Medicine D, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel.
Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.
J Antimicrob Chemother. 2018 Aug 1;73(8):2021-2029. doi: 10.1093/jac/dky124.
Ceftazidime/avibactam is approved for complicated intra-abdominal and urinary tract infections (UTIs) based on results from randomized controlled trials (RCTs). Data regarding its effectiveness in treating hospital-acquired infections or resistant pathogens have not been systematically compiled.
A systematic review and meta-analysis including RCTs evaluating ceftazidime/avibactam versus comparator for the treatment of any infection. Primary outcome was 30 day all-cause mortality. Subgroups of hospital-acquired infections and specific resistance phenotypes were planned.
Seven publications (eight trials, 4093 patients) were included, reporting a baseline ∼25% of ESBL-carrying Enterobacteriaceae. No significant difference between ceftazidime/avibactam and comparator (mostly carbapenem) was demonstrated for 30 day all-cause mortality, late follow-up mortality and clinical response [relative risk (RR) 1.10, 95% CI 0.70-1.72, P = 0.69; RR 1.23, 95% CI 0.87-1.76, P = 0.25; RR 0.98, 95% CI 0.96-1.01, P = 0.21, respectively, without significant heterogeneity]. Higher microbiological response rate was demonstrated with ceftazidime/avibactam in patients with UTI (RR 1.14, 1.0-1.29, P = 0.05, I2 = 51%). No significant difference in clinical response was demonstrated for patients with ceftazidime-resistant pathogens (RR 1.02, 95% CI 0.94-1.10, P = 0.66, I2 = 0%). Results for other subgroups of resistant pathogens or hospital-acquired infection were not available. Serious adverse events (SAEs) were significantly more common with ceftazidime/avibactam (RR 1.24, 95% CI 1.00-1.54, P = 0.05, I2 = 0%).
Ceftazidime/avibactam is clinically and microbiologically as effective as carbapenems for treatment of infections in a setting of ∼25% ESBL-carrying Enterobacteriaceae. Safety of the drug should be further evaluated owing to a higher rate of SAEs compared with carbapenems. Further studies should assess the drug's effectiveness in the treatment of carbapenemase-producing Enterobacteriaceae.
头孢他啶/阿维巴坦基于随机对照试验（RCT）的结果获得批准，用于治疗复杂性腹腔内和尿路感染（UTI）。尚未系统收集有关其治疗医院获得性感染或耐药病原体的有效性的数据。
对评估头孢他啶/阿维巴坦与对照药物治疗任何感染的 RCT 进行系统评价和荟萃分析。主要结局是 30 天全因死亡率。计划了医院获得性感染和特定耐药表型的亚组。
纳入了 7 篇文献（8 项试验，4093 名患者），基线时携带 ESBL 的肠杆菌科约占 25%。头孢他啶/阿维巴坦与对照药物（主要是碳青霉烯类）相比，30 天全因死亡率、后期随访死亡率和临床反应无显著差异[相对风险（RR）1.10，95%CI 0.70-1.72，P=0.69；RR 1.23，95%CI 0.87-1.76，P=0.25；RR 0.98，95%CI 0.96-1.01，P=0.21，无显著异质性]。头孢他啶/阿维巴坦在尿路感染患者中显示出更高的微生物学反应率[RR 1.14，1.0-1.29，P=0.05，I2=51%]。对于头孢他啶耐药病原体的患者，临床反应无显著差异[RR 1.02，95%CI 0.94-1.10，P=0.66，I2=0%]。对于其他耐药病原体或医院获得性感染亚组的结果尚不可用。头孢他啶/阿维巴坦的严重不良事件（SAE）发生率明显更高[RR 1.24，95%CI 1.00-1.54，P=0.05，I2=0%]。
头孢他啶/阿维巴坦在携带 ESBL 的肠杆菌科约占 25%的情况下，在治疗感染方面与碳青霉烯类药物在临床和微生物学上同样有效。由于与碳青霉烯类药物相比，SAE 发生率更高，该药的安全性应进一步评估。应进一步研究评估该药物在治疗产碳青霉烯酶肠杆菌科中的有效性。
