Early Antibiotic Stop in Neutropenic Fever Did Not Raise Severe Events

Early discontinuation of empiric intravenous antibiotics in adults with hematologic malignancies and high-risk febrile neutropenia did not increase death, septic shock, or ICU transfer in an interim analysis of the randomized END trial.¹ Patients in the early-stop arm had 10.5 antibiotic-free days during neutropenia vs 3.8 days with continued therapy. Alisse Hannaford, MD, of Brigham and Women's Hospital, presented the findings at IDWeek 2026, held October 21-24 in Washington, DC.¹

Two other studies at the meeting tested shorter or nonantibiotic prevention strategies: 5-day vs 10-day oseltamivir prophylaxis after hospital influenza exposure, and universal intranasal antisepsis in ICUs.^2,3 IDSA guidelines recommend continuing broad-spectrum antibiotics in high-risk febrile neutropenia until marrow recovery when no bacterial source is found, despite risks of multidrug resistance and Clostridioides difficile infection.¹

END Trial Interim Results for Early Antibiotic De-Escalation in Febrile Neutropenia

The open-label, single-center trial enrolled adults admitted with high-risk febrile neutropenia without an identified bacterial source after 48 hours of defervescence.¹ Participants were randomized 1:1 to early discontinuation of empiric antibiotics or continuation until count recovery. Prolonged antibiotic exposure contributes to multidrug resistance, microbiome disruption, and worse outcomes after cellular therapy, yet randomized data supporting early discontinuation have been limited.¹

From May 2024 to April 2026, 157 participants were randomized and 148 completed follow-up (73 early discontinuation, 75 continuation).¹ Severe events, defined as death, septic shock, or ICU transfer by day 60, occurred in 11.0% of the early-discontinuation arm vs 13.3% of the continuation arm.¹

Rates of grade 3 or higher adverse events were similar, and median length of stay was 25 days in both arms.¹ Antibiotic-free days made up 59.4% of neutropenic days with early discontinuation vs 30.2% with continuation.¹

The trial enrolled at a single cancer center, and key safety outcomes were death, ICU transfer, and septic shock by day 60.¹ Antibiotic exposure was assessed alongside those safety measures.¹

The investigators wrote final analyses from the completed trial will provide a more definitive assessment.¹ All authors on the END trial poster reported no financial relationships.¹

Five-Day Oseltamivir Prophylaxis and Intranasal Decolonization in Hospital Infection Prevention

At University Medical Center Ljubljana in Slovenia, 166 hospitalized adults with ongoing influenza exposure, who could not be separated from index cases, were randomized to 5 or 10 days of oseltamivir post-exposure prophylaxis.² Median age was 78.5 years, and median Charlson comorbidity index was 6. Median duration of exposure was 3 days, defined as sharing a room for at least 12 hours with an index case receiving treatment.²

In the intention-to-treat population, 0 of 82 patients in the 5-day group and 1 of 84 (1.2%) in the 10-day group developed influenza (difference, 1.2 percentage points; 95% CI, −1.15 to 3.55; P = .321).² No serious adverse events related to oseltamivir were observed. Current recommendations call for 7 to 10 days of prophylaxis after the last exposure, and the investigators concluded the 5-day regimen allows less antiviral exposure.²

In a stepped-wedge prospective cohort across 7 adult ICUs at 3 Geisinger hospitals, once-daily alcohol-based intranasal antisepsis did not significantly reduce hospital-onset bloodstream infections.³ Rates were 11.5 vs 10.4 per 10,000 patient-days before and after implementation (RR, 0.91; 95% CI, 0.50-1.62; P = .74), and the point estimate for primary bloodstream infection favored the intervention (RR, 0.66; 95% CI, 0.31-1.37).³

Compliance exceeded 90%, and only 1 adverse event occurred across more than 21,000 applications.³ Among the 46 infections recorded, the most common organisms were Candida species (14), gram-negative bacteria (12), and Enterococcus species (10).³

Those 46 events were about 40% fewer than anticipated, and all units already used daily chlorhexidine bathing, which may have blunted the effect.³ Unit-level infection rates ranged widely, from 5.8 to 24.8 per 10,000 patient-days, although the study was not powered to explain the difference between units.³

References

1. Hannaford A, Kovac V, Gupta S, et al. END (Early Neutropenic Fever De-escalation of) Antibiotics Study: an open-label, randomized, controlled phase 4 trial. Presented at: IDWeek 2026; October 21-24, 2026; Washington, DC. Poster P-213.

2. Stupica D, Gulin J, Pezdirec M, Velušček M. Post-exposure influenza chemoprophylaxis with oseltamivir for five days vs ten days in acute-care hospital: a randomized open-label study. Presented at: IDWeek 2026; October 21-24, 2026; Washington, DC. Poster P-216.

3. Nazeer Hussain R, Suryadevara V, Bitton N, et al. Impact of universal non-antibiotic intranasal decolonization on hospital-onset bloodstream infections in adult intensive care units. Presented at: IDWeek 2026; October 21-24, 2026; Washington, DC. Poster P-232.