Ceftazidime/avibactam for the treatment of bloodstream infection due to carbapenemase-producing Enterobacterales in onco-haematologic neutropenic patients (the TARZAN study)

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OBJECTIVES: To assess the clinical features, antibiotic therapy and outcomes of carbapenemase-producing Enterobacterales bloodstream infection (CPE-BSI) in neutropenic patients with haematological malignancies treated with ceftazidime/avibactam. METHODS: We conducted a multicentre, international, retrospective, descriptive study of CPE-BSI episodes in neutropenic onco-haematological patients treated with ceftazidime/avibactam as empirical and/or targeted therapy (2017-2022). RESULTS: Of 54 episodes of CPE-BSI in haematological patients with neutropenia, more than half presented acute myeloid leukaemia (32, 59.5%). Klebsiella pneumoniae was the most frequently isolated pathogen (79.5%) and KPC the most prevalent carbapenemase (52%). The source of BSI was mainly endogenous (57.5%). Up to 11% presented with septic shock. Initial empirical antibiotic therapy was inadequate in 47% of cases, particularly monotherapy with meropenem or piperacillin/tazobactam. Ceftazidime/avibactam was administered empirically in 30% of patients and targeted in all episodes, mainly in combination with aminoglycosides, colistin or tigecycline. Nephrotoxicity occurred in 15% of patients, being attributed to aminoglycosides or colistin. Intensive care unit admission was required in 20% of cases. All-cause 7-day and 30-day case-fatality rates were 11% and 24%, respectively. Multivariate analysis showed that septic shock at BSI onset was an independent risk factor for 30-day mortality. CONCLUSIONS: Ceftazidime/avibactam proved to be safe and efficacious for the treatment of CPE-BSI in this extremely high-risk population.

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