Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Br J Clin Pharmacol. 2023 Feb;89(2):617-629. doi: 10.1111/bcp.15586. Epub 2022 Nov 22.
The aim of this study is to assess clinical efficacy of ceftazidime-avibactam for the management of carbapenem-resistant Gram-negative infections in renal patients receiving recommended dosing adjustments compared to those treated with scheduled full-dose.
Two authors independently searched PubMed-MEDLINE and Scopus database from inception to 31 December 2021, to retrieve randomized controlled trials or observational studies comparing clinical efficacy of ceftazidime-avibactam in patients affected by carbapenem-resistant Gram-negative infections receiving recommended renal dosing adjustments compared to those treated with scheduled full-dose. Data were independently extracted by the 2 authors, and the quality of included studies was independently assessed according to ROBINS-I tool for observational studies. Mortality rate was selected as primary outcome. Meta-analysis was conducted by including only studies at low or moderate risk of bias providing adjustment for confounders.
In total, 1794 articles were screened, and 11 observational studies (1 prospective and 10 retrospective) were included. Serious or critical risk of bias was found in 4 studies, while the other 7 were classified at moderate risk of bias and included in the meta-analysis. Renal dosing adjustments of ceftazidime-avibactam were associated with higher risk of mortality (odds ratio 1.79; 95% confidence interval 1.18-2.72).
Renal dosing adjustment of ceftazidime-avibactam seems to be associated with a higher risk of mortality in patients affected by carbapenem-resistant Gram-negative infections. However, residual confounder associated with baseline conditions cannot be excluded. Further prospective studies including larger samples are warranted to definitively address this unmet clinical need.
本研究旨在评估头孢他啶-阿维巴坦在接受推荐剂量调整的肾损伤患者中治疗碳青霉烯类耐药革兰氏阴性感染的临床疗效，并与接受常规全剂量治疗的患者进行比较。
两位作者独立检索了 PubMed-MEDLINE 和 Scopus 数据库，检索时间从建库至 2021 年 12 月 31 日，以检索比较头孢他啶-阿维巴坦在接受推荐剂量调整的肾损伤患者中治疗碳青霉烯类耐药革兰氏阴性感染的临床疗效的随机对照试验或观察性研究，并与接受常规全剂量治疗的患者进行比较。两位作者独立提取数据，并根据 ROBINS-I 工具对观察性研究进行了独立评估。选择死亡率作为主要结局。仅纳入低或中度偏倚风险的研究进行荟萃分析，这些研究为混杂因素提供了调整。
共筛选出 1794 篇文章，纳入了 11 项观察性研究（1 项前瞻性和 10 项回顾性）。4 项研究存在严重或临界偏倚风险，而其余 7 项研究存在中度偏倚风险并纳入荟萃分析。头孢他啶-阿维巴坦的剂量调整与更高的死亡率风险相关（比值比 1.79；95%置信区间 1.18-2.72）。
头孢他啶-阿维巴坦的剂量调整似乎与碳青霉烯类耐药革兰氏阴性感染患者的死亡率增加相关。然而，不能排除与基线情况相关的残余混杂因素。需要进一步开展包括更大样本量的前瞻性研究，以明确解决这一未满足的临床需求。
