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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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Acknowledgements

This study was supported by grants from CNPq, CAPES, FUNDECT, FAPDF, EMBRAPA, UCB and UCDB.

Author information

Author notes

    • Thais Bergamin Lima
    • , Osmar Nascimento Silva
    •  & Keyla Caroline de Almeida

    These authors contributed equally to this work.

Affiliations

  1. Department of Biotechnology, Centro de Análises Proteômicas e Bioquímicas, Universidade Católica de Brasília, Brasilia, Brazil

    • Thais Bergamin Lima
    • , Keyla Caroline de Almeida
    • , Dielle de Oliveira Motta
    • , Simone Maria-Neto
    • , Michelle Brizolla Lara
    • , Carlos Roberto Souza Filho
    • , Alicia Simalie Ombredane
    • , Nadia Skorupa Parachin
    • , Beatriz Simas Magalhães
    •  & Octávio Luiz Franco
  2. UDF Centro Universitario, Brasilia, Brazil

    • Thais Bergamin Lima
  3. Department of Biotechnology, S-Inova Biotech, Universidade Católica Dom Bosco, Campo Grande, Brazil

    • Osmar Nascimento Silva
    • , Suzana Meira Ribeiro
    •  & Octávio Luiz Franco
  4. Department of Cell Biology, Universidade de Brasília, Campus Asa Norte, Brasília, Brazil

    • Keyla Caroline de Almeida
    •  & Octávio Luiz Franco
  5. Department of microbiology, Núcleo de Bacteriologia, Laboratório Central de Saúde Pública Distrito Federal, Brasília, Brazil

    • Celio de Faria Junior

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Correspondence to Octávio Luiz Franco.

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DOI

https://doi.org/10.1038/ja.2016.77

Supplementary Information accompanies the paper on The Journal of Antibiotics website (http://www.nature.com/ja)

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