Tara C. Smith

Methicillin-Resistant Staphylococcus aureus (MRSA) Strain ST398 Is Present in Midwestern U.S. Swine and Swine Workers

Background Recent research has demonstrated that many swine and swine farmers in the Netherlands and Canada are colonized with MRSA. However, no studies to date have investigated carriage of MRSA among swine and swine farmers in the United States (U.S.). Methods We sampled the nares of 299 swine and 20 workers from two different production systems in Iowa and Illinois, comprising approximately 87,000 live animals. MRSA isolates were typed by pulsed field gel electrophoresis (PFGE) using SmaI and EagI restriction enzymes, and by multi locus sequence typing (MLST). PCR was used to determine SCCmec type and presence of the pvl gene. Results In this pilot study, overall MRSA prevalence in swine was 49% (147/299) and 45% (9/20) in workers. The prevalence of MRSA carriage among production system As swine varied by age, ranging from 36% (11/30) in adult swine to 100% (60/60) of animals aged 9 and 12 weeks. The prevalence among production system As workers was 64% (9/14). MRSA was not isolated from production system Bs swine or workers. Isolates examined were not typeable by PFGE when SmaI was used, but digestion with EagI revealed that the isolates were clonal and were not related to common human types in Iowa (USA100, USA300, and USA400). MLST documented that the isolates were ST398. Conclusions These results show that colonization of swine by MRSA was very common on one swine production system in the midwestern U.S., suggesting that agricultural animals could become an important reservoir for this bacterium. MRSA strain ST398 was the only strain documented on this farm. Further studies are examining carriage rates on additional farms.

Staphylococcus aureus and staphylococcal food-borne disease: an ongoing challenge in public health.

Staphylococcal food-borne disease (SFD) is one of the most common food-borne diseases worldwide resulting from the contamination of food by preformed S. aureus enterotoxins. It is one of the most common causes of reported food-borne diseases in the United States. Although several Staphylococcal enterotoxins (SEs) have been identified, SEA, a highly heat-stable SE, is the most common cause of SFD worldwide. Outbreak investigations have found that improper food handling practices in the retail industry account for the majority of SFD outbreaks. However, several studies have documented prevalence of S. aureus in many food products including raw retail meat indicating that consumers are at potential risk of S. aureus colonization and subsequent infection. Presence of pathogens in food products imposes potential hazard for consumers and causes grave economic loss and loss in human productivity via food-borne disease. Symptoms of SFD include nausea, vomiting, and abdominal cramps with or without diarrhea. Preventive measures include safe food handling and processing practice, maintaining cold chain, adequate cleaning and disinfection of equipment, prevention of cross-contamination in home and kitchen, and prevention of contamination from farm to fork. This paper provides a brief overview of SFD, contributing factors, risk that it imposes to the consumers, current research gaps, and preventive measures.

The Emergence of Staphylococcus aureus ST398

The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) has changed dramatically over the past 15 years. Initially a nosocomial pathogen, newly emergent strains of MRSA have become increasingly common in the community among individuals lacking contact with healthcare. More recently, a third group of MRSA strains have been identified in association with livestock, particularly swine. These strains, termed livestock-associated MRSA, have now been identified in Europe, North America, and Asia in humans and animals. One molecular type, ST398, has been the dominant strain of livestock-associated MRSA identified to date. The emergence of this strain in animals and humans will be described in this review, including colonization and clinical infections caused by this strain. We also discuss lingering research questions and implications for controlling spread of this bacterium in an agricultural environment and beyond.

Prevalence of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) on retail meat in Iowa

Several recent studies have indicated a high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in retail-available meat. However, few studies have investigated MRSA in meat in the United States. The aim of this study was to determine the presence of Staphylococcus aureus (S. aureus) on meat samples available at retail stores. Samples of fresh raw pork, chicken, beef, and turkey were purchased from 22 food stores throughout Iowa. S. aureus strains were isolated from 27 of 165 samples, giving an overall prevalence of 16.4%. Turkey, pork, chicken, and beef had individual S. aureus prevalence rates of 19.4%, 18.2%, 17.8%, and 6.9%, respectively. Two isolates of MRSA were isolated from pork, giving an overall prevalence of 1.2%. One MRSA isolate was positive for the PVL gene. Common spa types included t034, t337, t008, and t002. These results suggest that MRSA is present on low numbers of retail meat in Iowa.

Isolation and Characterization of Methicillin-Resistant Staphylococcus aureus from Pork Farms and Visiting Veterinary Students

In the last decade livestock-associated methicillin-resistant S. aureus (LA-MRSA) has become a public health concern in many parts of the world. Sequence type 398 (ST398) has been the most commonly reported type of LA-MRSA. While many studies have focused on long-term exposure experienced by swine workers, this study focuses on short-term exposures experienced by veterinary students conducting diagnostic investigations. The objectives were to assess the rate of MRSA acquisition and longevity of carriage in students exposed to pork farms and characterize the recovered MRSA isolates. Student nasal swabs were collected immediately before and after farm visits. Pig nasal swabs and environmental sponge samples were also collected. MRSA isolates were identified biochemically and molecularly including spa typing and antimicrobial susceptibility testing. Thirty (30) veterinary students were enrolled and 40 pork farms were visited. MRSA was detected in 30% of the pork farms and in 22% of the students following an exposure to a MRSA-positive pork farm. All students found to be MRSA-positive initially following farm visit were negative for MRSA within 24 hours post visit. Most common spa types recovered were t002 (79%), t034 (16%) and t548 (4%). Spa types found in pork farms closely matched those recovered from students with few exceptions. Resistance levels to antimicrobials varied, but resistance was most commonly seen for spectinomycin, tetracyclines and neomycin. Non-ST398 MRSA isolates were more likely to be resistant to florfenicol and neomycin as well as more likely to be multidrug resistant compared to ST398 MRSA isolates. These findings indicate that MRSA can be recovered from persons visiting contaminated farms. However, the duration of carriage was very brief and most likely represents contamination of nasal passages rather than biological colonization. The most common spa types found in this study were associated with ST5 and expands the range of livestock-associated MRSA types.

MRSA in Conventional and Alternative Retail Pork Products

In order to examine the prevalence of Staphylococcus aureus on retail pork, three hundred ninety-five pork samples were collected from a total of 36 stores in Iowa, Minnesota, and New Jersey. S. aureus was isolated from 256 samples (64.8%, 95% confidence interval [CI] 59.9%–69.5%). S. aureus was isolated from 67.3% (202/300) of conventional pork samples and from 56.8% (54/95) of alternative pork samples (labeled “raised without antibiotics” or “raised without antibiotic growth promotants”). Two hundred and thirty samples (58.2%, 95% CI 53.2%–63.1%) were found to carry methicillin-sensitive S. aureus (MSSA). MSSA was isolated from 61.0% (183/300) of conventional samples and from 49.5% (47/95) of alternative samples. Twenty-six pork samples (6.6%, 95% CI 4.3%–9.5%) carried methicillin-resistant S. aureus (MRSA). No statistically significant differences were observed for the prevalence of S. aureus in general, or MSSA or MRSA specifically, when comparing pork products from conventionally raised swine and swine raised without antibiotics, a finding that contrasts with a prior study from the Netherlands examining both conventional and “biologic” meat products. In our study spa types associated with “livestock-associated” ST398 (t034, t011) were found in 26.9% of the MRSA isolates, while 46.2% were spa types t002 and t008—common human types of MRSA that also have been found in live swine. The study represents the largest sampling of raw meat products for MRSA contamination to date in the U.S. MRSA prevalence on pork products was higher than in previous U.S.-conducted studies, although similar to that in Canadian studies.

Methicillin-resistant Staphylococcus aureus in pigs and farm workers on conventional and antibiotic-free swine farms in the USA.

Much uncertainty remains about the origin and public health implications of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA). This study aimed to investigate the occurrence and prevalence of MRSA in general and LA-MRSA in particular in pigs and farm workers in five states. We collected nasal swabs from pigs and farm workers at 45 swine herds (21 antibiotic-free herds; 24 conventional herds) in Illinois, Iowa, Minnesota, North Carolina and Ohio. MRSA was isolated from 50 of 1085 pigs (4.6%) and 31 of 148 (20.9%) of farm workers. MRSA-positive pigs and people were clustered in four conventional swine farms in Iowa and Illinois. Based on genotyping, spa type t034, a common livestock associated variant, was predominant among both human and swine isolates. These results confirm the presence of LA-MRSA in pigs and swine farm workers in the USA, but the prevalence found is relatively low compared with European studies.

Comparative Effectiveness of Beta-lactams versus Vancomycin for Treatment of Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections among 122 Hospitals

BACKGROUND Previous studies indicate that vancomycin is inferior to beta-lactams for treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections. However, it is unclear if this association is true for empiric and definitive therapy. Here, we compared beta-lactams with vancomycin for empiric and definitive therapy of MSSA bloodstream infections among patients admitted to 122 hospitals. METHODS This retrospective cohort study included all patients admitted to Veterans Affairs hospitals from 2003 to 2010 who had positive blood cultures for MSSA. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression. Empiric therapy was defined as starting treatment 2 days before and up to 4 days after the first MSSA blood culture was collected. Definitive therapy was defined as starting treatment between 4 and 14 days after the first positive blood culture was collected. RESULTS Patients who received empiric therapy with a beta-lactam had similar mortality compared with those who received vancomycin (HR, 1.03; 95% CI, .89-1.20) after adjusting for other factors. However, patients who received definitive therapy with a beta-lactam had 35% lower mortality compared with patients who received vancomycin (HR, 0.65; 95% CI, .52-.80) after controlling for other factors. The hazard of mortality decreased further for patients who received cefazolin or antistaphylococcal penicillins compared with vancomycin (HR, 0.57; 95% CI, .46-.71). CONCLUSIONS For patients with MSSA bloodstream infections, beta-lactams are superior to vancomycin for definitive therapy but not for empiric treatment. Patients should receive beta-lactams for definitive therapy, specifically antistaphylococcal penicillins or cefazolin.

Methicillin-susceptible Staphylococcus aureus ST398, New York and New Jersey, USA.

To the Editor: Clinical infections with livestock-associated Staphylococcus aureus sequence type (ST) 398 have been reported in Europe, Canada, and the People’s Republic of China (1), as well as the Caribbean (2,3), and Colombia (4). Most reports describe infection with methicillin-resistant S. aureus; relatively few describe infection with methicillin-susceptible S. aureus (MSSA). In the United States, colonization of healthy adults by ST398 has been reported in Iowa (5) and in New York, New York (2); MSSA infections have been anecdotally reported in St. Louis, Missouri (6), and The Bronx, New York (7). We describe 8 infections with MSSA ST398 in the New York City area during a 7-year period (2004–2010). Five infections with a related ST (ST291) from clonal complex (CC) 398 also were identified. These findings highlight the emergence of clinical infections with 2 distinct CC398 sequence types in the New York City area. Retrospective typing of 4,167 clinical S. aureus isolates from various studies involving inpatients and outpatients in the New York City area identified 13 mecA-negative isolates with CC398-associated spa types (Table). Nine isolates were obtained from cultures of outpatients with skin and soft tissue infections; samples were submitted by physicians in the community. One isolate was associated with recurring skin and soft tissue infections in multiple body sites (BK21466); another was associated with genital infection (BK21732). Of the 4 ST398 isolates derived from bloodstream infections in hospitalized patients, 3 were recovered from intravenous drug users, 1 of whom died 1 day after admission for variceal bleeding (BK26722). Unlike the multidrug-resistant ST398 MSSA recently described in Colombia (4), most isolates in this study were susceptible to all antimicrobial drugs tested except penicillin, although several strains exhibited resistance to clindamycin and erythromycin. One isolate (BK23527) was submitted as oxacillin resistant (MIC ≥4 μg/mL) but lacked the mecA gene, which suggested that another mechanism was contributing to the resistance phenotype. Table Characteristics of Staphylococcus aureus clonal complex 398 isolates, New York and New Jersey, USA, 2004–2010* Multilocus sequence typing confirmed 8 isolates as ST398 (3–35–19–2–20–26–39); 5 isolates were assigned to ST291 (3–37–19–2–20–26–32), a double-locus variant of ST398 (Figure A1, panel A). Most of the ST398 strains were spa type 109 (t571), described in MSSA carriage isolates from New York City (2) and MSSA infections from China (1), France (8), Martinique (3), the Dominican Republic (2,3), and Colombia (4). BURP (based upon repeat pattern) analysis clustered all of the spa types into spa-CC t571 (Figure A1, panel B); ST398 isolates clustered with spa type 109 (t571), whereas ST291 isolates clustered with spa type 865 (t2313). Pulsed-field gel electrophoresis was also performed on the 11 available isolates. Although the ST291 isolates were sensitive to digestion with SmaI, pulsed-field gel electrophoresis was performed with Cfr9I to compare all isolates simultaneously. As expected, the ST398 and ST291 isolates clustered separately (data not shown); 4 distinct patterns were observed within each cluster (Table). Only the ST398 isolates were positive for a CC398 lineage-specific PCR that targets the unique restriction-modification system sau1-hsdS1 (9), further highlighting the differences between ST291 and ST398. None of the isolates harbored the genes coding for Panton-Valentine leukocidin. Because of the retrospective nature of the findings, epidemiologic information for each isolate was limited. One patient (BK19382) reported travel to the Dominican Republic; Caribbean nationality was reported for BK27037 (Puerto Rico) and BK31274 (Trinidad). The cases described here occurred in urban and suburban settings, reflecting the likelihood that exposure to livestock was relatively low; however, travel history was unknown for most of the patients. Previous reports have linked ST398 transmission to other reservoirs, including companion animals, live animal food markets, and commercial meat products (1,2). However, data from a recent genome sequencing study suggest that MSSA ST398 is human in origin (10); other evidence suggests that certain lineages, particularly spa type 109 (t571), might circulate at low levels in humans in the absence of livestock exposure (8). Our findings seem to support the hypothesis of low-level ST398 MSSA prevalence, and further surveillance might uncover additional cases of colonization or infection with ST398- and ST291-related strains in the New York City area. For example, active surveillance cultures performed at one of the 3 hospitals during January–March 2009 detected 7 additional ST398 and 3 additional ST291 isolates among 260 MSSA carriage strains (data not shown). In addition to the intrinsic virulence exhibited by ST398 MSSA in previous studies, the potential to acquire resistance to multiple classes of antimicrobial drugs (1,4,10), as well as virulence factors such as Panton-Valentine leukocidin (8), warrants continued surveillance in light of recent ST398 methicillin-resistant S. aureus outbreaks in health care settings (1).

Livestock-Associated Staphylococcus aureus: The United States Experience

Staphylococcus aureus is a gram-positive bacterium that colonizes a variety of animal species [1]. S. aureus infections in animals are most commonly reported as a cause of mastitis in dairyproducing animals (including cattle and goats) and “bumblefoot” in chickens [2], as well as being identified as a pathogen of farmed rabbits [3]. Most reports characterizing animalassociated S. aureus have demonstrated that strains affecting animals are distinct from those infecting humans, suggesting that there are host-specific lineages which only rarely cross species boundaries [4]. Livestock-associated strains may evolve on farms because of the use of antibiotics in animal husbandry. These may be used as feed additives for growth promotion in industrial livestock and poultry [5], for prevention of disease within a herd, or for treatment of an existing disease outbreak. Agricultural-use antibiotics include many classes that are relevant for human health, including tetracyclines, macrolides, penicillins, and sulfonamides, among others. Antimicrobial resistance generated during animal husbandry may then be spread to the general human population in a number of different manners: contact with contaminated meat products (via handling or ingestion); occupational contact (farmers, meat packers, butchers, etc.) and potential secondary spread into the larger community from those who are occupationally exposed; entry into and transmission via hospitals or other health care facilities; or spread via environmental routes including air, water, or manure in areas in proximity to live animal farms or crop farms where manure has been used as a fertilizer (Fig. 1). While methicillin resistance has been the most commonly investigated phenomenon and will be the main topic of this review, resistance to any of these antibiotics can occur and can potentially be a threat to successful treatment of S. aureus infections and therefore to human health outcomes. As such, my research group and others have begun to look more broadly at any S. aureus present on farms, including those that may be susceptible to methicillin but resistant to other antibiotics.