MRSP, What's changed in the past 2yrs?

posted: 28/Aug/2017

The change in incidence and antibiotic susceptibility of canine methicillin-resistant Staphylococcus pyoderma at Animal Skin and Ear Specialists, Melbourne over two years 
David Robson

(The following article is based on a study originally presented at the ANZCVS Dermatology Chapter Meeting July 2017.)

Introduction
Methicillin-resistant Staphylococcus (MRS) is defined by the presence of the mecA gene, a chromosomal gene that encodes production of a modified penicillin-binding protein (PBP2a) that has a low affinity for ?-lactam antibiotics, leading to clinical resistance to all of this drug family. In 2014 the we performed a prospective three-month study examining the incidence of MRS in canine pyoderma at the Animnal Skin and Ear Specialists (ASES) at Melbourne Veterinary Specialist Centre (MVSC).1 

In 2016 we repeated the study. The primary aim of the study was to examine any changes in incidence of MRS in dogs with pyoderma presenting to the clinic, and whether there had been any changes in patterns of antibiotic susceptibility overall, and between cases presenting to the Essendon (ESS) branch practice, the Glen Waverley (GW) clinic and Frankston (FR) branch practice.

Methods
The methodology of the study was similar to 2014.1 In summary, cases were presented to the ASES from September 19 to December 19, 2016. Inclusion criteria included any dog with a bacterial pyoderma (surface, superficial or deep) with consistent cytological findings (neutrophils with intracellular cocci) determined by the clinician to require oral antibiotic therapy. At least one follow up revisit to determine success or failure of therapy was mandatory, otherwise a case was considered lost to follow up (LTFU). If empirical therapy failed then a culture and susceptibility was performed. Cases were thus classified as responders to empirical therapy (RTET), confirmed methicillin susceptible Staphylococcus sp. (MSS), MRS or LTFU. 

The confirmed incidence of MRS pyoderma at each geographic site (ESS and GW) as well as the total overall was then calculated as the number of confirmed MRSP cases divided by the total number of included cases. The maximum possible incidence was calculated by adding MRS, LTFU (assuming all LTFU cases were MRS) as well as the proportion of RTET cases using non-B lactam antibiotics that may have inadvertently successfully treated MRS cases. 

Results
In 2016, 104 cases were included in the study (GW 70, ESS 30, FR 4). The confirmed incidence of MRS was 14.4% (GW 17.1%, ESS 10.0%, FR 0.0%) with a maximum possible incidence of 41.3% (GW 45.7%, ESS 33.3%). All cases, except for a single case of MR Staphylococcus epidermidis were MR Staphylococcus pseudintermedius. Both the confirmed incidence and maximum possible incidences were not significantly different to the 2014 incidences (18.1% and 38.3%; p=0.563 and p=0.666 respectively).  

Multiple antibiotic resistances were common in MRSP isolates with <33% MRS isolates susceptible to trimethoprim-sulphonamide (TMS), erythromycin, clindamycin, lincomycin, marbofloxacin and enrofloxacin. Only chloramphenicol and rifampicin were reported susceptible in >90% isolates tested. When comparing results between 2014 and 2016 there was no significant difference in the frequency of resistance to most antibiotics, but there was a significant decrease in the frequency of susceptibility to TMS (83.4% to 20.0%; p=0.001), and a significant increase in the frequency of susceptibility to chloramphenicol (29.4% to 80.0%; p=0.0017). Minocycline, which was not assessed in 2014, showed an overall susceptibility of 80%, consistent with the frequent findings of MRSP strain ST71 in a previous Australian survey2 with its frequent expression of tetK but not tetM resistance genes.3 

Discussion
MRS pyoderma in dogs remains a common problem in the caseload seen at ASES. While the incidence of new cases has not significantly increased from 2014 to 2016, the overall proportion of MRS cases seen has increased because the rate of MRS cure and decolonisation has been less than the rate of new case acquisition (data not shown). The incidence has remained similar between both GW and ESS. 

Resistance to multiple antibiotics remains common in MRS strains in this study. This emphasises the need to culture to identify susceptible antibiotics where MRS are suspected as a cause for pyoderma. The dermatologists at ASES often use daily topical chlorhexidine 0.5-3% alone,4 or two concurrent susceptible-reported antibiotics for the treatment of MRS pyoderma to minimise the risk of selection of further antibiotic resistance.

The identification of multiple antibiograms suggests multiple MRSP strains prevalent in the Melbourne region. Unique antibiograms remained present for the majority of isolates in both 2014 to 2016, with no evidence for a dominant antibiogram emerging. Only a single instance of two possible identical antibiograms was noted between 2014 to 2016 (data not shown). This variety of antibiograms continues to suggest that acquisition of infection directly or indirectly at ASES does not appear to be the primary source in most of these cases. 

The accuracy of the study results remains hampered by several limitations including the number of LTFU cases, low case numbers, reliance on susceptibility testing for identification of MRSP cases (some MRSP cases are still missed by this testing alone; mecA PCR detection remains the gold standard)5, and MRS cases responding to empirical use of clindamycin or fluoroquinolones. For 2016, the latter was incorporated into the estimate of incidence, and this was also applied retrospectively to the 2014 data. 

It does raise the issue though as to whether, in MRS prevalent regions, non-B-lactam antibiotics should be used empirically at all, and whether empirically selected topical antiseptics used at dose rates that may effect cure, should be used without prior culture to minimise the risk of inadvertent cure (and thus clinical non-diagnosis) of MRS pyoderma. 

Conclusion
Within the limitations of this study, the incidence of MRSP has not increased at ASES in Melbourne between 2014 and 2016. It confirms the 2014 findings that MRS pyoderma is common in dogs in Melbourne and that practitioners need to be aware of both this and it’s implications in clinical practice. Repeating this study in future years should detect trends in antibiotic resistance in cases of MRS canine pyoderma in Melbourne.

A. Gribbles Pathology (Vic) Pty Ltd, Clayton VIC

References 
1. Robson DC. The incidence of canine methicillin-resistant Staphylococcus pseudintermedius pyoderma in a specialist dermatology practice over a 3 month period in 2014: a prospective study. Australia College of Veterinary Scientists Dermatology Chapter Science Week Proceedings, Gold Coast, 10-11th July 2015: 52-54

2. Norris, J. Update on the antimicrobial susceptibility of clinical isolates of Staphylococcus in Australian dogs and cats. Australian and New Zealand College of Veterinary Scientists Dermatology Chapter Science Week Proceedings, Gold Coast, 10-11th July 2015: 48-51

3. Perreten V et al. Clonal spread of methicillin-resistant Staphylococcus pseudintermedius in Europe and North America: an international multicentre study. J Antimicrob Chemother. 2010; 65(6):1145-54

4. Borio S et al. Effectiveness of a combined (4% chlorhexidine digluconate shampoo and solution) protocol in MRS and non-MRS canine superficial pyoderma: a randomized, blinded, antibiotic-controlled study. Veterinary Dermatology 2015, 26: 339–e72

5. van Duijkeren et al; Scientific Advisory Group on Antimicrobials (SAGAM). Review on methicillin-resistant Staphylococcus pseudintermedius. J Antimicrob Chemother. 2011; 66(12): 2705-14

 




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