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Evaluation of the efficacy of ciprofloxacin against Streptococcus pneumoniae by using a mouse protection model
M C Sullivan1, B W Cooper, C H Nightingale
1Department of Pharmacy, Hartford Hospital, Connecticut 06115.
Abstract:
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.
Insights
Ciprofloxacin showed 83-fold less efficacy than penicillin G in treating Streptococcus pneumoniae infections in mice. Pharmacodynamic differences explain why ciprofloxacin is less successful clinically.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Streptococcus pneumoniae is a significant pathogen causing severe infections.
- Ciprofloxacin and penicillin G are antibiotics used to treat bacterial infections, but their clinical efficacy can vary.
- Understanding the pharmacokinetic and pharmacodynamic (PK/PD) properties of antibiotics is crucial for predicting in vivo efficacy.
Purpose of the Study:
- To compare the in vivo efficacy of ciprofloxacin and penicillin G against Streptococcus pneumoniae using a mouse protection model.
- To investigate the association between PK/PD parameters and the efficacy of these antibiotics.
- To elucidate the reasons for differing clinical success rates between ciprofloxacin and penicillin G.
Main Methods:
- A mouse model was established by intraperitoneal inoculation with Streptococcus pneumoniae ATCC 6303.
- Subcutaneous antibiotic administration (ciprofloxacin vs. penicillin G) commenced 1 hour post-infection and continued for 24 hours.
- The 50% protective dose (PD50) and drug concentration-dependent parameters (T > MIC, Peak/MIC) were determined.
Main Results:
- Ciprofloxacin demonstrated an 83-fold lower efficacy compared to penicillin G, with PD50 values of 25.52 mg/kg and 0.307 mg/kg, respectively.
- Achieving 100% protection with penicillin G required drug concentrations above the minimum inhibitory concentration (MIC) for 51 minutes.
- For 100% protection with ciprofloxacin, a peak concentration to MIC ratio of 10.6 was needed, a level rarely attained in clinical practice against S. pneumoniae.
Conclusions:
- Significant PK/PD differences exist between ciprofloxacin and penicillin G in treating S. pneumoniae infections.
- The high peak concentration/MIC ratio required for ciprofloxacin's efficacy is difficult to achieve clinically, contributing to its lower success rates compared to penicillin G.
- These findings highlight the importance of PK/PD profiling in guiding antibiotic selection and optimizing treatment strategies for bacterial infections.
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