Abstract

This in vitro study aimed to determine the activity of colistin plus sulbactam and colistin plus fosfomycin against carbapenem-resistant A. baumannii (CRAB). Fifteen clinical isolates were obtained from patients admitted to Phyathai II International Hospital, Bangkok, Thailand, from August 2014 to April 2015. The antimicrobial susceptibilities of colistin, sulbactam, and fosfomycin were evaluated using the E-test or broth microdilution and the synergistic activity of the antibacterial combinations (colistin plus sulbactam or fosfomycin) was determined using the chequerboard method. Clonal relationships were explored using repetitive element palindromic- (REP-) PCR. The CRAB isolates were categorized by REP-PCR in 8 groups [A-H]. All CRAB isolates were universally susceptible to colistin but only 20.0% were susceptible to sulbactam. The MIC ranges for colistin, sulbactam, and fosfomycin were 0.75–2 mg/L, 2–96 mg/L, and 64–256 mg/L, respectively. A chequerboard assay revealed that the rates of synergistic and additive effect rates of colistin plus sulbactam and colistin plus fosfomycin were 53.3% and 73.3% of isolates, respectively. No antagonistic effect in any colistin-based combination was observed. However, almost CRAB strains in clone A showed the synergy or additive effects of colistin-sulbactam combination, whereas the other clone (B-H) mostly showed indifferent effects. In conclusion, colistin plus sulbactam and colistin plus fosfomycin against CRAB seem to be interesting option but the efficacy in clinical use has to be evaluated.

Highlights

  • Carbapenem-resistant A. baumannii (CRAB) is the most important pathogen in nosocomial infections worldwide causing high morbidity and mortality and increasing medical expenditure [1, 2]

  • Colistin or polymyxin B-based combinations are recommended as treatments for CRAB because almost all strains of CRAB remain sensitive to polymyxins [5], while sulbactam and fosfomycin have better pharmacokinetic profiles with moderate and low protein Journal of Pathogens binding

  • Fifteen CRAB isolates were obtained from various sites

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Summary

Introduction

Carbapenem-resistant A. baumannii (CRAB) is the most important pathogen in nosocomial infections worldwide causing high morbidity and mortality and increasing medical expenditure [1, 2]. Data from the National Antimicrobial Resistant Surveillance, Thailand, in 2015, showed that A. baumannii was ranked the third and second of pathogens isolated from all specimens and sputum, respectively. Considering the various CRAB strains, the report showed that A. baumannii was up to 70% resistant to imipenem or meropenem (National Antimicrobial Resistant Surveillance, Thailand, 2015); CRAB infections are difficult to treat in an increasingly antimicrobial resistant era. Certain studies have focused on determining the synergist effect of colistin plus sulbactam and colistin plus fosfomycin against A. baumannii. Those previous studies of in vitro synergism showed that colistin plus sulbactam might be a combined therapeutic option for CRAB treatment [3]. Colistin combined with fosfomycin revealed a synergistic effect or additive effects against CRAB strains or extensively drug-resistant A. baumannii, but only two studies addressed the colistin-fosfomycin combination with discordant results [8, 9]

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