Clinical efficacy of renal dosing adjustments of ceftazidime‐avibactam in patients affected by carbapenem‐resistant Gram‐negative infections: a systematic review and meta‐analysis of observational studies

Aim: 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. Methods: 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 from two 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. Results: 1,794 articles were screened, and eleven observational studies (one prospective and ten retrospective) were included. Serious or critical risk of bias were found in four studies, while the other seven were classified at moderate risk of bias and included in the meta-analysis. Renal dosing adjustments of ceftazidime-avibactam was associated with higher risk of mortality (OR 1.79; 95%CI 1.18-2.72). Conclusions: 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.