In Vitro Synergistic Activity of Sulbactam in Combination with Imipenem, Meropenem and Cefoperazone Against Carbapenem-Resistant Acinetobacter baumannii Isolates

Acinetobacter baumannii which is an opportunistic pathogen leading to nosocomial epidemics, exhibit high rates of antimicrobial resistance. Treatment of Acinetobacter infections is a challenge since most of the isolates are multiple antibiotic resistant. The aim of this study was to investigate minimum inhibitory concentrations (MICs) of sulbactam, imipenem, meropenem, and cefoperazone and in vitro synergistic activity of sulbactam in combination with imipenem, meropenem and cefoperazone against A.baumannii isolates of hospitalized patients. Forty A.baumannii strains isolated from various clinical specimens and found to be resistant to carbapenems by disc diffusion method, were included in the study. The isolates were identified by conventional methods and VITEK 2 (bioMerieux, France) automated identification system. MICs of sulbactam, imipenem, meropenem, and cefoperazone were determined by the broth microdilution method according to the standards of CLSI and in vitro synergy test was performed using the checkerboard microdilution method. Synergistic, partial synergistic, additive, indifferent and antagonistic effects of drug combinations were evaluated with the fractional inhibitory concentration index (FICI). Interpretation of the FICI was as follows: ≤ 0.5 synergy; > 0.5 to < 1 partial synergy; 1 additive; > 1 to < 4 indifference; and ≥ 4 antagonism. Forty A.baumannii isolates were resistant to imipenem and cefoperazone, but two were susceptible, seven were moderately susceptible and 31 were resistant to meropenem with the microdilution method. MIC values of the isolates for sulbactam were found to be 4 μg/ml in two, 8 μg/ml in five, 16 μg/ml in three, 32 μg/ml in 13, 64 μg/ml in three, 128 μg/ml in six and > 128 μg/ml in eight isolates. According to the FICI; imipenem/sulbactam combination exhibited synergy in 18 (45%), partial synergy in 4 (10%) and indifferent effect in 2 (5%) isolates, the combination of meropenem and sulbactam showed synergy in 19 (48%), partial synergy in 3 (7.5%), and indifferent effect in 3 (7.5%) isolates, the combination of cefoperazone/sulbactam demonstrated synergy in 18 (45%), partial synergy in 2 (5%), and indifferent effect in 2 (5%) isolates. There was no antagonistic effect with the tested combinations. In conclusion, MIC values of sulbactam were generally high in carbapenem-resistant A.baumannii strains. However, synergistic effect was detected in approximately half of the strains with the sulbactam/carbapenem combinations. The data obtained in this study should be supported by further advanced in vitro and clinical studies to predict the accurate clinical efficacy of sulbactam containing combinations on A.baumannii infections.