A Descriptive Observational Study of Real-Time TDM-Guided Aggressive PK/PD Target Attainment and Microbiological/Clinical Outcome in Patients with Stenotrophomonas maltophilia Bloodstream Infections and/or Pneumonia Treated with Continuous Infusion C

Objectives: To assess whether attaining an aggressive pharmacokinetic/pharmacodynamic (PK/PD) target with continuous infusion (CI) cefiderocol could be an effective strategy for managing documented bloodstream infections (BSIs) and pneumonia caused by Stenotrophomonas maltophilia, and to identify independent predictors of microbiological and clinical failure. Methods: Patients receiving CI cefiderocol according to a real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program for managing documented BSIs and/or pneumonia caused by Stenotrophomonas maltophilia were retrospectively included. Free fractions of plasma cefiderocol steady-state concentrations (fCss) were calculated according to a protein binding of 58%, and aggressive PK/PD target was defined as the attainment of a fCss/MIC ratio > 4. Exploratory multivariate analysis was implemented for assessing potential independent predictors of microbiological and clinical failure. Results: Overall, 25 patients (14 BSIs, 10 pneumonia, and one bacteremic pneumonia) were included. Early and overall aggressive cefiderocol PK/PD target was attained in 100.0% of cases. Microbiological eradication rate was 75.0% (15/20) among patients having available follow-up cultures, whereas clinical cure rate was 60.0% (15/25). No case of resistance occurrence to cefiderocol emerged. Bacteremia emerged as the only potential predictor of reduced risk of microbiological failure (odds ratio [OR] 0.04; 95%CI 0.01–0.54; p = 0.016), whereas mechanical ventilation was potentially associated with higher risk of clinical failure (OR 15.17; 95%CI 2.03–111.35; p = 0.008). No significant differences between cefiderocol mono- or combination therapy in terms of microbiological and/clinical outcome were found. Conclusions: Our findings could suggest that CI cefiderocol could be a feasible way for attaining aggressive PK/PD target. This approach could represent a valuable strategy for favoring the microbiological eradication and/or clinical cure of documented Stenotrophomonas maltophilia infections with cefiderocol monotherapy in critical immunocompromised patients. Prospective comparative studies would be warranted for confirming our hypothesis.