title: Antibiotic combinations for controlling colistin-resistant Enterobacter cloacae.
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.
authors.affiliation: Department of Biotechnology, Centro de Análises Proteômicas e Bioquímicas, Universidade Católica de Brasília, Brasilia, Brazil.|UDF Centro Universitario, Brasilia, Brazil.
authors.forename: Thais Bergamin
authors.initials: TB
authors.lastname: Lima
authors.affiliation: Department of Biotechnology, S-Inova Biotech, Universidade Católica Dom Bosco, Campo Grande, Brazil.
authors.forename: Osmar Nascimento
authors.initials: ON
authors.lastname: Silva
authors.affiliation: Department of Biotechnology, Centro de Análises Proteômicas e Bioquímicas, Universidade Católica de Brasília, Brasilia, Brazil.|Department of Cell Biology, Universidade de Brasília, Campus Asa Norte, Brasília, Brazil.
authors.forename: Keyla Caroline
authors.initials: KC
authors.lastname: de Almeida
authors.affiliation: Department of Biotechnology, S-Inova Biotech, Universidade Católica Dom Bosco, Campo Grande, Brazil.
authors.forename: Suzana Meira
authors.initials: SM
authors.lastname: Ribeiro
authors.affiliation: Department of Biotechnology, Centro de Análises Proteômicas e Bioquímicas, Universidade Católica de Brasília, Brasilia, Brazil.
authors.forename: Dielle de Oliveira
authors.initials: DO
authors.lastname: Motta
authors.affiliation: Department of Biotechnology, Centro de Análises Proteômicas e Bioquímicas, Universidade Católica de Brasília, Brasilia, Brazil.
authors.forename: Simone
authors.initials: S
authors.lastname: Maria-Neto
authors.affiliation: Department of Biotechnology, Centro de Análises Proteômicas e Bioquímicas, Universidade Católica de Brasília, Brasilia, Brazil.
authors.forename: Michelle Brizolla
authors.initials: MB
authors.lastname: Lara
authors.affiliation: Department of Biotechnology, Centro de Análises Proteômicas e Bioquímicas, Universidade Católica de Brasília, Brasilia, Brazil.
authors.forename: Carlos Roberto Souza
authors.initials: CR
authors.lastname: Filho
authors.affiliation: Department of Biotechnology, Centro de Análises Proteômicas e Bioquímicas, Universidade Católica de Brasília, Brasilia, Brazil.
authors.forename: Alicia Simalie
authors.initials: AS
authors.lastname: Ombredane
authors.affiliation: Department of microbiology, Núcleo de Bacteriologia, Laboratório Central de Saúde Pública Distrito Federal, Brasília, Brazil.
authors.forename: Celio
authors.initials: C
authors.lastname: de Faria Junior
authors.affiliation: Department of Biotechnology, Centro de Análises Proteômicas e Bioquímicas, Universidade Católica de Brasília, Brasilia, Brazil.
authors.forename: Nadia Skorupa
authors.initials: NS
authors.lastname: Parachin
authors.affiliation: Department of Biotechnology, Centro de Análises Proteômicas e Bioquímicas, Universidade Católica de Brasília, Brasilia, Brazil.
authors.forename: Beatriz Simas
authors.initials: BS
authors.lastname: Magalhães
authors.affiliation: Department of Biotechnology, Centro de Análises Proteômicas e Bioquímicas, Universidade Católica de Brasília, Brasilia, Brazil.|Department of Biotechnology, S-Inova Biotech, Universidade Católica Dom Bosco, Campo Grande, Brazil.|Department of Cell Biology, Universidade de Brasília, Campus Asa Norte, Brasília, Brazil.
authors.forename: Octávio Luiz
authors.initials: OL
authors.lastname: Franco
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D002473:Cell Wall / Q000187:drug effects; D003091:Colistin / Q000494:pharmacology*; D004269:DNA, Bacterial; D024901:Drug Resistance, Multiple, Bacterial; D016972:Enterobacter cloacae / Q000187:drug effects*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D012329:RNA, Bacterial
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D012329:RNA, Bacterial; D003091:Colistin