A novel method to evaluate ceftazidime/avibactam therapy in patients with carbapenemase-producing Enterobactericeae (CPE) bloodstream infections

Introduction: This study reports experience managing eight patients with bloodstream infections treated with a continuous infusion of ceftazidime-avibactam.Methods: Patients who were treated for documented CPE BSIs susceptible to CAZ-AVI and who underwent real-time therapeutic drug monitoring were retrospectively assessed. Ceftazidime MICs were assessed in presence of increasing concentrations of avibactam by the broth microdilution method. An inhibitory sigmoid E-max model was used to characterize ceftazidime MIC reduction as a function of avibactam concentration, and the MICi was derived by conditioning the best-fit model using steady-state avibactam concentrations (C-ss). Ceftazidime fC(ss)/MICi ratio was calculated for each patient and correlated to microbiological outcome.Results: By adopting the innovative concept of effective MIC with an inhibitor (MICi), a trend towards higher microbiological failure and resistance development was found in patients with a lower ceftazidime fCss/MICi ratio (2/3 vs. 0/5).Conclusion: Assessment of changes in the ceftazidime MIC in relation to increasing avibactam concentration could represent a more robust pharmacokinetic/pharmacodynamic method for predicting microbiological failure given beta-lactam/beta-lactamase inhibitor combinations. (c) 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.