Genomics to detect transmission of livestock-associated methicillin-resistant Staphylococcus aureus from UK pigs in abattoirs during slaughter.

BACKGROUND: Livestock-associated MRSA (LA-MRSA) transmission/cross-contamination can occur at abattoir through colonized pigs, increasing occupational hazards and health concerns for workers. To assess this risk we used genomics to identify LA-MRSA lineages present in batches of pigs sent to slaughter and distribution of clones. METHODS: WGS was performed on 85 LA-MRSA previously isolated from six abattoirs from 105 batches of pigs sent from 100 UK farms. spa typing and MLST were performed on all isolates. A mashtree tree was constructed to compare genomes of the LA-MRSA with 1281 global isolates from livestock and humans. A phylogenetic tree and pairwise SNP distance matrices were built from whole genomes of 109 isolates closest to those from abattoirs to compare evolutionary relationships and identify clones. RESULTS: All abattoir isolates belonged to CC398 and were mainly of spa type t011, although other spa types were present. Phylogenetic analysis confirmed the abattoir isolates were most closely related to each other and to pig LA-MRSA from across Europe, indicating a common evolutionary origin with related lineages colonizing UK pigs.Comparison of genomes using SNPs suggested between one and four clones were transferring between pigs from different batches. Transmission likely occurred on farm premises, during transportation, and/or within abattoirs through contact with contaminated surfaces in lairage or post-stunning. CONCLUSIONS: Genomics forensically identified related isolates/clones circulating in pigs at slaughter, showing contamination occurs often. Results suggest that further genomic tracking will identify hotspots, and improvements in measures such as biosecurity and disinfection will help reduce risk for workers.

Pathogenicity island-directed transfer of unlinked chromosomal virulence genes.

In recent decades, the notorious pathogen Staphylococcus aureus has become progressively more contagious, more virulent, and more resistant to antibiotics. This implies a rather dynamic evolutionary capability, representing a remarkable level of genomic plasticity, most probably maintained by horizontal gene transfer. Here we report that the staphylococcal pathogenicity islands have a dual role in gene transfer: they not only mediate their own transfer, but they can independently direct the transfer of unlinked chromosomal segments containing virulence genes. While transfer of the island itself requires specific helper phages, transfer of unlinked chromosomal segments does not, so potentially any pac-type phage will serve. These results reveal that SaPIs can increase the horizontal exchange of accessory genes associated with disease and may shape pathogen genomes beyond the confines of their attachment sites.

Decolonization to Reduce Postdischarge Infection Risk among MRSA Carriers.

BACKGROUND: Hospitalized patients who are colonized with methicillin-resistant Staphylococcus aureus (MRSA) are at high risk for infection after discharge. METHODS: We conducted a multicenter, randomized, controlled trial of postdischarge hygiene education, as compared with education plus decolonization, in patients colonized with MRSA (carriers). Decolonization involved chlorhexidine mouthwash, baths or showers with chlorhexidine, and nasal mupirocin for 5 days twice per month for 6 months. Participants were followed for 1 year. The primary outcome was MRSA infection as defined according to Centers for Disease Control and Prevention (CDC) criteria. Secondary outcomes included MRSA infection determined on the basis of clinical judgment, infection from any cause, and infection-related hospitalization. All analyses were performed with the use of proportional-hazards models in the per-protocol population (all participants who underwent randomization, met the inclusion criteria, and survived beyond the recruitment hospitalization) and as-treated population (participants stratified according to adherence). RESULTS: In the per-protocol population, MRSA infection occurred in 98 of 1063 participants (9.2%) in the education group and in 67 of 1058 (6.3%) in the decolonization group; 84.8% of the MRSA infections led to hospitalization. Infection from any cause occurred in 23.7% of the participants in the education group and 19.6% of those in the decolonization group; 85.8% of the infections led to hospitalization. The hazard of MRSA infection was significantly lower in the decolonization group than in the education group (hazard ratio, 0.70; 95% confidence interval [CI], 0.52 to 0.96; P=0.03; number needed to treat to prevent one infection, 30; 95% CI, 18 to 230); this lower hazard led to a lower risk of hospitalization due to MRSA infection (hazard ratio, 0.71; 95% CI, 0.51 to 0.99). The decolonization group had lower likelihoods of clinically judged infection from any cause (hazard ratio, 0.83; 95% CI, 0.70 to 0.99) and infection-related hospitalization (hazard ratio, 0.76; 95% CI, 0.62 to 0.93); treatment effects for secondary outcomes should be interpreted with caution owing to a lack of prespecified adjustment for multiple comparisons. In as-treated analyses, participants in the decolonization group who adhered fully to the regimen had 44% fewer MRSA infections than the education group (hazard ratio, 0.56; 95% CI, 0.36 to 0.86) and had 40% fewer infections from any cause (hazard ratio, 0.60; 95% CI, 0.46 to 0.78). Side effects (all mild) occurred in 4.2% of the participants. CONCLUSIONS: Postdischarge MRSA decolonization with chlorhexidine and mupirocin led to a 30% lower risk of MRSA infection than education alone. (Funded by the AHRQ Healthcare-Associated Infections Program and others; ClinicalTrials.gov number, NCT01209234 .).

Mycotic Aneurysm of Internal Carotid Artery Secondary to Livestock-associated Methicillin-resistant Staphylococcus Aureus Clonal Complex CC398.

The aim of this article is to present a case of mycotic aneurysm of internal carotid artery secondary to livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) treated with resection and common-to-internal carotid artery bypass with autologous vein graft in a male pig farmer. A 69-year-old man, pig farmer, with recent dental extraction was admitted with a right cervical pulsatile mass, dysphonia, pain, leukocytosis and elevated C-reactive protein (CRP). Ultrasonography (US) and computed tomography angiography (CTA) showed a 3.9 × 4.5 cm mycotic aneurysm of right internal carotid artery with hypermetabolic uptake in positron emission tomography (PET) scan. Resection of the mycotic aneurysm and a common-to-internal carotid artery bypass with major saphenous vein graft were performed. LA-MRSA clonal complex (CC) 398 was detected in intraoperative samples and antibiotic therapy was changed according to antibiogram. Patient was discharged at the seventh postoperative day and received antibiotic therapy for 6 weeks. US 12 months later showed patency of the bypass without collections. Mycotic aneurysms of internal carotid artery are very infrequent. MRSA isolation is rare, and to the best of our knowledge this is the first case caused by multi-drug resistant LA-MRSA CC398. The treatment includes mycotic aneurysm resection and reconstruction with venous graft bypass plus intensive antibiotic therapy.

Quantifying the transmission dynamics of MRSA in the community and healthcare settings in a low-prevalence country.

Methicillin-resistant Staphylococcus aureus (MRSA) is a primarily nosocomial pathogen that, in recent years, has increasingly spread to the general population. The rising prevalence of MRSA in the community implies more frequent introductions in healthcare settings that could jeopardize the effectiveness of infection-control procedures. To investigate the epidemiological dynamics of MRSA in a low-prevalence country, we developed an individual-based model (IBM) reproducing the population's sociodemography, explicitly representing households, hospitals, and nursing homes. The model was calibrated to surveillance data from the Norwegian national registry (2008-2015) and to published household prevalence data. We estimated an effective reproductive number of 0.68 (95% CI 0.47-0.90), suggesting that the observed rise in MRSA infections is not due to an ongoing epidemic but driven by more frequent acquisitions abroad. As a result of MRSA importations, an almost twofold increase in the prevalence of carriage was estimated over the study period, in 2015 reaching a value of 0.37% (0.25-0.54%) in the community and 1.11% (0.79-1.59%) in hospitalized patients. Household transmission accounted for half of new MRSA acquisitions, indicating this setting as a potential target for preventive strategies. However, nosocomial acquisition was still the primary source of symptomatic disease, which reinforces the importance of hospital-based transmission control. Although our results indicate little reason for concern about MRSA transmission in low-prevalence settings in the immediate future, the increases in importation and global circulation highlight the need for coordinated initiatives to reduce the spread of antibiotic resistance worldwide.

Dynamics of the Human Nasal Microbiota and Staphylococcus aureus CC398 Carriage in Pig Truck Drivers across One Workweek.

Drivers of pig trucks constitute a potential route of human transmission of livestock-associated methicillin-resistant Staphylococcus aureus clonal complex 398 (LA-MRSA CC398). In this study, we determined MRSA prevalence in pig truck drivers (n = 47) and monitored the nasal microbiota of 9 drivers 3 times daily throughout 1 workweek (n = 113 samples) and compared it to that of their spouses (n = 25 samples from 6 spouses) and 89 nonexposed subjects. S. aureus isolates (n = 232) derived from a subset of nasal and truck samples were whole-genome sequenced. The nasal alpha diversity of drivers in the beginning of the workday was lower than that of nonexposed subjects. During the workday, it increased significantly. Similarly, the drivers' nasal composition shifted during the workday, becoming increasingly different from that of their spouses and nonexposed individuals. Clustering into community state types (CSTs) revealed frequent switches from either S. aureus- or Corynebacterium-dominated CSTs in the mornings to a Psychrobacter-dominated CST during the workday. Six intermittent MRSA carriers were mostly MRSA negative in the mornings, and their nasal microbiota resembled that of nonexposed subjects. When acquiring MRSA during the workday, they switched to the Psychrobacter-dominated CST. In contrast, the nasal microbiota of two persistent MRSA carriers was dominated by staphylococci. In conclusion, we show that the nasal microbiota of pig truck drivers is very dynamic, undergoes drastic changes during workdays, and differs from that of nonexposed subjects even before pig contact. MRSA-carrying drivers may eventually introduce MRSA into the community and health care facilities. Carriage dynamics, however, showed that for most drivers, CC398 MRSA is rapidly lost and only rarely causes transmission to spouses. IMPORTANCE In Denmark, the number of human methicillin-resistant Staphylococcus aureus (MRSA) cases has increased dramatically since the early 2000s, starting from imported cases and spreading in the community. However, today, approximately one-third of all new cases are attributed to livestock-associated MRSA clonal complex 398 (LA-MRSA CC398). This mirrors the increase in pig farms, of which 95% are now positive for LA-MRSA, and this has been caused mainly by three dominant lineages enriched for a number of key antimicrobial resistance genes. Although most human LA-MRSA CC398 infections in Denmark are linked to livestock contact, still up to one-third are not. Pig truck drivers constitute a previously understudied occupation group which may transmit LA-MRSA CC398 to household members, the community, and hospitals. In this study, we demonstrate dramatic work-related changes in the nasal microbiota of pig truck drivers, as well as in their carriage of LA-MRSA CC398. However, they likely do not constitute an important reservoir for LA-MRSA CC398 dissemination.

Protective effect of SARS-CoV-2 preventive measures against ESKAPE and Escherichia coli infections.

BACKGROUND/OBJECTIVES: We investigated whether behavioral precautions adopted during Coronavirus disease (COVID-19) pandemic also influenced the spreading and multidrug resistance (MDR) of ESKAPEEc (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii [AB], Pseudomonas aeruginosa, Enterobacter spp and Escherichia Coli, [EC]) among Intensive Care Unit (ICU) patients. SUBJECTS/METHODS: We performed a single-center retrospective study in adult patients admitted to our COVID-19-free surgical ICU. Only patients staying in ICU for more than 48 hours were included. The ESKAPEEc infections recorded during the COVID-19 period (June 1, 2020 - February 28, 2021) and in the corresponding pre-pandemic period (June 1, 2019 - February 28, 2020) were compared. An interrupted time series analysis was performed to rule out possible confounders. RESULTS: Overall, 173 patients in the COVID-19 period and 132 in the pre-COVID-19 period were investigated. The ESKAPEEc infections were documented in 23 (13.3%) and 35 (26.5%) patients in the pandemic and the pre-pandemic periods, respectively (p = 0.005). Demographics, diagnosis, comorbidities, type of surgery, Simplified Acute Physiology Score II, length of mechanical ventilation, hospital and ICU length of stay, ICU death rate, and 28-day hospital mortality were similar in the two groups. In comparison with the pre-pandemic period, no AB was recorded during COVID-19 period, (p = 0.017), while extended-spectrum beta-lactamase-producing EC infections significantly decreased (p = 0.017). Overall, the ESKAPEEc isolates during pandemic less frequently exhibited multidrug-resistant (p = 0.014). CONCLUSIONS: These findings suggest that a robust adherence to hygiene measures together with human contact restrictions in a COVID-19 free ICU might also restrain the transmission of ESKAPEEc pathogens.

Vertical transmission of methicillin-resistant Staphylococcus aureus at delivery and its clinical impact: An observational, prospective cohort study.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) infection has a significant clinical impact on both pregnant women and neonates. The aim of this study was to assess accurately the vertical transmission rate of MRSA and its clinical impacts on both pregnant mothers and neonates. MATERIAL AND METHODS: We conducted a prospective observational cohort study of 898 pregnant women who were admitted to our department and 905 neonates from August 2016 to December 2017. MRSA was cultured from nasal and vaginal samples taken from the mothers at enrollment and from nasal and umbilical surface swabs taken from neonates at the time of delivery. We examined the vertical transmission rate of MRSA in mother-neonate pairs. We used multivariable logistic regression to identify risk factors for maternal MRSA colonization and maternal/neonatal adverse outcomes associated with maternal MRSA colonization. RESULTS: The prevalence of maternal MRSA colonization was 6.1% (55 of 898) at enrollment. The independent risk factors were multiparity and occupation (healthcare provider) (odds ratio [OR] 2.35, 95% confidence interval [CI] 1.25-4.42 and OR 2.58, 95% CI 1.39-4.79, respectively). The prevalence of neonatal MRSA colonization at birth was 12.7% (7 of 55 mother-neonate pairs) in the maternal MRSA-positive group, whereas it was only 0.12% (one of 843 pairs) in the maternal MRSA-negative group (OR 121, 95% CI 14.6-1000). When maternal vaginal samples were MRSA-positive, vertical transmission was observed in four of nine cases (44.4%) in this study. Skin and soft tissue infections developed more frequently in neonates in the maternal MRSA-positive group than in the MRSA-negative group (OR 7.47, 95% CI 2.50-22.3). CONCLUSIONS: The prevalence of MRSA in pregnant women was approximately 6%. Vertical transmission caused by maternal vaginal MRSA colonization was observed in four of nine cases (44.4%). Although our study includes a limited number of maternal MRSA positive cases, the vertical transmission of MRSA may occur in up to 44% of neonates of mothers with vaginal MRSA colonization. Maternal MRSA colonization may be associated with increased development of skin and soft tissue infections in neonates via vertical transmission.

Whole-Genome Analysis of Livestock-Associated Methicillin-Resistant Staphylococcus aureus Sequence Type 398 Strains Isolated From Patients With Bacteremia in China.

Sequence type (ST) 398 is the most prevalent clone of livestock-associated methicillin-resistant Staphylococcus aureus (MRSA). To evaluate the molecular characteristics and phylogeny of Chinese ST398 isolates, 4 MRSA ST398 strains and 4 methicillin-susceptible S. aureus (MSSA) ST398 strains were collected from patients with bacteremia at 6 teaching hospitals in China between 1999 and 2016. Moreover, 689 ST398 genome sequences were downloaded from the GenBank database for comparison. The 4 MRSA ST398 strains were resistant to ß-lactam antibiotics, and 2 strains were also resistant to erythromycin. Among the 4 MSSA ST398 strains, 2 strains displayed multidrug resistance (MDR) and were resistant to penicillin, erythromycin, tetracycline, and gentamicin. The accessory genome of MSSA ST398 was more diverse than that of MRSA ST398. All 4 MRSA ST398 strains carried type V staphylococcal cassette chromosome mec elements; however, MSSA ST398 carried more resistance genes than MRSA ST398. These 4 MRSA ST398 strains carried hemolysin, along with virulence genes associated with immune invasion and protease. Phylogenic analysis showed that the 4 MRSA ST398 strains clustered in 1 clade. The global ST398 phylogeny showed that ST398 was divided into an animal clade and a human clade, and the ST398 strains of this study clustered in the human clade. A small number of human strains were also present in the animal clade and vice versa, suggesting transmission of ST398 between animals and humans. In conclusion, livestock-associated MRSA ST398 has caused severe infections in Chinese hospitals, and it should therefore be paid more attention to and monitored.

Phage-Mediated Immune Evasion and Transmission of Livestock-Associated Methicillin-Resistant Staphylococcus aureus in Humans.

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) can acquire phage-encoded immune modulators, such as the immune evasion cluster (IEC), which protects bacteria from components of the human innate immune system, and the enzyme TarP, which protects against antibody-mediated immune recognition. We used whole-genome sequencing and epidemiologic investigations to study the effects of IEC- and tarP-harboring phages on household transmission of LA-MRSA in North Denmark Region during 2004-2011. We reviewed information about all patients throughout Denmark who experienced LA-MRSA infection during 2007-2018 to determine whether IEC is associated with increased spread into the general population. Horizontal acquisition of IEC in the human host was associated with increased household transmission of LA-MRSA and spillover into the community and healthcare settings, whereas we found no evidence to suggest that IEC-positive LA-MRSA isolates have become self-sustainable in the general population. By contrast, TarP did not seem to influence household transmission of LA-MRSA.

Local and Transboundary Transmissions of Methicillin-Resistant Staphylococcus aureus Sequence Type 398 through Pig Trading.

Livestock-associated methicillin-resistant Staphylococcus aureus sequence type (ST) 398 (LA-MRSA ST398) is a genetic lineage for which pigs are regarded as the main reservoir. An increasing prevalence of LA-MRSA ST398 has been reported in areas with high livestock density throughout Europe. In this study, we investigated the drivers contributing to the introduction and spread of LA-MRSA ST398 through the pig farming system in southern Italy. Whole-genome sequencing (WGS) of LA-MRSA ST398 isolates collected in 2018 from pigs (n = 53) and employees (n = 14) from 10 farms in the Calabria region of Italy were comparatively analyzed with previously published WGS data from Italian ST398 isolates (n = 45), an international ST398 reference collection (n = 89), and isolates from Danish pig farms (n = 283), which are the main suppliers of pigs imported to Italy. Single-nucleotide polymorphisms (SNP) were used to infer isolate relatedness, and these data were used together with data from animal trading to identify factors contributing to LA-MRSA ST398 dissemination. The analyses support the existence of two concurrent pathways for the spread of LA-MRSA ST398 in southern Italy: (i) multiple introductions of LA-MRSA ST398 through the import of colonized pigs from other European countries, including Denmark and France, and (ii) the spread of distinct clones dependent on local trading of pigs between farms. Phylogenetically related Italian and Danish LA-MRSA ST398 isolates shared extensive similarities, including carriage of antimicrobial resistance genes. Our findings highlight the potential risk of transboundary transmission of antimicrobial-resistant bacterial clones with a high zoonotic potential during import of pigs from countries with high LA-MRSA prevalence.IMPORTANCE Over the past decade, livestock-associated methicillin-resistant Staphylococcus aureus sequence type 398 (LA-MRSA ST398) has spread among pig holdings throughout Europe, in parallel with the increased incidence of infections among humans, especially in intensive pig farming regions. Despite the growing prevalence of LA-MRSA ST398 in Italian pig farms, the transmission dynamics of this clone in Italy remains unclear. This work provides genome-based evidence to suggest transboundary LA-MRSA ST398 transmission through trading of colonized pigs between European countries and Italy, as well as between farms in the same Italian region. Our findings show that both international trading and local trading of colonized pigs are important factors contributing to the global spread of LA-MRSA ST398 and underscore the need for control measures on and off the farm to reduce the dissemination of this zoonotic pathogen.

Spread of clonal linezolid-resistant Staphylococcus epidermidis in an intensive care unit associated with linezolid exposure.

The aim of the study was to determine factors associated with spread of linezolid (LNZ)-resistant Staphylococcus epidermidis isolates in a surgical intensive care unit (ICU). A case-control study was conducted in one French adult surgical ICU. From January 2012 to December 2016, patients with at least a single positive LNZ-resistant S. epidermidis blood culture were matched to control with LNZ-susceptible S. epidermidis blood culture in a 1:4 manner. Cases were compared to controls regarding baseline clinical characteristics and LNZ exposure before positive blood culture. Bacterial isolates were genotyped by using pulsed-field gel electrophoresis (PFGE) and MLST. We identified 13 LNZ-resistant S. epidermidis isolates, 1 in 2012, 3 in 2014, 6 in 2015, and 3 in 2016. LNZ use increased steadily from 8 DDDs/100 patient days in 2010 to 19 in 2013 and further decrease by more of 50% in 2015 and 2016. The only independent risk factors associated to LNZ-resistant S. epidermidis isolation were length of stay in ICU before infection (OR 1.45; 95% CI 1.07-1.98), prior exposure to LNZ (OR 109; 95% CI 3.9-3034), and Charlson comorbidities score (OR 3.19; 95% CI 1.11-9.14). PFGE typing showed that all LNZ-resistant isolates were clonal belonging to ST2 and that LNZ-susceptible isolates were highly diverse. We report herein that previous exposure to LNZ substantially increased the risk of occurrence of LNZ resistance in S. epidermidis even in the case of clonal spread of LNZ-resistant isolates. These findings highlight the need for reducing the use of LNZ to preserve its efficacy in the future.

Costs and Benefits of Alternative Strategies to Control the Spread of Livestock-Acquired Methicillin-Resistant Staphylococcus Aureus From Pig Production.

BACKGROUND: Livestock-acquired methicillin-resistant Staphylococcus aureus (LA-MRSA) is a concern in healthcare and a political priority in some countries. OBJECTIVE: This study investigates the net societal costs of 2 alternative strategies for controlling LA-MRSA in Denmark: (1) eradicating LA-MRSA in all pig housing units, and (2) containing LA-MRSA within the units. METHODS: Benefits and costs are considered for affected economic sectors: healthcare, pig production, pig-related industries, and public administration. RESULTS: The cost to society of eradication is estimated at €2.3 to €2.5 billion (present value). Containment will cost €55 to €93 million. For both strategies, the main cost lies in primary pig production-for containment this is mainly due to establishing and operating anterooms and shower rooms, and for eradication it is due to production losses, loss of genetic resources, and costs of cleaning and disinfection. CONCLUSION: Compared with these costs, health economic benefits are moderate for both strategies. Containment is superior to eradication when measured by a benefit-cost ratio.

Quantifying the relative impact of contact heterogeneity on MRSA transmission in ICUs - a modelling study.

BACKGROUND: An efficient surface cleaning strategy would first target cleaning to surfaces that make large contributions to the risk of infections. METHODS: In this study, we used data from the literature about methicillin-resistant Staphylococcus aureus (MRSA) and developed an ordinary differential equations based mathematical model to quantify the impact of contact heterogeneity on MRSA transmission in a hypothetical 6-bed intensive care unit (ICU). The susceptible patients are divided into two types, these who are cared by the same nurse as the MRSA infected patient (Type 1) and these who are not (Type 2). RESULTS: The results showed that the mean MRSA concentration on three kinds of susceptible patient nearby surfaces was significantly linearly associated with the hand-touch frequency (p < 0.05). The noncompliance of daily cleaning on patient nearby high-touch surfaces (HTSs) had the most impact on MRSA transmission. If the HTSs were not cleaned, the MRSA exposure to Type 1 and 2 susceptible patients would increase 118.4% (standard deviation (SD): 33.0%) and 115.4% (SD: 30.5%) respectively. The communal surfaces (CSs) had the least impact, if CSs were not cleaned, the MRSA exposure to Type 1 susceptible patient would only increase 1.7% (SD: 1.3). The impact of clinical equipment (CE) differed largely for two types of susceptible patients. If the CE was not cleaned, the exposure to Type 1 patients would only increase 8.4% (SD: 3.0%), while for Type 2 patients, it can increase 70.4% (SD: 25.4%). CONCLUSIONS: This study provided a framework to study the pathogen concentration dynamics on environmental surfaces and quantitatively showed the importance of cleaning patient nearby HTSs on controlling the nosocomial infection transmission via contact route.

Low prevalence of livestock-associated methicillin-resistant Staphylococcus aureus clonal complex 398 and mecC MRSA among human isolates in North-West England.

AIMS: Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is an important public health problem in many countries. Despite reports of such isolates being found in both animals and humans in the United Kingdom few data are available on the prevalence in humans of such isolates. A prevalence study was therefore undertaken in the north-west of England. METHODS AND RESULTS: One thousand two hundred and forty-two human MRSA isolates collected during 2015 were screened by PCR to detect two of the major forms of LA-MRSA: clonal complex (CC)398 and mecC MRSA. Isolates identified were further characterized by antimicrobial susceptibility testing and whole-genome sequencing using HiSeq technology. A single mecC MRSA isolate and three CC398 LA-MRSA were identified among the isolates screened. All four isolates were from MRSA screening. A phylogenetic analysis, including previously sequenced isolates from the United Kingdom, provided strong evidence for the genomic and epidemiological linkage between a pair of animal and human isolates of CC398 LA-MRSA in England. These data are indicative of animal and humans isolates of CC398 LA-MRSA being involved in the same transmission network and is the first demonstration of such closely linked animal and human isolates of this lineage in the UK. CONCLUSIONS: The study indicates there is a low prevalence of CC398 LA-MRSA and mecC MRSA among MRSA isolates in the sampled population. SIGNIFICANCE AND IMPACT OF THE STUDY: While the study demonstrates that LA-MRSA were rare among human MRSA isolates in the sampled population, the data provide a baseline for the future surveillance of what is a significant public health challenge in some regions. The demonstration of linked human and animal isolates of CC398 LA-MRSA, supported by genomic and epidemiological data, reinforces the need for such surveillance and for continued awareness of the risks that LA-MRSA may pose in the UK.

Origin, evolution, and global transmission of community-acquired Staphylococcus aureus ST8.

USA300 is a pandemic clonal lineage of hypervirulent, community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) with specific molecular characteristics. Despite its high clinical relevance, the evolutionary origin of USA300 remained unclear. We used comparative genomics of 224 temporal and spatial diverse S. aureus isolates of multilocus sequence type (ST) 8 to reconstruct the molecular evolution and global dissemination of ST8, including USA300. Analyses of core SNP diversity and accessory genome variations showed that the ancestor of all ST8 S. aureus most likely emerged in Central Europe in the mid-19th century. From here, ST8 was exported to North America in the early 20th century and progressively acquired the USA300 characteristics Panton-Valentine leukocidin (PVL), SCCmec IVa, the arginine catabolic mobile element (ACME), and a specific mutation in capsular polysaccharide gene cap5E Although the PVL-encoding phage ϕSa2USA was introduced into the ST8 background only once, various SCCmec types were introduced to ST8 at different times and places. Starting from North America, USA300 spread globally, including Africa. African USA300 isolates have aberrant spa-types (t112, t121) and form a monophyletic group within the clade of North American USA300. Large parts of ST8 methicillin-susceptible S. aureus (MSSA) isolated in Africa represent a symplesiomorphic group of ST8 (i.e., a group representing the characteristics of the ancestor), which are rarely found in other world regions. Isolates previously discussed as USA300 ancestors, including USA500 and a "historic" CA-MRSA from Western Australia, were shown to be only distantly related to recent USA300 clones.

The first outbreak of methicillin-resistant Staphylococcus aureus in dairy cattle in Poland with evidence of on-farm and intrahousehold transmission.

Staphylococcus aureus is a widely recognized pathogen responsible for many serious diseases in both humans and animals. It is also one of the major causative agents of bovine mastitis. Methicillin-resistant S. aureus (MRSA), although relatively rare in this pathology, has been increasingly reported in livestock animals, mainly in pigs, but also cattle, sheep, and poultry. The recent emergence of livestock-associated (LA-)MRSA is cause for an immediate public health concern due to the risk of zoonotic transmission to humans, and is of particular concern for people who work in animal husbandry or have prolonged contact with livestock animals. This study reports on the first LA-MRSA outbreak in dairy cattle and the first probable case of MRSA transmission between humans and cows in Poland. A single dairy farm located in Eastern Poland was monitored on a regular basis for the occurrence of mastitis. Over a 1-yr study period, 717 quarter-milk samples from 583 cows were collected and examined microbiologically. A total of 5 MRSA isolates from as many cows with subclinical mastitis were cultured. They all belonged to the same outbreak, given a 2-mo time window in which they were identified. During the outbreak, 24 oral and nasal swabs were voluntarily taken from 6 people: a milker, a veterinarian, and 4 members of the veterinarian's family. Eight swabs from a milker, veterinarian, and 2 family members yielded positive MRSA cultures. All MRSA isolates were genotyped with a combination of multiple-locus variable number tandem repeat analysis, multilocus sequence typing, and staphylococcal protein A gene (spa) typing. Eleven bovine (n = 5; 5 cases) and human (n = 6; 4 cases) isolates showed an identical drug-susceptibility profile and were indistinguishable upon multiple-locus variable number tandem repeat analysis (pattern A), multilocus sequence typing (ST398) and spa (t034) typing. The results of this study provide the evidence of transmission of MRSA between humans and cows, and between humans in the family setting. This work, despite being a preliminary investigation, underscores the risk of intra- and interspecies transmission of LA-MRSA and urges enhancement of the existing biosecurity measures aimed at preventing MRSA (and other milk pathogens) spread at both the farm- and household levels.

Effect of Treating Parents Colonized With Staphylococcus aureus on Transmission to Neonates in the Intensive Care Unit: A Randomized Clinical Trial.

Importance: Staphylococcus aureus is a leading cause of health care-associated infections in the neonatal intensive care unit (NICU). Parents may expose neonates to S aureus colonization, a well-established predisposing factor to invasive S aureus disease. Objective: To test whether treating parents with intranasal mupirocin and topical chlorhexidine compared with placebo would reduce transmission of S aureus from parents to neonates. Design, Setting, and Participants: Double-blinded randomized clinical trial in 2 tertiary NICUs in Baltimore, Maryland. Neonates (n = 236) with S aureus-colonized parent(s) were enrolled. The study period was November 7, 2014, through December 13, 2018. Interventions: Parents were assigned to intranasal mupirocin and 2% chlorhexidine-impregnated cloths (active treatment, n = 117) or petrolatum intranasal ointment and nonmedicated soap cloths (placebo, n = 119) for 5 days. Main Outcomes and Measures: The primary end point was concordant S aureus colonization by 90 days, defined as neonatal acquisition of an S aureus strain that was the same strain as a parental strain at time of screening. Secondary outcomes included neonatal acquisition of any S aureus strain and neonatal S aureus infections. Results: Among 236 randomized neonates, 208 were included in the analytic sample (55% male; 76% singleton births; mean birth weight, 1985 g [SD, 958 g]; 76% vaginal birth; mean parent age, 31 [SD, 7] years), of whom 18 were lost to follow-up. Among 190 neonates included in the analysis, 74 (38.9%) acquired S aureus colonization by 90 days, of which 42 (56.8%) had a strain concordant with a parental baseline strain. In the intervention and placebo groups, 13 of 89 neonates (14.6%) and 29 of 101 neonates (28.7%), respectively, acquired concordant S aureus colonization (risk difference, -14.1% [95% CI, -30.8% to -3.9%]; hazard ratio [HR], 0.43 [95.2% CI, 0.16 to 0.79]). A total of 28 of 89 neonates (31.4%) in the intervention group and 46 of 101 (45.5%) in the control group acquired any S aureus strain (HR, 0.57 [95% CI, 0.31 to 0.88]), and 1 neonate (1.1%) in the intervention group and 1 neonate (1.0%) in the control group developed an S aureus infection before colonization. Skin reactions in parents were common (4.8% intervention, 6.2% placebo). Conclusions and Relevance: In this preliminary trial of parents colonized with S aureus, treatment with intranasal mupirocin and chlorhexidine-impregnated cloths compared with placebo significantly reduced neonatal colonization with an S aureus strain concordant with a parental baseline strain. However, further research is needed to replicate these findings and to assess their generalizability. Trial Registration: ClinicalTrials.gov Identifier: NCT02223520.

Optimizing Contact Precautions to Curb the Spread of Antibiotic-resistant Bacteria in Hospitals: A Multicenter Cohort Study to Identify Patient Characteristics and Healthcare Personnel Interactions Associated With Transmission of Methicillin-resistant Staphylococcus aureus.

BACKGROUND: Healthcare personnel (HCP) acquire antibiotic-resistant bacteria on their gloves and gowns when caring for intensive care unit (ICU) patients. Yet, contact precautions for patients with methicillin-resistant Staphylococcus aureus (MRSA) remains controversial despite existing guidelines. We sought to understand which patients are more likely to transfer MRSA to HCP and to identify which HCP interactions are more likely to lead to glove or gown contamination. METHODS: This was a prospective, multicenter cohort study of cultured HCP gloves and gowns for MRSA. Samples were obtained from patients' anterior nares, perianal area, and skin of the chest and arm to assess bacterial burden. RESULTS: Among 402 MRSA-colonized patients with 3982 interactions, we found that HCP gloves and gowns were contaminated with MRSA 14.3% and 5.9% of the time, respectively. Contamination of either gloves or gowns occurred in 16.2% of interactions. Contamination was highest among occupational/physical therapists (odds ratio [OR], 6.96; 95% confidence interval [CI], 3.51, 13.79), respiratory therapists (OR, 5.34; 95% CI, 3.04, 9.39), and when any HCP touched the patient (OR, 2.59; 95% CI, 1.04, 6.51). Touching the endotracheal tube (OR, 1.75; 95% CI, 1.38, 2.19), bedding (OR, 1.43; 95% CI, 1.20, 1.70), and bathing (OR, 1.32; 95% CI, 1.01, 1.75) increased the odds of contamination. We found an association between increasing bacterial burden on the patient and HCP glove or gown contamination. CONCLUSIONS: Gloves and gowns are frequently contaminated with MRSA in the ICU. Hospitals may consider using fewer precautions for low-risk interactions and more for high-risk interactions and personnel.

Development and Validation of a Clinical Prediction Rule to Predict Transmission of Methicillin-Resistant Staphylococcus aureus in Nursing Homes.

The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonization among nursing home residents is high. Health-care workers (HCWs) often serve as a vector in MRSA transmission. The ability to identify residents who are likely to transmit MRSA to HCWs' hands and clothing during clinical care is important so that infection control measures, such as Contact Precautions, can be employed. Using data on demographic and clinical characteristics collected from residents of community nursing homes in Maryland and Michigan between 2012 and 2014, we developed a clinical prediction rule predicting the probability of MRSA transmission to HCWs' gowns. We externally validated this model in a cohort of Department of Veterans Affairs nursing home residents from 7 states between 2012 and 2016. The prediction model, which included sex, race, resident dependency on HCWs for care, the presence of any medical device, diabetes mellitus, and chronic skin breakdown, showed good performance (C statistic = 0.70; sensitivity = 76%, specificity = 49%) in the development set. The decision curve analysis indicated that this model has greater clinical utility than use of a nares surveillance culture for MRSA colonization, which is current clinical practice for placing hospital inpatients on Contact Precautions. The prediction rule demonstrated less utility in the validation cohort, suggesting that a separate rule should be developed for residents of Veterans Affairs nursing homes.