The efficacy of
trovafloxacin against Staphylococcus aureus and viridans group streptococci was investigated in vitro and in an experimental model of
endocarditis. The MICs at which
trovafloxacin and
ciprofloxacin inhibited 90% of clinical isolates of such bacteria (MIC90s) were (i) 0.03 and 2 mg/liter, respectively, for 30
ciprofloxacin-susceptible S. aureus isolates, (ii) 32 and 128 mg/liter, respectively, for 20
ciprofloxacin-resistant S. aureus isolates, and (iii) 0.25 and 8 mg/liter, respectively, for 28 viridans group streptococci. Rats with aortic vegetations were infected with either of two
ciprofloxacin-susceptible but methicillin-resistant S. aureus strains (strains COL and P8), one
penicillin-susceptible Streptococcus sanguis strain, or one
penicillin-resistant Streptococcus mitis strain. Rats were treated for 3 or 5 days with doses that resulted in kinetics that simulated those achieved in humans with
trovafloxacin (200 mg orally once a day),
ciprofloxacin (750 mg orally twice a day),
vancomycin (1 g intravenously twice a day), or
ceftriaxone (2 g intravenously once a day). Against the staphylococci, the activities of both
trovafloxacin and
ciprofloxacin were equivalent to that of
vancomycin, and treatment of
endocarditis with these drugs was successful (P < 0.05). However,
ciprofloxacin selected for resistant derivatives in vitro and in vivo, whereas
trovafloxacin was 10 to 100 times less prone than
ciprofloxacin to select for resistance in vitro and did not select for resistance in vivo. Against the two streptococcal isolates,
trovafloxacin significantly (P < 0.05) decreased bacterial counts in the vegetations but was less effective than the control drug,
ceftriaxone. Thus, a simulated oral dose of
trovafloxacin (200 mg per day) was effective against
ciprofloxacin-susceptible staphylococci and was less likely than
ciprofloxacin to select for resistance. The simulated oral dose of
trovafloxacin also had some activity against streptococcal
endocarditis, but optimal treatment of
infections caused by such organisms might require higher doses of the
drug.