fr-264205 and Acinetobacter-Infections

We investigated the in vitro activity of various antimicrobial combinations against carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. The in vitro activity of six two-drug combinations against CRAB isolates collected from the blood samples of patients with bloodstream infection was evaluated using the checkerboard method and time-kill assay [0.5 ×, 1 ×, and 2 × minimum inhibitory concentration (MIC)] to identify potential synergistic and bactericidal two-drug combinations against CRAB isolates. The effects of meropenem, colistin, tigecycline, rifampin, and ceftolozane/tazobactam combinations were investigated. All 10 CRAB isolates in our study produced the OXA-58-type and OXA-23-type carbapenem-hydrolyzing oxacillinases. The colistin-ceftolozane/tazobactam combination showed synergistic effects in both the time-kill assay (using an antibiotic concentration of 1 × MIC) and the checkerboard method. It also showed bactericidal effects in the time-kill assay. For all 10 CRAB isolates, time-kill curves showed synergistic bactericidal activity of the colistin-ceftolozane/tazobactam combination at 0.5 × MIC. Overall, there was substantial discordance of synergistic activity between the checkerboard microdilution and time-kill assays (with a concordance of 31.7%). Our study demonstrated that two-drug combinations of colistin and ceftolozane/tazobactam could be useful treatment alternatives for CRAB infections. The effects of these antibiotic combinations should be evaluated using in vivo experimental models.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Cephalosporins; Colistin; Drug Combinations; Drug Synergism; Humans; Meropenem; Microbial Sensitivity Tests; Rifampin; Tazobactam; Tigecycline

Acinetobacter species lead to nosocomial infections in immunocompromised patients hospitalized in intensive care units or services. Acinetobacter baumannii is a bacterium that is difficult to treat because it is intrinsically resistant to many antibiotics and can develop resistance afterwards. This situation limits the use of existing antibiotics and directs the clinician to new agents, different treatment options and the use of various antibiotic combinations. The aim of this study was to determine the sensitivities of doripenem (DOR), tigecycline (TGC), minocycline (MIN), amikacin (AK) and a newly developed agent ceftolozane-tazobactam (CT) in multidrug resistant A.baumannii strains which were isolated from inpatients in intensive care units and to investigate the in vitro interactions of CT/DOR, CT/TGC, CT/MIN and CT/AK combinations by using antibiotic gradient test method. Thirty-five A.baumannii strains isolated from various clinical specimens (blood, urine, sputum, tracheal aspirate, wound, abscess and catheter) between January 2017 and July 2017 were included in the study. Strains isolated from inpatients in intensive care units and resistant to at least three antibiotic classes were selected. The identification of A.baumannii isolates and the determination of routine antibiotic susceptibility profile were performed according to EUCAST 2017 criteria by the use of BD Phoenix 100 (Becton Dickinson, USA) automated system. Minimum inhibitor concentration values of CT, DOR, TGC, MIN, AK and combinations of CT with four other antibiotics (CT/DOR, CT/TGC, CT/MIN and CT/AK) were determined by antibiotic gradient test method. Fractional inhibitor concentration index (FICI) was used to determine the interactions of the combinations in vitro. According to the data obtained; the FICI was evaluated as synergy if FICI ≤ 0.5, additive if 0.5 > FICI ≤ 1, indifferent (unidentified interaction) if 1

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cephalosporins; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Tazobactam