Pharmacodynamic target attainment of the synergism of ceftazidime-avibactam in combination with amikacin against OXA-producing extensively drug-resistant or pan drug-resistant (XDR/PDR) Pseudomonas aeruginosa.

Abstract

To investigate the pharmacodynamic target attainment of ceftazidime-avibactam (CZA) in combination with amikacin against OXA-producing extensively drug-resistant/ pan-drug-resistant Pseudomonas aeruginosa (XDR/PDR-PA). The minimum inhibitory concentrations (MICs) of CZA and amikacin against OXA-producing XDR/PDR-PA were determined by the checkerboard method, and the combined inhibitory index (FICI) was calculated to evaluate whether the combination of the two antimicrobials has a synergistic effect on OXA-producing XDR/PDR-PA in vitro. The pharmacokinetic (PK) and pharmacodynamic (PD) parameters of CZA and amikacin were combined by Monte Carlo simulation (MCS) to evaluate the cumulative fraction of response (CFR) of the two antimicrobials for the treatment of OXA-producing XDR/PDR-PA infection. The results of synergy tests of CZA in combination with amikacin suggested that 77.3% of XDR/PDR-PA showed synergistic effects. When the PK/PD target was greater than 50, CFR was 97.84% for CZA 2.5 g q8h when CZA in combination with amikacin. CZA in combination with AMK has a synergistic effect in vitro and could be a potential option for treating OXA-producing XDR/PDR-PA infections.