Effect of antibiotic de-escalation on clinical outcomes in patients with carbapenem-resistant Enterobacteriaceae bacteremia (CRE) in the hematology-oncology setting.

Introduction: Carbapenem-resistant Enterobacteriaceae (CRE) infections are associated with poor outcomes, particularly among hematology-oncology patients. Appropriate use (selection and de-escalation) of antibiotics is a key component of management of febrile neutropenia particularly in high CRE prevalence regions like India.

Methods: This was a retrospective study done (April 2019-December 2021) in a dedicated oncology center in North India, which assessed the case records of the patients undergoing therapy for hematological malignancies who were diagnosed with CRE bacteremia. Demographic, clinical and microbiological data, as well as antibiotic prescription patterns were studied. Inter-group analysis was done between an antibiotic stewardship cohort (avoiding CRE therapy empirically or stopping CRE therapy if cultures negative; as per suggestions of the AMS team) and a non-antibiotic stewardship cohort (continuation of empirical CRE therapy; de-escalation advice was not followed).

Results: A total of 139 patients were identified, with median age of 41 years (range 13-74) out of which 82 (58.9%) were males. Acute myeloid leukemia (66.2%) was the most common malignancy, followed by lymphoma (8.6%) and myeloma (8.6%). Nearly 30% of patients were post allogenic stem cell transplant. Klebsiella pneumoniae was the predominant organism (78.4%) and combination of NDM+OXA-48 (46.3%) was the most common carbapenemase gene detected followed by OXA-48 alone (34.7%). Overall, 28-day mortality was 26.6%. On binary logistic regression analysis, lack of compliance with antibiotic stewardship intervention was an independent predictor of mortality (p=0.005).

Conclusions: Prior exposure to empirical CRE therapy or failure to de-escalate was associated with poor outcomes in patients with CRE bacteremia, which gives us a window of antibiotic stewardship in febrile neutropenia.