Efficacy of levofloxacin for experimental aortic-valve endocarditis in rabbits infected with viridans group streptococcus or Staphylococcus aureus

Levofloxacin is among the more active fluoroquinolones against streptococci and staphylococci, It is effective against moderately severe infections ca used by these organisms, but its efficacy in the treatment of bacteremia an d serious infections such as endocarditis is not well defined. We compared the efficacy of levofloxacin to those of standard agents in the rabbit mode l of aortic-valve endocarditis caused by fluoroquinolone-susceptible strain s including a penicillin-susceptible strain of Streptococcus sanguis, a pen icillin-resistant strain of Streptococcus mitis, a methicillin-resistant st rain of Staphylococcus aureus, and a methicillin-susceptible strain of S, a ureus, Levofloxacin administered intramuscularly at dosages of 20 to 40 mg/ kg of body weight twice daily (b.i.d.) was completely ineffective against t he penicillin-susceptible strain, with mean vegetation titers after 3 days of therapy not statistically significantly different from those for control s. Levofloxacin was no more effective than penicillin against the penicilli n-resistant strain. Levofloxacin administered for 4 days at a dosage of 20 mg/kg b.i.d. was at least as effective as vancomycin administered intraveno usly at a dosage of 25 mg/kg b.i.d. against the methicillin-resistant S, au reus strain and was as effective as nafcillin administered intramuscularly at 100 mg three times daily against the methicillin-susceptible strain. Eme rgence of resistance to levofloxacin in vitro was less likely to occur than resistance to ciprofloxacin, and resistance to levofloxacin was not observ ed in vivo. Levofloxacin-rifampin combinations were antagonistic in vitro a nd in vivo. Levofloxacin was highly effective as a single agent against exp erimental staphylococcal endocarditis but was surprisingly ineffective agai nst streptococcal endocarditis, suggesting that it has a potential role as treatment for serious S, aureus but not viridans group streptococcal infect ions in humans.