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

Abstract

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.

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