A descriptive case series of pharmacokinetic/pharmacodynamic target attainment and microbiological outcome in critically ill patients with documented severe extensively drug-resistant Acinetobacter baumannii bloodstream infection and/or ventilator-associated pneumonia treated with cefiderocol. (December 2021)

• Record Type: Journal Article
• Authors: Gatti, Milo; Bartoletti, Michele; Cojutti, Pier Giorgio; Gaibani, Paolo; Conti, Matteo; Giannella, Maddalena; Viale, Pierluigi; Pea, Federico
• Is Part Of: Journal of global antimicrobial resistance. Volume 27(2021)
• Page Start: 294
• Page End: 298
• Publication Date: 2021-12
• Subjects: Cefiderocol -- Critically ill patients -- Extensively drug-resistant -- Acinetobacter baumannii -- PK/PD target attainment -- Microbiological failure; Drug resistance -- Periodicals; Drug resistance -- Periodicals; Drug resistance; Periodicals; 616.9041
• DOI: 10.1016/j.jgar.2021.10.014
• Languages: English
• ISSNs: 2213-7165

Abstract

Highlights: Cefiderocol showed a high failure rate for XDR-AB infections in the CREDIBLE-CR trial. A case series of ICU patients receiving cefiderocol for XDR-AB infections was analysed. Microbiological failure occurred in 54% of patients. Microbiological failure rate was higher in patients achieving suboptimal f Cmin /MIC. Attainment of suboptimal PK/PD target could explain the low eradication rate. Higher PK/PD targets could be desirable in VAP given the low penetration into ELF. ABSTRACT: Objectives: The aim of this study was to explore the relationship between cefiderocol pharmacokinetic/pharmacodynamic (PK/PD) target attainment and microbiological outcome in critically ill patients affected by extensively drug-resistant Acinetobacter baumannii (XDR-AB) bloodstream infection (BSI) and/or ventilator-associated pneumonia (VAP). Methods: Patients who received compassionate use of cefiderocol to treat documented XDR-AB infections at the intensive care unit of the IRCCS Azienda Ospedaliero–Universitaria of Bologna and who underwent therapeutic drug monitoring (TDM) from 15 March 2021 to 30 April 2021 were retrospectively assessed. Cefiderocol trough concentration ( C min ) was determined at steady-state, and the free fraction ( f Cmin ) was calculated according to a plasma protein binding of 58%. The f Cmin /MIC ratio was selected as a pharmacodynamic parameter of cefiderocol efficacy and was defined as optimal if ≥4, quasi-optimal if between 1 and 4, and suboptimal if <1. The association between f Cmin /MIC and microbiological outcome was assessed. Results: A total of 13 patients treated with cefiderocol for the management of XDR-AB infections (6 BSI plus VAP, 5 VAP and 2 BSI) were retrieved. f Cmin /MIC ratios were suboptimal in 3 cases (23%) and quasi-optimal or optimal in 5 cases each (38%). Microbiological failure occurred in seven cases (54%; six with VAP and one with VAP plus BSI). Microbiological failure occurred in 80% of patients with suboptimal f Cmin /MIC compared with 29% of those achieving optimal or quasi-optimal f Cmin /MIC ratio. Conclusion: Suboptimal attainment of PK/PD targets of cefiderocol may lead to microbiological failure of treatment with cefiderocol of critically ill patients affected by XDR-AB VAP.