Journal of Antimicrobial Chemotherapy (1999) 44, 775-786
© 1999 The British Society for Antimicrobial Chemotherapy
Efficacy of levofloxacin in the treatment of experimental endocarditis caused by viridans group streptococci
Division of Infectious Diseases, Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland
Levofloxacin was investigated against viridans group streptococci in vitro and in rats
with experimental aortic endocarditis. The MIC90s of levofloxacin and ciprofloxacin
for 20 independent isolates of such bacteria were 1 and 8 mg/L, respectively. Rats were infected
with two types of organism: either fully susceptible to levofloxacin MIC 
0.5 mg/L) or
borderline susceptible (MIC 1–2 mg/L). Fully levofloxacin-susceptible bacteria comprised
one penicillin-susceptible (MIC 0.004 mg/L) Streptococcus gordonii, and one
penicillin-tolerant as well as one intermediate penicillin-resistant (MIC 0.125 mg/L) isogenic
strains. Borderline levofloxacin-susceptible bacteria comprised one penicillin-susceptible Streptococcus sanguis and one highly penicillin-resistant Streptococcus mitis (MIC
2 mg/L). Rats were treated for 5 days with drug dosages simulating the following treatments in
humans: (i) levofloxacin 500 mg orally once a day (q24 h), (ii) levofloxacin 500 mg orally twice
a day (q12 h), (iii) levofloxacin 1 g orally q24 h, (iv) ciprofloxacin 750 mg orally q12 h, and (v)
ceftriaxone 2 g iv q24 h. Levofloxacin was equivalent or superior to ceftriaxone, and was
successful in treating experimental endocarditis irrespective of penicillin resistance.
Nevertheless, standard levofloxacin treatment equivalent to 500 mg q24 h in human was less
effective than twice daily 500 mg or once daily 1 g doses against borderline-susceptible
organisms. Ciprofloxacin, used as a negative control, was ineffective and selected for resistant
isolates. This underlines the importance of MIC determinations when treating severe
streptococcal infection with quinolones. In the case of borderline-susceptible pathogens, total
daily doses of 1 g of levofloxacin should be considered.
* Corresponding author. Tel. +41-21-314-10-26; Fax: +41-21-314-10-36 E-mail: pmoreill{at}chuv.hospvd.ch
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