Anette Loeffler

Companion animals: a reservoir for methicillin-resistant Staphylococcus aureus in the community?

This article reviews the literature on the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in dogs, cats and horses. Over the past 10 years, MRSA has emerged as an important pathogen in veterinary medicine, especially in countries with a high MRSA burden in human hospitals. During the same period, community-associated MRSA (CA-MRSA) infections in humans without apparent links to healthcare facilities have increased dramatically. Although animal infections occur outside human hospitals, significant epidemiological, clinical and genetic differences exist between CA-MRSA in humans and the majority of MRSA infections in the different animal species. The recognition of MRSA in animals has raised concern over their role as potential reservoirs or vectors for human MRSA infection in the community. However, available data on MRSA transmission between humans and companion animals are limited and the public health impact of such transmission needs to be the subject of more detailed epidemiological studies.

Risk factors for methicillin-resistant Staphylococcus aureus (MRSA) infection in dogs and cats: a case-control study

Risk factors for methicillin-resistant Staphylococcus aureus (MRSA) infection in dogs and cats were investigated in an unmatched case-control study. A total of 197 animals from 150 veterinary practices across the United Kingdom was enrolled, including 105 MRSA cases and 92 controls with methicillin-susceptible S. aureus (MSSA) infection. The association of owners and veterinarian staff with the human healthcare sector (HCS) and animal-related characteristics such as signalment, antimicrobial and immunosuppressive therapy, and surgery were evaluated as putative risk factors using logistic regression. We found that significant risk factors for MRSA infection were the number of antimicrobial courses (p = 0.005), number of days admitted to veterinary clinics (p = 0.003) and having received surgical implants (p = 0.001). In addition, the odds of contact with humans which had been ill and admitted to hospital (p = 0.062) were higher in MRSA infected pets than in MSSA controls. The risk factors identified in this study highlight the need to increase vigilance towards identification of companion animal groups at risk and to advocate responsible and judicious use of antimicrobials in small animal practice.

Meticillin-resistant Staphylococcus pseudintermedius: clinical challenge and treatment options

Meticillin-resistant Staphylococcus pseudintermedius (MRSP) has emerged as a major therapeutic challenge for small animal veterinarians over the past 10 years and continues to spread worryingly in many countries. This review focuses on the clinical aspects of MRSP infections seen in patients with skin disease and on currently available treatment options. In addition, it discusses the implications for in-contact people, other animals and the environment, because infection control strategies are likely to have a significant impact on treatment success and prevention of spread. There is currently no indication that MRSP is more virulent than meticillin-susceptible S. pseudintermedius, and reported infections have mostly been treated successfully, although possibly with a longer time to resolution than infections with more susceptible S. pseudintermedius. However, in vitro testing of MRSP isolates indicates resistance to most or all antibacterial agents licensed for use in pets. Based on susceptibility results, the most useful systemic antimicrobials may include chloramphenicol, rifampicin, amikacin, clindamycin and/or minocycline. Adverse effects of some of these medications may limit their usefulness. While in vitro susceptibility to vancomycin and linezolid is reported by some laboratories, use of these drugs in animals is strongly discouraged because of ethical considerations. Aggressive topical therapy has been effective as the only treatment in certain cases. Awareness, continued research and comprehensive management of infections are required by veterinary practitioners not only to help treat infected animals but also to limit the spread and prevent the establishment of this highly drug-resistant and zoonotic pathogen in veterinary facilities and in the community.

Prevalence of and risk factors for MRSA carriage in companion animals: a survey of dogs, cats and horses.

We investigated the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) carriage in a convenience sample of purposely selected populations of dogs, cats and horses in the Greater London area. Swabs from carriage sites were pooled, enriched and processed by standard bacteriological methods. The presence of nuc and mecA was confirmed for MRSA. Risk factors were investigated among veterinary treatment group animals using exact logistic regression analysis. Twenty-six (1.53%) MRSA carriers were identified in the 1692 animals (15/704 dogs, 8/540 cats, 3/152 horses). Animals presenting for veterinary treatment more frequently carried MRSA than healthy animals (OR 7.27, 95% CI 2.18-24.31, P<0.001). Concurrent carriage of non-MRSA coagulase-positive staphylococci was associated with MRSA carriage (OR 0.088, 95% CI 0.016-0.31, P<0.001); none of the other 13 putative risk factors was significant. MRSA carriage was rare in the selected companion animal populations. The absence of typical risk factors indicates that companion animals act as contaminated vectors rather than as true reservoirs.

Extensive horizontal gene transfer during Staphylococcus aureus co-colonization in vivo.

Staphylococcus aureus is a commensal and major pathogen of humans and animals. Comparative genomics of S. aureus populations suggests that colonization of different host species is associated with carriage of mobile genetic elements (MGE), particularly bacteriophages and plasmids capable of encoding virulence, resistance, and immune evasion pathways. Antimicrobial-resistant S. aureus of livestock are a potential zoonotic threat to human health if they adapt to colonize humans efficiently. We utilized the technique of experimental evolution and co-colonized gnotobiotic piglets with both human- and pig-associated variants of the lineage clonal complex 398, and investigated growth and genetic changes over 16 days using whole genome sequencing. The human isolate survived co-colonization on piglets more efficiently than in vitro. During co-colonization, transfer of MGE from the pig to the human isolate was detected within 4 h. Extensive and repeated transfer of two bacteriophages and three plasmids resulted in colonization with isolates carrying a wide variety of mobilomes. Whole genome sequencing of progeny bacteria revealed no acquisition of core genome polymorphisms, highlighting the importance of MGE. Staphylococcus aureus bacteriophage recombination and integration into novel sites was detected experimentally for the first time. During colonization, clones coexisted and diversified rather than a single variant dominating. Unexpectedly, each piglet carried unique populations of bacterial variants, suggesting limited transmission of bacteria between piglets once colonized. Our data show that horizontal gene transfer occurs at very high frequency in vivo and significantly higher than that detectable in vitro.

In vitro activity of fusidic acid and mupirocin against coagulase-positive staphylococci from pets

OBJECTIVES Methicillin-resistant Staphylococcus aureus (MRSA) and multiresistant Staphylococcus pseudintermedius (MRSP) have emerged as important pathogens in animal infections. Associated therapeutic problems and the zoonotic potential of staphylococci have renewed interest in topical antibiotics for treatment and carrier decolonization. Fusidic acid and mupirocin are used topically in humans and animals but resistant strains isolated from people are increasing. This study investigates the in vitro activity of fusidic acid and mupirocin against coagulase-positive staphylococci from pets. METHODS A collection of 287 staphylococci was examined, comprising 102 MRSA, 102 methicillin-susceptible S. aureus, 71 S. pseudintermedius and 12 MRSP from canine and feline infections and carrier sites isolated in the UK and Germany. MICs were determined by the agar dilution method according to CLSI (formerly NCCLS) standards. RESULTS The majority (89.7%) of all MICs were </=0.25 mg/L. High MICs were observed for seven MRSA isolates (five with an MIC of fusidic acid of 512 mg/L, one with an MIC of fusidic acid of 1024 mg/L and one with with an MIC of mupirocin of 16 mg/L). MICs of both antibiotics were </=2 mg/L for all MRSP. Infection isolates had higher MICs than those isolated from carriage sites for both antibiotics (P </= 0.001). CONCLUSIONS In all but seven MRSA isolates, MICs were below the concentrations achievable experimentally at application sites suggesting therapeutic efficacy of both antibiotics in infections involving multiresistant staphylococci and for decolonization of carriers. However, the seven MRSA with high MICs, all of the dominant UK human hospital lineages, highlight the importance of monitoring treatment success as resistant strains may occur in animals.

Case-control risk factor study of methicillin-resistant Staphylococcus pseudintermedius (MRSP) infection in dogs and cats in Germany

Methicillin-resistant Staphylococcus pseudintermedius (MRSP) has emerged as a highly drug-resistant small animal veterinary pathogen. Although often isolated from outpatients in veterinary clinics, there is concern that MRSP follows a veterinary-hospital-associated epidemiology. This studys objective was to identify risk factors for MRSP infections in dogs and cats in Germany. Clinical isolates of MRSP cases (n=150) and methicillin-susceptible S. pseudintermedius (MSSP) controls (n=133) and their corresponding host signalment and medical data covering the six months prior to staphylococcal isolation were analysed by multivariable logistic regression. The identity of all MRSP isolates was confirmed through demonstration of S. intermedius-group specific nuc and mecA. In the final model, cats (compared to dogs, OR 18.5, 95% CI 1.8-188.0, P=0.01), animals that had been hospitalised (OR 104.4, 95% CI 21.3-511.6, P<0.001), or visited veterinary clinics more frequently (>10 visits OR 7.3, 95% CI 1.0-52.6, P=0.049) and those that had received topical ear medication (OR 5.1, 95% CI 1.8-14.9, P=0.003) or glucocorticoids (OR 22.5, 95% CI 7.0-72.6, P<0.001) were at higher risk of MRSP infection, whereas S. pseudintermedius isolates from ears were more likely to belong to the MSSP-group (OR 0.09, 95% CI 0.03-0.34, P<0.001). These results indicate an association of MRSP infection with veterinary clinic/hospital settings and possibly with chronic skin disease. There was an unexpected lack of association between MRSP and antimicrobial therapy; this requires further investigation but may indicate that MRSP is well adapted to canine skin with little need for selective pressure.

Comparison of a chlorhexidine and a benzoyl peroxide shampoo as sole treatment in canine superficial pyoderma

The clinical and antibacterial efficacy of two shampoos used as a sole antibacterial treatment in dogs with superficial pyoderma were investigated and compared. In a randomised, partially blinded study, a 3 per cent chlorhexidine gluconate shampoo (Chlorhex 3; Leo Animal Health) was compared against a 2.5 per cent benzoyl peroxide shampoo (Paxcutol; Virbac) in 22 dogs with superficial pyoderma. Dogs were washed two to three times weekly with a 10-minute contact time over 21 days. Clinical scores and bacterial counts were assessed on days 1, 8 and 22 and compared within and between treatment groups; overall response was assessed at the end of the study. Twenty dogs completed the study; 15 (68.2 per cent) showed an overall clinical improvement and the clinical signs resolved in three chlorhexidine-treated dogs. In the chlorhexidine-treated group, scores for papules/pustules (P<0.001), investigator-assessed pruritus (P=0.003), total bacterial counts (P=0.003) and counts for coagulase-positive staphylococci (P=0.003) were reduced after three weeks. Scores and bacterial counts did not vary significantly in the benzoyl peroxide-treated group.

Lack of transmission of methicillin-resistant Staphylococcus aureus (MRSA) between apparently healthy dogs in a rescue kennel

Although it is widely accepted that methicillin-resistant Staphylococcus aureus (MRSA) can be transmitted between humans and animals in both directions, little is known about the dynamics of animal-to-animal transfer. This study aimed to investigate aspects of dog-to-dog MRSA transfer in a rescue facility in the South-East of England during an MRSA outbreak. One hundred and twenty-nine apparently healthy dogs, mostly housed in pairs, were swabbed at nasal, oral, axillary and perianal sites. Swabs were enriched in selective broth and staphylococci identified using standard biological methods. MRSA isolates were confirmed by demonstration of the thermonuclease gene (nuc) and mecA. After initial swabbing, a dog excluded from the study design but housed at the same facility was discovered to have a wound infection due to MRSA. MRSA carriage was identified in 10/129 dogs (7.8%) and all isolates were of the same lineage as the one isolated from the infected dog. All carrier dogs lived in shared kennels and their 16 kennel partners sampled negative on two occasions. Concurrently with successful antimicrobial treatment of the infected patient, MRSA carriage resolved spontaneously in all dogs within two weeks. In conclusion, MRSA did not transmit readily between apparently healthy dogs, MRSA carriage was not supported for long periods in a regularly cleaned environment and exposure alone may not lead to MRSA acquisition by dogs without the presence of additional risk factors.

Genomic insights into the rapid emergence and evolution of MDR in Staphylococcus pseudintermedius

OBJECTIVES MDR methicillin-resistant Staphylococcus pseudintermedius (MRSP) strains have emerged rapidly as major canine pathogens and present serious treatment issues and concerns to public health due to their, albeit low, zoonotic potential. A further understanding of the genetics of resistance arising from a broadly susceptible background of S. pseudintermedius is needed. METHODS We sequenced the genomes of 12 S. pseudintermedius isolates of varied STs and resistance phenotypes. RESULTS Nine distinct clonal lineages had acquired either staphylococcal cassette chromosome (SCC) mec elements and/or Tn5405-like elements carrying up to five resistance genes [aphA3, sat, aadE, erm(B), dfrG] to generate MRSP, MDR methicillin-susceptible S. pseudintermedius and MDR MRSP populations. The most successful and clinically problematic MDR MRSP clones, ST68 SCCmecV(T) and ST71 SCCmecII-III, have further accumulated mutations in gyrA and grlA conferring resistance to fluoroquinolones. The carriage of additional mobile genetic elements (MGEs) was highly variable, suggesting that horizontal gene transfer is frequent in S. pseudintermedius populations. CONCLUSIONS Importantly, the data suggest that MDR MRSP evolved rapidly by the acquisition of a very limited number of MGEs and mutations, and that the use of many classes of antimicrobials may co-select for the spread and emergence of MDR and XDR strains. Antimicrobial stewardship will need to be comprehensive, encompassing human medicine and veterinary disciplines to successfully preserve antimicrobial efficacy.