Abstract：
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).
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.
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.
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.
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.
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.
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.
摘要：
本研究的目的是探讨受广泛耐药鲍曼不动杆菌（XDR-AB）血流感染（BSI）和/或呼吸机相关性肺炎（VAP）影响的危重患者的头孢地洛药代动力学/药效学（PK/PD）目标达成与微生物学结局之间的关系。
回顾性评估了在博洛尼亚IRCCSAziendaOspedaliero-Universitaria的重症监护病房接受过头孢地洛治疗有记录的XDR-AB感染并在2021年3月15日至2021年4月30日接受治疗药物监测（TDM）的患者。在稳态下确定头孢地洛谷浓度(Cmin)，并且根据58%的血浆蛋白结合计算游离分数(fCmin)。选择fCmin/MIC比率作为头孢地洛功效的药效学参数，如果≥4则定义为最佳，如果在1和4之间则定义为准最佳，如果<1则定义为次优。评估fCmin/MIC与微生物学结果之间的关联。
共有13例接受头孢地洛治疗的患者用于治疗XDR-AB感染（6BSI加VAP，检索到5个VAP和2个BSI)。fCmin/MIC比值在3例（23％）中次优，在5例（38％）中准最佳或最佳。7例发生微生物失败（54％；6例发生VAP，1例发生VAP加BSI）。微生物失败发生在80％的fCmin/MIC次优患者中，而达到最佳或准最佳fCmin/MIC比率的患者中有29％发生。
头孢地洛的PK/PD目标的次优实现可能导致受XDR-ABVAP影响的危重患者头孢地洛治疗的微生物学失败。
回顾性评估了在博洛尼亚IRCCSAziendaOspedaliero-Universitaria的重症监护病房接受过头孢地洛治疗有记录的XDR-AB感染并在2021年3月15日至2021年4月30日接受治疗药物监测（TDM）的患者。在稳态下确定头孢地洛谷浓度(Cmin)，并且根据58%的血浆蛋白结合计算游离分数(fCmin)。选择fCmin/MIC比率作为头孢地洛功效的药效学参数，如果≥4则定义为最佳，如果在1和4之间则定义为准最佳，如果<1则定义为次优。评估fCmin/MIC与微生物学结果之间的关联。
共有13例接受头孢地洛治疗的患者用于治疗XDR-AB感染（6BSI加VAP，检索到5个VAP和2个BSI)。fCmin/MIC比值在3例（23％）中次优，在5例（38％）中准最佳或最佳。7例发生微生物失败（54％；6例发生VAP，1例发生VAP加BSI）。微生物失败发生在80％的fCmin/MIC次优患者中，而达到最佳或准最佳fCmin/MIC比率的患者中有29％发生。
头孢地洛的PK/PD目标的次优实现可能导致受XDR-ABVAP影响的危重患者头孢地洛治疗的微生物学失败。
