In vitro interaction of some drug combinations to inhibit rapidly growing mycobacteria isolates from cats and dogs and these isolates' susceptibility to cefovecin and clofazimine

ObjectivesTo investigate whether selected drug combinations used to treat rapidly growing mycobacteria (RGM) have drug-drug interactions that affect efficacy and to investigate each isolate's susceptibility to cefovecin and clofazimine, individually. DesignIn vitro susceptibility testing of bacterial isolates. MethodsInitially, five feline isolates and one canine isolate from both Mycobacterium fortuitum and M. smegmatis clusters (n = 12) underwent microbroth susceptibility testing to individual drugs to establish minimum inhibitory concentrations (MIC) of cefovecin, ciprofloxacin, clarithromycin, clofazimine, doxycycline, enrofloxacin, trimethoprim and sulfanilamide (the latter two as a combination). Checkerboard assays were then performed for susceptible M. smegmatis isolates for the following combinations: clarithromycin (one isolate only) versus enrofloxacin, clarithromycin vs doxycycline, clarithromycin vs trimethoprim/sulfanilamide; enrofloxacin vs doxycycline (six isolates); enrofloxacin vs trimethoprim/sulfanilamide (six isolates). Susceptible M. fortuitum isolates were tested against enrofloxacin versus doxycycline (four isolates only). ResultsAll six M. fortuitum isolates were susceptible to enrofloxacin, but only four of six were susceptible to doxycycline. All six M. smegmatis isolates were susceptible to doxycycline, enrofloxacin and trimethoprim/sulfanilamide. A single isolate from the 12, a M. smegmatis isolate, was susceptible to clarithromycin. The fractional inhibitory concentration of each drug ranged from 0.64 to 1.84, indicating that neither synergism nor antagonism was evident. All 12 isolates were resistant to cefovecin. The clofazimine MIC50 to inhibit isolate growth was approximately 3.3g/mL for both strains. ConclusionDrugs commonly used for treatment of RGM, when tested as combinations, do not appear to antagonise one another in vitro. Cefovecin is not efficacious for treatment of RGM infections.