Varied synergistic activity of colistin and polymyxin B with meropenem, rifampicin and tigecycline: An in vitro study on carbapenem resistant Acinetobacter baumannii from India

Document Type

Article

Publication Title

Indian Journal of Medical Microbiology

Abstract

Purpose: Effective therapeutic choices for infections by carbapenem resistant Acinetobacter baumannii (CRAB) in resource constrained settings is limited. Prospective antimicrobial combinations with polymyxins, need to be tested for synergy to mitigate further development of resistance. This study evaluates the synergistic effects of colistin and polymyxin B combined with meropenem, rifampicin, and tigecycline against CRAB isolates from bloodstream infections. Methods: Twenty-five epidemiologically distinct CRAB strains were included. The minimum inhibitory concentrations (MICs) of the antimicrobials were determined by broth microdilution. The synergistic activities of the antimicrobial combinations were evaluated by checkerboard broth microdilution (CBM). Antimicrobials were tested at concentrations from 4 to 8 times down to 1/8–1/16 of their expected MIC, with a final inoculum of 105 CFU/mL. The antimicrobial combinations that demonstrated greater synergistic activity were confirmed using the time-kill assay (TKA). Results: None of the strains were resistant to polymyxins (MIC ≤4 mg/L). Colistin-meropenem, colistin-rifampicin and colistin-tigecycline combinations achieved superior synergy over the polymyxin B-meropenem, polymyxin B-rifampicin and polymyxin B-tigecycline combinations (P=<0.001, P = 0.03, and P = 0.01, respectively) in the CBM assay. In the TKA, combinations of colistin (0.1–0.5 mg/L) with subinhibitory concentrations of meropenem (4–8 mg/L), rifampicin (1–4 mg/L), and tigecycline (0.06–0.25 mg/L) exhibited synergistic and bactericidal activity against a subset of isolates at 24 h. Conclusions: Significant concordance between the CBM and TKA was observed. Our findings suggest that subinhibitory antimicrobial concentrations in combinations can improve therapeutic efficacy and minimize polymyxin side effects. Additionally, in vivo studies are warranted to optimize the combinational therapy.

DOI

10.1016/j.ijmmb.2025.100889

Publication Date

7-1-2025

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