Risk factors and outcome of extended-spectrum β-lactamase-producing Enterobacterales bacteraemia in high-risk neutropenic patients in haematology: A multicentre retrospective study.

OBJECTIVE

Extended-spectrum β-lactamase-producing Enterobacterales (ESBL-EB) infections are associated with poor outcomes in febrile neutropenia. The early identification of patients at risk during prolonged chemotherapy-induced neutropenia remains challenging.

METHODS

This multicentre retrospective cohort study included patients with a first Enterobacterales bacteraemia during neutropenia following induction, consolidation, or stem cell transplantation (2015-2022). ESBL-EB bacteraemia was compared with non-ESBL-EB bacteraemia using multivariable logistic regression. Secondary analysis assessed the association between specific antibiotic classes and ESBL-EB, and the impact of prior antibiotic exposure on phenotypic β-lactam resistance profiles.

RESULTS

Amongst 574 patients with Enterobacterales bacteraemia, 74 (12.9%) had ESBL-EB bacteraemia. The mean neutropenia duration was 15.8 ± 10.4 d. Inappropriate empirical therapy (73% vs. 10%, P < 0.001) was more frequent in ESBL-EB bacteraemia. In multivariable analysis, antibiotic exposure within 30 d (aOR 2.46, 95% confidence interval [CI] 1.38-4.38, P = 0.002) and mucosal lesions (aOR 3.20, 95% CI 1.58-7.23, P = 0.002) were associated with ESBL-EB bacteraemia. Prior cefepime exposure (adjusted odds ratio [aOR] 2.91, 95% CI 1.07-8.34; P = 0.04) and exposure to multiple antibiotics (aOR 2.88, 95% CI 1.09-7.99; P = 0.03) were associated with ESBL-EB bacteraemia compared with piperacillin-tazobactam exposure. Cefepime exposure was associated with a higher proportion of ESBL-producing isolates (37.2% vs. 18.6%, P = 0.04), whereas piperacillin-tazobactam exposure was associated with high-level penicillinase producers (37.3% vs. 2.3%, P < 0.001).

CONCLUSIONS

Recent antibiotic exposure and mucosal lesions are independent risk factors for ESBL-EB bacteraemia in high-risk neutropenic patients. Prior cefepime exposure was associated with ESBL-EB bacteraemia in comparison with piperacillin-tazobactam exposure; this exploratory finding requires confirmation in prospective studies.