Journal Article

Antibiotic combinations for controlling colistin-resistant Enterobacter cloacae

Ribeiro, Suzana Meira, Lima, Thais Bergamin, Maria-Neto, Simone, Silva, Osmar Nascimento, Magalhães, Beatriz Simas, Parachin, Nadia Skorupa, de Almeida, Keyla Caroline, Lara, Michelle Brizolla, Franco, Octávio Luiz, de Faria Junior, Celio, Filho, Carlos Roberto Souza, Motta, Dielle de Oliveira, Ombredane, Alicia Simalie

2017

Overview

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 .

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/45 / 82/58 / Anti-Bacterial Agents - administration & dosage / Anti-Bacterial Agents - pharmacology / Antibiotics / Bacteria / Bacteriology / Biomedical and Life Sciences / Bioorganic Chemistry / Cell Wall - drug effects / Cephalosporins / Chloramphenicol / Chloromycetin / Colistin / Colistin - pharmacology / Cross-resistance / Cytotoxicity / DNA, Bacterial / Drug Resistance, Multiple, Bacterial / Enterobacter cloacae / Enterobacter cloacae - drug effects / Gene Expression Regulation, Bacterial - drug effects / Gram-negative bacteria / Life Sciences / Medicinal Chemistry / Microbiology / Morbidity / Organic Chemistry / original-article / Penicillin / RNA, Bacterial / Side effects / Strains (organisms) / Synergistic effect / β Lactamase