In Vitro Synergistic Activity of Biapenem Combination with Sulbactam, Colistin, and Fosfomycin Sodium Against Multidrug-resistant Acinetobacter baumannii Isolates from Tertiarycare Hospitals in Thailand

Abstract

Background Acinetobacter baumannii has become a major cause of nosocomial infections worldwide due to highly resistance to various groups of antibacterial agents. This in vitro study was determine the MICs for sulbactam, colistin, fosfomycin sodium individually and synergistic activity of both in combination with biapenem against multidrug-resistant A. baumannii.MethodsThe MICs and synergistic interaction of sulbactam, colistin, fosfomycin sodium and biapenem were determined according to the Clinical and Laboratory Standards Institute (CLSI) guidelines (2016) by the chequerboard technique. 40 clinical MDR-Acinetobacter baumannii isolates from 13 tertiarycare hospitals in Thailand were tested. The synergistic effect was evaluated by the fractional inhibitory concentration index (FICI).ResultsThe MICs for MDR- Acinetobacter baumannii results of biapenem and other agents are shown in Figure 1. The FICI results showed all 40 strains (100%) had an FICI ≤ 0.5, suggesting a synergistic effect of colistin in combination with biapenem (Table 1). MICs of mostly strains were decreased two to four doubling dilutions for both antibacterial agents. Moreover, 95% of isolates have MICs to colistin and fosfomycin sodium lower than sensitivity breakpoint when combined with biapenem. The result showed no data on the antagonistic effect (FICI ˃4) of all biapenem-based combination.ConclusionThe combination of colistin or fosfomycin sodium with biapenem show synergistic pattern and MICs improvement for all strains. For that reason, the use of colistin, fosfomycin sodium combined with biapenem could be a promising treatment option for MDR- Acinetobacter baumannii.FIGURE 1.MIC for multidrug resistant Acinetobacter baumannii biapenem (n = 63), sulbactam (n = 40), colistin (n = 40), and fosfomycin sodium(n = 40).TABLE 1.Synergistic effect of sulbactam, colistin, and fosfomycin sodium with biapenem against MDR A. baumannii (n = 40) by using the checkerboard assayEffectNumber of Isolates (%)Sulbactam + BiapenemColistin + BiapenemFosfomycin sodium + BiapenemSynergy (FICI≤0.5)30 (75)40 (100)33 (82.5)Partial synergy (FICI>0.5-<1)9 (20)07 (17.5)Additive (FICI=1)1 (5)00Indifference (FICI>1-≤4)000Antagonism (FICI>4)000Disclosures J. Houngsaitong, Thai Meiji Co.,Ltd: No relationship, Research grant