Postantibiotic and Post-Beta-Lactamase Inhibitor Effect of Carbapenems Combined with EDTA against Pseudomonas aeruginosa Strains Producing VIM-Metallo Beta-Lactamases

Abstract

Background and Aim: Postantibiotic effect (PAE) is a delay of bacterial growth after short exposure to antibiotics. The phenomenon of continuing suppression of bacterial growth after removal of β-lactamase inhibitors is termed post-β-lactamase inhibitor effect (PLIE). Recently, Pseudomonas aeruginosa strains producing metallo-β-lactamases were described in many countries of the world. The aim of the study was to investigate the PLIE of carbapenems in combinations with EDTA against VIM-MBL-positive strains of P. aeruginosa. Methods: The experiments were performed on two Pseudomonas aeruginosa isolates, one producing VIM-1 and the other producing VIM-2 metallo-β-lactamase. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBC) of imipenem and meropenem alone and combined with EDTA, time-kill curves, PAE and PLIE were performed as described previously. Results: The duration of PAE with meropenem combined with EDTA at 8 × MIC was longer against both VIM-1 and VIM-2 producer than that of imipenem with EDTA on VIM-1- and VIM-2-positive strains. The duration of PLIE was similar on both strains of P. aeruginosa regardless of the sort of carbapenem. At lower concentrations, meropenem with EDTA induced slightly longer PAE and PLIE than imipenem with EDTA. Conclusions: This study has shown that EDTA combined with carbapenems produced a significant PLIE on VIM-MBL-positive P. aeruginosa strains. The results do not have any clinical relevance so far since metal chelators such as EDTA are not used as therapeutic agents due to their toxicity.