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.
Journal
Current microbiology
ISSN: 1432-0991
Titre abrégé: Curr Microbiol
Pays: United States
ID NLM: 7808448
Informations de publication
Date de publication:
22 Sep 2024
22 Sep 2024
Historique:
received:
05
08
2024
accepted:
11
09
2024
medline:
23
9
2024
pubmed:
23
9
2024
entrez:
22
9
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39307852
doi: 10.1007/s00284-024-03897-1
pii: 10.1007/s00284-024-03897-1
doi:
Substances chimiques
Polymyxin B
J2VZ07J96K
Rifampin
VJT6J7R4TR
Anti-Bacterial Agents
0
Carbapenems
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
371Subventions
Organisme : Conselho Nacional de Desenvolvimento Científico e Tecnológico
ID : 406192/2023-5
Organisme : Conselho Nacional de Desenvolvimento Científico e Tecnológico
ID : 140875/2024-7
Organisme : Instituto Nacional de Pesquisas em Resistência a Antimicrobianos
ID : INCT - MCTI/CNPq/CAPES/FAPs nº 16/2014
Organisme : Instituto Nacional de Pesquisas em Resistência a Antimicrobianos
ID : INCT - MCTI/CNPq/CAPES/FAPs nº 16/2014
Organisme : Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
ID : 88887.670254/2022-0
Organisme : Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
ID : 8887.716776/2022-00
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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