Shields Ryan K, Abbo Lilian M, Ackley Renee, Aitken Samuel L, Albrecht Benjamin, Babiker Ahmed, Burgoon Rachel, Cifuentes Renzo, Claeys Kimberly C, Curry Brooke N, DeSear Kathryn E, Gallagher Jason C, Golnabi Esther Y, Gross Alan E, Hand Jonathan, Heil Emily L, Hornback Krutika M, Kaye Keith S, Khuu Trieu-Vi, Klatt Megan E, Kline Ellen G, Kubat Ryan C, Kufel Wesley D, Lee Jae Hyoung, Lepak Alexander J, Lim Ahmi, Ludwig Justin M, Macdougall Conan, Majumdar Anjali, Mathers Amy J, McCreary Erin K, Miller William R, Monogue Marguerite L, Moore W Justin, Olson Shannon, Oxer Jessica, Pearson Jeffrey C, Pham Christine, Pinargote Paulette, Polk Christopher, Satlin Michael J, Satola Sarah W, Shah Sunish, Tamma Pranita D, Tran Truc T, van Duin David, VanNatta Mollie, Vega Ana, Venugopalan Veena, Veve Michael P, Wangchinda Walaiporn, Witt Lucy S, Wu Janet Y, Pogue Jason M
Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, PA, USA.
Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, FL, USA; Department of Infection Control and Antimicrobial Stewardship, Jackson Memorial Hospital, Miami, FL, USA.
Lancet Infect Dis. 2025 May;25(5):574-584. doi: 10.1016/S1473-3099(24)00648-0. Epub 2024 Dec 16.
Ceftolozane-tazobactam and ceftazidime-avibactam are preferred treatment options for multidrug-resistant Pseudomonas aeruginosa infections; however, real-world comparative effectiveness studies are scarce. Pharmacokinetic and pharmacodynamic differences between the agents might affect clinical response rates. We aimed to compare the effectiveness of ceftolozane-tazobactam and ceftazidime-avibactam for treatment of invasive multidrug-resistant P aeruginosa infections.
This multicentre, retrospective, observational study was conducted at 28 hospitals in the USA between Jan 1, 2016, and Dec 31, 2023. Eligible patients were adults (age ≥18 years old) with microbiologically confirmed multidrug-resistant P aeruginosa pneumonia or bacteraemia treated with ceftolozane-tazobactam or ceftazidime-avibactam for more than 48 h. Patients were matched (1:1) by study site, severity of illness, time to treatment initiation (≤72 h or >72 h), and infection type. The primary outcome was clinical success at day 30, which was defined as survival, resolution of signs and symptoms of infection with the intended treatment course, and the absence of recurrent infection due to P aeruginosa. Secondary outcomes included all-cause mortality and development of resistance to study drug.
420 eligible patients were included (210 in each treatment group), of whom 350 (83%) had pneumonia and 70 (17%) had bacteraemia. Baseline demographics, comorbidities, and severity of illness indicators were similar between groups. On treatment initiation, 336 (80%) patients were in the intensive care unit, 296 (70%) were receiving mechanical ventilation, and 168 (40%) required vasopressor support. Clinical success was observed in 128 (61%) of 210 patients treated with ceftolozane-tazobactam and 109 (52%) of 210 patients treated with ceftazidime-avibactam. By conditional logistic regression analysis, the adjusted odds ratio (aOR) of success after treatment with ceftolozane-tazobactam compared with ceftazidime-avibactam was 2·07 (95% CI 1·16-3·70). For patients with pneumonia, clinical success was observed in 110 (63%) of 175 patients in the ceftolozane-tazobactam group and 89 (51%) of 175 patients in the ceftazidime-avibactam group (aOR 2·34 [95% CI 1·22-4·47]). Among patients with bacteraemia, rates of clinical success were 51% (18 of 35 patients) for patients treated with ceftolozane-tazobactam and 57% (20 of 35 patients) for those treated with ceftazidime-avibactam (0·76 [0·23-2·57]). There were no significant differences between groups in 30-day or 90-day mortality. Among patients whose baseline isolates were tested for susceptibility, resistance developed in 22% (38 of 173) of patients treated with ceftolozane-tazobactam and 23% (40 of 177) of patients treated with ceftazidime-avibactam.
Treatment with ceftolozane-tazobactam resulted in higher rates of clinical success compared with ceftazidime-avibactam for invasive infections due to multidrug-resistant P aeruginosa. Differences were driven by improved response rates for patients with pneumonia who were treated with ceftolozane-tazobactam. There were no significant differences between study groups with respect to all-cause mortality; treatment-emergent resistance was common with both agents.
Merck Sharp & Dohme.
头孢洛扎-他唑巴坦和头孢他啶-阿维巴坦是耐多药铜绿假单胞菌感染的首选治疗方案；然而，真实世界中的比较有效性研究较少。这两种药物之间的药代动力学和药效学差异可能会影响临床反应率。我们旨在比较头孢洛扎-他唑巴坦和头孢他啶-阿维巴坦治疗侵袭性耐多药铜绿假单胞菌感染的有效性。
本多中心、回顾性、观察性研究于2016年1月1日至2023年12月31日在美国的28家医院进行。符合条件的患者为成年（年龄≥18岁），经微生物学确诊为耐多药铜绿假单胞菌肺炎或菌血症，且接受头孢洛扎-他唑巴坦或头孢他啶-阿维巴坦治疗超过48小时。患者按研究地点、疾病严重程度、开始治疗时间（≤72小时或>72小时）和感染类型进行匹配（1:1）。主要结局是第30天的临床成功，定义为存活、在预期治疗疗程中感染的体征和症状消失，以及无铜绿假单胞菌引起的反复感染。次要结局包括全因死亡率和对研究药物的耐药性发展。
纳入420例符合条件的患者（每个治疗组210例），其中350例（83%）患有肺炎，70例（17%）患有菌血症。两组之间的基线人口统计学、合并症和疾病严重程度指标相似。开始治疗时，336例（80%）患者在重症监护病房，296例（70%）接受机械通气，168例（40%）需要血管活性药物支持。接受头孢洛扎-他唑巴坦治疗的210例患者中有128例（61%）临床成功，接受头孢他啶-阿维巴坦治疗的210例患者中有109例（52%）临床成功。通过条件逻辑回归分析，与头孢他啶-阿维巴坦相比，头孢洛扎-他唑巴坦治疗后成功的调整优势比（aOR）为2.07（95%CI 1.16-3.70）。对于肺炎患者，头孢洛扎-他唑巴坦组175例患者中有110例（63%）临床成功，头孢他啶-阿维巴坦组175例患者中有89例（51%）临床成功（aOR 2.34 [95%CI 1.22-4.47]）。在菌血症患者中，接受头孢洛扎-他唑巴坦治疗的患者临床成功率为51%（35例中的18例），接受头孢他啶-阿维巴坦治疗的患者为57%（35例中的20例）（0.76 [0.23-2.57]）。两组在30天或90天死亡率方面无显著差异。在对基线分离株进行药敏试验的患者中，接受头孢洛扎-他唑巴坦治疗的患者中有22%（173例中的38例）出现耐药，接受头孢他啶-阿维巴坦治疗的患者中有23%（177例中的40例）出现耐药。
对于耐多药铜绿假单胞菌引起的侵袭性感染，与头孢他啶-阿维巴坦相比，头孢洛扎-他唑巴坦治疗的临床成功率更高。差异是由接受头孢洛扎-他唑巴坦治疗的肺炎患者反应率提高所致。研究组之间在全因死亡率方面无显著差异；两种药物治疗后出现的耐药情况均很常见。
默克夏普&多美。
