对持续输注β-内酰胺类药物的药代动力学/药效学靶点进行评估，该靶点有助于预防确诊革兰氏阴性菌感染的重症患者发生微生物学治疗失败和/或耐药性产生。
Assessment of a PK/PD Target of Continuous Infusion Beta-Lactams Useful for Preventing Microbiological Failure and/or Resistance Development in Critically Ill Patients Affected by Documented Gram-Negative Infections.
作者信息
Gatti Milo, Cojutti Pier Giorgio, Pascale Renato, Tonetti Tommaso, Laici Cristiana, Dell'Olio Alessio, Siniscalchi Antonio, Giannella Maddalena, Viale Pierluigi, Pea Federico
机构信息
Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy.
SSD Clinical Pharmacology, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40126 Bologna, Italy.
出版信息
Antibiotics (Basel). 2021 Oct 27;10(11):1311. doi: 10.3390/antibiotics10111311.
BACKGROUND
Emerging data suggest that more aggressive beta-lactam PK/PD targets could minimize the occurrence of microbiological failure and/or resistance development. This study aims to assess whether a PK/PD target threshold of continuous infusion (CI) beta-lactams may be useful in preventing microbiological failure and/or resistance development in critically ill patients affected by documented Gram-negative infections.
METHODS
Patients admitted to intensive care units from December 2020 to July 2021 receiving continuous infusion beta-lactams for documented Gram-negative infections and having at least one therapeutic drug monitoring in the first 72 h of treatment were included. A receiver operating characteristic (ROC) curve analysis was performed using the ratio between steady-state concentration and minimum inhibitory concentration (C/MIC) ratio as the test variable and occurrence of microbiological failure as the state variable. Area under the curve (AUC) and 95% confidence interval (CI) were calculated. Independent risk factors for the occurrence of microbiological failure were investigated using logistic regression.
RESULTS
Overall, 116 patients were included. Microbiological failure occurred in 26 cases (22.4%). A C/MIC ratio ≤ 5 was identified as PK/PD target cut-off with sensitivity of 80.8% (CI 60.6-93.4%) and specificity of 90.5% (CI 74.2-94.4%), and with an AUC of 0.868 (95%CI 0.793-0.924; < 0.001). At multivariate regression, independent predictors of microbiological failure were C/MIC ratio ≤ 5 (odds ratio [OR] 34.54; 95%CI 7.45-160.11; < 0.001) and infection (OR 4.79; 95%CI 1.11-20.79; = 0.036).
CONCLUSIONS
Early targeting of CI beta-lactams at C/MIC ratio > 5 during the treatment of documented Gram-negative infections may be helpful in preventing microbiological failure and/or resistance development in critically ill patients.
背景
新出现的数据表明，更积极的β-内酰胺类药物药代动力学/药效学（PK/PD）目标可将微生物学治疗失败和/或耐药性产生的发生率降至最低。本研究旨在评估持续输注（CI）β-内酰胺类药物的PK/PD目标阈值是否有助于预防确诊为革兰氏阴性菌感染的重症患者发生微生物学治疗失败和/或耐药性产生。
方法
纳入2020年12月至2021年7月入住重症监护病房、因确诊革兰氏阴性菌感染接受持续输注β-内酰胺类药物且在治疗的前72小时内至少进行一次治疗药物监测的患者。以稳态血药浓度与最低抑菌浓度之比（C/MIC）作为检验变量，微生物学治疗失败的发生情况作为状态变量，进行受试者工作特征（ROC）曲线分析。计算曲线下面积（AUC）和95%置信区间（CI）。采用逻辑回归分析微生物学治疗失败发生的独立危险因素。
结果
共纳入116例患者。26例（22.4%）发生微生物学治疗失败。确定C/MIC比值≤5为PK/PD目标临界值，敏感性为80.8%（CI 60.6 - 93.4%），特异性为90.5%（CI 74.2 - 94.4%），AUC为0.868（95%CI 0.793 - 0.924；P < 0.001）。多因素回归分析显示，微生物学治疗失败的独立预测因素为C/MIC比值≤5（比值比[OR] 34.54；95%CI 7.45 - 160.11；P < 0.001）和感染（OR 4.79；95%CI 1.11 - 20.79；P = 0.036）。
结论
在确诊革兰氏阴性菌感染的治疗过程中，早期将CIβ-内酰胺类药物的C/MIC比值目标设定为>5，可能有助于预防重症患者发生微生物学治疗失败和/或耐药性产生。
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