Is less always more? Ceftazidime/avibactam alone or in combination to treat infections caused by Pseudomonas aeruginosa: a retrospective observational multi-centre cohort study

Purpose: In vitro and in vivo studies suggest adding a second agent to ceftazidime/avibactam (CZA) to enhance bactericidal activity against Pseudomonas aeruginosa (PA). Nevertheless, evidence supporting this practice is scarce. Methods: We conducted a retrospective cohort study of patients admitted to 9 Italian hospitals with microbiologically confirmed PA infection and treated with CZA alone or in combination from 01/01/2015 to 31/12/2021. The primary endpoint was 14-day clinical cure. Secondary endpoints were 28-day all-cause mortality, 56-day microbiological failure, 56-day infection relapse, and emergence of CZA resistance. A generalized linear model extended to the binomial family, with identity link, weighted for IPTW (inverse probability of treatment weighting), was fitted to compare the two groups for 14-day clinical cure. Results were reported in terms of risk difference (RD) and 90% Confidence Interval (90%CI). Results: Eighty-seven patients with infection due to PA were included; 17 were treated with CZA monotherapy, and 70 with combination therapy with CZA plus another anti-pseudomonal agent. Sequential organ failure assessment was significantly higher (median 6 [3-9]) in the combination group compared to monotherapy (median 3 [1-5]; p = 0.049). After weighting patients according to the IPTW, CZA monotherapy did not reach the clinical equipoise to combination therapy in terms of 14-day clinical cure (RD -0.28, 90% CI -0.41 to -0.14). No significant risk difference between groups was found for any of the secondary endpoints. Conclusion: Our findings suggest that combination therapy with CZA for treating PA infections may provide some clinical benefit over monotherapy despite the absence of a definitive survival advantage.