“You will encounter neutropenic fever in your career as a hospitalist,” emphasized David Goese, MD, an academic hospitalist and assistant professor of medicine at the Northwestern University Feinberg School of Medicine in Chicago, during his presentation at SHM Converge 2025 in Las Vegas. The potentially life-threatening condition demands early recognition and quick intervention, as mortality rates still hover around 11% despite modern advances. The presentation highlighted the approaches in the management of a patient while also noting that some patients can be safely managed as outpatients, which could be considered a shift from traditional practices.
Dr. Goese began by providing working definitions as well as epidemiological data. He noted that severe neutropenia is classified as an absolute neutrophil count (ANC) less than 500 per microliter, and febrile neutropenia as a single oral temperature of greater than or equal to 101° F (38.3° C) or a temperature of 100.4° F (38.0° C) that is sustained for more than an hour in a neutropenic patient.
He then focused on the sobering epidemiological data: an overall mortality rate of 11%, with an incidence in solid tumors ranging from 10% to 50% among patients receiving chemotherapy, and an incidence in hematologic malignancies as high as 80%.
Later in the session, Dr. Goese references a study from December 2016 to May 2019 that looked at 343 patients in 14 U.S. cancer centers. Of those, 68% were hematologic malignancy patients and 32% were hematopoietic stem cell transplant patients. This represents a fair proportion of the oncology admissions a hospitalist will manage, either primarily or in consultation.
He further provided a review of neutropenia causes beyond chemotherapy, including medication-induced (such as antimicrobials, antipsychotics, and anticonvulsants), nutritional deficiencies, infections (such as HIV or AIDS, influenza, Hepatitis B, respiratory syncytial virus, cytomegalovirus, tuberculosis, and Shigella), immune-related disorders (such as autoimmune chronic benign neutropenia), and congenital causes such as Cohen syndrome, Kostmann syndrome, Barth Syndrome, and Chediak-Higashi syndrome. Dr. Goese noted that while chemotherapy-induced neutropenia remains the most common, as hospitalists, we need to keep a broader differential that includes patients with known malignancies who present to the emergency department with fever and unexplained neutropenia.
A highlight of the session was a detailed case presentation of a 68-year-old male with metastatic pancreatic cancer presenting with acute-on-chronic abdominal pain and a neutropenic fever. He was noted to be febrile and slightly hypotensive, and to have tachycardia. He was also noted to be non-toxic in appearance and had mild mucositis of the right soft palate.
Labs (which showed an absolute neutrophil count of 360) and diagnostics were ordered, as well as IV fluids and antibiotics. The audience was polled, and the majority concluded that antibiotics should be started once the labs were drawn and should start within one hour of presentation. As Dr. Goese walked through the case progression, he illustrated critical decision points. In this case, the patient initially responded to empiric antibiotics but on day four developed a persistent fever. At that point, he noted, antifungals should be considered.
Which patients could go home? According to a study published in The Journal of Clinical Oncology in 2018, the Clinical Index of Stable Febrile Neutropenia, or CISNE, is a validated tool for identifying low-risk patients who may be safely managed as outpatients. Patients who receive a very low risk score for serious complications and have access to reliable follow-up care can be considered for outpatient management. This represents a shift from the traditional practice of admitting all patients with neutropenic fever.
Dr. Goese noted that risk stratification tools are available to inform the hospitalist’s management of the patient. Although useful, they should never delay antibiotics or admission decisions. He further emphasized that even low-risk patients generally warrant at least a brief observation with IV antibiotics.
Every hospitalist should play a role as an antibiotic steward and follow the most current recommendations. The recent multicenter VANC-FN trial data demonstrated no mortality benefit but significant nephrotoxicity with routine vancomycin addition. Current recommendations presented include: antipseudomonal beta-lactam monotherapy; piperacillin-tazobactam 4.5 g IV every six hours, cefepime 2 g IV every eight hours, and meropenem 1 g IV every eight hours. Add vancomycin only for hemodynamic instability or septic shock, pneumonia with substantial infiltrates, known methicillin-resistant Staphylococcus aureus colonization with signs of skin or soft tissue infection, and severe mucositis. Consider empiric antifungals only after four to seven days of fever persisting despite appropriate antibacterial coverage (earlier if clinically deteriorating or having high-risk factors for fungal infection).
One of the biggest practice-changing updates is that neutrophil recovery is no longer the sole determinant for antibiotic duration. Dr. Goese explained by presenting evidence from the ANTIBIOSTOP trial published in 2024 that outlines a simplified approach to therapy duration.
If the patient has a documented infection, the hospitalist should follow standard duration guidelines such as for non-neutropenic patients (e.g., seven days for uncomplicated bacteremia, 14 days for pneumonia). For fever of unknown origin, if the patient is afebrile for 48 hours and clinically stable, consider stopping antibiotics even with ongoing neutropenia. Finally, continue until count recovery only with high-risk patients (acute myeloid leukemia induction, stem cell transplant).
We were asked the question, “What is new in the care of patients with febrile neutropenia?” This inquiry focuses on the evaluation of antimicrobial duration for gram-negative bacteremia in patients with neutropenia resulting from hematologic malignancies or hematopoietic stem cell transplantation.
In a retrospective cohort study involving 206 patients, the authors examined various durations of treatment: less than 10 days, 11 to 14 days, and more than 14 days. The primary outcomes of the study included a composite measure of all-cause mortality and microbiologic relapse within 90 days. Secondary outcomes assessed included Clostridium difficile infections and multidrug-resistant gram-negative colonization within the same 90-day period.
Outpatient management for neutropenic fever is now possible through remote monitoring. In a pilot study involving 25 patients undergoing autologous hematopoietic stem cell transplantation and chimeric antigen receptor T-cell, or CAR-T, therapy, the TempTraq® device was used for remote temperature monitoring. This device identified fever in the range of 100.4° F to 100.7° F. Out of the participants, 12 sought treatment on the same day they were alerted, while 10 delayed seeking care.
A multicenter prospective trial was conducted on clinical metagenomic sequencing of plasma microbial cell-free DNA in patients with febrile neutropenia, particularly those with acute leukemia. The study included 442 participants. Blood cultures and metagenomic next-generation sequencing (mGNGS) produced 230 positive results. Of these, 33.5% were diagnosed by both blood cultures and mGNGS, 2.2% were identified by blood cultures only, and 59.1% were diagnosed by mGNGS alone. Additionally, 5.2% of the results were positive in both tests but had discordant findings.
Mr. Facklam is an adult hospitalist, nurse practitioner, and nocturnist with Apogee Physicians at South Georgia Medical Center in Valdosta, Ga