Abstract: Background: Infections caused by carbapenemase-producing Enterobacterales (CPE) are not well represented in pivotal trials with ceftazidime/avibactam. The best strategy for the treatment of these infections is unknown. Methods: We conducted a multicentre retrospective observational study of patients who received ?48 h of ceftazidime/avibactam or best available therapy (BAT) for documented CPE infections. The primary outcome was 30 day crude mortality. Secondary outcomes were 21 day clinical response and microbiological response. A multivariate logistic regression model was used to identify factors predictive of 30 day crude mortality. A propensity score to receive treatment with ceftazidime/avibactam was used as a covariate in the analysis. Results: The cohort included 339 patients with CPE infections. Ceftazidime/avibactam treatment was used in 189 (55.8%) patients and 150 (44.2%) received BAT at a median of 2 days after diagnosis of infection. In multivariate analysis, ceftazidime/avibactam treatment was associated with survival (OR 0.41, 95% CI 0.20?0.80; P=0.01), whereas INCREMENT-CPE scores of .7 points (OR 2.57, 95% CI 1.18?1.5.58; P=0.01) and SOFA score (OR 1.20, 95% CI 1.08?1.34; P=0.001) were associated with higher mortality. In patients with INCREMENT-CPE scores of .7 points, ceftazidime/avibactam treatment was associated with lower mortality compared with BAT (16/73, 21.9% versus 23/49, 46.9%; P=0.004). Ceftazidime/avibactam was also an independent factor of 21 day clinical response (OR 2.43, 95% CI 1.16?5.12; P=0.02) and microbiological eradication (OR 0.40, 95% CI 0.18?0.85; P=0.02). Conclusions: Ceftazidime/avibactam is an effective alternative for the treatment of CPE infections, especially in patients with INCREMENT-CPE scores of .7 points. A randomized controlled trial should confirm these findings.

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