2405. In vitro Synergistic Activity of Sitafloxacin in Combination With Colistin Against Clinical Isolates of Multidrug-Resistant Acinetobacter baumannii in Thailand

Abstract

BackgroundMultidrug-resistant Acinetobacter baumannii (MDR-AB) is a major cause of nosocomial infections, and associated with high mortality rate. The objective of this study was to test synergistic effect of sitafloxacin and colistin against MDR-AB clinical isolates in Thailand.MethodsThe synergistic effect of sitafloxacin in combination with colistin against the 264 MDR-AB clinical isolates from 13 tertiary care hospitals in Thailand were tested. The fractional inhibitory concentration index (FICI) of combination was determined using the checkerboard method according to CLSI 2016. Time–kill assays were performed for 2 strains (H25 and K21) using sitafloxacin alone and in combination with colistin.ResultsThe MICs of sitafloxacin and colistin range from 0.0156 to 8 µg/mL, and 0.5–16 µg/mL, respectively. The results of synergy testing for the 264 MDR-AB isolates are shown in Table 1. Sitafloxacin reduced the MIC of colistin 2-fold to 8-fold from the original concentrations (Figure 1). From 43 colistin-resistant isolates in combination tested, 39 isolates (90.7%) become susceptible to colistin. In the time-kill assay, synergistic effects were found for two isolates in all concentrations tested, and bactericidal activity was observed within 4 hours and maintained over 24 hours (Figures 2 and 3).Table 1:Synergistic Effect of Sitafloxacin and Colistin Against MDR-AB Isolates (n = 264) Using the Checkerboard AssayAntimicrobial AgentsNo. of Isolates (%)Synergy (FICI ≤0.5)Partial Synergy (FICI >0.5–<1)Additive (FICI = 1)Indifference (FICI >1–<4)Antagonism (FICI ≥4)Sitafloxacin and colistin9(3.4)99(37.5)75(28.4)81(30.7)0(0)Figure 1:MIC reduction of colistin in combination with sitafloxacin against MDR-AB (n = 264).Figure 2:Time–kill curves for sitafloxacin and colistin alone against two isolates of MDR-AB.Figure 3:Time–kill curves with various concentrations of colistin (C) and sitafloxacin (S) in combination against two isolates of MDR-AB.ConclusionThe synergistic effect of sitafloxacin and colistin combination was found. Most of isolates had at least a 2-fold decrease in MIC of colistin, which could be implied to reduce dose of colistin 50% from regular dose. Sitafloxacin combined with colistin may be benefit for alternative treatment of MDR-AB infections.Disclosures T. Paiboonvong, Daiichi Sankyo (Thailand) Ltd.: Grant support, Research support. P. Montakantikul, Daiichi Sankyo (Thailand) Ltd.: Grant support, Research grant.