Pharmacodynamic Analysis of Meropenem and Fosfomycin Combination Against Carbapenem-ResistantAcinetobacter baumanniiin Patients with Normal Renal Clearance: Can It Be a Treatment Option?

Background and Objective:Combination therapy may be a treatment option against carbapenem-resistantAcinetobacter baumannii(CR-AB) infections. In this study, we explored the utility of fosfomycin in combination with meropenem (FOS/MEM) against CR-AB isolates. Materials and Methods:Screening of synergistic activity of FOS/MEM was performed using the checkerboard assay. A pharmacokinetic/pharmacodynamic analysis was performed for various FOS/MEM regimens using Monte Carlo simulations. Results:The minimum inhibitory concentration (MIC) required to inhibit the growth of 50% of the isolates (MIC50) and MIC required to inhibit the growth of 90% of the isolates (MIC90) of FOS and MEM were reduced fourfold and twofold, respectively. The combination was synergistic against 14/50 isolates. No antagonism was observed. Sixteen out of fifty isolates had MEM MICs of <= 8 mg/L when subjected to combination therapy, compared to none with monotherapy. Forty-one out of 50 isolates had FOS MICs of <= 128 mg/L when subjected to combination therapy, compared to 17/50 isolates with monotherapy. The cumulative fraction response for MEM and FOS improved from 0% to 40% and 40% to 80%, with combination therapy, respectively. Conclusions:Addition of MEM improved thein vitroactivity of FOS against the CR-AB isolates. FOS/MEM could be a plausible option to treat CR-AB for a small fraction of isolates.

Automated summary

The study explored the utility of fosfomycin in combination with meropenem against carbapenem-resistant Acinetobacter baumannii isolates. The combination therapy showed synergistic effects on a fraction of isolates, reducing the minimum inhibitory concentrations required to inhibit bacterial growth.