Corbella Laura, Boán Jorge, San-Juan Rafael, Fernández-Ruiz Mario, Carretero Octavio, Lora David, Hernández-Jiménez Pilar, Ruiz-Ruigómez María, Rodríguez-Goncer Isabel, Silva José Tiago, López-Medrano Francisco, Lizasoain Manuel, Villa Jennifer, Caro-Teller Jose Manuel, Aguado José M
Unit of Infectious Diseases, University Hospital '12 de Octubre', Instituto de Investigación Sanitaria Hospital '12 de Octubre' (imas12), School of Medicine, Universidad Complutense, Madrid, Spain; Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Infecciosas, Spain.
Department of Internal Medicine, University Hospital '12 de Octubre', Instituto de Investigación Sanitaria Hospital '12 de Octubre' (imas12), School of Medicine, Universidad Complutense, Madrid, Spain.
Int J Antimicrob Agents. 2022 Feb;59(2):106517. doi: 10.1016/j.ijantimicag.2021.106517. Epub 2022 Jan 3.
Clinical experience with ceftazidime-avibactam (CAZ-AVI) for treatment of infections due to multidrug or extremely resistant (MDR/XDR) Pseudomonas aeruginosa (P. aeruginosa) is limited.
A retrospective cohort study was conducted on patients with MDR/XDR P. aeruginosa infections treated with CAZ-AVI. The primary outcome was clinical cure by day 14, evaluated by logistic regression adjusted for the propensity score to receive CAZ-AVI as combination therapy. Secondary outcomes were 30-day all-cause mortality, 90-day recurrence, emerging CAZ-AVI resistance, and safety of therapy.
Sixty-one first episodes of MDR/XDR P. aeruginosa infection were included. The most common source was lower respiratory tract infection (34.4%), 14.8% episodes developed bloodstream infection and 50.8% had sepsis at presentation. Ceftazidime-avibactam therapy was initiated at a median of 7.0 (interquartile range [IQR]: 3.5-12.0) days from symptom onset; it was used as combined therapy in 29 (47.5%) episodes. Clinical cure rate by day 14 was 54.1% and predictors of response were days to source control (adjusted odds ratio [aOR]: 0.84; 95% confidence interval [CI]: 0.72-0.98; P = 0.024), days until the initiation of CAZ-AVI therapy (aOR: 0.65; 95% CI: 0.49-0.86; P = 0.003), age (aOR: 1.07; 95% CI: 0.99-1.15; P = 0.066) and CAZ-AVI combination therapy (aOR: 0.02; 95% CI: 0.01-0.38; P = 0.009). Rates of 30-day all-cause mortality and 90-day recurrence were 13.1% and 12.5%, respectively. Emergence of drug resistance to CAZ-AVI was not detected. Treatment-related adverse events occurred in three episodes (4.9%).
CAZ-AVI constitutes a valid alternative for the treatment of infections due to MDR/XDR P. aeruginosa.
头孢他啶-阿维巴坦（CAZ-AVI）治疗多重耐药或极耐药（MDR/XDR）铜绿假单胞菌感染的临床经验有限。
对接受CAZ-AVI治疗的MDR/XDR铜绿假单胞菌感染患者进行回顾性队列研究。主要结局是第14天的临床治愈情况，通过对接受CAZ-AVI联合治疗的倾向评分进行调整的逻辑回归进行评估。次要结局包括30天全因死亡率、90天复发率、新出现的CAZ-AVI耐药性以及治疗安全性。
纳入61例MDR/XDR铜绿假单胞菌感染的首发病例。最常见的感染源是下呼吸道感染（34.4%），14.8%的病例发生血流感染，50.8%的病例在就诊时患有脓毒症。头孢他啶-阿维巴坦治疗从症状出现到开始的中位时间为7.0天（四分位间距[IQR]：3.5 - 12.0天）；29例（47.5%）病例采用联合治疗。第14天的临床治愈率为54.1%，反应的预测因素包括达到感染源控制的天数（调整优势比[aOR]：0.84；95%置信区间[CI]：0.72 - 0.98；P = 0.024）、开始CAZ-AVI治疗前的天数（aOR：0.65；95% CI：0.49 - 0.86；P = 0.003）、年龄（aOR：1.07；95% CI：0.99 - 1.15；P = 0.066）以及CAZ-AVI联合治疗（aOR：0.02；95% CI：0.01 - 0.38；P = 0.009）。30天全因死亡率和90天复发率分别为13.1%和12.5%。未检测到对CAZ-AVI的耐药性出现。3例（4.9%）病例发生了与治疗相关的不良事件。
CAZ-AVI是治疗MDR/XDR铜绿假单胞菌感染的一种有效替代方案。
