Comparison of ceftazidime-avibactam with other appropriate antimicrobial therapy for the treatment of OXA-48- or KPC-producing Enterobacterales infections in Türkiye: A multi-centre retrospective matched-cohort study

OBJECTIVE: Due to underrepresentation of carbapenemase-producing Enterobacterales infections in randomized controlled trials with ceftazidime-avibactam (CZA) and high cost of CZA therapy, other appropriate antimicrobial therapies (OAAT) are still being used for OXA-48- or KPC-producing Enterobacterales infections in Türkiye. METHODS: We conducted a multicentre retrospective 1:1 matched cohort study of patients who received ≥48 h of CZA or OAAT for documented OXA-48- or KPC-producing Enterobacterales infections. Patients were matched based on (1) the number of days (± 1 d) from the infection onset to the initiation of therapy, (2) INCREMENT-CPE score (± 1), (3) source of infection, (4) year of infectious episode, and (5) type of causative microorganism. RESULTS: From 5 Turkish university hospitals, 180 patients were enrolled. Baseline characteristics were all similar between treatment groups. At the time of treatment initiation, 63.9% of patients were in the intensive care unit, 35.6% had septic shock and 41.1% required mechanical ventilation support. Thirty-day mortality occurred in 35.6% (32/90) of patients treated with CZA and in 56.7% (51/90) of those receiving OAAT regimens (P = 0.004). Twenty-one-day clinical response was seen in 50% (45/90) and 26.7% (24/90) of patients receiving CZA and OAAT, respectively (P = 0.002). In multivariable logistic regression analyses, CZA treatment was associated with less likelihood of mortality (aOR = 0.37; 95% CI: 0.19-0.71; P = 0.003) and higher likelihood of 21-d clinical response (aOR = 3.32; 95% CI: 1.68-6.53; P < 0·001). CONCLUSIONS: Treatment with CZA is associated with more favourable clinical outcomes in treatment of OXA-48- or KPC-producing Enterobacterales infections. A randomized controlled trial is needed to confirm these results.