Utility of a TDM-Guided Expert Clinical Pharmacological Advice Program for Optimizing the Use of Novel Beta-Lactam/Beta-Lactamase Inhibitor Combinations and Cefiderocol in a Tertiary University Hospital: An Interim Analysis

Background: This study assessed the utility of a therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program to optimize aggressive pharmacokinetic/pharmacodynamic (PK/PD) target attainment of novel beta-lactam/beta-lactamase inhibitor (BL/BLIc) combinations and cefiderocol. Methods: All hospitalized patients who received TDM-guided ECPA with BL/BLIc (ceftazidime–avibactam, ceftolozane–tazobactam, or meropenem–vaborbactam) or cefiderocol were assessed retrospectively. Three performance indicators were identified: the average number of ECPAs delivered per month of availability of the program and the ratio between the total number of ECPAs recommending dosing adjustment and the total number of ECPAs, at the first and at subsequent TDM assessments. The relationships between aggressive PK/PD target attainment and clinical and microbiological outcomes were assessed. Results: A total of 595 ECPAs were administered to 263 patients to optimize 319 treatment courses. Novel agents were mostly used for targeted therapy (79.6%) by continuous infusion (CI; 82.8%). In the first TDM assessment, dose increases were mostly required for patients receiving intermittent/extended infusion (II/EI) (51.9% vs. 6.4%; P < 0.0001), whereas dose decreases were mostly recommended for patients receiving CI (60.3% vs. 23.1%; P < 0.001). In subsequent TDM assessments, the overall proportion of ECPAs recommending dosing adjustments decreased in both groups (57.1% and 39.3% in the II/EI and CI groups, respectively). Aggressive PK/PD target attainment was associated with the highest microbiological eradication rate for ceftazidime–avibactam (79.6% out of 86.0%; P < 0.001), and the highest clinical cure rate for ceftazidime–avibactam (64.2% out of 78.1%; P < 0.001) and cefiderocol (50.0% out of 51.5%; P = 0.006). Conclusions: A dedicated TDM-guided ECPA program may be helpful for optimizing the use of novel agents in settings with a high prevalence of multidrug-resistant pathogens.