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 10⁶ 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–·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.