De-escalation of empiric broad spectrum antibiotics in hematopoietic stem cell transplant recipients with febrile neutropenia

Abstract

Febrile neutropenia (FN) is a common serious complication in patients undergoing hematopoietic stem cell transplantation (HSCT) requiring urgent evaluation and initiation of empiric broad spectrum antibiotics (BSA). The appropriate duration of BSA for FN in patients with negative cultures and no identifiable infection remains undefined. We retrospectively analyzed allogenic and autologous HSCT patients with FN and negative infectious work-up at our facility from 2012 to 2018. The early deescalation group (EDG) included those who had BSA de-escalation to fluoroquinolone prophylaxis at least 24 h prior to absolute neutrophil count (ANC) recovery after the patient was fever-free for at least 48 h. Among 297 patients undergoing their first HSCT who experienced FN with negative infectious work-up, 83 patients were de-escalated early with the remaining 214 in the standard of care group (SCG) whose BSA were continued until ANC was > 500. Duration of broad-spectrum antibiotics was shorter in EDG compared to SCG (3.86 days vs. 4.62 days, p = 0.03). Rates of mortality, new infections, and clinical decompensation requiring intensive care unit transfer and/or pressor use within 30 days were all similar between the two groups (0% vs. 0.4% p = 1.00, 0% vs. 1.4% p = 0.56, 13.2% vs. 8.4% p = 0.27). This indicates that it is safe to de-escalate antibiotics prior to ANC recovery, leading to less BSA exposure.

Antibiotic resistance in the patient with cancer: Escalating challenges and paths forward

“…152 Early discontinuation of empirical antibacterial therapy in patients with fever of unknown origin has been demonstrated to be safe, 153,154 and emerging data indicate that continuation of empirical antibiotics until absolute neutrophil count recovery could be unnecessary. 155,156 De-escalating and discontinuation strategies have been successfully demonstrated in highrisk neutropenic patients who have cancer, with a significant reduction in antibiotic use. [157][158][159]…”

The post-hematopoietic cell transplantation microbiome: relationships with transplant outcome and potential therapeutic targets

“… 32 Of note, shortening the duration of administration of empiric broad-spectrum antibiotics in patients with febrile neutropenia without an identifiable infectious cause has been studied and appears to be safe; however, it remains unclear whether the shortened exposure also reduced intestinal dysbiosis in these patients. 83 Other strategies that are currently being developed to prevent antibiotic-mediated microbial disruption include molecules that degrade or neutralize antibiotic residues in the intestinal tract. 84 , 85 …”

Prevention and management of carbapenem-resistant Enterobacteriaceae in haematopoietic cell transplantation

“…Several large retrospective studies on HCT recipients with febrile neutropenia without any identifiable infectious focus show that early cessation of antimicrobials has no adverse impact on mortality, rehospitalisation, clinical deterioration and recurrence of fever at ⩾72 h. 75 – 83 A multicentre, randomised controlled trial (HOW LONG study) evaluated cessation of antimicrobials before neutrophil recovery in febrile neutropenic patients without an aetiological diagnosis who are clinically recovered and apyrexic for >72 h and compared this approach with continual antimicrobials until neutrophil recovery to >500 cells/mm 3 . 84 Almost a fourth of participants in this study were HCT recipients.…”