Kunz Coyne Ashlan J, Orzol Carolina, Veve Michael P, Rybak Michael J
Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.
Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA.
Open Forum Infect Dis. 2023 Aug 28;10(9):ofad454. doi: 10.1093/ofid/ofad454. eCollection 2023 Sep.
is a leading cause of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP). Novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations are often used for these infections; however, limited data exist to guide the dosing of BL/BLI in patients who are morbidly obese. Thus, we sought to evaluate the clinical and safety endpoints of patients who are morbidly obese (body mass index ≥35 kg/m) and non-morbidly obese (<35 kg/m) and receiving BL/BLI for HABP/VABP.
This retrospective study was based on a cohort of patients hospitalized at 2 urban academic medical centers in Detroit, Michigan, from August 2014 through February 2021 with HABP/VABP who were receiving BL/BLI (ceftazidime/avibactam, ceftolozane/tazobactam, or meropenem/vaborbactam) for ≥72 continuous hours. The primary endpoint was presumed treatment failure, defined as the presence of all-cause in-hospital mortality or the continuation of infectious symptoms. Analyses were adjusted for possible confounding with inverse probability of treatment weighting. Multivariable regression was used to identify predictors of treatment failure.
In total, 285 patients with HABP (61.4%) and/or VABP (56.1%) were enrolled (morbidly obese, n = 95; non-morbidly obese, n = 190). The median Acute Physiology and Chronic Health Evaluation II score was 23 (IQR, 13-26), and 60% of patients were admitted to the intensive care unit at index culture collection. Patients who were morbidly obese demonstrated significantly greater odds of presumed treatment failure vs those who were non-morbidly obese (58.9% vs 37.9%, respectively; adjusted odds ratio, 1.675 [95% CI, 1.465-1.979]). In multivariable analysis, morbid obesity (1.06; 95% CI, 1.02-1.79), prolonged time to BL/BLI initiation (1.47; 95% CI, 1.28-2.66), renal dose-adjusted BL/BLI in the first 48 hours of therapy (1.12; 95% CI, 1.09-1.75), and continuous renal replacement therapy during BL/BLI therapy (1.35; 95% CI, 1.06-1.68) were independently associated with increased odds of presumed treatment failure.
Among hospitalized patients receiving BL/BLI for HABP/VABP, those who were morbidly obese had significantly greater odds of presumed treatment failure when compared with those who were non-morbidly obese.
是医院获得性和呼吸机相关性细菌性肺炎（HABP/VABP）的主要病因。新型β-内酰胺/β-内酰胺酶抑制剂（BL/BLI）组合常用于这些感染；然而，关于病态肥胖患者BL/BLI给药的指导数据有限。因此，我们试图评估病态肥胖（体重指数≥35 kg/m）和非病态肥胖（<35 kg/m）且接受BL/BLI治疗HABP/VABP患者的临床和安全性终点。
这项回顾性研究基于2014年8月至2021年2月在密歇根州底特律市的2家城市学术医疗中心住院的一组HABP/VABP患者，这些患者接受BL/BLI（头孢他啶/阿维巴坦、头孢洛扎/他唑巴坦或美罗培南/瓦博巴坦）持续≥72小时。主要终点是推测的治疗失败，定义为全因院内死亡或感染症状持续存在。分析采用治疗权重逆概率法对可能的混杂因素进行校正。多变量回归用于确定治疗失败的预测因素。
共纳入285例HABP（61.4%）和/或VABP（56.1%）患者（病态肥胖患者95例，非病态肥胖患者190例）。急性生理与慢性健康状况评估II评分中位数为23（四分位间距，13 - 26），60%的患者在首次培养采集时入住重症监护病房。与非病态肥胖患者相比，病态肥胖患者推测的治疗失败几率显著更高（分别为58.9%和37.9%；校正优势比，1.675 [95%置信区间，1.465 - 1.979]）。在多变量分析中，病态肥胖（1.06；95%置信区间，1.02 - 1.79）、开始使用BL/BLI的时间延长（1.47；95%置信区间，1.28 - 2.66）、治疗前48小时肾剂量调整的BL/BLI（1.12；95%置信区间，1.09 - 1.75）以及BL/BLI治疗期间的持续肾脏替代治疗（1.35；95%置信区间，1.06 - 1.68）与推测的治疗失败几率增加独立相关。
在接受BL/BLI治疗HABP/VABP的住院患者中，与非病态肥胖患者相比，病态肥胖患者推测的治疗失败几率显著更高。
