Milo Gatti1, Michele Bartoletti2, Pier Giorgio Cojutti3, Paolo Gaibani4, Matteo Conti3, Maddalena Giannella2, Pierluigi Viale2, Federico Pea5. 1. Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy; SSD Clinical Pharmacology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. 2. Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy; Infectious Diseases Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. 3. SSD Clinical Pharmacology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. 4. Division of Microbiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy. 5. Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy; SSD Clinical Pharmacology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. Electronic address: federico.pea@unibo.it.
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 (Cmin) was determined at steady-state, and the free fraction (fCmin) was calculated according to a plasma protein binding of 58%. The fCmin/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 fCmin/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. fCmin/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 fCmin/MIC compared with 29% of those achieving optimal or quasi-optimal fCmin/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.
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 (Cmin) was determined at steady-state, and the free fraction (fCmin) was calculated according to a plasma protein binding of 58%. The fCmin/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 fCmin/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. fCmin/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 fCmin/MIC compared with 29% of those achieving optimal or quasi-optimal fCmin/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.