Methicillin-resistant Staphylococcus aureus in animals

Methicillin-resistant Staphylococcus aureus (MRSA) is a critically important human pathogen that is also an emerging concern in veterinary medicine and animal agriculture. It is present in a wide range of animal species, including dogs, cats, rabbits, horses, cattle, pigs, poultry, and exotic species, both as a cause of infection and in healthy carriers. Identification of MRSA in various species and in food has led to concerns about the roles of animals, both pets and livestock, in the epidemiology of MRSA infection and colonization in humans. There is evidence of the role of food animals in human MRSA infections in some countries and of pets as a possible source of human infection. Some groups of individuals who work closely with animals, such as veterinarians, have high MRSA colonization rates. This article includes discussions of MRSA in human medicine, animals, and food, as well as its interspecies transmission, colonization, infection, strains, and affected populations. However, clear answers are lacking in many of these areas and limited studies may lead to premature conclusions. It is certain that animals are a source of human MRSA infection in some circumstances--but humans may also serve as sources of infection in animals. Changes in the epidemiology of MRSA in one species may be reflected in changes in other species. The true scope of MRSA in animals and its impact on human health are still only superficially understood, but it is clear that MRSA is a potentially important veterinary and public health concern that requires a great deal more study to enhance understanding and effective response.     

Antibiotic Resistance of Commensal Staphylococcus aureus and Coagulase-Negative Staphylococci in an International Cohort of Surgeons: A Prospective Point-Prevalence Study

Nasal colonization with antibiotic resistant bacteria represents both a risk factor for the colonized individual and their immediate contacts. Despite the fact that healthcare workers such as orthopedic surgeons are at a critical interface between the healthcare environment and an at-risk patient population, the prevalence of antibiotic resistant bacteria within the surgical profession remains unclear. This study offers a snapshot of the rate of nasal colonization of orthopedic surgeons with multi-resistant staphylococci including methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCoNS). We performed a prospective, observational study obtained at a single time point in late 2013. The participants were active orthopedic, spine and head & neck surgeons from 75 countries. The prevalence of nasal carriage of the different bacteria and the corresponding 95% confidence interval were calculated. From a cohort of 1,166 surgeons, we found an average S. aureus nasal colonization rate of 28.0% (CI 25.4;30.6) and MRSA rate of 2.0% (CI 1.3;2.9), although significant regional variations were observed. The highest rates of MRSA colonization were found in Asia (6.1%), Africa (5.1%) and Central America (4.8%). There was no MRSA carriage detected within our population of 79 surgeons working in North America, and a low (0.6%) MRSA rate in 657 surgeons working in Europe. High rates of MRCoNS nasal carriage were also observed (21.4% overall), with a similar geographic distribution. Recent use of systemic antibiotics was associated with higher rates of carriage of resistant staphylococci. In conclusion, orthopedic surgeons are colonized by S. aureus and MRSA at broadly equivalent rates to the general population. Crucially, geographic differences were observed, which may be partially accounted for by varying antimicrobial stewardship practices between the regions. The elevated rates of resistance within the coagulase-negative staphylococci are of concern, due to the increasing awareness of their importance in hospital acquired and device-associated infection.     

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) colonization and infection in intravenous and inhalational opiate drug abusers

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant pathogen in hospital-acquired and community-acquired infections. We hypothesized that drug abuse is a risk factor for community-acquired MRSA (CA-MRSA) infection, and we employed a rapid multiplex PCR technique for MRSA identification. The study was conducted on MRSA isolates from 60 opiate addicts (intravenous and inhalational drug users) to detect the rate and location of MRSA colonization and infection among them in comparison to 60 non-addict patients and 15 healthy volunteer controls. The proportion of addicts with MRSA colonization (and/or infection) was significantly higher than non-addict patients with MRSA colonization. MRSA colonization was associated with infection in 58% of MRSA-colonized addicts. The MRSA nasal carriage in the addicts was significantly higher than MRSA carriage elsewhere, whether in the addicts group or in the non-addict patients group. Moreover, the nasopharyngeal carriage rate of MRSA among addicts was significantly higher than among the non-addict patients. Increasing the duration of addiction resulted in a significant increase in CA-MRSA colonization in opiate addicts. Both inhalational and intravenous drug use led to significant MRSA colonization in the addict population. In conclusion, this study demonstrated how drug abusers, a high-risk group for infections with MRSA, could be a source or a reservoir of CA-MRSA infection in the non-addict population.     

耐甲氧西林金黄色葡萄球菌在动物流行病学中的研究进展

葡萄球菌是动物中重要的机会性病原体,耐甲氧西林金黄色葡萄球菌（MRSA）因其多药耐药的特征日益成为动物和公众健康的主要威胁。由于动物与动物及人畜间存在相互传染的风险,在控制MRSA感染的整个体系中,分析MRSA在动物中的流行显得尤为重要。     

Colonization kinetics of different methicillin-resistant Staphylococcus aureus sequence types in pigs and host susceptibilities

In this study we investigated the kinetics of colonization, the host susceptibility and transmissibility of methicillin-resistant Staphylococcus aureus (MRSA) after nasal treatment of pigs with three different MRSA strains of distinctive clonal lineages (sequence type 398 [ST398], ST8, and ST9), and origin in weaning piglets. The colonization dose of 5.0 × 10(8) CFU/animal was determined in preliminary animal studies. A total of 57 piglets were randomly divided into four test groups and one control group. Each of three test groups was inoculated intranasally with either MRSA ST8, MRSA ST9, or MRSA ST398. The fourth group was a mixture of animals inoculated with MRSA ST398 and noninoculated "sentinel" animals. Clinical signs, the nasal, conjunctival, and skin colonization of MRSA, fecal excretion, and organ distribution of MRSA, as well as different environmental samples were examined. After nasal inoculation with MRSA piglets of all four test groups showed no clinical signs of an MRSA infection. MRSA was present on the nasal mucosa, skin, and conjunctiva in all four test groups, including sentinel animals. Likewise, fecal excretion and internal colonization of MRSA ST8, ST9, and ST398 could be shown in each group. However, fecal excretion and the colonization rate of the nasal mucosa with MRSA ST9 were significantly lower in the first days after infection than in test groups infected with ST8 and ST398. The results of this study suggest differences in colonization potential of the different MRSA types in pigs. Furthermore, colonization of lymph nodes (e.g., the ileocecal lymph node) with MRSA of the clonal lineage ST398 was demonstrated.     

Clinical Significance of Methicillin-Resistant Staphylococcus aureus Colonization on Hospital Admission: One-Year Infection Risk

Background

Methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization among inpatients is a well-established risk factor for MRSA infection during the same hospitalization, but the long-term risk of MRSA infection is uncertain. We performed a retrospective cohort study to determine the one-year risk of MRSA infection among inpatients with MRSA-positive nasal polymerase chain reaction (PCR) tests confirmed by positive nasal culture (Group 1), patients with positive nasal PCR but negative nasal culture (Group 2), and patients with negative nasal PCR (Group 3).

Methodology/Principal Findings

Subjects were adults admitted to a four-hospital system between November 1, 2006 and March 31, 2011, comprising 195,255 admissions. Patients underwent nasal swab for MRSA PCR upon admission; if positive, nasal culture for MRSA was performed; if recovered, MRSA was tested for Panton-Valentine Leukocidin (PVL). Outcomes included MRSA-positive clinical culture and skin and soft tissue infection (SSTI). Group 1 patients had a one-year risk of MRSA-positive clinical culture of 8.0% compared with 3.0% for Group 2 patients, and 0.6% for Group 3 patients (p<0.001). In a multivariable model, the hazard ratios for future MRSA-positive clinical culture were 6.52 (95% CI, 5.57 to 7.64) for Group 1 and 3.40 (95% CI, 2.70 to 4.27) for Group 2, compared with Group 3 (p<0.0001). History of MRSA and concurrent MRSA-positive clinical culture were significant risk factors for future MRSA-positive clinical culture. Group 1 patients colonized with PVL-positive MRSA had a one-year risk of MRSA-positive clinical culture of 10.1%, and a one-year risk of MRSA-positive clinical culture or SSTI diagnosis of 21.7%, compared with risks of 7.1% and 12.5%, respectively, for patients colonized with PVL-negative MRSA (p = 0.04, p = 0.005, respectively).

Conclusions/Significance

MRSA nasal colonization is a significant risk factor for future MRSA infection; more so if detected by culture than PCR. Colonization with PVL-positive MRSA is associated with greater risk than PVL-negative MRSA.     

Screening of <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> nasal strains isolated from medical students for toxin genes

Three hundred twenty-one students (156 students with no clinical exposure and 165 students with clinical exposure) were screened for nasal colonization by Staphylococcus aureus; 20.9% of students were S. aureus nasal carriers, and 40.3% of S. aureus isolates harbored toxin genes. The most prevalent genes were tst (15.0 %) and sec (13.4 %). Isolates with multiple genes were only found among clinical students (p = 0.045). Six of 11 PFGE clones were positive for toxin genes. Methicillin-resistant (MRSA) isolates were only detected in the clinical students (4.5 %). The exposure of students to the hospital environment neither radically increased S. aureus nasal carriage, nor the frequency of clinically important toxin gene presence, but it could have influenced the positive selection of toxigenic MRSA strains.     

Impact and control of methicillin-resistant Staphylococcus aureus (MRSA) in long-term care facilities

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a growing concern in long-term care facilities (LTCF). Epidemiologic studies performed in our area have shown high rates of MRSA colonization in elderly residents, and very high rates in some centres. However, the clinical impact of nasal MRSA colonization is often slight. Prevention of MRSA transmission in LTCF includes the application of simple preventive measures with proven effectiveness, such as hand washing, adequately covering of infected wounds, and proper use of antibiotics, without limiting the activities of colonized residents or carrying out active surveillance.     

Clonal Dynamics of Nasal Staphylococcus aureus and Staphylococcus pseudintermedius in Dog-Owning Household Members. Detection of MSSA ST398

The objective of this study was to investigate the dynamics of nasal carriage by Staphylococcus aureus (SA) and Staphylococcus pseudintermedius (SP) among healthy dog-owning household members involved in 7 previous index cases of suspected anthropozoonotic (n = 4) and zoonotic (n = 3) interspecies transmission [4 direct cases, identical SA (n = 3) or SP (n = 1) in owner and dog; three indirect, SP in owner (n = 2) or SA in dog (n = 1)]. Co-carriage with methicillin-resistant coagulase-negative staphylococci (MRCoNS) was also evaluated. Sixteen owners and 10 dogs were sampled once every three months for one year. In total, 50 SA and 31 SP were analysed by MLST, and SA also by spa typing. All isolates were subjected to ApaI/SmaI-PFGE and antimicrobial resistance and virulence profiles were determined. All index owners were persistent SA carriers in all direct-anthropozoonotic transmission cases, while only one dog was persistent SA carrier. Owner and dog exhibited a persistent SP carriage status in the direct-zoonotic transmission case. SP was maintained in the index human over time in one indirect-zoonotic transmission case. Only one SP was methicillin-resistant. SA belonged to genetic backgrounds of MRSA pandemic clones: CC45, CC121, CC30, CC5 and CC398. Three individuals carried a MSSA t1451-ST398 clone with the erm(T)-cadD/cadX resistance genes. SA or SP were persistently detected in the nasal cavity of 7 (43.8%) and 2 (12.5%) owners, and in one and 2 dogs, respectively. SA was recovered as the single species in 10 owners and in one dog; SP in 3 owners and 4 dogs; and both bacterial species in one owner and 4 dogs. Co-carriage of SA or SP with MRCoNS isolates was common (30.7%). This is the first study on the dynamics of nasal carriage of SA and SP in healthy pet-owning household members. Dog-contact may play a role in the staphylococcal species distribution of in-contact individuals.     

An Ex Vivo Porcine Nasal Mucosa Explants Model to Study MRSA Colonization

Staphylococcus aureus is an opportunistic pathogen able to colonize the upper respiratory tract and skin surfaces in mammals. Methicillin-resistant S. aureus ST398 is prevalent in pigs in Europe and North America. However, the mechanism of successful pig colonization by MRSA ST398 is poorly understood. To study MRSA colonization in pigs, an ex vivo model consisting of porcine nasal mucosa explants cultured at an air-liquid interface was evaluated. In cultured mucosa explants from the surfaces of the ventral turbinates and septum of the pig nose no changes in cell morphology and viability were observed up to 72 h. MRSA colonization on the explants was evaluated followed for three MRSA ST398 isolates for 180 minutes. The explants were incubated with 3×10⁸ CFU/ml in PBS for 2 h to allow bacteria to adhere to the explants surface. Next the explants were washed and in the first 30 minutes post adhering time, a decline in the number of CFU was observed for all MRSA. Subsequently, the isolates showed either: bacterial growth, no growth, or a further reduction in bacterial numbers. The MRSA were either localized as clusters between the cilia or as single bacteria on the cilia surface. No morphological changes in the epithelium layer were observed during the incubation with MRSA. We conclude that porcine nasal mucosa explants are a valuable ex vivo model to unravel the interaction of MRSA with nasal tissue.     

The occurrence and comparative phenotypic characteristics of Staphylococcus spp. from healthy and diseased, household and shelter dogs, based on routine biochemical diagnostic methods

To determine the staphylococcal colonization pattern in healthy and diseased dogs, living in two particular environments, a number of microbiological samples were taken. Overall, twenty dogs, either healthy or with infected skin lesions, were examined. In each case bacterial swabs were collected from the nasal mucosa, ear, perineum, lumbo-sacralis triangle, and from the infection sites if such were present. A total number of 104 isolates representing different staphylococcal species were isolated and identified using routine biochemical methods applied in diagnostic laboratories. Among 17 isolated staphylococcal species, Staphylococcus intermedius was the most common species isolated from both healthy or diseased dogs living either in animal shelter or household environments. The pattern of Staphylococcus sp. colonization differs considerably for animals living in the two tested habitats. In particular, S. aureus MRSA and MSSA isolates were detected only in infected skin lesion samples from animals that dwelled in the animal shelter. As could be expected, S. intermedius was found to be a predominant causative agent in canine skin infections. In our study, we demonstrated that S. intermedius in its carrier-state, inhabits mainly the mucosal membrane of the nasal vestibule. It was also found in the samples taken from the skin, the lumbo-sacralis triangle and perineum, but was rarely isolated from the ears.     

Intranasal application of S. epidermidis prevents colonization by methicillin-resistant Staphylococcus aureus in mice

Methicillin-resistant S. aureus emerged in recent decades to become a leading cause of infection worldwide. Colonization with MRSA predisposes to infection and facilitates transmission of the pathogen; however, available regimens are ineffective at preventing MRSA colonization. Studies of human nasal flora suggest that resident bacteria play a critical role in limiting S. aureus growth, and prompted us to query whether application of commensal resident bacteria could prevent nasal colonization with MRSA. We established a murine model system to study this question, and showed that mice nasally pre-colonized with S. epidermidis became more resistant to colonization with MRSA. Our study suggests that application of commensal bacteria with antibiotics could represent a more effective strategy to prevent MRSA colonization.     

Alarming Proportions of Methicillin-Resistant Staphylococcus aureus (MRSA) in Wound Samples from Companion Animals,Germany 2010–2012

Staphylococcus (S.) aureus is an important cause of wound infections in companion animals, and infections with methicillin-resistant S. aureus (MRSA) are of particular concern due to limited treatment options and their zoonotic potential. However, comparable epidemiological data on MRSA infections in dogs, cats and horses is scarce, also limiting the knowledge about possible links to MRSA isolates from human populations. To gain more knowledge about the occurrence and genotypic variation of MRSA among wound swabs of companion animal origin in Germany we performed a survey (2010–2012) including 5,229 samples from 1,170 veterinary practices. S. aureus was identified in 201 (5.8%) canine, 140 (12.2%) feline and 138 (22.8%) equine swabs from a total of 3,479 canine, 1,146 feline and 604 equine wounds, respectively. High MRSA rates were identified with 62.7%, 46.4% and 41.3% in S. aureus of canine, feline and equine origin, respectively. Further genotyping including spa typing and multilocus sequence typing (MLST) revealed a comparable distribution of spa types among canine and feline MRSA with CC22 (47.6%; 49.2%) and CC5 (30.2%; 29.2%) as predominant lineages followed by CC398 (13.5%; 7.7%) and CC8 (4.0%; 9.2%). In contrast, the majority of equine MRSA belonged to CC398 (87.7%). Our data highlight the importance of S. aureus and MRSA as a cause of wound infections, particularly in cats and horses in Germany. While “human-associated” MRSA lineages were most common in dogs and cats, a remarkable number of CC398-MRSA was detected in horses, indicating a replacement of CC8-MRSA as the predominant lineage within horses in Germany. These data enforce further longitudinal epidemiological approaches to examine the diversity and temporal relatedness of MRSA populations in humans and animals to assess probable sources of MRSA infections. This would enable a sound risk assessment and establishment of intervention strategies to limit the additional spread of MRSA.     

MRSA epidemic linked to a quickly spreading colonization and virulence determinant

The molecular processes underlying epidemic waves of methicillin-resistant Staphylococcus aureus (MRSA) infection are poorly understood(1). Although a major role has been attributed to the acquisition of virulence determinants by horizontal gene transfer(2), there are insufficient epidemiological and functional data supporting that concept. We here report the spread of clones containing a previously extremely rare(3,4) mobile genetic element–encoded gene, sasX. We demonstrate that sasX has a key role in MRSA colonization and pathogenesis, substantially enhancing nasal colonization, lung disease and abscess formation and promoting mechanisms of immune evasion. Moreover, we observed the recent spread of sasX from sequence type 239 (ST239) to invasive clones belonging to other sequence types. Our study identifies sasX as a quickly spreading crucial determinant of MRSA pathogenic success and a promising target for therapeutic interference. Our results provide proof of principle that horizontal gene transfer of key virulence determinants drives MRSA epidemic waves.     

Methicillin-resistant Staphylococcus aureus nasal colonization among adult patients visiting emergency department in a medical center in Taiwan

Background

Within the past 10 years, methicillin-resistant Staphylococcus aureus (MRSA) has not only been a hospital pathogen but also a community pathogen. To understand the carriage rate of methicillin-resistant Staphylococcus aureus (MRSA) among the adult patients visiting emergency department (ED), we conducted this study.

Methodology/Principal Findings

From May 21 to August 12, 2009, a total of 502 adult patients visiting emergency department (ED) of a tertiary care hospital in northern Taiwan were recruited in this study and surveyed for nasal carriage of MRSA. A questionnaire regarding the risk factors for MRSA acquisition was also obtained.The overall prevalence of MRSA nasal carriage among the patients was 3.8%. The carriage rate was significantly higher in patients with risk factors for MRSA acquisition (5.94%) than those without risk factors (2.12%). Patients with urinary complaints, diabetes mellitus, chronic kidney disease and current percutaneous tube usage were significantly associated with MRSA colonization. By multiple logistic regression analysis, only current usage of catheters or tubes was the independent predictor for MRSA nasal colonization. Of the 19 MRSA, most isolates belonged to one of two linages, characterized as sequence type (ST) 239 (32%) and ST 59 (58%). The latter linage, accounting for 83% of 6 isolates from patients without risk factors, is a community-associated (CA) clone in Taiwan, while the former linage is among healthcare-associated clones.

Conclusion/Significance

A substantial proportion of patients visiting ED, particularly with current usage of percutaneous catheter or tubes, in northern Taiwan carried MRSA, mostly community strains, in nares.     

Molecular characterization and antimicrobial susceptibility of nasal Staphylococcus aureus isolates from a Chinese medical college campus

Staphylococcus aureus colonization and infection occur more commonly among persons living or working in crowded conditions, but characterization of S. aureus colonization within medical communities in China is lacking. A total of 144 (15.4%, 144/935) S. aureus isolates, including 28 (3.0%, 28/935) MRSA isolates, were recovered from the nares of 935 healthy human volunteers residing on a Chinese medical college campus. All S. aureus isolates were susceptible to vancomycin, quinupristin/dalfopristin and linezolid but the majority were resistant to penicillin (96.5%), ampicillin/sulbactam (83.3%) and trimethoprim/sulfamethoxazole (93.1%). 82%, (23/28) of the MRSA isolates and 66% (77/116) of the MSSA isolates were resistant to multiple antibiotics, and 3 MRSA isolates were resistant to mupirocin--an agent commonly used for nasal decolonization. 16 different sequence types (STs), as well as SCCmec genes II, III, IVd, and V, were represented among MRSA isolates. We also identified, for the first time, two novel STs (ST1778 and ST1779) and 5 novel spa types for MRSA. MRSA isolates were distributed in different sporadic clones, and ST59-MRSA-VId- t437 was found within 3 MRSA isolates. Moreover, one isolate with multidrug resistance belonging to ST398-MRSA-V- t571 associated with animal infections was identified, and 3 isolates distributed in three different clones harbored PVL genes. Collectively, these data indicate a high prevalence of nasal MRSA carriage and molecular heterogeneity of S. aureus isolates among persons residing on a Chinese medical college campus. Identification of epidemic MRSA clones associated with community infection supports the need for more effective infection control measures to reduce nasal carriage and prevent dissemination of MRSA to hospitalized patients and health care workers in this community.     

Persistence of nasal colonization with livestock-associated methicillin-resistant Staphylococcus aureus in pig farmers after holidays from pig exposure

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is frequently transmitted from pigs to farmers. This study analyzed whether an absence from direct contact with pigs during holidays had an impact on nasal MRSA colonization rates of pig farmers. Overall, 59% of the farmers did not clear MRSA colonization during their leave.     

Public transport as a reservoir of methicillin‐resistant staphylococci

Aims: The aim of this study was to explore the occurrence of methicillin‐resistant staphylococci in a large urban public transport system. Methods and Results: Samples were taken from hand rails, which passengers hold onto when they are standing. In total, 1400 swabs taken from 55 vehicles (trolleybuses, trams and buses) were examined. As many as 30·1% samples were positive for the presence of methicillin‐resistant coagulase‐negative staphylococci (MRCoNS), but none for methicillin‐resistant Staphylococcus aureus (MRSA). MRCoNS were isolated from all 55 vehicles. Nearly 50% of MRCoNS isolates displayed resistance not only to beta‐lactams, but at least to two or more other classes of antimicrobials as well. Conclusions: This study demonstrated widespread occurrence of MRCoNS on hand rails in public transport vehicles. MRSA was not detected. Significance and Impact of the Study: The recovery of methicillin‐resistant staphylococci from public transport system implies a potential risk for transmission of these bacteria in an out‐hospital environment.     

Methicillin-resistant Staphylococcus aureus ST398 contamination and transmission in pigs after a low dose inoculation

Aims: Methicillin‐resistant Staphylococcus aureus (MRSA) ST398 has recently been described as a zoonotic agent. Its transmission between animals seems to be a pivotal factor in its emergence and dissemination. This experimental trial was performed to describe MRSA ST398 contamination and transmission in pigs after a low dose inoculation. Methods and results: Twelve specific pathogen‐free (SPF) pigs were randomly divided between two separate pens. Three pigs in each pen received a nasal inoculation of 2 × 10⁴ colony‐forming units per animal, and three naïve pigs were left in contact with them. Every 2 days and at necropsy, different samples were screened for MRSA. It was detected in nasal swabs from five inoculated and three naïve contact pigs, as early as 1 day after inoculation. MRSA was also found in environmental wipes but never in faecal samples. At necropsy, MRSA was detected in the lymph nodes of two contact pigs and in the tonsils and lymph nodes of three inoculated pigs. Twelve other SPF pigs were included as negative control in a separate room. Conclusion: This experiment showed that inoculation of a low dose of MRSA ST398 could lead to the horizontal transmission of the bacterium between pigs, the contamination of mandibular lymph nodes and the contamination of the environment without faecal carriage. Significance and Impact of the Study: The minimal inoculated dose via nasal route to observe transmission of MRSA ST398 between pigs is equal or lower to 2 × 10⁴ colony‐forming units per animal, and faecal excretion seems not to be a necessary condition for horizontal transmission.