant strain traditionally associated with hospital infections, but is now increasingly associated with illness in typically healthy individuals outside healthcare facilities. Pulsed-field gel electrophoresis (PFGE) genotyping of staphylococcal isolates by the CDC categorized MRSA strains into two groups, community-acquired methicillin resistant S. aureus (CA-MRSA) and hospital-acquired methicillin resistant S. aureus (HAMRSA). The two groups clustered into ten lineages which were designated as pulsetypes USA100- USA1100. More recently, distinctions between HA-MRSA and CA-MRSA have become less apparent, presumably due to recombination events giving rise to new MRSA strains that differ from the USA pulsetypes. Methods: S. aureus isolates from previous hospital and community outbreaks occurring in
Virginia as early as 1997 were subjected to PFGE genotyping, generating a DNA fingerprint database at the Division of Consolidated Laboratory Services (DCLS), the Virginia state laboratory. Archived isolates from 2005-2007 (N=258) were compared to the prototype USA fingerprint patterns and classified based on pattern similarities. Clusters of isolates possessing >80% similarity to the USA pulsetypes were further evaluated. Results: Forty percent of the 258 MRSA isolates examined clustered with USA100, the most common HA-MRSA pulsetype. Of these strains, 23% were associated with community outbreaks not hospital infections based on epidemiologic investigations. In contrast, 22% of the 258 isolates clustered with USA300, the most common CA-MRSA pulsetype. Of these, 88% were previously determined to be
associated with nosocomial infections. Conclusions: This study has identified a subset of MRSA strains designated as outliers based on PFGE pulsetype patterns and epidemiology. Additional molecular characterization is ongoing to understand these findings, determine if this is a representative trend in Virginia and whether the most invasive form of MRSA has become endemic to Virginia’s healthcare facilities.
Board 7. Community-Associated Methicillin-Resistant Staphylococcus aureus
Infection Risk Factor Study
K. Como-Sabetti1, K. Harriman2, S. Fridkin3, R. Lynfield4; 1Minnesota Department of Health, Minneapolis, MN, 2California Department of Public Health, Richmond, CA, 3Centers for Disease Control and Prevention, Atlanta, GA, 4Minnesota Department of Health, Saint Paul, MN.
Background: Little is known about risk factors for methicillin-resistant Staphylococcus aureus (CA-MRSA) infection in non-outbreak settings. Methods: MN Department of Health initiated a hypothesis-generating CA-MRSA case control study in 2003. 150 patients with S. aureus infections, including both CA-MRSA and CA methicillinsensitive SA (MSSA), were identified by 3 sentinel labs. 2-3 age-group matched healthy community controls (CC) were identified by sequential digit dialing. Participants were interviewed about possible risk factors and an antibiotic history was obtained from healthcare providers. Univariate and multivariate conditional logistic regression were conducted using SAS for 3 separate analyses to avoid biased estimates: CA-MRSA cases vs. CA-MSSA cases, CAMRSA cases vs. CA-MRSA CCs, and CA-MSSA cases vs. CA-MSSA CCs.Results: 75 CA-MRSA and CA-MSSA cases and 438 CCs were enrolled. Antibiotic use in the prior 1-6 months (recent ABX) was more frequent among CAMRSA cases than CA-MSSA cases or CCs (33% vs. 17% vs. 14%). History of boils was infrequent (10% CA-MSSA, 1% CA-MSSA, 1% CCs). Race, education, income, household members per room, dog in the home, history of boils, and towel sharing were associated with CA-MRSA when compared to CA-MSSA or CA-MRSA CCs. Recent ABX and number of recent ABX courses were associated with CA-MRSA when compared to CA-MSSA cases (p=0.03;
OR=2.5, and p<0.01; OR=2.2 respectively) and persisted when compared to CA-MRSA CCs (p=0.05; OR=2.3, and p=0.02; OR=1.9 respectively), but were not associated with CA-MSSA cases compared to CA-MSSA CCs. After adjusting for socioeconomic factors, history of boils was associated with CA-MRSA compared to CA-MSSA (p=0.002; AOR=76.8) but not when compared to CA-MRSA CCs. Recent ABX and ABX courses were associated with CAMRSA compared to CA-MSSA (p=0.02, AOR=1.9, and p=0.01, AOR=2.2 respectively) and compared to CA-MRSA CCs (p=0.05, AOR=2.4, and p=0.02 and AOR = 1.9 respectively). Conclusions: In non-outbreak settings, antibiotic use and history of boils (which may be a proxy for prior CA-MRSA skin disease) appear to be risk factors for CAMRSA. Further investigation of antibiotic use and specific antibiotic classes is needed. Although not definitive, this study reinforces the importance of careful antibiotic stewardship.
Board 83. Critical or Fatal Illness Due to Community-associated Staphylococcus aureus (CA-SA) Infection, Minnesota (MN), 2005-2007
Page 121 of 262 L. Lesher1, J. Buck1, J. Bartkus1, S. Jawahir1, D. Boxrud1, K. Harriman2, R. Lynfield1; 1Minnesota Department of Health, Saint Paul, MN, 2California Department of Public Health, Richmond, CA.
Background: CA-SA infections have been associated with critical illness and death. Methods: Reporting for rapidly fatal or critical illness due to CA-SA infection, including isolate collection, was instituted statewide in MN in 2005. Cases were defined as previously healthy people who had fatal illness or ICU admission and no healthcareassociated (HA) MRSA risk factors per CDC definition, excluding hospitalization for birth. Isolates were characterized by pulsed-field gel electrophoresis (PFGE) and PCR for toxic shock syndrome toxin 1 (TSST1), Panton-Valentine leukocidin (PVL), and staphylococcal enterotoxin (SE) genes A, B, C, D. Results: 32 cases were reported January 2005 through October 2007; 21 (66%) methicillin-resistant SA (MRSA) and 11 (34%) methicillin-susceptible SA (MSSA) cases. 14 (67%) MRSA cases were male; median age, 17 years (12 days-88 years), and 5 (45%) MSSA cases were male; median age, 18 years (1 day-59 years). Two cases had multifocal infections; MRSA with pneumonia and septic arthritis; MSSA with meningitis, lumbar wound, pneumonia (fatal). Of MRSA cases, 11 (52%) had pneumonia (3 fatal), 5 (24%) had skin infections (4 bacteremic - 1 fatal; 1 necrotizing fasciitis - fatal), 2 (9%) had sepsis (1 fatal), 1 (5%) had meningitis, 1 (5%) had osteomyelitis. Of MSSA cases, 4 (36%) had pneumonia (2 fatal), 2 (18%) had skin infections with bacteremia, 2 (18%) had TSS, 1 (9%) had meningitis (fatal), 1 (9%) had sepsis. The median age of fatal cases was 58 years for MRSA, 27 years for MSSA. PFGE typing and toxin PCR were performed on 17 MRSA and 7 MSSA isolates. All MRSA isolates belonged to clonal groups associated with CAMRSA; USA300 (15), USA400 (1), USA1000 (1). MSSA isolates were found in groups associated with CA and HAMRSA; USA200 (1), USA400 (1), USA600 (2), USA700 (1), USA1000 (2). Among MRSA, toxin PCR found PVL in 14 USA300 isolates (2 fatal) and 1 USA400 (fatal), which also had SEA and SEC. Among MSSA, SEB was found in 1 USA1000 isolate (fatal) and TSST1 in 1 USA200 (clinical TSS), and 2 MSSA isolates from fatal cases were negative for all toxins tested. Conclusions: Most critical/fatal CA-SA reported cases were MRSA. A high fatality rate was observed in cases with meningitis or pneumonia. Fatal MRSA cases were older than MSSA cases. Most isolates contained toxins previously implicated in severe disease. Molecular
Epidemiology Board 109. Staphylococcal Cassette Chromosome mec (SCCmec) Characterization and Panton-Valentine Leukocidin Gene Occurrence for Methicillin-Resistant Staphylococcus aureus in Turkey, from 2003 to 2006
A. Kilic, A. Uskudar Guclu, Z. Senses, H. Aydogan, A. C. Basustaoglu; Gulhane Military Medical Academy, Ankara, TURKEY.
Background: Methicillin-resistant Staphylococcus aureus (MRSA) cause serious community-acquired and nosocomial diseases all over the world. Methods: We determined the SCCmec types and occurrence of the PVL gene by using TaqMan real-time PCR method, and correlated these with phenotypic antibiotic susceptibility patterns for MRSA strains collected from Gulhane Military Medical Academy Hospital (GMMAH) during four years study period. To our knowledge, this is the first report from Turkey of molecular SCCmec typing analysis of MRSA stains. From 2003 through 2006, a total of 385 clinical MRSA strains were collected in the Clinical Microbiology Laboratory at GMMAH were included in the study. Results: Overall, SCCmec types-I, II, II, IV, V, nontypeable and PVL occurrence were detected in 11 (2.8%), 3 (0.8%), 316 (82.1%), 20 (5.1%), 20 (5.1%), 15 (3.9%) and 5 (1.3%) isolates, respectively. A total of 330 (85.5%) were SCCmec-I/II/III, and of 40 (10.3%) were SCCmec-IV/V. SCCmec-I/II/III isolates were recovered more from serious infections in surgical departments especially having intensive care units than the SCCmec-IV/V isolates (?2=13.560, p<0.001). SCCmec-I/II/III MRSA strains were predominantly recovered from the blood stream as 53.0% (?2=6.016, p=0.014), while SCCmec-IV/V strains were predominantly isolated from skin, soft tissue and abscess as 55.0% (?2= 11.025, p<0.001). The PVL gene was detected in 10.0% of SCCmec- IV/V isolates in contrast to 0.3% in SCCmec-I/II/III (?2= 25.164, p<0.001). SCCmec-I/II/III MRSA strains were more resistant to clindamycin (?2=5.078, p=0.024), amoxicillin-clavulanate (?2=84.912, p<0.001), erythromycin (?2=4.651, p=0.031), gentamicin (?2=24.869, p<0.001), and rifampin (?2=18.878, p<0.001) than SCCmec-IV/V MRSA strains. Conclusions: These data indicate that SCCmec-III MRSA strains not to carrying PVL gene are the predominant MRSA strains in our hospital settings in Ankara, capital of Turkey. SCCmec-I/II/III MRSA strains may cause serious infections in surgical department especially having intensive care units.
Board 227. Staphylococcus aureus and Methicillin Resistant Staphylococcus aureus on surfaces in a University and a Jail Setting
M. Felkner1, K. Bartlett2, K. Andrews2, L. Field2, J. Taylor1, T. Baldwin1, J. Presley2, J. Duncan2, S. Newsome1; 1Texas Department of State Health Services, Austin, TX, 2The University of Texas at Austin, Austin, TX.
Background: Longtime pathogen Staphylococcus aureus has become more threatening with its evolution of antibiotic resistance, particularly the emergence of methicillin resistance outside health care settings. Commonly touched surfaces may harbor methicillin resistant S. aureus (MRSA) and be possible reservoirs of organisms facilitating disease transmission in the community. This study provides information regarding the presence of MRSA on commonly touched objects in both a university and a jail setting. Methods: University surface samples were obtained from bathrooms, common use areas, and recreational and sports facilities. Samples were collected at the jail from bathrooms, cells, common use areas, the clinic, laundry, and vehicles. Samples were collected using sterile, cotton-tipped swabs. Specimens were screened for S. aureus and MRSA using standard media. Susceptibility was determined using the ETest strip. Percentages of contaminated surfaces were calculated and chi-square comparisons were made between university and jail settings. Results: Seventeen (7.0%) of 244 university samples and 10 (7.5%) of 132 jail samples grew S. aureus. MRSA was recovered from 3 (1.2%) university samples, constituting 17.6% of S. aureus samples. Eight (6.1%) jail samples were MRSA, comprising 80% of jail S. aureus samples. The proportion of MRSA-contaminated surfaces and the ratio of MRSA to methicillin susceptible S. aureus were significantly greater at the jail that at the university (p<0.05). Conclusions: Our results indicate that environmental contamination with MRSA may be positively correlated with the carriage rate within the population. Page 191 of 262 Implementation of environmental sanitation should be of particular concern in populations with high MRSA nasal carriage rates.
Board 264. 30-Day and 180-Day Case Fatality Rates among Invasive Methicillin-Resistant Staphylococcus aureus Patients (Tennessee, 2004–2007)
K. R. Glenn, M. A. Kainer; Tennessee Department of Health, Nashville, TN.
Background: Tennessee had the second highest incidence of invasive MRSA (I-MRSA) of 10 EIP study sites in 2005, with an incidence of 53 per 100,000. The national in-hospital case-fatality was 17.8%. U.S. in-hospital mortality rate from I-MRSA was 6.3 per 100,000. We wanted to assess the 30-day and 180-day crude case-fatality (CFR) and mortality rates of I-MRSA and determine factors associated with death. Methods: Vital statistics data was available up to Oct. 31, 2007. We used data from the Active Bacterial Core (ABC) surveillance component of the Emerging Infections Program in Davidson County. Cases from Oct. 2004-Jul. 2007 were included for 30-day CFR/mortality rates. Cases from Oct. 2004-Apr. 2007 were included to determine 180-day CFR/mortality rates. We reviewed Tennessee vital statistic data to determine patient outcomes; we matched by name and birthdate. We
Page 208 of 262
calculated the number of days between the initial MRSA-positive culture and date of death recorded on death certificates for each matched case to determine the numerator for the 30- and 180-day CFR/mortality rates. Results: I-MRSA rates for 2004-2007 were 59.1 per 100,000. The 30-day I-MRSA mortality rate was 7.3; 180-day I-MRSA mortality rate was 9.9 per 100,000. Fifty-four of 192 deaths (28%) were identified from vital statistic records alone (i.e., occurred following discharge). The overall 30- and 180-day CFRs were 13.2% and 19.1%, respectively. Blood stream infections (BSI) accounted for 85% of I-MRSA. Patients with MRSA BSI had higher 30- and 180-day crude CFRs compared to patients with non-BSI I-MRSA (14.7% vs. 4.5% [relative risk {RR}= 3.3, 95% CI: 1.5-7.3] and 21.4% vs. 5.7%, [RR= 3.8, 95% CI: 1.8-7.9], respectively). 30-day CFRs were not statistically significant among Blacks and Whites (12.6% vs. 14.3%, respectively). Healthcare-associated I-MRSA had a higher 30- and 180-day CFR compared to community-associated MRSA (14.4% vs. 9% [RR= 1.7, 95% CI: 1.0-2.9] and 21.0% vs. 12.7%, [RR= 1.7, 95% CI: 1.1- 2.8] respectively). Conclusions: MRSA BSI is associated with much higher CFR than other IMRSA. Policy and practices aimed toward the reduction of I-MRSA rates in Tennessee are necessary to decrease the number of deaths annually associated with I-MRSA.
Board 268. Dissemination of Community-Associated Methicillin-Resistant Staphylococcus aureus CMRSA7 (USA400) in Northern Saskatchewan, Canada
J. Irvine1, B. Quinn1, D. Stockdale1, S. Woods2, M. Nsugngu2, P. Levett3, R. McDonald3, G. Golding4, G. Horsman3, M. Mulvey4, the Northern Antibiotic Resistance Partnership; 1Population Health Unit, LaRonge, SK, CANADA, 2Northern Inter-tribal Health Authority, Prince Albert, SK, CANADA, 3Saskatchewan Disease Control Laboratory, Regina, SK, CANADA, 4National Microbiology Laboratory, Winnipeg, MB, CANADA.
Background: Although the USA300 (CMRSA10) strain of community-associated methicillin-resistance (CAMRSA) is rapidly disseminating across North America, some reports have described the emergence of CA-MRSA in northern Canadian communities. This study examines the incidence and molecular epidemiology of CA-MRSA in Page 210 of 262 three of the most northerly Saskatchewan health regions. Methods: Surveillance was conducted over six years beginning in 2001 in three of the most northerly Saskatchewan health regions for all communities (on and offreserve). Specimens from clinical indications were collected from remote community health centers and small rural hospitals (<35 beds) and MRSA positive cases were reported to the respective health authorities. Cases with asymptomatic carriage were excluded. In order to calculate total CA-MRSA rates of recurrence, cases occurring more than 2 months of the preceding episode and / or at a different site, were considered a recurrent episode. Pulsed-field gel electrophoresis (PFGE) of SmaI digested genomic DNA and RT-PCR for the mecA, nuc, and PVL-encoding genes was used to characterize a subset of the isolates. Results: A total of 1,927 MRSA events in 1,409 individuals were reported over the study period with 99% being community-associated. Fifty-six percent (N=783) of the individuals were < 20 years of age, while the majority of their cases (80.8%) were skin and soft tissue infections. The annual rate of CA-MRSA distinct individuals reported in these health regions increased from 9 per 10,000 population in 2001 (range to 4-10 per 10,000) to 169 per 10,000 in 2006 (range 43-233 per 10,000). An annual periodicity was observed with the highest number of cases being reported during the third quarter (July-September). Of the CAMRSA cases, 15.1% of the individuals had at least one recurrent episode after 2 months. A subset of strains (N=192) were typed and 97.4% (N=187) were found to be Canadian PFGE epidemic type CMRSA7 (USA400) with 3 strains being CMRSA2 (USA100/800) and 2 strains being CMRSA10 (USA300). Conclusions: This report describes the rapid emergence of CA-MRSA in Northern Saskatchewan. The molecular epidemiology appears to be different from urban centers in southern Canada with the majority of cases being caused by CMRSA7 (USA400). Antimicrobial Resistance
Board 294. Daptomycin Resistance and hVISA Development in MRSA Endocarditis
M. Pastagia1, N. Casau-Schulhof1, S. G. Jenkins2, J. Jao2; 1Mount Sinai Hospital, New York, New York, NY, 2Mount Sinai Medical Center, New York, NY.
Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a common etiology of endocarditis in hemodialysis patients. We present a patient without any prior hospitalizations or vancomycin usage within the past ten years who developed MRSA endocarditis with persistent bacteremia while on daptomycin therapy. She then became resistant to daptomycin while on therapy, and ultimately cleared her bacteremia only after valve replacement. We performed microbiological tests on her blood and valve isolates. Methods: We performed E-strip testing of the four blood isolates with MRSA bacteremia as well as the tissue heart valve after replacement with vancomycin, daptomycin, linezolid, and tigecycline E-strips to establish the MIC. These specimens were also tested for
Page 222 of 262
heterogeneously vancomycin intermediate Staphylococcus aureus (hVISA) via teicoplanin E-strips of 0.5 and 2 McFarland standards. Results: The initial positive blood culture with MRSA was shown to have a MIC to vancomycin of 6 and 3 for daptomycin. These numbers remained similar for the subsequent two positive blood cultures a few days later while she remained on daptomycin, renally dosed. The fourth positive blood culture nearly one week later while on daptomycin was found to have a vancomycin MIC of 6 and a daptomycin MIC of 4. The heart valve was subsequently replaced, and the MICs of the tissue valve to vancomycin was 3, and to daptomycin was 6. All of these isolates were then tested for hVISA via teicoplanin E-strip testing at 0.5 and 2 McFarland standards. This testing revealed MICs of 3 and 4 at 0.5 and 2 McFarland, respectively for the initial blood culture. The subsequent two blood cultures showed MICs of 6 and 8 respectively. By the fourth blood culture, the MICs were 12 and 8 respectively. Ultimately the tissue valve’s MICs to teicoplanin were tested, and found to be 12 and 16, respectively. Conclusions: It is quite uncommon for patients who have not been on prior vancomycin therapy extensively to develop resistance to daptomycin so quickly. Here, we present such a case and were able to demonstrate that this isolate became a heterogeneously vancomyin intermediate Staphylococcus aureus after nearly one week of daptomycin therapy. This transformation from a non-hVISA to an hVISA strain may be predictive of antibiotic failure in this case.
Board 295. Laboratory Analysis of Staphylococcus aureus in Florida: January 1, 2003 to December 31, 2005 with an Emphasis on Methicillin Resistance
S. K. Kolar1, R. Sanderson2, A. Sanchez-Anguiano1; 1University of South Florida, Tampa, FL, 2Florida Department of Health, Tampa, FL. Background: Methicillin resistance among S. aureus has been a concern in the healthcare setting. Recently, MRSA has emerged in the community setting. Methods: This cross-sectional study examines methicillin resistance among S. aureus laboratory isolates in an outpatient population in the state of Florida. The database included all S. aureus laboratory results from a large commercial laboratory from January 1, 2003 to December 31, 2005 provided to the Florida Department of Health. Results: There was a total of 61,596 isolates in the database with the number of isolates doubling each year. The percent of isolates that were methicillin resistant significantly increased each year from 35.1% in 2003 to 49.7% in 2005. Isolates from skin and soft tissue comprised 79.6% of the reported site of infections, of which 52.7% were methicillin resistant in 2005. Methicillin resistance varied by year, age group, gender, county, and region. There was little difference in methicillin resistance between males and females (49.0% and 50.2% in 2005). There was some variation between the age groups, the 21- 30 age group had the highest percentage of MRSA (51% in 2005) and the <1 age group the lowest (40.2% in 2005). Variation by region and county was noted with the western panhandle having the highest percentage of MRSA (62.5% in 2005) and the southwest region the lowest (41.7% in 2005). The percentage of MRSA isolates that were resistant to trimethoprim-sulfamethoxazole, gentamycin, and rifampin was less than three percent. Discussion: The percent of isolates that were methiclillin resistant significantly increased during the study period. The differences by age group and region of the state were larger and may be important to consider when evaluating a potential S. aureus infection. Resistance to non beta-lactam antibiotics remains low and these could be alternative for empiric antimicrobial therapy in the outpatient setting.
New or Rapid
Diagnostics Board 38.
Novel Method and Medium for Detecting and Identifying both Methicillin Susceptible (MSSA) and Methicillin resistant(MRSA) Staphylococcus aureus
S. C. Edberg; Yale-New Haven Hospital, New Haven, CT.
Background: Currently, to detect MSSA or MRSA two pathways are available. The first uses semi-selective culture media; incubation 18-24h, then a series of tests for identification; subculture to a mec A inducing medium for an additional 18 to 24h. Accordingly, considerable skilled labor and time are required. The second pathway utilizes specific genetic amplification of the mecA gene for MRSA, and another amplification for MSSA. Each is quite costly in materials and equipment, thus precluding its use from all but the largest hospitals. A novel specific method and medium for detection of (MSSA) and (MRSA) [AureusAlert®, Pilots Point LLC] (AA) is presented. It requires no skilled labor, determines the presence of S. aureus (SA) within 4h, and differentiates MSSA and MRSA in an additional 12- 16h, and costs 25% of PCR. Methods: The testing procedure first utilizes an enhanced plasma substrate. The specimen (e.g., nasal swab) is inoculated into this plasma substrate and incubated at 35C. If SA is present, in from 2 to 6 hours on average, a clot forms because of the detection of coagulase. Hence, the observation of the clot is Page 99 of 262 specific for the presence of SA.. The clot is then dissolved, freeing the SA. An aliquot from the liquefied clot is added to a culture medium that promotes the growth of SA and also has cefoxitin to ascertain methicillin resistance. After incubation (8-18 h), growth, as evidenced by a color change, is specific for MRSA; no color change indicates the presence of MSSA. A total of 60 MSSA and 60 MRSA from patient nasal cultures were constructed to determine minimum SA sensitivity. In addition, 50 ICU patient samples were tested and compared to the mannitol salt agar (MSA) procedure. Results: From the 60 MSSA constructed, all were positive in 5 h; 49 in 4 h; 38 in 3 h; and 26 in 2. From the 60 MRSA constructed, all were positive in 6 h; 54 in 5h; 49 in 4h; 36 in 3h, and 24 in 2h. Detection limit in all were 102-3. From the 50 patients, there were no false positives. MSA and AA both detected MSSA in 9; AA alone in 2. For MRSA, both MSA and MRSA detected 13, MSA alone detected 1, and AA alone detected 2. Conclusions: AureusAlert® offers the prospect for all sized institutions at risk for SA a low cost, rapid means to detect both MSSA and MRSA utilizing unskilled labor. Widespread clinical evaluation is warranted.
Transmission of Methicillin-Resistant Staphylococcus intermedius between Animals and Humans
E. van Duijkeren1, D. Houwers1, A. Schoormans1, M. Broekhuizen-Stins1, R. Ikawaty2, A. Fluit2, J. Wagenaar1; 1Faculty of Veterinary Medicine, Utrecht University, Utrecht, THE NETHERLANDS, Page 19 of 262 2Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, THE NETHERLANDS.
Background: Staphylococcus intermedius is a commensal and a pathogen in dogs and cats, but is rarely isolated from humans. However, S. intermedius in humans has been associated with dog bite wounds, bacteraemia, pneumonia and ear infections. In the Netherlands, the prevalence of canine and feline infections with methicillin-resistant S. intermedius (MRSI) is increasing and therefore also the risk of their zoonotic transmission. Methods: At Utrecht University MRSI were cultured from infected surgical wounds of five dogs and one cat which had undergone surgery at the same veterinary clinic (clinic A). Samples were taken from the nose of the surgeon, from six technicians and from the nose and coat of two healthy dogs living at the clinic in order to identify the source. In addition, 22 environmental samples were taken from several sites at the clinic. S. intermedius was identified in these samples using standard techniques. Antimicrobial susceptibilities were determined by an agar diffusion method. The mecA gene was detected by PCR. The isolates were genotyped by PFGE using SmaI as restriction enzyme. Four epidemiologically unrelated MRSI isolates from patients at other veterinary clinics were also included. Results: MRSI was cultured from the nose of the surgeon, three technicians, one healthy dog and four environmental samples. The isolates were resistant against ampicillin, amoxicillin with clavulanic acid, cephalexin, ceftiofur, ceftazidime, enrofloxacin, gentamicin, kanamycin, chloramphenicol, lincomycin, clindamycin, tetracycline and trimethoprim/sulphamethoxazole and susceptible to fusidic acid and rifampicin. This was the same resistance pattern as the initial isolates from the six patients. All isolates were mecA positive by PCR. The PFGE profiles from the MRSI isolates from clinic A were all indistinguishable and differed from the profiles of the isolates from other clinics. Conclusions: Together, these data suggest transmission of MRSI between animals and humans. To our knowledge, this is the first report on the transmission of MRSI between humans and animals. People working at veterinary clinics should be aware of this risk for their own and their patients’ sake.
Methicillin-resistant Staphylococcus aureus (MRSA) Infections among Pets in Minnesota
J. B. Bender1, K. Coughlan1, K. Waters1, D. Boxrud2, K. Peterson3, J. Buck4; 1University of Minnesota, Veterinary Public Health, St. Paul, MN, 2Minnesota Department of Health, Public Health Laboratory, St. Paul, MN, 3University of Minnesota, Veterinary Medical Center, St. Paul, MN, 4Minnesota Department of Health, St. Paul, MN.
Background: Methicillin-resistant Staphylococcus aureus (MRSA) infections are increasingly being reported in dogs, horses, pigs, and cats. The zoonotic potential from these infections is unknown and requires further assessment. To document the occurrence among select animal populations, samples were collected from animals residing in a long-term care facility, pets of patients recently diagnosed with MRSA infection, and clinically ill animals presenting to a veterinary hospital. Methods: Nasal and rectal swabs were collected from asymptomatic animals in a long-term care facility and pets of patients recently diagnosed with MRSA. Culture-confirmed MRSA recovered from ill animals were identified through surveillance in a veterinary hospital. Collected isolates were sent to the Minnesota Department of Health for confirmation, antimicrobial susceptibility testing, and molecular subtyping. Results: Two of 11 resident Page 39 of 262 cats from the long-term care facility were identified with MRSA. All isolates were genotype USA100. MRSA was isolated from 2 of 28 asymptomatic pets of pet owners diagnosed with community-associated MRSA. Isolates from the 2 animals were genotype USA300. Since October 2003, MRSA has been identified in 18 refractory cases presented to the veterinary medical clinic. Isolates were obtained from 12 dogs, 5 cats, and 1 horse. Thirteen of 16 available isolates were genotype USA100 and the remaining 3 were genotype USA300. Nine of 12 interviewed family members of the infected pet were recently hospitalized or had on-going severe illnesses (i.e. chemotherapy), or were healthcare providers. Spread within the veterinary clinic was suspected from several case clusters supported by isolation of indistinguishable strains among case isolates. Conclusions: Pets with MRSA likely acquire their infection from their owners as demonstrated by the presence of common genotypes among the various populations. There is a need to re-enforce precautionary measures and hand hygiene to pet owners diagnosed with MRSA infection. Owner education should describe the potential risk of transmission from and/or to pets. Further research to quantify this household risk, the length of carriage in pets, and the potential treatment options is needed.
http://www.cdc.gov/eid/content/14/3/ICEID2008.pdf
TSS
Tuesday, January 29, 2008
Fight to curtail antibiotics in animal feed
Fight to curtail antibiotics in animal feed
Sabin Russell, Chronicle Medical Writer
Monday, January 28, 2008
Consumer advocates have been campaigning for years to curb the use of antibiotics in agriculture, citing studies that show that 70 percent of all U.S. antibiotics are administered in low doses - not to treat disease, but to promote the growth of pigs, sheep, chicken and cattle.
Low doses of antibiotics in animal feeds have been shown to boost the speed of food-to-muscle conversion by 5 percent, and can prevent the spread of disease in the tight quarters of modern factory farms.
But as early as 1963, British researchers tied the emergence of drug-resistant strains of salmonella in humans to antibiotics fed to cattle. Among the drugs routinely found in animal feed are erythromycin, penicillin and streptomycin. Critics warn that the use of antibiotics in feed at low dosages helps to breed resistant bacteria in the gut of farm animals - threatening the future of these drugs for use in animals or humans.
Major antibiotic classes such as tetracyclines and the Cipro-like fluoroquinolones have already been compromised, according to Keep Antibiotics Working, a coalition backed by environmental groups and the American Medical Association.
The stakes are high. The Union of Concerned Scientists calculated in 2001 that U.S. farm interests were using 24.6 million pounds of anti-microbials - almost 40 percent higher than industry estimates.
Ron Phillips, vice president of the Animal Health Institute, a Washington trade group for agricultural drugmakers, maintains that growth promotion accounts for only 4.5 percent of antibiotic consumption in agriculture. The rest are used to prevent, treat or control the spread of disease. "Antibiotics," he says, "are a net positive for both animal health and human health."
After antibiotics were banned from animal feed in Europe beginning in 1995, Phillips said, farmers there found they had to use more antibiotics to care for illnesses that cropped up in their livestock.
Keep Antibiotics Working nevertheless is pushing for a federal ban on antibiotics in feed. Introduced by Sens. Edward Kennedy, D-Mass, and Olympia Snow, R-Maine, the "Preservation of Antibiotics for Medical Treatment Act" would phase out in two years antibiotics deemed "important in human medicine."
In response to pressure from consumer groups, McDonald's declared four years ago its intention to phase out the purchase of meats from chicken and livestock fed the drugs to promote growth. The Food and Drug Administration in 2005 banned the use of a Cipro-like drug, Baytril, to treat bacterial infections in poultry, after drug-resistant strains of Campylobacter - a common food-poisoning organism - were found in chicken. Cases of Cipro-resistant Campylobacter were also rising in humans.
The FDA is considering an application for approval of the antibiotic cefquinome, a proposed veterinary drug that is similar to the human drug cefepime. In the fall of 2006, an FDA advisory committee recommended against approval.
"It was surprising what the committee did, because it was stacked with veterinarians and animal science people," said Stephen Roach, director of public health programs for Keep Antibiotics Working.
"The USDA is very reluctant to say that antibiotic use causes a problem, and the FDA has traditionally been in the middle. But I feel that in the last several years, they have been more accommodating to industry," said Roach.
A final decision on approving cefquinome is still pending.
E-mail Sabin Russell at srussell@sfchronicle.com.
http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2008/01/28/MNSTUGD8E.DTL
Public Health Service
Food and Drug Administration
Baltimore District Office
6000 Metro Drive
Suite 101
Baltimore, MD 21215-3215
Telephone: (410) 779-5454
FEI: 3000203759
January 16 , 2008
WARNING LETTER
08-BLT-03
CERTIFIED MAIL
RETURN RECEIPT REQUESTED
Mr. Francis H. Roderick
Old Carolina Farms
10802 Cook Brothers Road
Ijamsville, Maryland 21754
Dear Mr. Roderick:
An inspection of your dairy operation located at 10802 Cook Brothers Road, Ijamsville, Maryland, conducted by a representative of the U.S. Food and Drug Administration (FDA) between October 16, 2007, and November 27, 2007, confirmed that you offered a bob veal calf for sale for slaughter as food that was adulterated under sections 402(a)(2)(C)(ii) [21 U.S.C. § 342(a)(2)(C)(ii)] and 402(a)(4) [21 U.S.C. § 342(a)(4)] of the Federal Food, Drug, and Cosmetic Act (the Act) . The inspection also revealed that you caused the new animal drug, [redacted] (sulfamethazine) [redacted] to become unsafe under section 512(a) [21 U.S.C. § 360b(a)] of the Act and adulterated within the meaning of section 501(a)(5) [21 U.S.C. § 351(a)(5)] of the Act. In addition, the inspection revealed that you provided a false guaranty, a prohibited act under section 301(h) of the Act [21 U.S.C. § 331(h)], You can find the Act and its associated regulations on the Internet through links on the FDA's web page at
www.fda.gov.
On or about July 25, 2007, you consigned a bob veal calf, identified with tag [redacted], for slaughter as food an [redacted]. On or about July 26, 2007, this animal was slaughtered at [redacted] United States Department of Agriculture, Food Safety and Inspection Service (USDA/FSIS) analysis of tissue samples collected from that animal identified the presence of 131.89 parts per million (ppm) of sulfamethazine in the liver tissue and 179.88 ppm of sulfarnethazine in the muscle tissue of this animal. A tolerance of 0.1 ppm has been established for residues of sulfamethazine in the edible tissues of cattle as codified in Title 21, Code of Federal Regulations, section 556.670 [21 C.F.R. 556.670]. The presence of this drug in these amounts in edible) tissues from this animal causes the food to be adulterated within the meaning of section 402(a)(2)(C)(ii)[(21 U.S.C. § 342(a)(2)(C)(ii)] of the Act.
Our investigation also found that you hold animals under conditions that are so inadequate that medicated animals bearing potentially harmful drug residues are likely to enter the food supply. You lackS an adequate system to ensure that animals medicated by you have been withheld from slaughter for appropriate periods of time to permit depletion of potentially hazardous residues of drugs from edible tissues. For example, you failed to maintain treatment records. Food from animals held under such conditions is adulterated within the meaning of section 402(a)(4) [21 U.S.C. § 342(a)(4)] of the Act.
Furthermore, on or about April 9, 2001, you provided [redacted] with a signed certification, which states that you will not supply [redacted] with any livestock that is "adulterated within the meaning of the Federal Food (Drug] and Cosmetic Act (i.e., none of the cattle or other ruminants will have been fed any feed containing protein derived from mammalian tissues, e.g. meat and bone meal, as that term is defined in 21 C.F.R. 589.2000 and none of the livestock will have an illegal level of drug residues)." On July 25, 2007, you delivered to [redacted] a bob veal calf containing illegal levels of sulfamethazine residues. Providing such a false guaranty is a prohibited act under section 301(h) [21 U.S.C. § 331(h)) of the Act.
In addition, you adulterated [redacted] (sulfamethazine) [redacted] within the meaning of section 501(a)(5) [21 U.S.C. § 351(a)(5)] of the Act when you failed to use the drug in conformance with its approved labeling. "Extralabel use," i.e., the actual or intended use of a drug in an animal in a manner that is not in accordance with the approved labeling, is only permitted if the use is by or on the lawful order of a licensed veterinarian within the context of a valid veterinarian/client/patient relationship. The extralabel use of approved veterinary or human drugs must comply with sections 512(a)(4) [21 U.S.C. § 360b(a)(4)] and 512(a)(5) [21 U.S.C. § 360b(a)(5)] of the Act and 21 C.F.R. Part 530. Our investigation found that your extralabel use of [redacted] (sulfamethazine) [redacted] failed to comply with these requirements. For example, you administered these [redacted] (sulfamethazine) [redacted] without following the withdrawal period set forth in the approved labeling and you did so without the supervision of a licensed veterinarian, in violation of 21 C.F.R. 530.11(a). Furthermore, your extralabel use resulted in an illegal drug residue, in violation of 21 C.F.R. 530.11(d). Because your extralabel use of this drug was not in compliance with 21 C.F.R. Part 530, the drug was unsafe under section 512(a) [21 U.S.C. § 360b(a)} of the Act and your use caused it to be adulterated within the meaning of section 501(a)(5) [21 U.S.C. § 351(a)(5)] of the Act.
The above is not intended to be an all-inclusive list of violations. As a producer of animals offered for use as food, you are responsible for ensuring that your overall operation and the food you distribute is in compliance with the law. You should take prompt action to correct the above violations and to establish procedures whereby such violations do not recur. Failure to do so may result in regulatory action without further notice such as seizure and/or injunction.
You should notify this office in writing of the steps you have taken to bring your firm into compliance with the law within fifteen (15) working days of receiving this letter . Your response should include each step that has been taken or will be taken to correct the violations and prevent their recurrence, If corrective action cannot be completed within fifteen (15) working days, state the reason for the delay and the time frame within which the corrections will be completed. Please include copies of any available documentation demonstrating that corrections have been made.
Your written response should be sent to Steven B. Barber, Compliance Officer, U.S. Food and Drug Administration, 6000 Metro Drive, Suite 101, Baltimore, Maryland 21215. If you have any questions about this letter, please contact Mr. Barber at 410-779-5134.
Sincerely yours,
/S/
Kirk Sooter
Acting District Director
cc: Dr. David F. Vogt
USDA, APHIS, VS
1598 Whitehall Road, Suite A
Annapolis, Maryland 21401
FSIS District Office
5601 Sunnyside Avenue Suite 1-2288 B
Beltsville, Maryland 20705
[redacted]
[redacted]
http://www.fda.gov/foi/warning_letters/s6642c.htm
Public Health Service
Food and Drug Administration
New York District
300 Pearl Street, Suite 100
Buffalo, NY 14202
January 11, 2008
WARNING LETTER NYK 2008-05
CERTIFIED MAIL
RETURN RECEIPT REOUESTED
Aaron G. Poupore, Co-Owner/Herdsman
Papas Dairy, LLC
322 Wheeler Road
North Bangor, New York 12966
Dear Mr. Poupore:
An inspection of your dairy operation located at 322 Wheeler Road, North Bangor, New York, conducted by a representative of the U.S. Food and Drug Administration (FDA) on October 17-19, 2007, confirmed that you offered a cow for sale for slaughter as food that was adulterated under sections 402(a)(2)(C)(ii) [21 U.S.C. § 342(a)(2)(C)(ii)] and 402(a)(4) [21 U.S.C. § 342(a)(4)] of the Federal Food, Drug, and Cosmetic Act (the Act). The inspection also revealed that you caused the new animal drugs, ALBON® (sulfadimethoxine) boluses and penicillin G procaine, to become unsafe under section 512 [21 U.S.C. § 360b] of the Act and adulterated within the meaning of section 501(a)(5) [21 U.S.C. § 351(a)(5)] of the Act. You can find the Act and its associated regulations on the Internet through links on FDA's web page at www.fda.gov.
On or about September 11, 2007, you consigned a cow identified with farm [redacted] for slaughter as food to [redacted] where it was picked up the next day by [redacted]. On or about September 13, 2007, this animal was slaughtered at [redacted] United States Department of Agriculture, Food Safety and Inspection Service (USDA/FSIS) analysis of tissue samples collected from that cow identified the presence of 0.60 parts per million (ppm) of sulfadimethoxine in liver tissue and 0.41 ppm of sulfadimethoxine in muscle tissue. A tolerance of 0.1 ppm has been established for residues of sulfadimethoxine in the uncooked edible tissues of cattle as codified in Title 21, Code of Federal Regulations, Section 556.640(21 C.F.R. 556.640). The presence of this drug in these amounts in the uncooked edible tissues of this animal causes the food to be adulterated within the meaning of section 402(a)(2)(C)(ii) [21 U.S.C. § 342(a)(2)(C)(ii)] of the Act.
Our investigation also found that you hold animals under conditions that are so in adequate that medicated animals bearing potentially harmful drug residues are likely to enter the food supply. You lack an adequate system to ensure that animals medicated by you have been withheld from slaughter for appropriate periods of time to permit depletion of potentially hazardous residues of drugs from edible tissues. For example, you failed to maintain complete treatment records. Food from animals held under such conditions is adulterated within the meaning ofsection402(a)(4)[21 U.S.C. §342(a)(4)] of the Act.
In addition, you adulterated Albon® sulfadimethoxine boluses and Penicillin G Procaine within the meaning of section 501(a)(5) [21 U.S.C. § 351(a)(5)] of the Act when you failed to use these drugs in conformance with their approved labeling. "Extralabel use," i.e., the actual or intended use of a drug in an animal in a manner that is not in accordance with the approved labeling, is only permitted if the use is by or on the lawful order of a licensed veterinarian within the context of a valid veterinarian/client/patient relationship. The extralabel used of approved veterinary or human drugs must comply with sections 512(a)(4) [21 U.S.C. § 360b(a)(4)] and 512(a)(5) [21 U.S.C. § 360b(a)(5)] of the Act and 21 C.F.R. Part 530. Our investigation found that your extralabel use of Albon® sulfadimethoxine boluses and Penicillin G Procaine failed to comply with these requirements.
For example, you administered Albon® sulfadimethoxine without following the dosage level set forth in the approved labeling and you did so without the supervision of a licensed veterinarian, in violation of 21 C.F.R. 530.11(a). Furthermore,your extralabel use resulted in an illegal residue, in violation of 21 C.F.R. 530.11(d). In addition, you administered IBA Penicillin G Procaine Injectable Suspension to cows on your farm without following the dosage level, route of administration, and duration of treatment set forth in the approved labeling, and you did so without the supervision of a licensed veterinarian, in violation of 21 C.F.R. 530.11(a). Because your extralabel use of these drugs was not in compliance with 21 C.F.R. Part 530, the drugs were unsafe under section 512(a) [21 U.S.C. § 360b(a)] of the Act and your use caused them to be adulterated within the meaning of section 501(a)(5) [21 U.S.C. § 351(a)(5)] of the Act.
The above is not intended to be an all-inclusive list of violations. As a producer of animals offered for use as food, you are responsible for ensuring that your overall operation and the food you distribute is in compliance with the law.
You should take prompt action to correct the above violations and to establish procedures whereby such violations do not recur. Failure to do so may result in regulatory action without further notice such as seizure and/or injunction.
You should notify this office in writing of the steps you have taken to bring your firm into compliance with the law within fifteen (15) working days of receiving this letter. Your response should include each step that has been taken or will be taken to correct the violations and prevent their recurrence. If corrective action cannot be completed within fifteen (15) working days, state the reason for the delay and the time frame within which the corrections will be completed. Please include copies of any available documentation demonstrating that corrections have been made.
Your written response should be sent to Edward W. Thomas,Director Compliance Branch, U.S. Food and Drug Administration, 300 Pearl Street, Suite 100, Buffalo, New York 14202. If you have any questions about this letter, please contact Mr. Thomas at (716) 541-0316
Sincerely yours,
/S/
Otto D. Vitillo
Director, New York District
http://www.fda.gov/foi/warning_letters/s6637c.htm
What Do We Feed to Food-Production Animals? A Review of Animal Feed
Ingredients and Their Potential Impacts on Human Health
Amy R. Sapkota,1,2 Lisa Y. Lefferts,1,3 Shawn McKenzie,1 and Polly Walker1
1Johns Hopkins Center for a Livable Future, Bloomberg School of Public
Health, Baltimore, Maryland, USA; 2Maryland Institute for
Applied Environmental Health, College of Health and Human Performance,
University of Maryland, College Park, Maryland, USA;
3Lisa Y. Lefferts Consulting, Nellysford, Virginia, USA
snip...
Table 1. Animal feed ingredients that are legally used in U.S. animal feeds
Animal
Rendered animal protein from Meat meal, meat meal tankage, meat and bone
meal, poultry meal, animal the slaughter of food by-product meal, dried
animal blood, blood meal, feather meal, egg-shell production animals and
other meal, hydrolyzed whole poultry, hydrolyzed hair, bone marrow, and
animal animals digest from dead, dying, diseased, or disabled animals
including deer and elk Animal waste Dried ruminant waste, dried swine waste,
dried poultry litter, and undried processed animal waste products
snip...
Conclusions
Food-animal production in the United States has changed markedly in the past
century, and these changes have paralleled major changes in animal feed
formulations. While this industrialized system of food-animal production may
result in increased production efficiencies, some of the changes in animal
feeding practices may result in unintended adverse health consequences for
consumers of animal-based food products. Currently, the use of animal feed
ingredients,
including rendered animal products, animal waste, antibiotics, metals, and
fats, could result in higher levels of bacteria, antibioticresistant
bacteria, prions, arsenic, and dioxinlike compounds in animals and resulting
animal-based food products intended for human consumption. Subsequent human
health effects among consumers could include increases in bacterial
infections (antibioticresistant and nonresistant) and increases in the risk
of developing chronic (often fatal) diseases
such as vCJD. Nevertheless, in spite of the wide range of potential human
health impacts that could result from animal feeding practices, there are
little data collected at the federal or state level concerning the amounts
of specific ingredients that are intentionally included in U.S. animal feed.
In addition, almost no biological or chemical testing is conducted on
complete U.S. animal feeds; insufficient testing is performed on retail meat
products; and human health effects data are not appropriately linked to this
information. These surveillance inadequacies make it difficult to conduct
rigorous epidemiologic studies and risk assessments
that could identify the extent to which specific human health risks are
ultimately associated with animal feeding practices. For example, as noted
above, there are insufficient data to determine whether other human
foodborne bacterial illnesses besides those caused by S. enterica serotype
Agona are associated with animal feeding practices. Likewise, there are
insufficient data to determine the percentage of antibiotic-resistant human
bacterial infections that are attributed to the nontherapeutic use of
antibiotics in animal feed. Moreover, little research has been conducted to
determine whether the use of organoarsenicals in animal feed, which can lead
to elevated levels of arsenic in meat products (Lasky et al. 2004),
contributes to increases in cancer risk. In order to address these research
gaps, the following principal actions are necessary within the United
States: a) implementation of a nationwide reporting system of the specific
amounts and types of feed ingredients of concern to public health that are
incorporated into animal feed, including antibiotics, arsenicals, rendered
animal products, fats, and animal waste; b) funding and development of
robust surveillance systems that monitor biological, chemical, and other
etiologic agents throughout the animal-based food-production chain “from
farm to fork” to human health outcomes; and c) increased communication and
collaboration among feed professionals, food-animal producers, and
veterinary and public health officials.
REFERENCES...snip...end
Sapkota et al.
668 VOLUME 115 NUMBER 5 May 2007 • Environmental Health Perspectives
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1867957&blobtype=pdf
MRSA/VRSA
http://staphmrsa.blogspot.com/
TSS
Sabin Russell, Chronicle Medical Writer
Monday, January 28, 2008
Consumer advocates have been campaigning for years to curb the use of antibiotics in agriculture, citing studies that show that 70 percent of all U.S. antibiotics are administered in low doses - not to treat disease, but to promote the growth of pigs, sheep, chicken and cattle.
Low doses of antibiotics in animal feeds have been shown to boost the speed of food-to-muscle conversion by 5 percent, and can prevent the spread of disease in the tight quarters of modern factory farms.
But as early as 1963, British researchers tied the emergence of drug-resistant strains of salmonella in humans to antibiotics fed to cattle. Among the drugs routinely found in animal feed are erythromycin, penicillin and streptomycin. Critics warn that the use of antibiotics in feed at low dosages helps to breed resistant bacteria in the gut of farm animals - threatening the future of these drugs for use in animals or humans.
Major antibiotic classes such as tetracyclines and the Cipro-like fluoroquinolones have already been compromised, according to Keep Antibiotics Working, a coalition backed by environmental groups and the American Medical Association.
The stakes are high. The Union of Concerned Scientists calculated in 2001 that U.S. farm interests were using 24.6 million pounds of anti-microbials - almost 40 percent higher than industry estimates.
Ron Phillips, vice president of the Animal Health Institute, a Washington trade group for agricultural drugmakers, maintains that growth promotion accounts for only 4.5 percent of antibiotic consumption in agriculture. The rest are used to prevent, treat or control the spread of disease. "Antibiotics," he says, "are a net positive for both animal health and human health."
After antibiotics were banned from animal feed in Europe beginning in 1995, Phillips said, farmers there found they had to use more antibiotics to care for illnesses that cropped up in their livestock.
Keep Antibiotics Working nevertheless is pushing for a federal ban on antibiotics in feed. Introduced by Sens. Edward Kennedy, D-Mass, and Olympia Snow, R-Maine, the "Preservation of Antibiotics for Medical Treatment Act" would phase out in two years antibiotics deemed "important in human medicine."
In response to pressure from consumer groups, McDonald's declared four years ago its intention to phase out the purchase of meats from chicken and livestock fed the drugs to promote growth. The Food and Drug Administration in 2005 banned the use of a Cipro-like drug, Baytril, to treat bacterial infections in poultry, after drug-resistant strains of Campylobacter - a common food-poisoning organism - were found in chicken. Cases of Cipro-resistant Campylobacter were also rising in humans.
The FDA is considering an application for approval of the antibiotic cefquinome, a proposed veterinary drug that is similar to the human drug cefepime. In the fall of 2006, an FDA advisory committee recommended against approval.
"It was surprising what the committee did, because it was stacked with veterinarians and animal science people," said Stephen Roach, director of public health programs for Keep Antibiotics Working.
"The USDA is very reluctant to say that antibiotic use causes a problem, and the FDA has traditionally been in the middle. But I feel that in the last several years, they have been more accommodating to industry," said Roach.
A final decision on approving cefquinome is still pending.
E-mail Sabin Russell at srussell@sfchronicle.com.
http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2008/01/28/MNSTUGD8E.DTL
Public Health Service
Food and Drug Administration
Baltimore District Office
6000 Metro Drive
Suite 101
Baltimore, MD 21215-3215
Telephone: (410) 779-5454
FEI: 3000203759
January 16 , 2008
WARNING LETTER
08-BLT-03
CERTIFIED MAIL
RETURN RECEIPT REQUESTED
Mr. Francis H. Roderick
Old Carolina Farms
10802 Cook Brothers Road
Ijamsville, Maryland 21754
Dear Mr. Roderick:
An inspection of your dairy operation located at 10802 Cook Brothers Road, Ijamsville, Maryland, conducted by a representative of the U.S. Food and Drug Administration (FDA) between October 16, 2007, and November 27, 2007, confirmed that you offered a bob veal calf for sale for slaughter as food that was adulterated under sections 402(a)(2)(C)(ii) [21 U.S.C. § 342(a)(2)(C)(ii)] and 402(a)(4) [21 U.S.C. § 342(a)(4)] of the Federal Food, Drug, and Cosmetic Act (the Act) . The inspection also revealed that you caused the new animal drug, [redacted] (sulfamethazine) [redacted] to become unsafe under section 512(a) [21 U.S.C. § 360b(a)] of the Act and adulterated within the meaning of section 501(a)(5) [21 U.S.C. § 351(a)(5)] of the Act. In addition, the inspection revealed that you provided a false guaranty, a prohibited act under section 301(h) of the Act [21 U.S.C. § 331(h)], You can find the Act and its associated regulations on the Internet through links on the FDA's web page at
www.fda.gov.
On or about July 25, 2007, you consigned a bob veal calf, identified with tag [redacted], for slaughter as food an [redacted]. On or about July 26, 2007, this animal was slaughtered at [redacted] United States Department of Agriculture, Food Safety and Inspection Service (USDA/FSIS) analysis of tissue samples collected from that animal identified the presence of 131.89 parts per million (ppm) of sulfamethazine in the liver tissue and 179.88 ppm of sulfarnethazine in the muscle tissue of this animal. A tolerance of 0.1 ppm has been established for residues of sulfamethazine in the edible tissues of cattle as codified in Title 21, Code of Federal Regulations, section 556.670 [21 C.F.R. 556.670]. The presence of this drug in these amounts in edible) tissues from this animal causes the food to be adulterated within the meaning of section 402(a)(2)(C)(ii)[(21 U.S.C. § 342(a)(2)(C)(ii)] of the Act.
Our investigation also found that you hold animals under conditions that are so inadequate that medicated animals bearing potentially harmful drug residues are likely to enter the food supply. You lackS an adequate system to ensure that animals medicated by you have been withheld from slaughter for appropriate periods of time to permit depletion of potentially hazardous residues of drugs from edible tissues. For example, you failed to maintain treatment records. Food from animals held under such conditions is adulterated within the meaning of section 402(a)(4) [21 U.S.C. § 342(a)(4)] of the Act.
Furthermore, on or about April 9, 2001, you provided [redacted] with a signed certification, which states that you will not supply [redacted] with any livestock that is "adulterated within the meaning of the Federal Food (Drug] and Cosmetic Act (i.e., none of the cattle or other ruminants will have been fed any feed containing protein derived from mammalian tissues, e.g. meat and bone meal, as that term is defined in 21 C.F.R. 589.2000 and none of the livestock will have an illegal level of drug residues)." On July 25, 2007, you delivered to [redacted] a bob veal calf containing illegal levels of sulfamethazine residues. Providing such a false guaranty is a prohibited act under section 301(h) [21 U.S.C. § 331(h)) of the Act.
In addition, you adulterated [redacted] (sulfamethazine) [redacted] within the meaning of section 501(a)(5) [21 U.S.C. § 351(a)(5)] of the Act when you failed to use the drug in conformance with its approved labeling. "Extralabel use," i.e., the actual or intended use of a drug in an animal in a manner that is not in accordance with the approved labeling, is only permitted if the use is by or on the lawful order of a licensed veterinarian within the context of a valid veterinarian/client/patient relationship. The extralabel use of approved veterinary or human drugs must comply with sections 512(a)(4) [21 U.S.C. § 360b(a)(4)] and 512(a)(5) [21 U.S.C. § 360b(a)(5)] of the Act and 21 C.F.R. Part 530. Our investigation found that your extralabel use of [redacted] (sulfamethazine) [redacted] failed to comply with these requirements. For example, you administered these [redacted] (sulfamethazine) [redacted] without following the withdrawal period set forth in the approved labeling and you did so without the supervision of a licensed veterinarian, in violation of 21 C.F.R. 530.11(a). Furthermore, your extralabel use resulted in an illegal drug residue, in violation of 21 C.F.R. 530.11(d). Because your extralabel use of this drug was not in compliance with 21 C.F.R. Part 530, the drug was unsafe under section 512(a) [21 U.S.C. § 360b(a)} of the Act and your use caused it to be adulterated within the meaning of section 501(a)(5) [21 U.S.C. § 351(a)(5)] of the Act.
The above is not intended to be an all-inclusive list of violations. As a producer of animals offered for use as food, you are responsible for ensuring that your overall operation and the food you distribute is in compliance with the law. You should take prompt action to correct the above violations and to establish procedures whereby such violations do not recur. Failure to do so may result in regulatory action without further notice such as seizure and/or injunction.
You should notify this office in writing of the steps you have taken to bring your firm into compliance with the law within fifteen (15) working days of receiving this letter . Your response should include each step that has been taken or will be taken to correct the violations and prevent their recurrence, If corrective action cannot be completed within fifteen (15) working days, state the reason for the delay and the time frame within which the corrections will be completed. Please include copies of any available documentation demonstrating that corrections have been made.
Your written response should be sent to Steven B. Barber, Compliance Officer, U.S. Food and Drug Administration, 6000 Metro Drive, Suite 101, Baltimore, Maryland 21215. If you have any questions about this letter, please contact Mr. Barber at 410-779-5134.
Sincerely yours,
/S/
Kirk Sooter
Acting District Director
cc: Dr. David F. Vogt
USDA, APHIS, VS
1598 Whitehall Road, Suite A
Annapolis, Maryland 21401
FSIS District Office
5601 Sunnyside Avenue Suite 1-2288 B
Beltsville, Maryland 20705
[redacted]
[redacted]
http://www.fda.gov/foi/warning_letters/s6642c.htm
Public Health Service
Food and Drug Administration
New York District
300 Pearl Street, Suite 100
Buffalo, NY 14202
January 11, 2008
WARNING LETTER NYK 2008-05
CERTIFIED MAIL
RETURN RECEIPT REOUESTED
Aaron G. Poupore, Co-Owner/Herdsman
Papas Dairy, LLC
322 Wheeler Road
North Bangor, New York 12966
Dear Mr. Poupore:
An inspection of your dairy operation located at 322 Wheeler Road, North Bangor, New York, conducted by a representative of the U.S. Food and Drug Administration (FDA) on October 17-19, 2007, confirmed that you offered a cow for sale for slaughter as food that was adulterated under sections 402(a)(2)(C)(ii) [21 U.S.C. § 342(a)(2)(C)(ii)] and 402(a)(4) [21 U.S.C. § 342(a)(4)] of the Federal Food, Drug, and Cosmetic Act (the Act). The inspection also revealed that you caused the new animal drugs, ALBON® (sulfadimethoxine) boluses and penicillin G procaine, to become unsafe under section 512 [21 U.S.C. § 360b] of the Act and adulterated within the meaning of section 501(a)(5) [21 U.S.C. § 351(a)(5)] of the Act. You can find the Act and its associated regulations on the Internet through links on FDA's web page at www.fda.gov.
On or about September 11, 2007, you consigned a cow identified with farm [redacted] for slaughter as food to [redacted] where it was picked up the next day by [redacted]. On or about September 13, 2007, this animal was slaughtered at [redacted] United States Department of Agriculture, Food Safety and Inspection Service (USDA/FSIS) analysis of tissue samples collected from that cow identified the presence of 0.60 parts per million (ppm) of sulfadimethoxine in liver tissue and 0.41 ppm of sulfadimethoxine in muscle tissue. A tolerance of 0.1 ppm has been established for residues of sulfadimethoxine in the uncooked edible tissues of cattle as codified in Title 21, Code of Federal Regulations, Section 556.640(21 C.F.R. 556.640). The presence of this drug in these amounts in the uncooked edible tissues of this animal causes the food to be adulterated within the meaning of section 402(a)(2)(C)(ii) [21 U.S.C. § 342(a)(2)(C)(ii)] of the Act.
Our investigation also found that you hold animals under conditions that are so in adequate that medicated animals bearing potentially harmful drug residues are likely to enter the food supply. You lack an adequate system to ensure that animals medicated by you have been withheld from slaughter for appropriate periods of time to permit depletion of potentially hazardous residues of drugs from edible tissues. For example, you failed to maintain complete treatment records. Food from animals held under such conditions is adulterated within the meaning ofsection402(a)(4)[21 U.S.C. §342(a)(4)] of the Act.
In addition, you adulterated Albon® sulfadimethoxine boluses and Penicillin G Procaine within the meaning of section 501(a)(5) [21 U.S.C. § 351(a)(5)] of the Act when you failed to use these drugs in conformance with their approved labeling. "Extralabel use," i.e., the actual or intended use of a drug in an animal in a manner that is not in accordance with the approved labeling, is only permitted if the use is by or on the lawful order of a licensed veterinarian within the context of a valid veterinarian/client/patient relationship. The extralabel used of approved veterinary or human drugs must comply with sections 512(a)(4) [21 U.S.C. § 360b(a)(4)] and 512(a)(5) [21 U.S.C. § 360b(a)(5)] of the Act and 21 C.F.R. Part 530. Our investigation found that your extralabel use of Albon® sulfadimethoxine boluses and Penicillin G Procaine failed to comply with these requirements.
For example, you administered Albon® sulfadimethoxine without following the dosage level set forth in the approved labeling and you did so without the supervision of a licensed veterinarian, in violation of 21 C.F.R. 530.11(a). Furthermore,your extralabel use resulted in an illegal residue, in violation of 21 C.F.R. 530.11(d). In addition, you administered IBA Penicillin G Procaine Injectable Suspension to cows on your farm without following the dosage level, route of administration, and duration of treatment set forth in the approved labeling, and you did so without the supervision of a licensed veterinarian, in violation of 21 C.F.R. 530.11(a). Because your extralabel use of these drugs was not in compliance with 21 C.F.R. Part 530, the drugs were unsafe under section 512(a) [21 U.S.C. § 360b(a)] of the Act and your use caused them to be adulterated within the meaning of section 501(a)(5) [21 U.S.C. § 351(a)(5)] of the Act.
The above is not intended to be an all-inclusive list of violations. As a producer of animals offered for use as food, you are responsible for ensuring that your overall operation and the food you distribute is in compliance with the law.
You should take prompt action to correct the above violations and to establish procedures whereby such violations do not recur. Failure to do so may result in regulatory action without further notice such as seizure and/or injunction.
You should notify this office in writing of the steps you have taken to bring your firm into compliance with the law within fifteen (15) working days of receiving this letter. Your response should include each step that has been taken or will be taken to correct the violations and prevent their recurrence. If corrective action cannot be completed within fifteen (15) working days, state the reason for the delay and the time frame within which the corrections will be completed. Please include copies of any available documentation demonstrating that corrections have been made.
Your written response should be sent to Edward W. Thomas,Director Compliance Branch, U.S. Food and Drug Administration, 300 Pearl Street, Suite 100, Buffalo, New York 14202. If you have any questions about this letter, please contact Mr. Thomas at (716) 541-0316
Sincerely yours,
/S/
Otto D. Vitillo
Director, New York District
http://www.fda.gov/foi/warning_letters/s6637c.htm
What Do We Feed to Food-Production Animals? A Review of Animal Feed
Ingredients and Their Potential Impacts on Human Health
Amy R. Sapkota,1,2 Lisa Y. Lefferts,1,3 Shawn McKenzie,1 and Polly Walker1
1Johns Hopkins Center for a Livable Future, Bloomberg School of Public
Health, Baltimore, Maryland, USA; 2Maryland Institute for
Applied Environmental Health, College of Health and Human Performance,
University of Maryland, College Park, Maryland, USA;
3Lisa Y. Lefferts Consulting, Nellysford, Virginia, USA
snip...
Table 1. Animal feed ingredients that are legally used in U.S. animal feeds
Animal
Rendered animal protein from Meat meal, meat meal tankage, meat and bone
meal, poultry meal, animal the slaughter of food by-product meal, dried
animal blood, blood meal, feather meal, egg-shell production animals and
other meal, hydrolyzed whole poultry, hydrolyzed hair, bone marrow, and
animal animals digest from dead, dying, diseased, or disabled animals
including deer and elk Animal waste Dried ruminant waste, dried swine waste,
dried poultry litter, and undried processed animal waste products
snip...
Conclusions
Food-animal production in the United States has changed markedly in the past
century, and these changes have paralleled major changes in animal feed
formulations. While this industrialized system of food-animal production may
result in increased production efficiencies, some of the changes in animal
feeding practices may result in unintended adverse health consequences for
consumers of animal-based food products. Currently, the use of animal feed
ingredients,
including rendered animal products, animal waste, antibiotics, metals, and
fats, could result in higher levels of bacteria, antibioticresistant
bacteria, prions, arsenic, and dioxinlike compounds in animals and resulting
animal-based food products intended for human consumption. Subsequent human
health effects among consumers could include increases in bacterial
infections (antibioticresistant and nonresistant) and increases in the risk
of developing chronic (often fatal) diseases
such as vCJD. Nevertheless, in spite of the wide range of potential human
health impacts that could result from animal feeding practices, there are
little data collected at the federal or state level concerning the amounts
of specific ingredients that are intentionally included in U.S. animal feed.
In addition, almost no biological or chemical testing is conducted on
complete U.S. animal feeds; insufficient testing is performed on retail meat
products; and human health effects data are not appropriately linked to this
information. These surveillance inadequacies make it difficult to conduct
rigorous epidemiologic studies and risk assessments
that could identify the extent to which specific human health risks are
ultimately associated with animal feeding practices. For example, as noted
above, there are insufficient data to determine whether other human
foodborne bacterial illnesses besides those caused by S. enterica serotype
Agona are associated with animal feeding practices. Likewise, there are
insufficient data to determine the percentage of antibiotic-resistant human
bacterial infections that are attributed to the nontherapeutic use of
antibiotics in animal feed. Moreover, little research has been conducted to
determine whether the use of organoarsenicals in animal feed, which can lead
to elevated levels of arsenic in meat products (Lasky et al. 2004),
contributes to increases in cancer risk. In order to address these research
gaps, the following principal actions are necessary within the United
States: a) implementation of a nationwide reporting system of the specific
amounts and types of feed ingredients of concern to public health that are
incorporated into animal feed, including antibiotics, arsenicals, rendered
animal products, fats, and animal waste; b) funding and development of
robust surveillance systems that monitor biological, chemical, and other
etiologic agents throughout the animal-based food-production chain “from
farm to fork” to human health outcomes; and c) increased communication and
collaboration among feed professionals, food-animal producers, and
veterinary and public health officials.
REFERENCES...snip...end
Sapkota et al.
668 VOLUME 115 NUMBER 5 May 2007 • Environmental Health Perspectives
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1867957&blobtype=pdf
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