In Vitro Activity of Imipenem-Relebactam Alone or in Combination with Amikacin or Colistin against Pseudomonas aeruginosa.

ABSTRACT: Relebactam is a novel class A/C ?-lactamase inhibitor that restores imipenem in vitro activity against multidrug-resistant and carbapenem-nonsusceptible Pseudomonas aeruginosa Time-kill analyses were performed to evaluate the potential role of imipenem-relebactam in combination with amikacin or colistin against P. aeruginosa Ten clinical P. aeruginosa isolates (9 imipenem nonsusceptible) with imipenem-relebactam MICs ranging from 1/4 to 8/4??g/ml were included. The isolates had varied susceptibilities to imipenem (1 to 32??g/ml), amikacin (4 to 128??g/ml), and colistin (0.5 to 1??g/ml). Duplicate 24-h time-kill studies were conducted using the average steady-state concentrations (Cssavg) observed after the administration of imipenem-relebactam at 500?mg/250?mg every 6 hours (q6h) alone and in combination with the Cssavg of 25?mg/kg of body weight/day amikacin and 360?mg/day colistin in humans. Imipenem-relebactam alone resulted in 24-h bacterial densities of -2.93?±?0.38, -1.67?±?0.29, +0.38?±?0.96, and +0.15?±?0.65 log10 CFU/ml at imipenem-relebactam MICs of 1/4, 2/4, 4/4, and 8/4??g/ml, respectively. No synergy was demonstrated against the single imipenem-susceptible isolate. Against the imipenem-nonsusceptible isolates (n?=?9), imipenem-relebactam combined with amikacin resulted in synergy (-2.61?±?1.50 log10 CFU/ml) against all amikacin-susceptible isolates and in two of three amikacin-intermediate (i.e., MIC, 32??g/ml) isolates (-2.06?±?0.19 log10 CFU/ml). Synergy with amikacin was not observed when the amikacin MIC was >32 ?g/ml. Imipenem-relebactam combined with colistin demonstrated synergy in eight out of the nine imipenem-resistant isolates (-3.17?±?1.00 log10 CFU/ml). Against these 10?P. aeruginosa isolates, imipenem-relebactam combined with either amikacin or colistin resulted in synergistic activity against the majority of strains. Further studies evaluating combination therapy with imipenem-relebactam are warranted.

SUBMITTER: Asempa TE 

PROVIDER: S-EPMC6709505 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature