Susceptibility in vitro of canine methicillin-resistant and -susceptible staphylococcal isolates to fusidic acid, chlorhexidine and miconazole: opportunities for topical therapy of canine superficial pyoderma.

S M Clark,R Bond,A Loeffler

doi:10.1093/jac/dkv056

Abstract

ObjectivesIncreasing multidrug resistance amongst canine pathogenic staphylococci has renewed interest in topical antibacterial therapy for skin infections in the context of responsible veterinary prescribing. We therefore determined the activity in vitro of three clinically relevant topical agents and synergism between two of them against Staphylococcus pseudintermedius and Staphylococcus aureus.MethodsThe MICs of fusidic acid (n = 199), chlorhexidine (n = 198), miconazole (n = 198) and a 1:1 combination of miconazole/chlorhexidine (n = 198) were determined for canine isolates [50 MRSA and 49 methicillin-resistant S. pseudintermedius (MRSP), 50 MSSA and 50 methicillin-susceptible S. pseudintermedius (MSSP)] collected from the UK and Germany using an agar dilution method (CLSI VET01-A4). Fractional inhibitory concentration (FIC) indices were calculated to assess the interaction of miconazole with chlorhexidine.ResultsMICs of each drug/combination were significantly (P < 0.0005) higher for S. aureus when compared with S. pseudintermedius. Most strains (n = 172) had an MIC of fusidic acid of ≤0.03 mg/L (MIC ≥64 mg/L, n = 5 MRSA). All strains had MICs of chlorhexidine of 0.5–4 mg/L, except for one MRSA (MIC = 8 mg/L). All but four strains had MICs of miconazole of 1–4 mg/L (MIC = 16 mg/L, n = 3; MIC = 256 mg/L, n = 1). Miconazole/chlorhexidine (1:1 ratio) had a synergistic effect against 49/50 MRSA, 31/50 MSSA, 12/49 MRSP and 23/49 MSSP.ConclusionsSince the majority of these staphylococci, including methicillin-resistant isolates, had MICs that should be readily exceeded by topical skin application of these agents, their therapeutic efficacy for canine superficial pyoderma should be assessed. The synergistic interaction shown in vitro supports further clinical evaluation of miconazole/chlorhexidine combination therapy for staphylococcal infection.

Highlights

The alarming increase in canine skin infections caused by methicillin-resistant Staphylococcus pseudintermedius (MRSP) and MRSA1 paralleled by recognition of zoonotic infections,2 highlights the urgent need to develop strategies to limit further emergence of MDR strains
One methicillin-susceptible S. pseudintermedius (MSSP) strain failed to grow in studies of MICs of chlorhexidine, miconazole and miconazole plus chlorhexidine
The low MICs of fusidic acid, miconazole and chlorhexidine for the great majority of these canine staphylococcal isolates in vitro provide strong support for their use topically in clinical cases of surface and superficial pyoderma, including cases caused by methicillin-resistant bacteria

Summary

Introduction

The alarming increase in canine skin infections caused by methicillin-resistant Staphylococcus pseudintermedius (MRSP) and MRSA1 paralleled by recognition of zoonotic (and reverse-zoonotic) infections, highlights the urgent need to develop strategies to limit further emergence of MDR strains. Topical antibacterial therapy can provide an alternative treatment option for many dogs with bacterial skin infections and limit the need for oral antibiotics.. There is concern in human medicine over reduced efficacy of agents such as chlorhexidine and fusidic acid, clinical evidence for treatment failure remains inconsistent. Assessment of resistance is hampered by lack of breakpoint standards for agents used topically. In dog-derived staphylococci, MICs of fusidic acid, chlorhexidine and miconazole have been low, – but geographical differences can be expected.. Since previous MIC studies have evaluated mainly North American staphylococcal isolates, we determined current susceptibility in vitro of dog-derived European In dog-derived staphylococci, MICs of fusidic acid, chlorhexidine and miconazole have been low, – but geographical differences can be expected. Since previous MIC studies have evaluated mainly North American staphylococcal isolates, we determined current susceptibility in vitro of dog-derived European

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