Emergence of Methicillin-Resistant Staphylococcus aureus of Animal Origin in Humans

Volume 13, Number 12–December 2007Research

Emergence of Methicillin-Resistant Staphylococcus aureus of Animal Origin in Humans

Inge van Loo,*1 Xander Huijsdens,†1 Edine Tiemersma,† Albert de Neeling,† Nienke van de Sande-Bruinsma,† Desiree Beaujean,† Andreas Voss,‡ and Jan Kluytmans§¶ *Elisabeth Hospital, Tilburg, the Netherlands; †National Institute for Public Health and the Environment, Bilthoven, the Netherlands; ‡Wilhelmina Hospital, Nijmegen, the Netherlands; §Amphia Hospital, Breda, the Netherlands; and ¶VUmc Medical Center, Amsterdam, the Netherlands


Abstract

In 2003 in the Netherlands, a new methicillin-resistant Staphylococcus aureus (MRSA) strain emerged that could not be typed with Sma1 pulsed-field gel electrophoresis (NT-MRSA). The association of NT-MRSA in humans with a reservoir in animals was investigated. The frequency of NT-MRSA increased from 0% in 2002 to >21% after intensified surveillance was implemented in July 2006. Geographically, NT-MRSA clustered with pig farming. A case–control study showed that carriers of NT-MRSA were more often pig or cattle farmers (pig farmers odds ratio [OR] 12.2, 95% confidence interval [CI] 3.1–48.6; cattle farmers OR 19.7, 95% CI 2.3–169.5). Molecular typing showed that the NT-MRSA strains belonged to a new clonal complex, ST 398. This study shows that MRSA from an animal reservoir has recently entered the human population and is now responsible for >20% of all MRSA in the Netherlands.

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On the basis of the above-mentioned findings, we conclude that this new MRSA strain is of animal origin (pigs and probably cows). Transmission of MRSA between animals and humans has previously been described, e.g., associated with colonized companion animals, horses, and persons who take care of them (16–19). However, the MRSA clones in these reports were known human clones, suggesting human-to-animal transmission in origin. Baptiste et al. found specific PFGE clones in horses that were never observed before (20). Until now, transmission of these clones to humans has not been reported.

We assume that this problem is not limited to the Netherlands. First, widespread dissemination in pigs in the Netherlands has been found. When one considers the intensive international transport of pigs, it is unlikely that this situation is limited to the Netherlands. Second, 3 of the case-patients came from abroad, 1 tourist and 2 adopted children from Asia. Also, MLST 398 was recently found in animals (pig, dog, and foal) and in humans in Germany (21). Finally, in Hong Kong Special Administrative Region, People's Republic of China, MRSA with MLST 398 has been found in 2 patients with bacteremia (22).

The origin of the current NT-MRSA situation is difficult to elucidate. One earlier study can be found on carriage of S. aureus in pig farmers and pigs in France (23). It reported an increased carriage rate in pig farmers caused by transmission of S. aureus from pigs that also carried MLST ST 9 and 398. Further typing of the French ST 398 isolates at RIVM showed homology with the Dutch isolates. However, in the French study most of the MLST 398 strains were susceptible to β-lactam antimicrobial agents. The most likely explanation for the current findings is that MLST 398 is a commensal strain in pigs, which originally was methicillin susceptible. As most NT-MRSA isolates were resistant to doxycycline, the spread is facilitated by the abundant use of tetracyclines in pig and cattle farming (15).

What are the implications of these findings? Persons working or living in close contact with pigs or cows are at increased risk of becoming colonized and infected with MRSA. Infections can be severe, as is indicated by the hospital admission rate. Also, a case of endocarditis has been reported recently (24). At present, whether this strain is spreading further in the community is not clear. Before final recommendations for control can be made, the current size of the reservoir in farm animals and in humans has to be determined at an international level.

Acknowledgments


http://www.cdc.gov/eid/content/13/12/1834.htm?s_cid=eid1834_e


Volume 13, Number 12–December 2007Research

Hospitalizations and Deaths Caused by Methicillin-Resistant Staphylococcus aureus, United States, 1999–2005

Eili Klein,* David L. Smith,† and Ramanan Laxminarayan* *Resources for the Future, Washington DC, USA; and †National Institutes of Health, Bethesda, Maryland, USA

Suggested citation for this article

Abstract

Hospital-acquired infections with Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA) infections, are a major cause of illness and death and impose serious economic costs on patients and hospitals. However, the recent magnitude and trend of these infections have not been reported. We used national hospitalization and resistance data to estimate the annual number of hospitalizations and deaths associated with S. aureus and MRSA from 1999 through 2005. During this period, the estimated number of S. aureus–related hospitalizations increased 62%, from 294,570 to 477,927, and the estimated number of MRSA-related hospitalizations more than doubled, from 127,036 to 278,203. Our findings suggest that S. aureus and MRSA should be considered a national priority for disease control.

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DiscussionMRSA, a common cause of nosocomial infections, has emerged as an increasingly common cause of community-associated infections (20). Our analysis extends the work of Kuehnert et al. (13) and quantifies recent trends and the effect of S. aureus and MRSA on the US healthcare system.

This study focused on the effect and trends in the incidence of S. aureus–related infections generally and MRSA-related infections specifically. Although the number of hospitalizations associated with an S. aureus infection increased 62% or ≈8.4% per year, the number of S. aureus infections resistant to methicillin increased 119% or ≈14% per year. In addition, although steady growth was observed in the incidence of S. aureus– and MRSA-related septicemia, pneumonia, and device-associated infections that are typically nosocomial, dramatic increases were observed in the incidence of skin and soft tissue infections that are typically community associated. We also found no trend in the number of deaths caused by MRSA, and a decreasing trend in the percentage of S. aureus– and MRSA-related hospitalizations that resulted in death. These results suggest a change in the ecology of the disease; community-associated MRSA is spreading more rapidly and possibly making its way into hospitals.

The indication that community-associated MRSA is spreading rapidly into hospitals has implications for hospital and community infection control as well as empirical treatment. In hospitals, handwashing practices, which have been shown to be the leading intervention for limiting the spread of nosocomial infections, should be improved to meet recommended guidelines (21). Because of the increase in skin and soft tissue infections, standard precautions, including use of gloves, are likely warranted when dealing with all skin and soft tissue infections in outpatient clinics and acute-care facilities. Contact precautions, including use of gowns and gloves, should be implemented for all wound care in acute-care facilities, and institutional programs to enhance antimicrobial drug stewardship should be implemented. Programs to increase community awareness to control spread of infections and initiatives to reduce inappropriate use of antimicrobial drugs should also be implemented, especially in institutions that are focal institutions such as daycare centers, schools, and prisons, as well as in high-risk groups such as immunodeficient persons, children, and elderly persons. Clinicians should be aware of the magnitude of the issue and consider MRSA a highly likely cause of skin and soft skin tissue infections, even in areas where the prevalence of MRSA is believed to be low.

Previous hospitalization has been associated with community MRSA carriage (22), and some recent studies have suggested that MRSA infection rates in the community are positively correlated with S. aureus infection rates in the hospital (23,24). Although a recent study suggests that community-associated MRSA is causing hospital-acquired MRSA (25), it is unclear from our study whether community-associated MRSA is responsible for increasing rates of nosocomial MRSA or the other way around. In all likelihood, MRSA is spreading in hospitals and communities and complicating efforts to prevent infections in hospitalized patients. Regardless, our findings demonstrate that recent reports of localized increases in community-acquired MRSA (7,26–28) are part of a larger trend of MRSA becoming rapidly endemic in communities all over the United states, emulating the wave-like pattern of emerging resistance to penicillin in the middle of the 20th century (5).

Hospital-acquired infections from all causes are estimated to cause >90,000 deaths per year in the United States and are the sixth leading cause of death nationally. Nosocomial infections increase patient illness and the length of hospital stays. The direct cost has been estimated to be >$6 billion (inflation adjusted) (29); costs of longer inpatient visits are shared by hospitals. The increasing trend in hospitalizations associated with S. aureus infections has considerable cost implications for the healthcare system, including costs when community-associated infections require hospitalization and the additional expenses from associated nosocomial infections.

Antimicrobial drug–resistant infections impose even greater costs than susceptible infections. Several studies have estimated that antimicrobial drug–resistant infections increase death, illness, and direct costs by 30%–100% (30). Estimates of the excess cost of an infection with MRSA compared with an infection with methicillin-sensitive S. aureus range from ≈$3,000 to $35,000 (31–33). This suggests that MRSA cost the healthcare system (patients and hospitals) an extra $830 million–$9.7 billion in 2005, even without taking into account indirect costs related to patient pain, illness, and time spent in the hospital.

Another important implication of our analysis is that the increasing incidence of MRSA in hospitalized patients, whether the infection was acquired in the hospital or the community, is likely to increase the demand for vancomycin. Despite several new (daptomycin, linezolid, tigecycline) and old (trimethoprim-sulfamethoxazole, clindamycin) antimicrobial drugs available for treatment of MRSA infections, vancomycin has remained the first-line drug for treating MRSA (12,34). This pattern has broad implications for the future control of MRSA as well as other pathogens. S. aureus infections resistant to vancomycin are already emerging (35), and vancomycin-resistant enterococci are already a major problem in hospitals. Vancomycin use should be restricted to methicillin-resistant S. aureus infections and used only for MRSA infections in situations where other drugs are not appropriate.

Our analysis has some limitations. First, it was restricted to the incidence of disease associated with acute-care management within the hospital setting. Recent reports suggest that MRSA has been increasing in outpatients (36,37). Thus, our results represent only a part of the problem, although hospitalizations outweigh outpatient visits by ≈4 to 1.

Second, NHDS data enables the coding of only 7 diagnosis codes; hospital information systems typically include 15–20 diagnosis codes for each admission (38). Thus, additional diagnoses in which S. aureus played a role may have been excluded. Errors in ICD coding when transcribing from doctors' discharge summaries are another potential source of bias, as is the possibility that multiorgan failure, an end stage of sepsis, was coded as septicemia. One study concluded that the positive predictive value of the 038 code on NHDS records to predict sepsis was 88.9%–97.7%, depending on the criteria, and the negative predictive value was 80.0% (39). The authors of another study that examined whether sepsis was coded correctly on hospital bills concluded that strict reliance on administrative data may be prone to bias because only 75.4% of sepsis cases were accurately coded (38). Thus, our results may be an underestimate of the true effect, although trends are likely robust to coding errors.

Third, TSN data provide information concerning only the site of isolate collection and not the infection. Thus, some isolates from blood or the lung area may not be associated with septicemia or pneumonia, respectively. In addition, the code for S. aureus septicemia was given priority over the other more site-specific codes; this could have affected the estimates of MRSA infections. However only a limited number of records had overlapping codes.

Fourth, although the 2 data sources from TSN and NHDS used in this article are nationally representative, they may not represent a stratified random sample of hospitals by type and region. However, the trends are likely robust enough to avoid bias. In addition, the percentage of S. aureus isolates resistant to methicillin reported in the TSN database has increased similar to that reported by other national studies (Figure 4). Finally, our estimates of the number of hospitalizations and deaths are associated with, but cannot be directly attributed to, S. aureus and MRSA because NHDS does not report the immediate cause of death, and older, sicker patients are more likely to contract a nosocomial infection (40).

Our findings suggest that S. aureus and MRSA should become a national priority for disease control. Possible responses include expanding national surveillance or reporting requirements for S. aureus and MRSA infections, more research to quantify the relative importance and interaction between community- and healthcare-associated colonization and infection, improved investments in hospital-infection control, and greater public investment to support research and development of an S. aureus vaccine.

Acknowledgments

http://www.cdc.gov/eid/content/13/12/1840.htm?s_cid=eid1840_e



http://staphmrsa.blogspot.com/



TSS

MRSA

Oct. 17, 2007, 12:43AMU.S. deaths from staph surpass AIDSStudy shows majority of cases of drug-resistant infection originate in health settings


By ALEXIS GRANTCopyright 2007 Houston Chronicle

http://chron.com/disp/story.mpl/front/5220692.html



CDC estimates 94,000 invasive drug-resistant staph infections occurred inthe U.S. in 2005

For more information on MRSA, please visit


http://www.cdc.gov/ncidod/diseases/submenus/sub_mrsa.htm


For moreinformation on CDC's guidelines for the prevention of MRSA in health caresettings, visit


http://www.cdc.gov/ncidod/dhqp/ar_mrsa_prevention.html

###DEPARTMENT OF HEALTH AND HUMAN SERVICES



Content Source: Office of Enterprise CommunicationPage last modified: October 16, 2007

http://www.cdc.gov/od/oc/media/pressrel/2007/r071016.htm


>>>>MRSA and related bloodstream infections afflict about 350,000 patients a year, and kill 90,000. Recently, the Centers for Medicare and Medicaid Services announced it would no longer pay hospitals to treat infections the agency believes were preventable.<<<<

http://www.news-press.com/apps/pbcs.dll/article?AID=/20070918/NEWS01/70917049/1075


THIS is outrageous. SO, there going to fix the Medicare problem by just letting the old people die that contract MRSA or VRSA in the hospital. no place like the USA, BIG insurance and tort laws, and now Medicare. What's happened to us? I would not be surprised if GW thought of this. He does not want to give the kids health insurance because he chooses to fund Iraq I guess. Now Medicare wants to let the old folks die if they go to the hospital and acquire MRSA or VRSA, just let them die. How much damage can one President do? Now, here is the 600+ billion dollar question, and please think about this very hard. Since it is totally impossible to sue a hospital for MRSA or VRSA acquired infections, due to the lack of science to prove it (to date), even though everyone knows it was a hospital acquired infection after surgery. SO then tell me how in the hell can Medicare refuse to pay for MRSA infections? MRSA damn near killed me in December of 2001 after another neck surgery. After 7+ weeks of vancomycin straight to the heart via pic long-line, I pulled through, with a huge hole in my hip bone, that still hurts to this day. But this really ticks me off, as you can see, and it is just not right for this Adminstration to pull this with Medicare. They better stock up on body bags, because the elderly (for the most part) don't have other insurance. But like I said, this is one way to fix the Medicare problem. I suggest the old folks stay home and don't go to the hospital. I was in one of the finest hospitals in the world too, with one of the best neurosurgeons in the world, so don't think it is just in some old run down hospital.

I will not even go into antibiotic resistance issue and the cattle industry and the antibiotics and hormones they pump those cattle up when they are so sick and diseased they cannot even make it to slaughter. but that is a fact, and it is another part of the problem i.e. overuse of antibiotics. If you don't believe me, it's a weekly event, and has been for years, just look at the FDA website, on there weekly warning letters. lets look real quick at this week;

Specifically, you treated the calf bearing tag 904 with 10 cc Duo Pen (Penicillin G Benzathine and Penicillin G Procaine Injectable Suspension) subcutaneously for a navel infection each day between September 18 and 30, 2006. The approved labeling instructions state, "Do not use in calves to be processed for veal." Your veterinarian's protocol instructed you to administer [redacted] to treat ear and navel infections with a [redacted] withdrawal period before slaughter. The sales invoices indicates the calf weighed 176 pounds at the time of sale. Nevertheless, you treated this veal calf at a higher dose and higher frequency than prescribed by your veterinarian, and you shipped this veal calf for slaughter on October 17, 2006 -- only 17 days after the last treatment. You administered this drug contrary to both the approved labeling instructions and those of your veterinarian.

In addition, you adulterated the animal feed that you fed to your veal calves within the meaning of section 501(a)(6) of the Act [21 U.S.C. 351 (a)(6)] by adding NeoMed 325 Soluable Powder (Neomycin Sulfate) and Uniprim Power for Horses (Trimethoprim and Sulfadiazine) to Strauss Veal Feed Market Blend milk replacer. The extralabel use of drugs in or on animal feed is specifically prohibited by section 512(a)(4) [21 USC 360b(a)(4)] of the Act, and 21 CFR Part 530.

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 be aware that your illegal extralabel use of drugs resulted in high levels of drug residues in the edible tissues of veal calves you offered for slaugthter.

http://www.fda.gov/foi/warning_letters/s6534c.htm

On or about September 20, 2006, you sold a dairy cow with Back Tag 9135 for slaughter as food to [redacted]. On or about September 20, 2006, this animal was slaughtered at [redacted] United States Department of Agriculture, Food Safety and Inspection Service (USDA/FSLS) analysis of tissue samples collected from that animal identified the presence of flunixin in the liver at 0.852 parts per million (ppm). A tolerance of 125 parts per billion (or 0.125 ppm) has been established for residues of flunixin in the liver of cattle as codified in Title 21, Code of Federal Regulations, Part 556.286 (21 C.F.R. 556.286). The presence of this amount of this drug in the liver 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 inadequate 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 adequate treatment records to assure that appropriate withdrawal times have been observed. 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.

In addition,

http://www.fda.gov/foi/warning_letters/s6530c.htm

I think you can get the just from just these two from this week, but these type warning letters are there just aboutevery week, and have been for years. just go through the archives and see for yourself.

And don't even get me going on mad cow disease in the USA, and the fact we have all been _exposed_, and the fact our federal friends have been conviently covering that up. I know, my mother died from the US version of mad cow disease the Heidenhain Variant of CJD, confirmed. The USA version of mad cow i.e. BASE, is more virulent than the UK BSE. but that's another story. funny, during my surgeries, I bank my own blood when needed, and NEVER used bone grafts due to risk factors of CJD/TSE risk factors and other infectious disease, and what did they do, damn near kill me with MRSA, and then Infectious Disease Team came through the door and the first thing they tried to tell me that everybody has MRSA on there skin. but every nurse I spoke with said it was hospital acquired, and then I found out later that 7 people the week I was in that surgical arena acquired MRSA. Go figure.

SAD, part is, there is no cure for CJD, and it is spreading via the medical, surgical, and dental arena, due to the fact it is very very difficult to kill this agent. course they will not tell you this either. The USA is going to hell in a handbag, while GW destroys and builds Iraq back. Yep, I am pissed, and have been for years, and I don't care who knows anymore. ...

ABSTRACTS SPORADIC CJD AND H BASE MAD COW ALABAMA AND TEXAS SEPTEMBER 2007

Date: Mon, 24 Sep 2007 21:31:55 -0500

I suggest that you all read the data out about h-BASE and sporadic CJD, GSS,blood, and some of the other abstracts from the PRION2007. ...

http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0709&L=sanet-mg&T=0&F=&S=&P=19744


*** PLEASE READ AND UNDERSTAND THE RAMIFICATIONS OF THIS !!! THE PRICE OFPOKER INDEED GOES UP. ...TSS

USA BASE CASE, (ATYPICAL BSE), AND OR TSE (whatever they are calling ittoday), please note that both the ALABAMA COW, AND THE TEXAS COW, both were''H-TYPE'', personal communication Detwiler et al Wednesday, August 22, 200711:52 PM. ...TSS

http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=19779


CREUTZFELDT JAKOB DISEASE MAD COW BASE, CWD, SCRAPIE UPDATE OCT 2007

http://cjdmadcowbaseoct2007.blogspot.com/


PLEASE NOTE IN USA CJD UPDATE AS AT JUNE 2007, please note steady increasein ''TYPE UNKNOWN''. ...TSS

1 Acquired in the United Kingdom; 2 Acquired in Saudi Arabia; 3 Includes 17 inconclusive and 9 pending (1 from 2006, 8from 2007); 4 Includes 17 non-vCJD type unknown (2 from 1996, 2 from 1997, 1 from 2001, 1 from 2003, 4 from 2004, 3from 2005, 4 from 2006) and 36 type pending (2 from 2005, 8 from 2006, *** 26 from 2007)

http://www.cjdsurveillance.com/pdf/case-table.pdf


still disgusted in Baycliff, Texas USA