Lodise Thomas, Yang Joe, Puzniak Laura A, Dillon Ryan, Kollef Marin
Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
Merck & Co., Inc., Kenilworth, NJ, USA.
Infect Dis Ther. 2020 Dec;9(4):953-966. doi: 10.1007/s40121-020-00343-0. Epub 2020 Sep 30.
Hospital-acquired and ventilator-associated bacterial pneumonia (HABP and VABP) are associated with significant healthcare resource utilization (HCRU). This a priori, exploratory, secondary analysis from the ASPECT-NP clinical trial evaluated resource utilization among patients with ventilated HABP (vHABP)/VABP treated with ceftolozane/tazobactam or meropenem.
This analysis used data from the randomized, double-blind, noninferiority phase 3 ASPECT-NP trial of patients with vHABP/VABP randomized to receive ceftolozane/tazobactam 3 g (ceftolozane 2 g/tazobactam 1 g) or meropenem 1 g for 8-14 days. Day 28 outcomes included hospital length of stay (LOS), intensive care unit (ICU) LOS, and time to mechanical ventilation extubation in the microbiological intention-to-treat (mITT) population and in an HCRU population. The HCRU population, a subset of patients from the mITT population that were alive at day 28, was used to remove resource use bias influenced by mortality rates.
Ceftolozane/tazobactam-treated versus meropenem-treated patients, respectively, had fewer deaths (20.1% vs. 25.5%), fewer hospital discharges (30.7% vs. 32.4%), and higher ICU discharges (60.0% vs. 58.3%) and extubations (51.9% vs. 48.2%) by day 28. In the HCRU population, adjusted LOS differences (95% confidence intervals) for ceftolozane/tazobactam compared with meropenem were 0.1 (- 1.4 to 1.6) hospitalization days, - 1.4 (- 2.9 to 0.2) ICU days, and - 0.9 (- 2.4 to 0.7) mechanical ventilation days. Patterns were similar among the VABP and Pseudomonas aeruginosa subgroups.
Similar 28-day resource utilization outcomes were observed between ceftolozane/tazobactam and meropenem in the mITT population of patients from ASPECT-NP with vHABP/VABP due to gram-negative pathogens. ASPECT-NP was not powered to detect differences in resource utilization outcomes between treatment groups; however, numerical differences in ICU LOS and duration of mechanical ventilation were noted. Further study is needed to assess resource utilization in the real-world practice setting, especially among patients excluded from ASPECT-NP, including those with resistant P. aeruginosa infections.
ClinicalTrials.gov: NCT02070757, registered February 25, 2014; EudraCT: 2012-002862-11.
医院获得性肺炎和呼吸机相关性细菌性肺炎（HABP和VABP）与大量医疗资源利用（HCRU）相关。这项来自ASPECT-NP临床试验的先验性、探索性、二次分析评估了接受头孢洛扎/他唑巴坦或美罗培南治疗的通气型HABP（vHABP）/VABP患者的资源利用情况。
该分析使用了来自ASPECT-NP 3期随机、双盲、非劣效性试验的数据，该试验将vHABP/VABP患者随机分为接受3克头孢洛扎/他唑巴坦（头孢洛扎2克/他唑巴坦1克）或1克美罗培南治疗8至14天。第28天的结局包括微生物意向性治疗（mITT）人群和HCRU人群的住院时间（LOS）、重症监护病房（ICU）住院时间以及机械通气撤机时间。HCRU人群是mITT人群中在第28天存活的患者子集，用于消除受死亡率影响的资源使用偏差。
到第28天时，接受头孢洛扎/他唑巴坦治疗的患者与接受美罗培南治疗的患者相比，死亡人数更少（20.1%对25.5%），出院人数更少（30.7%对32.4%），ICU出院率更高（60.0%对58.3%），撤机率更高（51.9%对48.2%）。在HCRU人群中，与美罗培南相比，头孢洛扎/他唑巴坦的调整后LOS差异（95%置信区间）为住院天数0.1（-1.4至1.6）天、ICU天数-1.4（-2.9至0.2）天、机械通气天数-0.9（-2.4至0.7）天。VABP和铜绿假单胞菌亚组中的模式相似。
在ASPECT-NP中因革兰氏阴性病原体导致vHABP/VABP的患者的mITT人群中，观察到头孢洛扎/他唑巴坦和美罗培南在28天资源利用结局方面相似。ASPECT-NP没有足够的能力检测治疗组之间资源利用结局的差异；然而，注意到ICU住院时间和机械通气持续时间存在数值差异。需要进一步研究以评估实际临床环境中的资源利用情况，特别是在被排除在ASPECT-NP之外的患者中，包括那些患有耐铜绿假单胞菌感染的患者。
ClinicalTrials.gov：NCT02070757，于2014年2月25日注册；EudraCT：2012-002862-11。
