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Repositioning of Benzodiazepine Drugs and Synergistic Effect with Ciprofloxacin Against ESKAPE Pathogens

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Abstract

Infectious diseases are among the leading causes of morbidity and mortality worldwide. Combating them becomes more complex when caused by the pathogens of the ESKAPE group, which are Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. The purpose of this study was to investigate the repositioning potential of the benzodiazepines clonazepam and diazepam individually and in combination with the antibacterial ciprofloxacin against ESKAPE. The minimum inhibitory concentration and minimum bactericidal concentration against seven American Type Culture Collection (ATCC) reference standard strains and 64 ESKAPE clinical isolates were determined. In addition, the interaction with ciprofloxacin was determined by the checkerboard method and fractional inhibitory concentration index (FICI) of clonazepam against 11 ESKAPE and diazepam against five ESKAPE. We also list the results found and their clinical significance. Benzodiazepines showed similar antibacterial activity against Gram-positive and Gram-negative. The checkerboard and FICI results showed a synergistic effect of these drugs when associated with ciprofloxacin against almost all tested isolates. Viewing the clinical cases studied, benzodiazepines have potential as treatment alternatives. The results allow us to conclude that clonazepam and diazepam, when in combination with ciprofloxacin, have promising activity against ESKAPE, therefore, assuming the position of candidates for repositioning.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES) [Finance Code 001] for financial support.

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Authors and Affiliations

  1. Laboratory of Bacteriology, Health Sciences Center, Federal University of Santa Maria, Santa Maria, RS, Brazil

    Taciéli F. da Rosa, Marissa B. Serafin, Vitória S. Foletto, Laísa N. Franco, Bruno R. de Paula, Luana B. Fuchs & Rosmari Hörner

  2. Department of Clinical and Toxicological Analysis, Health Sciences Center, Federal University of Santa Maria, Santa Maria, RS, Brazil

    Taciéli F. da Rosa, Marissa B. Serafin, Vitória S. Foletto, Laísa N. Franco, Bruno R. de Paula, Luana B. Fuchs & Rosmari Hörner

  3. University Hospital of Santa Maria, Federal University of Santa Maria, Santa Maria, RS, Brazil

    Luciano Calegari

  4. Bacteriology Laboratory, Department of Clinical and Toxicological Analysis (DACT)-Health Sciences Center (CCS)., Building 26, Room 1201, UFSM, Santa Maria, RS, 97105-900, Brazil

    Rosmari Hörner

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  1. Taciéli F. da Rosa
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Contributions

The conception and design of the study: TFR, MBS, VSF, LNF, BRP, LF, LC and R.H; Acquisition of data: TFR, MBS, VSF, LNF, BRP, LF, LC and RH; Analysis and interpretation of the data: TFR, MBS, VSF, LNF, BRP, LF, LC and RH; Drafting and critical revision of the manuscript: TFR, MBS, VSF, LNF, BRP, LF, LC and RH; Final approval of the version to be submitted: TFR, MBS, VSF, LNF, BRP, LF, LC and RH.

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Correspondence to Rosmari Hörner.

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The research was approved by the Research Ethics Committee of the Federal University of Santa Maria, being registered under the number of the CAAE Ethical Appreciation Certificate 928.497. Registration in the National System of Genetic Heritage Management and Associated Traditional Knowledge (SisGen) is registered under number R4B27A6—Federal University of Santa Maria.

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da Rosa, T.F., Serafin, M.B., Foletto, V.S. et al. Repositioning of Benzodiazepine Drugs and Synergistic Effect with Ciprofloxacin Against ESKAPE Pathogens. Curr Microbiol 80, 160 (2023). https://doi.org/10.1007/s00284-023-03242-y

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