Comparative efficacies of levofloxacin and ciprofloxacin against Streptococcus pneumoniae in a mouse model of experimental septicaemia

The in vivo efficacies of levofloxacin and ciprofloxacin were compared agai nst three clinical isolates of Streptococcus pneumoniae, using a mouse prot ection model. Two strains (SP 22 and SP 28) were penicillin-sensitive while one strain (SP 46) was penicillin-resistant. Each strain had identical sus ceptibility to both drugs. Using mice with renal impairment induced by uran yl nitrate injection, the elimination half-life of each antibiotic was prol onged to approximate human pharmacokinetic profiles of the drugs. The dosin g regimen of each drug that yielded serum levels in mice which mimic human therapeutic concentrations of the drugs, were designed. One hour after intr aperitoneal inoculation with minimum lethal dose of each strain, either lev ofloxacin at a dosing regimen of 10.6 mg/kg every 8 h or ciprofloxacin at 9 .5 mg/kg every 8 h was subcutaneously administered for a total of six or 15 doses. In treatment, monitored daily for 5-8 days, levofloxacin resulted i n higher survival compared with ciprofloxacin for the three strains. For ex ample, percent survival following levofloxacin treatment recorded at day 4 postinfection with SP 22, SP 28 and SP 46 were 41, 90 and 30%, respectively , while the corresponding values after ciprofloxacin treatment were 27, 75 and 16%, respectively. However, statistical analysis did not reveal a signi ficant difference (p > 0.05). The lack of significant difference observed i n the efficacies of both drugs reflected the comparability of their 24-h AU C/MIC ratios. It is suggested that, with some strains of S. pneumoniae, the efficacy of levofloxacin may be equivalent to that of ciprofloxacin in the treatment of systemic pneumococcal infections caused by susceptible strain s of the organism. (C) 1999 Published by Elsevier Science B.V. and Internat ional Society of Chemotherapy. All rights reserved.