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Synergistic activity of polymyxin B combined with vancomycin against carbapenem-resistant and polymyxin-resistant Acinetobacter baumannii: first in vitro study

2019; Microbiology Society; Volume: 68; Issue: 3 Linguagem: Inglês

10.1099/jmm.0.000920

1473-5644

Danielle Rosani Shinohara, Thatiany Cevallos Menegucci, Nayara Helisandra Fedrigo, Letícia Busato Migliorini, Floristher Elaine Carrara-Marroni, Márcia Maria dos Anjos, Celso Luíz Cardoso, Sheila Alexandra Belini Nishiyama, Maria Cristina Bronharo Tognim,

Antibiotics Pharmacokinetics and Efficacy

Purpose. The effect of a combination of polymyxin B (PMB) and vancomycin (VAN) was assessed against six Acinetobacter baumannii clinical isolates belonging to six different clusters (three PMB-susceptible and three PMB-resistant). Methodology. The synergistic effect of the PMB–VAN combination was determined with the checkerboard, time-kill, disk-diffusion and M.I.C.Evaluator assays. PMB-resistance was investigated with mcr-1 gene amplification and a mutant frequency assay. Results. In the checkerboard assay, all PMB-resistant isolates showed a synergistic effect. The time-kill assay demonstrated that the PMB–VAN combination had a bactericidal effect at 24 h against isolates with a high mutant rate for PMB, suggesting that this combination may block the hypermutation of some isolates. No antagonism was detected. All PMB-resistant isolates also showed synergism in the disk-diffusion test, and a significant decrease in VAN MICs in the M.I.C.Evaluator assay. Conclusion. Our findings indicate that the PMB–VAN combination has a synergistic effect on A. baumannii , especially against PMB-resistant isolates.