Temkin Elizabeth, Torre-Cisneros Julian, Beovic Bojana, Benito Natividad, Giannella Maddalena, Gilarranz Raúl, Jeremiah Cameron, Loeches Belén, Machuca Isabel, Jiménez-Martín María José, Martínez José Antonio, Mora-Rillo Marta, Navas Enrique, Osthoff Michael, Pozo Juan Carlos, Ramos Ramos Juan Carlos, Rodriguez Marina, Sánchez-García Miguel, Viale Pierluigi, Wolff Michel, Carmeli Yehuda
Department of Epidemiology and Preventive Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Department of Infectious Diseases, Hospital Universitario Reina Sofía, Córdoba, Spain.
Antimicrob Agents Chemother. 2017 Jan 24;61(2). doi: 10.1128/AAC.01964-16. Print 2017 Feb.
Ceftazidime-avibactam (CAZ-AVI) is a recently approved β-lactam-β-lactamase inhibitor combination with the potential to treat serious infections caused by carbapenem-resistant organisms. Few patients with such infections were included in the CAZ-AVI clinical trials, and clinical experience is lacking. We present a case series of patients with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) or Pseudomonas aeruginosa (CRPa) who were treated with CAZ-AVI salvage therapy on a compassionate-use basis. Physicians who had prescribed CAZ-AVI completed a case report form. We used descriptive statistics to summarize patient characteristics and treatment outcomes. We used the Wilcoxon rank sum test and Fisher's exact test to compare patients by treatment outcome. The sample included 36 patients infected with CRE and two with CRPa. The most common infections were intra-abdominal. Physicians categorized 60.5% of patients as having life-threatening infections. All but two patients received other antibiotics before CAZ-AVI, for a median of 13 days. The median duration of CAZ-AVI treatment was 16 days. Twenty-five patients (65.8%) concurrently received other antibiotics to which their pathogen was nonresistant in vitro Twenty-eight patients (73.7%, 95% confidence interval [CI], 56.9 to 86.6%) experienced clinical and/or microbiological cure. Five patients (20.8%) with documented microbiological cure died, whereas 10 patients (71.4%) with no documented microbiological cure died (P = 0.01). In three-quarters of cases, CAZ-AVI (alone or combined with other antibiotics) cured infections caused by carbapenem-resistant organisms, 95% of which had failed previous therapy. Microbiological cure was associated with improved survival. CAZ-AVI shows promising clinical results for infections for which treatment options are limited.
头孢他啶-阿维巴坦（CAZ-AVI）是一种最近获批的β-内酰胺-β-内酰胺酶抑制剂组合，有潜力治疗由耐碳青霉烯类微生物引起的严重感染。CAZ-AVI临床试验纳入的此类感染患者很少，缺乏临床经验。我们报告了一系列耐碳青霉烯类肠杆菌科细菌（CRE）或铜绿假单胞菌（CRPa）感染患者，他们在同情用药的基础上接受了CAZ-AVI挽救治疗。开具CAZ-AVI的医生填写了病例报告表。我们使用描述性统计来总结患者特征和治疗结果。我们使用Wilcoxon秩和检验和Fisher精确检验按治疗结果比较患者。样本包括36例CRE感染患者和2例CRPa感染患者。最常见的感染是腹腔内感染。医生将60.5%的患者归类为患有危及生命的感染。除两名患者外，所有患者在使用CAZ-AVI之前都接受了其他抗生素治疗，中位时间为13天。CAZ-AVI治疗的中位持续时间为16天。25例患者（65.8%）同时接受了其病原体在体外不耐药的其他抗生素。28例患者（73.7%，95%置信区间[CI]，56.9至86.6%）实现了临床和/或微生物学治愈。5例记录有微生物学治愈的患者死亡，而10例无微生物学治愈记录的患者死亡（P = 0.01）。在四分之三的病例中，CAZ-AVI（单独或与其他抗生素联合使用）治愈了由耐碳青霉烯类微生物引起的感染，其中95%的感染先前治疗失败。微生物学治愈与生存率提高相关。对于治疗选择有限的感染，CAZ-AVI显示出有前景的临床结果。
