Antibiotic Combinations for Controlling Colistin-resistant Enterobacter Cloacae

Overview

Journal J Antibiot (Tokyo)

Specialties Infectious Diseases
Pharmacology

Date 2016 Jul 7

PMID 27381521

Citations 4

Authors

Thais Bergamin Lima

Osmar Nascimento Silva

Keyla Caroline de Almeida

Suzana Meira Ribeiro

Dielle de Oliveira Motta

Simone Maria-Neto

Michelle Brizolla Lara

Carlos Roberto Souza Filho

Alicia Simalie Ombredane

Celio de Faria Junior

Nadia Skorupa Parachin

Beatriz Simas Magalhaes

Octavio Luiz Franco

Affiliations

Soon will be listed here.

Abstract

Enterobacter cloacae is a Gram-negative bacterium associated with high morbidity and mortality in intensive care patients due to its resistance to multiple antibiotics. Currently, therapy against multi-resistant bacteria consists of using colistin, in spite of its toxic effects at higher concentrations. In this context, colistin-resistant E. cloacae strains were challenged with lower levels of colistin combined with other antibiotics to reduce colistin-associated side effects. Colistin-resistant E. cloacae (ATCC 49141) strains were generated by serial propagation in subinhibitory colistin concentrations. After this, three colistin-resistant and three nonresistant replicates were isolated. The identity of all the strains was confirmed by MALDI-TOF MS, VITEK 2 and MicroScan analysis. Furthermore, cross-resistance to other antibiotics was checked by disk diffusion and automated systems. The synergistic effects of the combined use of colistin and chloramphenicol were observed via the broth microdilution checkerboard method. First, data here reported showed that all strains presented intrinsic resistance to penicillin, cephalosporin (except fourth generation), monobactam, and some associations of penicillin and β-lactamase inhibitors. Moreover, a chloramphenicol and colistin combination was capable of inhibiting the induced colistin-resistant strains as well as two colistin-resistant clinical strains. Furthermore, no cytotoxic effect was observed by using such concentrations. In summary, the data reported here showed for the first time the possible therapeutic use of colistin-chloramphenicol for infections caused by colistin-resistant E. cloacae.

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