In vitro activities of rifampin, colistin, sulbactam and tigecycline tested alone and in combination against extensively drug-resistant Acinetobacter baumannii

Abstract

The aim of this study was to investigate the in vitro activities of rifampin, colistin, sulbactam and tigecycline alone and in combination against extensively drug-resistant Acinetobacter baumannii (XDR-Ab). Twenty-five XDR-Ab strains were isolated from patients. Broth microdilution assay was used to determine the minimum inhibitory concentration (MIC) for rifampin, colistin, sulbactam and tigecycline against XDR-Ab strains. The checkerboard microdilution method was used to determine the in vitro activities of potential therapeutic combinations of these four antimicrobial agents. Accordingly, the fractional inhibitory concentration (FIC) and FIC index (FICI) were calculated for each of the combinations. According to our results, when tested as single drugs, rifampin, colistin or tigecycline had good bacteriostatic activity against XDR-Ab, whereas sulbactam was not as active against XDR-Ab isolates. On the other hand, when tested in combination, the combinations of colistin/rifampin, rifampin/sulbactam, rifampin/tigecycline and sulbactam/tigecycline showed good in vitro activities against XDR-Ab isolates. More importantly, these combination regimens could exert addictive or partially synergistic effects at the sub-MIC levels against XDR-Ab strains. Compared with single drugs, most of the combinations of these antimicrobial agents could exert partially synergistic and/or addictive effects, which might provide a better alternative when treating XDR-Ab infections.

Investigation of Colistin Heteroresistance and Some Factors Affecting Heteroresistance in Carbapenem-Resistant A. baumannii Strains

“…In a study in 2013, Lee et al [29] have shown that the combination of colistin and rifampin increased killing rate of both multidrug resistant colistin susceptible and resistant A. baumannii and that combination therapy prevented or suppressed the emergence of colistin-resistant subpopulations. Dong et al [30] showed that the combinations of Col+Rif, rifampin-sulbactam, rifampin-tigecycline and sulbactam-tigecycline showed good in vitro activities (addictive or partially synergistic) against extensively drug-resistant A. baumannii isolates even at subinhibitory concentrations. Our findings were in accordance with these studies.…”

“…Several in vitro studies reported synergistic effects between diverse drugs for the treatment of Acinetobacter [26,[29][30][31][32]37] . However, more in vivo studies about these combinations are needed to provide high grade of evidence.…”

β-Lactams and β-Lactamase Inhibitors: An Overview

“…Clavulanic acid alone has been reported to have an MIC as low as 1 mg/mL against N. gonorrhoeae (Wise et al 1978); sulbactam has modest activity against wild-type Acinetobacter spp. 8 and 10 mg/mL, respectively (Jacoby and Sutton 1989;Fass et al 1990), but does not retain activity against isolates with multiple resistance mechanisms (Dong et al 2014). None of these inhibitors is effective in inhibiting the hydrolytic activity of MBLs (Bush 2015), and their modest activity against serine carbapenemases does not translate into clinical susceptibility (Yigit et al 2003;Woodford et al 2004) owing, at least in part, to the presence of multiple b-lactamases in the producing organisms (Moland et al 2007).…”

Antibiotic Resistance Profiles and Genotypes of <i>Acinetobacter baumannii</i> Isolates and <i>In Vitro</i> Interactions of Various Antibiotics in Combination with Tigecycline and Colistin

“…27 Principe et al 7 for the first time reported that they have noticed the synergy between TGC and CL by TK method in one A. baumannii isolate. In two studies conducted by CB method in TGC-CL combination 28 and in TGC-sulbactam, TGC-CL combinations 29 a synergistic effect was observed.…”