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The in-vivo postantibiotic effect of imipenem and other new antimicrobials
Abstract:
The postantibiotic effect (PAE) in vivo of imipenem, cefoperazone and latamoxef was investigated in a neutropenic mouse thigh model. Two hours after inoculation of 10(6) cfu of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa into each thigh, the neutropenic mice were treated with single doses of 50-200 mg/kg imipenem, 40-1200 mg/kg cefoperazone and 50-100 mg/kg latamoxef. Serum levels exceeded the MIC for 1.1-2.9 h. Cefoperazone and latamoxef induced PAEs of 2.1-5.6 h for S aureus, but no significant PAEs were induced for the Gram-negative bacilli. In contrast imipenem produced PAE of 0.9-4.6 h with P. aeruginosa. However, strain variation was observed in the duration of the PAE after imipenem. These data are in concordance with the PAEs of the antimicrobials under study when these are determined in vitro. The implications of these findings for clinical use of these drugs need further evaluation.
Insights
This study investigated the in vivo postantibiotic effect (PAE) of imipenem, cefoperazone, and latamoxef against Staphylococcus aureus and Gram-negative bacteria in neutropenic mice. Cefoperazone and latamoxef showed significant PAE against S. aureus, while imipenem demonstrated effectiveness against Pseudomonas aeruginosa.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- The postantibiotic effect (PAE) is crucial for understanding antibiotic efficacy.
- Neutropenic hosts are highly susceptible to bacterial infections, necessitating effective antimicrobial strategies.
Purpose of the Study:
- To evaluate the in vivo postantibiotic effect (PAE) of imipenem, cefoperazone, and latamoxef.
- To compare the PAE of these antibiotics against Staphylococcus aureus and Gram-negative bacilli (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa) in a neutropenic mouse model.
Main Methods:
- A neutropenic mouse thigh infection model was established using 10^6 CFU of S. aureus, E. coli, K. pneumoniae, or P. aeruginosa.
- Mice were treated with single doses of imipenem (50-200 mg/kg), cefoperazone (40-1200 mg/kg), or latamoxef (50-100 mg/kg).
- Serum drug levels and PAE were determined, comparing in vivo results with in vitro data.
Main Results:
- Cefoperazone and latamoxef induced significant PAEs (2.1-5.6 hours) against S. aureus but not against Gram-negative bacteria.
- Imipenem demonstrated a PAE (0.9-4.6 hours) against P. aeruginosa, with observed strain variation.
- Serum antibiotic levels exceeded the minimum inhibitory concentration (MIC) for 1.1-2.9 hours.
Conclusions:
- The in vivo PAE findings for imipenem, cefoperazone, and latamoxef generally align with in vitro observations.
- Cefoperazone and latamoxef exhibit specific PAE against S. aureus, while imipenem shows activity against P. aeruginosa.
- Further clinical evaluation is warranted to understand the implications of these PAE findings for patient treatment.