Evaluation of the efficacy of ciprofloxacin against Streptococcus pneumoniae by using a mouse protection model.
A mouse protection model was used to investigate the association of the pharmacokinetics and pharmacodynamics with the in vivo efficacy of ciprofloxacin compared with that of penicillin G in the treatment of mice infected with Streptococcus pneumoniae ATCC 6303. Mice were inoculated intraperitoneally with 10 times the minimum lethal dose of S. pneumoniae. For determination of the 50% protective dose, subcutaneous antibiotics were begun 1 h after infection and were continued for 24 h. The 50% protective doses of ciprofloxacin and penicillin G were 25.52 +/- 1.95 and 0.307 +/- 0.006 mg/kg of body weight, respectively, an 83-fold difference in efficacy. For 100% protection with penicillin G, the time that the drug concentration needed to remain above the MIC was 51 min, a value easily achieved in most clinical situations. For 100% protection with ciprofloxacin, the peak concentration/MIC ratio must reach a value of 10.6. This ratio is rarely achieved with this drug against S. pneumoniae in clinical practice. These pharmacodynamic differences probably contribute to the reported differences in clinical success between these agents.
Sullivan
M C
MC
Department of Pharmacy, Hartford Hospital, Connecticut 06115.
Cooper
B W
BW
Nightingale
C H
CH
Quintiliani
R
R
Lawlor
M T
MT
D000818:Animals; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006207:Half-Life; D051379:Mice; D008826:Microbial Sensitivity Tests; D010400:Penicillin G / Q000008:administration & dosage / Q000627:therapeutic use; D011008:Pneumococcal Infections / Q000382:microbiology / Q000517:prevention & control*; D013296:Streptococcus pneumoniae / Q000187:drug effects
D002939:Ciprofloxacin; D010400:Penicillin G