Development ofResistance toFleroxacin during Therapy ofExperimental Methicillin-Susc eptible Staphylococcus aureus Endocarditis

Theefficacy offleroxacin was compared withthatofvancomycin byusing therabbit modelofmethicillinsusceptible Staphylococcus aureus endocarditis. Animals received intravenous therapy withfleroxacin, 30 mg/kg every8h,orvancomycin, 17.5mg/kg every6h,for4days. Bothantimicrobial agents effectively cleared bacteremia andsignificantly reduced bacterial countsinvegetations andtissues compared withthose in untreated controls. However, resistance tofieroxacin at5-and10-fold theMIC aroseintheteststrain ofS. aureusin73and27%,respectively, ofanimals thatreceived thedrug. Resistant isolates were foundmainly in vegetations andwere composed ofup to7% oftheresidual population recovered fromthatsite. We conclude that fieroxacin isaseffective asvancomycin inthis modelofaserious systemic S.aureusinfection, butresistance tothedrugmay develop during therapy. Ifsimilar results arefoundwithother strains ofS.aureusduring therapy withthis orother fluoroquinolones, suchdata, whenthey arecombined withthehighincidence of fluoroquinolone resistance among S.aureusisolates being reported fromselected institutions, wouldsupport thecontention that these drugs should notbeusedasfirst-line therapeutic agents forS.aureusinfections.