Efficacy of levofloxacin in the treatment of experimental endocarditis caused by viridans group streptococci

Levofloxacin was investigated against viridans group streptococci in vitro and in rats with experimental aortic endocarditis. The MIC(90)s of levoflox acin and ciprofloxacin for 20 independent isolates of such bacteria were 1 and 8 mg/L, respectively. Rats were infected with two types of organism: ei ther fully susceptible to levofloxacin (MIC less than or equal to 0.5 mg/L) or borderline susceptible (MIC 1-2 mg/L). Fully levofloxacin-susceptible b acteria comprised one penicillin-susceptible (MIC 0.004 mg/L) Streptococcus gordonii, and one penicillin-tolerant as well as one intermediate penicill in-resistant (MIC 0.125 mg/L) isogenic strains. Borderline levofloxacin-sus ceptible bacteria comprised one penicillin-susceptible Streptococcus sangui s and one highly penicillin-resistant Streptococcus mitis (MIC 2 mg/L). Rat s were treated for 5 days with drug dosages simulating the following treatm ents in humans: (i) levofloxacin 500 mg orally once a day (q24 h), (ii) lev ofloxacin 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 q 24 h. Levofloxacin was equivalent or superior to ceftriaxone, and was succe ssful in treating experimental endocarditis irrespective of penicillin resi stance. 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 n egative control, was ineffective and selected for resistant isolates. This underlines the importance of MIC determinations when treating severe strept ococcal infection with quinolones. In the case of borderline-susceptible pa thogens, total daily doses of 1 g of levofloxacin should be considered.