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Current microbiology
Sep 22, 2024;81 (11): 371.

In Vitro Synergistic Activity of Rifampicin Combined with Minimal Effective Antibiotic Concentration (MEAC) of Polymyxin B Against Extensively Drug-Resistant, Carbapenem-, and Polymyxin B-Resistant Klebsiella pneumoniae Clinical Isolates.

Nathália Abichabki, Gilberto Gambero Gaspar, Luísa Vieira Zacharias, Renata Helena Cândido Pocente, Denissani Aparecida Ferrari Santos Lima, Natália Augusta Barbosa de Freitas, Guilherme Thomaz Pereira Brancini, Natália Columbaro Moreira, Gilberto Úbida Leite Braga, Fernando Bellissimo-Rodrigues, Valdes Roberto Bollela, Ana Lúcia Costa Darini, Leonardo Neves Andrade
Author Information
  1. Nathália Abichabki: School of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo (USP), Av. Prof. Dr. Zeferino Vaz - Vila Monte Alegre, Ribeirão Preto, SP, 14040-903, Brazil.
  2. Gilberto Gambero Gaspar: Ribeirão Preto Medical School (FMRP), University of São Paulo (USP), Av. Bandeirantes, 3900, Campus da USP - Cidade Universitária, Ribeirão Preto, SP, 14040-900, Brazil.
  3. Luísa Vieira Zacharias: School of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo (USP), Av. Prof. Dr. Zeferino Vaz - Vila Monte Alegre, Ribeirão Preto, SP, 14040-903, Brazil.
  4. Renata Helena Cândido Pocente: University Hospital of Ribeirão Preto Medical School (HCFMRP), University of São Paulo (USP), R. Ten. Catão Roxo, 3900 - Vila Monte Alegre, Ribeirão Preto, SP, 14015-010, Brazil.
  5. Denissani Aparecida Ferrari Santos Lima: University Hospital of Ribeirão Preto Medical School (HCFMRP), University of São Paulo (USP), R. Ten. Catão Roxo, 3900 - Vila Monte Alegre, Ribeirão Preto, SP, 14015-010, Brazil.
  6. Natália Augusta Barbosa de Freitas: University Hospital of Ribeirão Preto Medical School (HCFMRP), University of São Paulo (USP), R. Ten. Catão Roxo, 3900 - Vila Monte Alegre, Ribeirão Preto, SP, 14015-010, Brazil.
  7. Guilherme Thomaz Pereira Brancini: School of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo (USP), Av. Prof. Dr. Zeferino Vaz - Vila Monte Alegre, Ribeirão Preto, SP, 14040-903, Brazil.
  8. Natália Columbaro Moreira: School of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo (USP), Av. Prof. Dr. Zeferino Vaz - Vila Monte Alegre, Ribeirão Preto, SP, 14040-903, Brazil.
  9. Gilberto Úbida Leite Braga: Department of Clinical Analyses, Toxicology and Food Science (DACTB), School of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo (USP), Av. Prof. Dr. Zeferino Vaz - Vila Monte Alegre, Ribeirão Preto, SP, 14040-903, Brazil.
  10. Fernando Bellissimo-Rodrigues: Ribeirão Preto Medical School (FMRP), University of São Paulo (USP), Av. Bandeirantes, 3900, Campus da USP - Cidade Universitária, Ribeirão Preto, SP, 14040-900, Brazil.
  11. Valdes Roberto Bollela: Ribeirão Preto Medical School (FMRP), University of São Paulo (USP), Av. Bandeirantes, 3900, Campus da USP - Cidade Universitária, Ribeirão Preto, SP, 14040-900, Brazil.
  12. Ana Lúcia Costa Darini: Department of Clinical Analyses, Toxicology and Food Science (DACTB), School of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo (USP), Av. Prof. Dr. Zeferino Vaz - Vila Monte Alegre, Ribeirão Preto, SP, 14040-903, Brazil.
  13. Leonardo Neves Andrade: Department of Clinical Analyses, Toxicology and Food Science (DACTB), School of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo (USP), Av. Prof. Dr. Zeferino Vaz - Vila Monte Alegre, Ribeirão Preto, SP, 14040-903, Brazil. leonardo@fcfrp.usp.br. ORCID
PMID: 39307852 DOI: 10.1007/s00284-024-03897-1

Abstract

We investigated the in vitro antibacterial activity of the combination rifampicin (RIF) + polymyxin B (PB) against extensively drug-resistant (XDR) Klebsiella pneumoniae isolates. We evaluated clinical isolates co-resistant to PB (non-mcr carriers; eptB, mgrB, pmr operon, and ramA mutations) and to carbapenems (KPC, CTX-M, and SHV producers; including KPC + NDM co-producer), belonging to sequence types (ST) ST16, ST11, ST258, ST340, and ST437. We used the standard broth microdilution method to determine RIF and PB minimum inhibitory concentration (MIC) and the checkerboard assay to evaluate the fractional inhibitory concentration index (FICI) of RIF + PB as well as to investigate the lowest concentrations of RIF and PB that combined (RIF + PB) had antibacterial activity. Time-kill assays were performed to evaluate the synergistic effect of the combination against selected isolates. PB MIC (32-256 µg/mL) and RIF MIC (32-1024 µg/mL) were determined. FICI (<0.5) indicated a synergistic effect for all isolates evaluated for the combination RIF + PB. Our results showed that low concentrations of PB (PB minimal effective antibiotic concentration [MEAC], ≤0.25-1 µg/mL) favor RIF (≤0.03-0.125 µg/mL) to reach the bacterial target and exert antibacterial activity against PB-resistant isolates, and the synergistic effect was also observed in time-kill results. The combination of RIF + PB showed in vitro antibacterial activity against XDR, carbapenem-, and PB-resistant K. pneumoniae and could be further studied as a potential combination therapy, with cost-effectiveness and promising efficacy.

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Grants

  1. 406192/2023-5/Conselho Nacional de Desenvolvimento Científico e Tecnológico
  2. 140875/2024-7/Conselho Nacional de Desenvolvimento Científico e Tecnológico
  3. INCT - MCTI/CNPq/CAPES/FAPs nº 16/2014/Instituto Nacional de Pesquisas em Resistência a Antimicrobianos
  4. INCT - MCTI/CNPq/CAPES/FAPs nº 16/2014/Instituto Nacional de Pesquisas em Resistência a Antimicrobianos
  5. 88887.670254/2022-0/Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
  6. 8887.716776/2022-00/Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

MeSH Term

Polymyxin B
Rifampin
Klebsiella pneumoniae
Microbial Sensitivity Tests
Anti-Bacterial Agents
Drug Synergism
Humans
Carbapenems
Drug Resistance, Multiple, Bacterial
Klebsiella Infections

Chemicals

Polymyxin B
Rifampin
Anti-Bacterial Agents
Carbapenems
Journal Article

Word Cloud

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