Holger Dana J, Rebold Nicholas S, Alosaimy Sara, Morrisette Taylor, Lagnf Abdalhamid, Belza Ana Christine, Coyne Ashlan J Kunz, El Ghali Amer, Veve Michael P, Rybak Michael J
Wayne State University, Detroit, MI, USA.
Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI, 48201, USA.
Infect Dis Ther. 2022 Oct;11(5):1965-1980. doi: 10.1007/s40121-022-00687-9. Epub 2022 Sep 1.
Infections caused by multidrug-resistant (MDR), extensively drug-resistant (XDR), and difficult-to-treat (DTR) Pseudomonas aeruginosa are increasingly challenging to combat. Ceftolozane-tazobactam (C/T) is a novel β-lactam-β-lactamase inhibitor combination now commonly used to treat MDR and XDR P. aeruginosa. Lower respiratory tract infections (LRTIs) remain the most common source of infection caused by MDR/XDR P. aeruginosa. Comparative effectiveness studies to date have been limited by the type of comparator agents (i.e., aminoglycosides and polymyxins) and the inclusion of multiple infection sources (i.e., urinary tract, abdominal, skin and soft tissue, etc.).
We performed a multicenter, retrospective analysis of adults with LRTI caused by MDR or XDR P. aeruginosa admitted from January 2014 to December 2019. We aimed to compare clinical outcomes between patients who received C/T (n = 118) versus best alternative therapy (n = 88). The primary outcome was clinical failure, defined as 30-day mortality and/or an adverse drug reaction on antibiotic therapy.
Two hundred and six patients met inclusion criteria. The C/T group had a significantly higher proportion of XDR P. aeruginosa and ventilator-associated bacterial pneumonia (VABP). After multivariable logistic regression, C/T treatment was independently associated with a 73.3% reduction in clinical failure compared to those who received best alternative therapy (P < 0.001). The number needed to harm with best alternative therapy was 3.
Our results suggest that C/T is a safe and effective therapeutic regimen for patients with MDR and XDR P. aeruginosa LRTI.
耐多药（MDR）、广泛耐药（XDR）和难治性（DTR）铜绿假单胞菌引起的感染在治疗上越来越具有挑战性。头孢洛扎坦-他唑巴坦（C/T）是一种新型的β-内酰胺-β-内酰胺酶抑制剂组合，目前常用于治疗MDR和XDR铜绿假单胞菌感染。下呼吸道感染（LRTIs）仍然是MDR/XDR铜绿假单胞菌引起的最常见感染源。迄今为止，比较有效性研究受到对照药物类型（即氨基糖苷类和多黏菌素）以及多种感染源（即尿路、腹部、皮肤和软组织等）纳入的限制。
我们对2014年1月至2019年12月收治的由MDR或XDR铜绿假单胞菌引起的LRTI成年患者进行了一项多中心回顾性分析。我们旨在比较接受C/T治疗的患者（n = 118）与最佳替代治疗的患者（n = 88）之间的临床结局。主要结局是临床失败，定义为30天死亡率和/或抗生素治疗时出现的药物不良反应。
206例患者符合纳入标准。C/T组中XDR铜绿假单胞菌和呼吸机相关性细菌性肺炎（VABP）的比例显著更高。经过多变量逻辑回归分析，与接受最佳替代治疗的患者相比，C/T治疗与临床失败率降低73.3%独立相关（P < 0.001）。最佳替代治疗的伤害所需人数为3。
我们的结果表明，C/T是治疗MDR和XDR铜绿假单胞菌LRTI患者的一种安全有效的治疗方案。
