Abstract

The aim was to explore the antimicrobial activity of a synthetic peptide (AMP38) and its synergy with imipenem against imipenem-resistant Pseudomonas aeruginosa. The main mechanism of imipenem resistance is the loss or alteration of protein OprD. Time-kill and minimal biofilm eradication concentration (MBEC) determinations were carried out by using clinical imipenem-resistant strains. AMP38 was markedly synergistic with imipenem when determined in imipenem-resistant P. aeruginosa. MBEC obtained for the combination of AMP38 and imipenem was of 62.5 μg/mL, whereas the MBEC of each antimicrobial separately was 500 μg/mL. AMP38 should be regarded as a promising antimicrobial to fight MDR P. aeruginosa infections. Moreover, killing effect and antibiofilm activity of AMP38 plus imipenem was much higher than that of colistin plus imipenem.

Highlights

  • Pseudomonas aeruginosa is a nosocomial opportunistic pathogen causing a wide variety of both acute and chronic infections, such as pneumonia, bacteraemia, and urinary tract infections.Immunocompromised patients and those suffering cystic fibrosis show a high susceptibility to infection by this microorganism [1].the increasing frequency of the isolation of multidrug-resistant Pseudomonas aeruginosa (MDRPA) is a major cause for concern

  • The aim of this study was to explore the antimicrobial activity of a novel synthetic cyclolipopeptide analog of polymyxin (AMP38) and its synergy with carbapenems in order to contribute to the improvement of treatments for infections caused by carbapenem-resistant P. aeruginosa

  • When assays were performed with AMP38, the fractional inhibitory concentrations (FICs) index (FICi) value to be considered as indifferent

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Summary

Introduction

Pseudomonas aeruginosa is a nosocomial opportunistic pathogen causing a wide variety of both acute and chronic infections, such as pneumonia, bacteraemia, and urinary tract infections.Immunocompromised patients and those suffering cystic fibrosis show a high susceptibility to infection by this microorganism [1].the increasing frequency of the isolation of multidrug-resistant Pseudomonas aeruginosa (MDRPA) is a major cause for concern. Pseudomonas aeruginosa is a nosocomial opportunistic pathogen causing a wide variety of both acute and chronic infections, such as pneumonia, bacteraemia, and urinary tract infections. Immunocompromised patients and those suffering cystic fibrosis show a high susceptibility to infection by this microorganism [1]. Carbapenems— imipenem—are broad-spectrum antimicrobials commonly used for the treatment of MDRPA infections. Their mechanism of action is based in the inhibition of the third step of the synthesis of bacterial cell wall by binding to certain penicillin-binding proteins (PBPs)

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