title: 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.
abstract: OBJECTIVE
  To 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.
  
  
  METHODS
  In vitro susceptibility testing of bacterial isolates.
  
  
  METHODS
  Initially, 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).
  
  
  RESULTS
  All 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 3.3 μg/mL for both strains.
  
  
  CONCLUSIONS
  Drugs 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.
authors.affiliation: Faculty of Veterinary Science, McMaster Building, B14, The University of Sydney, NSW, 2006, Australia.
authors.forename: C J M
authors.initials: CJ
authors.lastname: Bennie
authors.forename: J L K
authors.initials: JL
authors.lastname: To
authors.forename: P A
authors.initials: PA
authors.lastname: Martin
authors.forename: M
authors.initials: M
authors.lastname: Govendir
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents; D002371:Cat Diseases / Q000188:drug therapy; D002415:Cats; D002511:Cephalosporins / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology; D017291:Clarithromycin / Q000494:pharmacology; D002991:Clofazimine / Q000494:pharmacology*; D004283:Dog Diseases / Q000188:drug therapy; D004285:Dogs; D004318:Doxycycline / Q000494:pharmacology; D004338:Drug Combinations; D024881:Drug Resistance, Bacterial; D000077422:Enrofloxacin; D024841:Fluoroquinolones / Q000494:pharmacology; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests / Q000662:veterinary; D009164:Mycobacterium Infections / Q000188:drug therapy / Q000662:veterinary; D019907:Mycobacterium fortuitum / Q000187:drug effects*; D020102:Mycobacterium smegmatis / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects; D000077145:Sulfanilamide; D013424:Sulfanilamides / Q000494:pharmacology; D014295:Trimethoprim / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D002511:Cephalosporins; D004338:Drug Combinations; D024841:Fluoroquinolones; D013424:Sulfanilamides; C516253:cefovecin; D000077145:Sulfanilamide; D000077422:Enrofloxacin; D002939:Ciprofloxacin; D014295:Trimethoprim; D002991:Clofazimine; D017291:Clarithromycin; D004318:Doxycycline
keywords: antibacterial drug combinations; cats; cefovecin; clofazimine; dogs; rapidly growing mycobacteria