Prevalence and molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) among pigs on German farms and import of livestock-related MRSA into hospitals

In 2003, a new MRSA clone exhibiting MLST CC398 (spa types t108, t011 and relatives) emerged among patients in Dutch hospitals. Since the occurrence of this MRSA type was shown to be epidemiologically linked to regions with a high density of pig farming [37], and as screening of pigs yielded high colonization rates [9], it was assumed that pigs might be a potential zoonotic source for MRSA transmissions.

It is unknown how often pigs at German farms, which are major European pig producers (Eurostat yearbook 2008, http://epp.eurostat.ec.europa.eu), are colonized with MRSA. In this study, we identified MRSA colonization in pigs on 70% of the regional farms. This corresponds to data from The Netherlands where 23–80% of the pig farms were affected [9, 38], and it clearly reflects that porcine MRSA colonization is a common phenomenon on farms in Germany, at least in the study area. However, genotypic investigations on MRSA isolates from pigs with acute diseases (urinary tract infection, skin infection, metritis mastitis agalactia syndrome) [16] and screening of clinical specimens and cadavers [24] recently indicated that other German geographic regions may also be involved.

Molecular typing revealed that the regional pigs’ isolates were associated with a subset of spa types associated with MLST CC398, agr type I and SCCmec types V and IV, as observed in other countries [9, 18]. All isolates derived from pigs in this study did not harbour genes encoding exfoliative toxin, the toxic shock syndrome toxin 1 and enterotoxins. Moreover, the porcine isolates lacked leukocidal toxin genes lukE/lukD, lukM and the PVL-encoding lukS/lukF. These results confirm previous investigations [38] and suggest a low capacity of regionally disseminated porcine MRSA subtypes to induce toxin-mediated diseases among humans. The importance of these findings is highlighted against the background that MRSA CC398 have entered the food chain [22] and an outbreak of foodborne disease caused by enterotoxin-producing MRSA exhibiting a different (non-CC398) molecular type has been described previously [39]. Hence, a close surveillance of S. aureus from different species and from food samples should reveal the potential emergence of toxin-producing MRSA isolates.

Logistic regression modelling in our case control study yielded that, in addition to contact with pigs, contact with cattle was also independently associated with an increased risk for MRSA CC398 colonization. This finding confirms recent observations by van Loo et al. who also found a correlation of human MRSA CC398 carriage and contact to cattle [37]. Since no data on the prevalence of MRSA among cattle on German farms are published, further studies are warranted to investigate this issue.

It has previously been observed that rates of antimicrobial resistance in the commensal flora of (pig) farmers are significantly higher than in the general population [40]. The recent emergence of MRSA among farmers [17] therefore might reflect another facet of a long-known phenomenon. Nevertheless, we showed that the proportion of MRSA with presumptively livestock-associated spa types among all MRSA isolated from admission screenings at the UHM increased from 13% in 2005 to 22.4% in 2008. This proportion is higher than suggested by national German surveillance data [20, 41]. It has been confirmed that MRSA CC398 are not only found locally at the UHM, but are frequently isolated from admission screenings in an entire region of Northwestern Germany [42, 43]. The high burden of this MRSA subtype might therefore primarily reflect a regional situation, which could be explainable by the fact that the region involved is the area with the highest pig density (number of pigs/km²) in Germany (information.medien.agrar e.V., Agraratlas Jan 2005, http://www.ima-agrar.de).

In this retrospective case control study, we showed a significant association of the spa types t011 and relatives with contact to pigs and cattle. We recognize the limitations (recall bias) inherent within this study type and state that our findings, which represent correlation data, are not suitable for proving a direct transmission of MRSA between animals and humans. However, we demonstrated that 36% of presumptive livestock-related MRSA carriers lacked classical risk factors hitherto used for admission screening of patients. Moreover, carriers of MRSA CC398 in this study comprised younger patient groups who are usually less frequent carriers of MRSA [42] and less frequently associated with classical MRSA risk factors. This raises the question of whether commonly used recommendations for admission screening are convenient to detect patients harbouring livestock-associated strains. Therefore, we favour considering adding “contact to livestock” as a risk factor to the admission screening schedule for hospitals, at least in regions with a high density of farming. Otherwise the floodgates for a clonal spread of MRSA CC398 could be opened in these regions. Furthermore, efforts of molecular MRSA surveillance and reports on prevalence will fail to reflect the actual epidemiological situation. In The Netherlands, current reports show that an adaptation of the on-admission MRSA screening protocol in this manner revealed that 32% of pig-exposed patients admitted to a Dutch hospital were colonized by MRSA. This led to a three-fold increase in the local MRSA incidence in a predominantly agriculturally structured region [44]. Moreover, our observation that the increase of MRSA CC398 at the UHM was related to the introduction of a new local MRSA “search policy” performing screening in all patients, irrespective of risk factors, emphasizes the importance of the risk patient definition for the identification of these isolates. This is highlighted by the threat that continuous introduction of MRSA CC398 to the hospital setting, might cause nosocomial spread to patient groups with underlying comorbidities and thereby facilitate infections. This threat has recently been increased by the first nosocomial outbreak of MRSA ST398 in a Dutch hospital [45].

Apart from giving impetus to antimicrobial resistance import to hospitals, colonization with MRSA CC398 might set livestock-exposed persons under risk of developing severe S. aureus CC398-associated infections [21, 46]. First, this highlights the special need to consider MRSA as causative agents when treating such patient groups. Second, it raises the question as to whether the implementation of preventive measures (consequent alcoholic hand disinfection, wearing of gloves and prevention of dust inhalation) could forestall MRSA colonization of livestock-exposed workers.

In conclusion, our findings confirm that MRSA associated with spa type t011 and relatives can be found on German pig farms and indicate that livestock might represent a relevant source for MRSA imports to hospitals.