Inhibition of metallo-β-lactamases in carbapenem resistant Gram negative bacilli by omeprazole and pantoprazole.

Abstract

Background: Carbapenems are the most commonly used antibiotics for severe infections induced by metallo-beta-lactamases producing Enterobacteriaceae and Pseudomonas aeruginosa. Resistance to almost all β-lactam antibiotics, including carbapenems, is conferred by metallo-β-lactamases (MBLs).

Objectives: Detection and inhibition of MBLs production as a promising approach to overcome resistance to carbapenems.

Methods: 160 clinical isolates of Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae were tested for antimicrobial susceptibility by The disk-diffusion method. The ability of the isolates to produce MBL enzyme was detected phenotypically and genotypically by PCR. The potential ability of pantoprazole and omeprazole to inhibit metallo-β-lactamases (MBLs) was confirmed by real-time PCR.

Results: Omeprazole and pantoprazole reduced the hydrolytic activities of MBLs. Both drugs had synergistic effects with meropenem. Meropenem minimum inhibitory concentration decreased in the presence of pantoprazole (2-16) folds, and omeprazole (2-32) folds. The metallo-β-lactamases genes bla_NDM , bla_IMP and bla_VIM were downregulated by both drugs. In silico study showed that both drugs had reasonable binding energy and revealed that omeprazole had higher binding energy and chelating activity of zinc ions of the enzymes.

Conclusion: The combination between meropenem and omeprazole or pantoprazole could be useful for treating infections caused by MBLs producing bacteria.