Rapid communications
First detection of livestock-associated meticillinresistant Staphylococcus
aureus CC398 in bulk tank milk in the United Kingdom, January to July 2012
G K Paterson1, J Larsen2, E M Harrison1, A R Larsen2, F J Morgan1, S J
Peacock3,4, J Parkhill4, R N Zadoks5, M A Holmes (mah1@cam.ac.uk)1
1. Department of Veterinary Medicine, University of Cambridge, Cambridge,
United Kingdom
2. Microbiology and Infection Control, Statens Serum Institut, Copenhagen,
Denmark
3. School of Clinical Medicine, University of Cambridge, Cambridge, United
Kingdom
4. The Wellcome Trust Sanger Institute, Wellcome Trust, Cambridge, United
Kingdom
5. Moredun Research Institute, Penicuik, United Kingdom
Citation style for this article:
Paterson GK, Larsen J, Harrison EM, Larsen AR, Morgan FJ, Peacock SJ,
Parkhill J, Zadoks RN, Holmes MA. First detection of livestock-associated
meticillin-resistant Staphylococcus aureus CC398 in bulk tank milk in the United
Kingdom, January to July 2012. Euro Surveill. 2012;17(50):pii=20337. Available
online: http://www.
eurosurveillance.org/ViewArticle.aspx?ArticleId=20337
Article submitted on 27 November 2012 / published on 13 December 2012
Livestock-associated meticillin-resistant Staphylococcus aureus belonging
to clonal complex 398 (LA-MRSA CC398) is an important cause of zoonotic
infections in several countries, but there is only a single published report of
this lineage from the United Kingdom (UK). Here, we describe the isolation of
LA-MRSA CC398 from bulk tank milk from five geographically dispersed farms in
the UK. Our findings suggest that LA-MRSA CC398 is established in livestock in
the UK. Awareness of the potential occupational risks and surveillance in other
food-producing animal species should be promoted.
Isolation of meticillin-resistant Staphylococcus aureus from dairy
cattle
During a study, performed from January to July 2012, to detect mecC
meticillin-resistant Staphylococcus aureus (MRSA) in dairy cattle in the United
Kingdom (UK), ca. 1,500 bulk tank milk samples were supplied by National Milk
Laboratories Ltd., (Chippenham, UK). These were collected aseptically by trained
technicians for quality assurance purposes and stored at 4 °C for up to five
days prior to testing. Enrichment for S. aureus was performed using a
modification of a published technique [1] omitting the incubation in phenol red
mannitol broth supplemented with 4 mg/L oxacillin (24 h at 37°C). Identification
of potential MRSA colonies (blue colour) was confirmed by subculture on Staph
Brilliance 24 plates (Oxoid, Baskingstoke, UK) and these were subsequently
screened for mecA, mecC and femB by multiplex PCR as described previously [2].
Approximately 300 potential MRSA colonies were identified and subjected to PCR
testing, yielding a total of seven mecA MRSA isolates from five farms, including
three isolates from the same farm. These isolates were found to be mecA,
femB-positive by PCR (Table). All seven isolates were resistant to penicillin,
meticillin and cefoxitin by disk diffusion according to the European Committee
on Antimicrobial Susceptibility Testing (EUCAST) guidelines [3].
Molecular and phenotypic characterisation of LA-MRSA CC398 from dairy
cattle in the United Kingdom
Multi-locus sequence typing found all seven isolates belonged to sequence
type ST398, and CC398-specific PCR based on the restriction–modification system
sau1–hsdS1 confirmed that all the isolates belonged to clonal complex CC398 [4].
Isolates from three farms exhibited spa type t011 and carried a composite
staphylococcal cassette chromosome mec (SCCmec) V(5C2&5)c element, whereas
isolates from the remaining two farms had spa types t011 and t2546 and harboured
SCCmec IVa. All isolates lacked the lukS-PV and lukF-PV genes encoding
Panton-Valentine leukocidin and the scn gene (Table). Antimicrobial
susceptibility testing using disk diffusion according to the EUCAST guidelines
revealed that all isolates were resistant to tetracycline, and PCR [10]
demonstrated the presence of the tetracycline resistance gene tet(M) in all
seven, and of tet(K) in three isolates (Table).
Discussion
Here we describe the first isolation of LA-MRSA CC398 from dairy cattle in
the UK. This is only the second published instance of LA-MRSA CC398 in this
country following the report of isolates (t011 and SCCmec IVa) from two horses
in south-eastern England [11]. In many countries in continental Europe and
elsewhere, LA-MRSA CC398 poses an occupational risk for those in close contact
with livestock, particularly pigs and veal calves. For instance, significantly
higher rates of MRSA nasal carriage by humans in contact with pigs (farm
workers, abattoir workers, veterinarians) have been noted in several
epidemiological studies, with the isolates typically belonging to CC398 [12-16].
Further studies have shown an association between clinical disease resulting
from LA-MRSA CC398 infection and contact with pigs or pig farms [16-20]. The
impact of this can be significant locally, and this lineage can be imported into
healthcare settings. For example, in a German hospital in an area with a large
number of pigs, 22% of patients colonised with MRSA at admission carried ST398
[21]. Nosocomial transmission has also been reported [22]. LA-MRSA CC398, like
other MRSA, may be responsible for life-threatening infections during long or
frequent hospitalisations, or following wound or surgery site infections, and
also increases healthcare costs resulting from screening, isolation of carriers,
and decolonisation. Although pasteurisation of milk should ensure that CC398
MRSA will not enter the food chain, our finding of LA-MRSA CC398 in dairy cattle
has clear public health implications for the UK. Workers on dairy farms, or
individuals with regular contact with dairy cows, are likely to have a higher
risk of colonisation or infection with LA-MRSA CC398 compared to the general
population in the UK. LA-MRSA CC398 isolates from three of the farms where
isolated were found carried SCCmec type IVa. The isolates from the other two
farms carried SCCmec type V(5C2&5) c. Both of these SCCmec types have
previously been found in LA-MRSA CC398 isolates [23].
Heterogeneity is seen in S. aureus CC398, with human and
livestock-associated lineages being differentiated by the presence or absence of
specific resistance and virulence-related genes [23-24]. In all of our isolates
the absence of the scn gene, encoding the humanspecific staphylococcal
complement inhibitor, and the presence of tet(M) suggested that they were all
livestock-associated, as opposed to S. aureus CC398 strains which circulate in
the human population independent of a livestock reservoir [23-24]. Likewise, all
seven isolates lacked the lukS-PV and lukF-PV genes encoding Panton-Valentine
leukocidin which is absent in LA-MRSA CC398, but is present in some, but not
all, human-associated CC398 isolates [23]. Three consecutive samples from the
same farm over a seven-month period were positive for LA-MRSA CC398 isolates
with identical spa (t011) and SCCmec types (IVa), suggesting that this strain is
able to persist in dairy herds over prolonged periods. While there are
relatively few reports of LA-MRSA CC398 from dairy cattle compared to pig farms,
it has been found to cause bovine mastitis [25-27]. Our findings therefore have
significance to veterinary medicine, in addition to public health. The relative
absence of CC398 MRSA from the UK prior to this study, when it is widespread in
the rest of Europe suggests that the geographical separation of the UK from
continental Europe may have delayed the spread of this lineage to the UK rather
than there being any fundamental difference in husbandry or biosecurity in the
UK. The authors are aware of unpublished surveys looking for potential LA-MRSA
in UK dairy and pig herds that have been negative before now. These
CC398-positive samples were not part of a formal prevalence study, and it is
therefore unclear how common LA-MRSA CC398 isolates are in UK dairy farms or if
they are present in other livestock. However, the five farms with positive
samples were identified from a sample of ca. 1,500 farms, indicating a low
prevalence currently.
Conclusions
This is the first description of LA-MRSA CC398 in foodproducing animals in
the UK. The ability of this lineage to colonise a wide range of host species,
coupled with its zoonotic potential, make this finding of significance to both
veterinary and human health. Future surveillance for this LA-MRSA CC398 strain
in all food-producing animal species in the UK and the evaluation of
occupational risk factors for MRSA carriage and infection should be considered.
SNIP.
Table Molecular and phenotypic characteristics of meticillin-resistant
Staphylococcus aureus CC398 from bulk tank milk in the United Kingdom, January
to July 2012 (n=7)
SNIP...
Acknowledgments
SNIP...
New MRSA superbug strain found in UK milk
84 21 712B/y Jeremy Laurance Wednesday, 26 December 2012
A new strain of MRSA has been found in British milk, indicating that the
superbug is spreading through the livestock population and poses a growing
threat to human health.
The new strain, MRSA ST398, has been identified in seven samples of bulk
milk from five different farms in England.
The discovery, from tests on 1,500 samples, indicates that
antibiotic-resistant organisms are gaining an increasing hold in the dairy
industry.
The disclosure comes amid growing concern over the use of modern
antibiotics on British farms, driven by price pressure imposed by the big
supermarket chains. Intensive farming with thousands of animals raised in
cramped conditions means infections spread faster and the need for antibiotics
is consequently greater.
Three classes of antibiotics rated as “critically important to human
medicine” by the World Health Organisation – cephalosporins, fluoroquinolones
and macrolides – have increased in use in the animal population by eightfold in
the last decade.
The more antibiotics are used, the greater the likelihood that
antibiotic-resistant bacteria, such as MRSA, will evolve.
Experts say there is no risk of MRSA infection to consumers of milk or
dairy products so long as the milk is pasteurised. The risk comes from
farmworkers, vets and abattoir workers, who may become infected through contact
with livestock and transmit the bug to others.
The discovery was made by scientists from Cambridge University who first
identified MRSA in milk in 2011. They say the latest finding of a different
strain is worrying.
Mark Holmes, of the department of veterinary medicine, who led the study,
published in Eurosurveillance, said: “This is definitely a worsening situation.
In 2011 when we first found MRSA in farm animals, the Department of Environment,
Food and Rural Affairs [Defra] initially didn’t believe it. They said we don’t
have MRSA in the dairy industry in this country.”
“Now we definitely have MRSA in livestock. What is curious is that it has
turned up in dairy cows when in other countries on the Continent it is
principally in pigs. Could it be in pigs or poultry in this country? We don’t
know.”
The MRSA superbug can cause serious infections in humans which are
difficult to treat, require stronger antibiotics, and take longer to resolve.
Human cases of infection with the new strain have been found in Scotland and
northern England according to Defra, but no details are available.
Dr Holmes said supermarket pressure on farmers to hold down prices was
leading to the overuse of antibiotics to prevent cattle getting mastitis, an
infection of the udder, that might interrupt the milk supply.
“If farmers were not screwed into the ground by the supermarkets and
allowed to get a fair price for their milk they would be able to use fewer
antibiotics,” he said.
“Common sense tells us that anything we can do to reduce use of antibiotics
will reduce the growth of resistant bugs. We want to wean our farmers off
antibiotics and the only way we can do that is with better regulation.”
Vets in Norway and Denmark had much more limited prescribing powers than in
the UK, he added.
MRSA found in our milk: Superbug strain can cause serious infections in
humans and is resistant to antibiotics
Scientists tested 1,500 samples of bulk milk and found seven cases of MRSA
ST398 from five farms in England, Scotland and Wales
The superbug can cause serious and occasionally deadly infections in humans
By Sean Poulter PUBLISHED:19:52 EST, 20 December 2012| UPDATED: 02:46 EST,
21 December 2012 Comments (47) Share
. . A potentially deadly MRSA superbug has been found in British milk for
the first time.
The superbug – already a problem in farm animals on the Continent – can
cause serious and occasionally deadly infections in humans and is becoming a
cause of udder infections in dairy cows.
The strain of MRSA known as ST398 is resistant to antibiotics, so doctors
find it difficult to treat infected people effectively.
Superbug: A strain of MRSA has been found in British milk for the first
time In theory the bug should be killed off when milk is heat-treated in the
pasteurisation process before it reaches the high street or doorstep. However,
some people prefer unpasteurised milk and cheese in the belief it is better for
them or tastes nicer.
More... Exterminate! Doctor Who-villain lookalike robot taking on superbugs
could save NHS £200 million per year Scientists halt deadly MRSA outbreak by
cracking genetic code and tracking down carrier in breakthrough that could save
hundreds of lives each year
And farmers, vets and abattoir workers who come into contact with the cows
and their calves can become infected, allowing the bug to spread into the wider
community. That has happened in the Netherlands where the same strain of MRSA
has caused illness among nursing home residents.
MRSA ST398 was first seen in pigs in Holland in 2003. It has since become
epidemic in European and North American pig populations and has spread to
poultry and cattle.
It is one of a number of superbugs that have emerged in recent years,
apparently as a result of the overuse of antibiotics by farmers treating sick
animals. Over time the farm animal bugs develop a resistance.
Strain: Farmers, vets and abbatoir workers who come into contact with cows
and their calves can become infected The Soil Association, which campaigns for
organic farming, is calling for a government investigation to establish the
spread of the MRSA and a crackdown on the use of antibiotics on UK farms.
Scientists from the department of veterinary medicine at the University of
Cambridge tested 1,500 samples of bulk milk and found seven cases of MRSA ST398
from five farms in England, Scotland and Wales.
They said the high level of antibiotic resistance in the bug means the
findings are ‘of significance to both veterinary and human health’. Dr Mark
Holmes, a senior lecturer in preventive veterinary medicine, said the discovery
was made while looking for a different strain of MRSA found in cows and
people.
He said: ‘Until this discovery it was always assumed that this form of
livestock MRSA was a problem on the Continent, but it has now jumped the
Channel. It now seems that it is established in this country – perhaps one in
every 200 farms.
‘If it ends up becoming more commonplace it will, sooner or later, cause
disease in people here.’
Dr Holmes said the major question is why MRSA is appearing in farm animals
and whether this is linked to intensive farming and the associated heavy use of
antibiotics.
He asked: ‘Should we be thinking again about the type and range of
antibiotics we use in farm animals? Is it wise to have a lot of preventive use
of antibiotics, particularly in dairy cows?
‘They get a lot of mastitis – udder infection – because they are driven
hard to produce a lot of milk, which is the only way farmers can make
money.
‘I think you have to look at the pressures the supermarkets create by
screwing the farmers down so tightly on costs.’
Letter
Lethal Necrotizing Pneumonia Caused by an ST398 Staphylococcus aureus
Strain
Letter
Ventilator-associated Pneumonia and MRSA ST398, Italy
Letter
Livestock-associated Methicillin-Susceptible Staphylococcus aureus ST398
Infection in Woman, Colombia
Letter
Suspected Horse-to-Human Transmission of MRSA ST398
Letter
Lethal Necrotizing Pneumonia Caused by an ST398 Staphylococcus aureus
Strain
Dispatch
Methicillin-Resistant Staphylococcus aureus ST398 in Swine Farm Personnel,
Belgium
Dispatch
Staphylococcus aureus ST398, New York City and Dominican Republic
Abstract
Closely related Staphylococcus aureus strains of ST398, an
animal-associated strain, were identified in samples collected from humans in
northern Manhattan, New York, NY, USA, and in the Dominican Republic. A large
population in northern Manhattan has close ties to the Dominican Republic,
suggesting international transmission.
Letter
Methicillin-Resistant Staphylococcus aureus ST398, Italy
Monday, April 18, 2011
Multidrug-Resistant Staphylococcus aureus in US Meat and Poultry
Wednesday, May 11, 2011
Methicillin-resistant Staphylococcus aureus in Retail Meat, Detroit,
Michigan, USA
Thursday, June 9, 2011
New Superbug Found in Cows and People
Thursday, August 12, 2010
Escherichia coli sequence type ST131 as the major cause of serious
multidrug-resistant E. coli infections in the United States
Clin Infect Dis. 2010 Aug 1;51(3):286-94.
MRSA damn near killed me in 2001 after one of my many neck surgeries, and
it’s some nasty stuff. 8 weeks vancomycin straight through top of heart via PIC
long line, twice daily, and the vanco almost stopped working, had to double dose midway
through. ...
NOW, today we have VRSA. no telling where that will take us...
Comparative Genomics of Vancomycin-Resistant Staphylococcus aureus Strains
and Their Positions within the Clade Most Commonly Associated with
Methicillin-Resistant S. aureus Hospital-Acquired Infection in the United States
doi: 10.1128/mBio.00112-12 22 May 2012 mBio vol. 3 no. 3 e00112-12
Veronica N. Kosa,b, Christopher A. Desjardinsb, Allison Griggsb, Gustavo
Cerqueirab, Andries Van Tonderc, Matthew T. G. Holdenc, Paul Godfreyb, Kelli L.
Palmera, Kip Bodid, Emmanuel F. Mongodine, Jennifer Wortmanb, Michael
Feldgardenb, Trevor Lawleyc, Steven R. Gillf, Brian J. Haasb, Bruce Birrenb, and
Michael S. Gilmorea,b
Address correspondence to Michael S. Gilmore, michael_gilmore@meei.harvard.edu.
Editor Paul Keim, Northern Arizona University
ABSTRACT
Methicillin-resistant Staphylococcus aureus (MRSA) strains are leading
causes of hospital-acquired infections in the United States, and clonal cluster
5 (CC5) is the predominant lineage responsible for these infections. Since 2002,
there have been 12 cases of vancomycin-resistant S. aureus (VRSA) infection in
the United States—all CC5 strains. To understand this genetic background and
what distinguishes it from other lineages, we generated and analyzed
high-quality draft genome sequences for all available VRSA strains. Sequence
comparisons show unambiguously that each strain independently acquired Tn1546
and that all VRSA strains last shared a common ancestor over 50 years ago, well
before the occurrence of vancomycin resistance in this species. In contrast to
existing hypotheses on what predisposes this lineage to acquire Tn1546, the
barrier posed by restriction systems appears to be intact in most VRSA strains.
However, VRSA (and other CC5) strains were found to possess a constellation of
traits that appears to be optimized for proliferation in precisely the types of
polymicrobic infection where transfer could occur. They lack a bacteriocin
operon that would be predicted to limit the occurrence of non-CC5 strains in
mixed infection and harbor a cluster of unique superantigens and lipoproteins to
confound host immunity. A frameshift in dprA, which in other microbes influences
uptake of foreign DNA, may also make this lineage conducive to foreign DNA
acquisition.
IMPORTANCE
Invasive methicillin-resistant Staphylococcus aureus (MRSA) infection now
ranks among the leading causes of death in the United States. Vancomycin is a
key last-line bactericidal drug for treating these infections. However, since
2002, vancomycin resistance has entered this species. Of the now 12 cases of
vancomycin-resistant S. aureus (VRSA), each was believed to represent a new
acquisition of the vancomycin-resistant transposon Tn1546 from enterococcal
donors. All acquisitions of Tn1546 so far have occurred in MRSA strains of the
clonal cluster 5 genetic background, the most common hospital lineage causing
hospital-acquired MRSA infection. To understand the nature of these strains, we
determined and examined the nucleotide sequences of the genomes of all available
VRSA. Genome comparison identified candidate features that position strains of
this lineage well for acquiring resistance to antibiotics in mixed infection.
Footnotes
Citation Kos VN, et al. 2012. Comparative genomics of vancomycin-resistant
Staphylococcus aureus strains and their positions within the clade most commonly
associated with methicillin-resistant S. aureus hospital-acquired infection in
the United States. mBio 3(3):e00112-12. doi:10.1128/mBio.00112-12.
Received 13 April 2012 Accepted 24 April 2012 Published 22 May 2012
Copyright © 2012 Kos et al.
This is an open-access article distributed under the terms of the Creative
Commons Attribution-Noncommercial-Share Alike 3.0 Unported License, which
permits unrestricted noncommercial use, distribution, and reproduction in any
medium, provided the original author and source are credited.
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