TY - JOUR
T1 - Varied synergistic activity of colistin and polymyxin B with meropenem, rifampicin and tigecycline
T2 - An in vitro study on carbapenem resistant Acinetobacter baumannii from India
AU - Tantry, Manasa
AU - Varma, Muralidhar
AU - Rao, Shwethapriya
AU - Mukhopadhyay, Chiranjay
AU - Eshwara, Vandana Kalwaje
N1 - Publisher Copyright:
© 2025 Indian Association of Medical Microbiologists
PY - 2025/7/1
Y1 - 2025/7/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105007044566
UR - https://www.scopus.com/pages/publications/105007044566#tab=citedBy
U2 - 10.1016/j.ijmmb.2025.100889
DO - 10.1016/j.ijmmb.2025.100889
M3 - Article
AN - SCOPUS:105007044566
SN - 0255-0857
VL - 56
JO - Indian Journal of Medical Microbiology
JF - Indian Journal of Medical Microbiology
M1 - 100889
ER -
