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 against three clinical isolates of Streptococcus pneumoniae, using a mouse protection model. Two strains (SP 22 and SP 28) were penicillin-sensitive while one strain (SP 46) was penicillin-resistant. Each strain had identical susceptibility to both drugs. Using mice with renal impairment induced by uranyl nitrate injection, the elimination half-life of each antibiotic was prolonged to approximate human pharmacokinetic profiles of the drugs. The dosing regimen of each drug that yielded serum levels in mice which mimic human therapeutic concentrations of the drugs, were designed. One hour after intraperitoneal inoculation with minimum lethal dose of each strain, either levofloxacin 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 in higher survival compared with ciprofloxacin for the three strains. For example, 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 significant difference (p > 0.05). The lack of significant difference observed in the efficacies of both drugs reflected the comparability of their 24-h AUC/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 strains of the organism.
Onyeji
C O
CO
Department of Pharmacy Research, Hartford Hospital, CT 06102, USA.
Bui
K Q
KQ
Owens
R C
RC
Nicolau
D P
DP
Quintiliani
R
R
Nightingale
C H
CH
D058186:Acute Kidney Injury / Q000139:chemically induced; D000279:Administration, Cutaneous; D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D002939:Ciprofloxacin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004352:Drug Resistance, Microbial; D006801:Humans; D007928:Lethal Dose 50; D064704:Levofloxacin; D051379:Mice; D008826:Microbial Sensitivity Tests / Q000379:methods; D015242:Ofloxacin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010406:Penicillins / Q000494:pharmacology; D011008:Pneumococcal Infections / Q000188:drug therapy* / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D016019:Survival Analysis; D013997:Time Factors; D014502:Uranyl Nitrate / Q000009:adverse effects
D000890:Anti-Infective Agents; D010406:Penicillins; D014502:Uranyl Nitrate; D002939:Ciprofloxacin; D064704:Levofloxacin; D015242:Ofloxacin