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
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 infect...
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2021
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oai:doaj.org-article:696473e9b97a4ff88719b689adddd76e2021-11-26T04:29:10ZA 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 cefiderocol2213-716510.1016/j.jgar.2021.10.014https://doaj.org/article/696473e9b97a4ff88719b689adddd76e2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2213716521002290https://doaj.org/toc/2213-7165ABSTRACT: 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.Milo GattiMichele BartolettiPier Giorgio CojuttiPaolo GaibaniMatteo ContiMaddalena GiannellaPierluigi VialeFederico PeaElsevierarticleCefiderocolCritically ill patientsExtensively drug-resistantAcinetobacter baumanniiPK/PD target attainmentMicrobiological failureMicrobiologyQR1-502ENJournal of Global Antimicrobial Resistance, Vol 27, Iss , Pp 294-298 (2021) |
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Cefiderocol Critically ill patients Extensively drug-resistant Acinetobacter baumannii PK/PD target attainment Microbiological failure Microbiology QR1-502 |
| spellingShingle |
Cefiderocol Critically ill patients Extensively drug-resistant Acinetobacter baumannii PK/PD target attainment Microbiological failure Microbiology QR1-502 Milo Gatti Michele Bartoletti Pier Giorgio Cojutti Paolo Gaibani Matteo Conti Maddalena Giannella Pierluigi Viale Federico Pea 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 |
| description |
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. |
| format |
article |
| author |
Milo Gatti Michele Bartoletti Pier Giorgio Cojutti Paolo Gaibani Matteo Conti Maddalena Giannella Pierluigi Viale Federico Pea |
| author_facet |
Milo Gatti Michele Bartoletti Pier Giorgio Cojutti Paolo Gaibani Matteo Conti Maddalena Giannella Pierluigi Viale Federico Pea |
| author_sort |
Milo Gatti |
| title |
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 |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| publisher |
Elsevier |
| publishDate |
2021 |
| url |
https://doaj.org/article/696473e9b97a4ff88719b689adddd76e |
| work_keys_str_mv |
AT milogatti adescriptivecaseseriesofpharmacokineticpharmacodynamictargetattainmentandmicrobiologicaloutcomeincriticallyillpatientswithdocumentedsevereextensivelydrugresistantacinetobacterbaumanniibloodstreaminfectionandorventilatorassociatedpneumoniatreatedwithcefide AT michelebartoletti adescriptivecaseseriesofpharmacokineticpharmacodynamictargetattainmentandmicrobiologicaloutcomeincriticallyillpatientswithdocumentedsevereextensivelydrugresistantacinetobacterbaumanniibloodstreaminfectionandorventilatorassociatedpneumoniatreatedwithcefide AT piergiorgiocojutti adescriptivecaseseriesofpharmacokineticpharmacodynamictargetattainmentandmicrobiologicaloutcomeincriticallyillpatientswithdocumentedsevereextensivelydrugresistantacinetobacterbaumanniibloodstreaminfectionandorventilatorassociatedpneumoniatreatedwithcefide AT paologaibani adescriptivecaseseriesofpharmacokineticpharmacodynamictargetattainmentandmicrobiologicaloutcomeincriticallyillpatientswithdocumentedsevereextensivelydrugresistantacinetobacterbaumanniibloodstreaminfectionandorventilatorassociatedpneumoniatreatedwithcefide AT matteoconti adescriptivecaseseriesofpharmacokineticpharmacodynamictargetattainmentandmicrobiologicaloutcomeincriticallyillpatientswithdocumentedsevereextensivelydrugresistantacinetobacterbaumanniibloodstreaminfectionandorventilatorassociatedpneumoniatreatedwithcefide AT maddalenagiannella adescriptivecaseseriesofpharmacokineticpharmacodynamictargetattainmentandmicrobiologicaloutcomeincriticallyillpatientswithdocumentedsevereextensivelydrugresistantacinetobacterbaumanniibloodstreaminfectionandorventilatorassociatedpneumoniatreatedwithcefide AT pierluigiviale adescriptivecaseseriesofpharmacokineticpharmacodynamictargetattainmentandmicrobiologicaloutcomeincriticallyillpatientswithdocumentedsevereextensivelydrugresistantacinetobacterbaumanniibloodstreaminfectionandorventilatorassociatedpneumoniatreatedwithcefide AT federicopea adescriptivecaseseriesofpharmacokineticpharmacodynamictargetattainmentandmicrobiologicaloutcomeincriticallyillpatientswithdocumentedsevereextensivelydrugresistantacinetobacterbaumanniibloodstreaminfectionandorventilatorassociatedpneumoniatreatedwithcefide AT milogatti descriptivecaseseriesofpharmacokineticpharmacodynamictargetattainmentandmicrobiologicaloutcomeincriticallyillpatientswithdocumentedsevereextensivelydrugresistantacinetobacterbaumanniibloodstreaminfectionandorventilatorassociatedpneumoniatreatedwithcefider AT michelebartoletti descriptivecaseseriesofpharmacokineticpharmacodynamictargetattainmentandmicrobiologicaloutcomeincriticallyillpatientswithdocumentedsevereextensivelydrugresistantacinetobacterbaumanniibloodstreaminfectionandorventilatorassociatedpneumoniatreatedwithcefider AT piergiorgiocojutti descriptivecaseseriesofpharmacokineticpharmacodynamictargetattainmentandmicrobiologicaloutcomeincriticallyillpatientswithdocumentedsevereextensivelydrugresistantacinetobacterbaumanniibloodstreaminfectionandorventilatorassociatedpneumoniatreatedwithcefider AT paologaibani descriptivecaseseriesofpharmacokineticpharmacodynamictargetattainmentandmicrobiologicaloutcomeincriticallyillpatientswithdocumentedsevereextensivelydrugresistantacinetobacterbaumanniibloodstreaminfectionandorventilatorassociatedpneumoniatreatedwithcefider AT matteoconti descriptivecaseseriesofpharmacokineticpharmacodynamictargetattainmentandmicrobiologicaloutcomeincriticallyillpatientswithdocumentedsevereextensivelydrugresistantacinetobacterbaumanniibloodstreaminfectionandorventilatorassociatedpneumoniatreatedwithcefider AT maddalenagiannella descriptivecaseseriesofpharmacokineticpharmacodynamictargetattainmentandmicrobiologicaloutcomeincriticallyillpatientswithdocumentedsevereextensivelydrugresistantacinetobacterbaumanniibloodstreaminfectionandorventilatorassociatedpneumoniatreatedwithcefider AT pierluigiviale descriptivecaseseriesofpharmacokineticpharmacodynamictargetattainmentandmicrobiologicaloutcomeincriticallyillpatientswithdocumentedsevereextensivelydrugresistantacinetobacterbaumanniibloodstreaminfectionandorventilatorassociatedpneumoniatreatedwithcefider AT federicopea descriptivecaseseriesofpharmacokineticpharmacodynamictargetattainmentandmicrobiologicaloutcomeincriticallyillpatientswithdocumentedsevereextensivelydrugresistantacinetobacterbaumanniibloodstreaminfectionandorventilatorassociatedpneumoniatreatedwithcefider |
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