Neutropenic fever needs a fast response

David Goese, MD, offered several good reasons to care about neutropenic fever at Converge 2025, the annual meeting of the Society of Hospital Medicine.

“Well, it is deadly. … The rate of in-hospital mortality from neutropenic fever is 9.5%,” he told attendees, citing a study published in 2006 by the journal Cancer. The analysis of more than 40,000 patients found an even higher death rate in those with comorbidities.

The problem is also common. “Ten to 50% of all patients with solid tumors getting chemotherapy will at some point get neutropenic fever, and over 80% of those with hematologic malignancies [will],” said Dr. Goese, who is an assistant professor of medicine at Northwestern Memorial Hospital in Chicago.

The positive side is that early diagnosis can significantly change the results. “Prompt recognition of this condition and proper treatment improves outcomes,” he said.

The American Society of Clinical Oncology (ASCO) and Infectious Diseases Society of America (IDSA) have a joint clinical practice guideline on outpatient management of neutropenic fever that specifies how prompt you need to be—it calls for antibiotic administration within an hour of presentation. This is the latest official word on the subject, even though it was published in the Journal of Clinical Oncology back in 2018, Dr. Goese noted.

Of course, to recognize and rapidly treat the problem, it's helpful to know the relevant definitions.

A neutrophil count less than 500 cells/µL is severe neutropenia, and if it lasts more than seven days, it's high-risk neutropenia. That greater staying power may be more or less likely depending on the treatment a patient undergoes, Dr. Goese noted. “With certain chemotherapy regimens, you might expect a longer duration of neutropenia,” he said.

The febrile part of febrile neutropenia is defined as a single oral temperature greater than 38.3 °C (101 °F) or a temperature of greater than 38.0 °C (100.4 °F) sustained for more than an hour.

In healthy adults, those temperatures may not cause as much concern, but in someone with neutropenia, “even a slight fever like that could be a harbinger of a severe infection,” said Dr. Goese.

Although chemotherapy is the most common cause of neutropenia, there are many others, he noted. “All kinds of other drugs can cause this, including NSAIDs, rheumatologic medications, nutritional deficiencies. I took care of a patient recently who ironically was taking zinc because he wanted to keep his immune system up since COVID started. He took it for three years at high dose and got a copper deficiency from it, and then he got pancytopenia and developed neutropenic fever.”

In addition, infections such as HIV or the flu, immune-related conditions, and congenital diseases can cause neutropenia.

There's also an array of infectious agents that can be involved. “The most common causative bacterial pathogens are GI flora and flora that live in the mouth, also some health care-associated bacteria,” said Dr. Goese. “It used to be gram-negative organisms that were more prevalent, but especially with more prophylactic antibiotics, it selects more for gram-positive organisms.”

Gram-negative and gram-positive organisms were each responsible for about half of bloodstream infections in neutropenic patients in a study published in 2022 in Open Forum Infectious Diseases. The analysis of 343 patients found that cefepime and piperacillin-tazobactam were most commonly prescribed as empiric therapy, and among gram-negative isolates, 49% were susceptible to fluoroquinolones, 84% to cefepime, 88% to piperacillin-tazobactam, and 96% to carbapenems.

When choosing initial antibiotic therapy, “you also definitely want to know if a patient has had a history of infection with a drug-resistant organism,” Dr. Goese noted. Higher-risk patients should get more antibiotic coverage, specifically, the addition of vancomycin to whatever initial therapy you choose.

Another important choice to make at this point is whether a patient requires hospital admission. “So next up is the risk assessment,” said Dr. Goese. “This is important to do for all patients with neutropenic fever. You want to get a sense of what their risk is of severe complications.”

That same ASCO/IDSA guideline clarifies what factors to consider. It calls for risk assessment using the Multinational Association of Supportive Care in Cancer (MASCC) scoring system. “This is one of those scores where the higher the score, the lower risk for this patient, and 21 is the magic number,” he said. A patient with 21 or more points can be considered for outpatient treatment.

There are some exceptions to that cutoff, though. The guideline includes a table of “additional specific clinical criteria that may be used to exclude patients with cancer who have fever and neutropenia from initial outpatient care,” even if they have a MASCC score of 21 or above. The long list includes factors such as severe thrombocytopenia, altered mental status, and impaired renal function.

In practice, though, there are even more exceptions to the rules, according to Dr. Goese. “Ultimately, these 2018 guidelines say really you need to use your clinical judgment,” he said.

Risk factor assessment can also guide whether to prescribe additional treatments, such as antifungal medications. “The IDSA's 2010 guidelines [on antimicrobial agents in neutropenic patients with cancer] suggest empiric antifungal therapy for patients with a fever for four to seven days, despite appropriate antibiotics,” noted Dr. Goese.

And how long does the patient need to take antibiotics? The answer to that question has followed broader trends. “We've seen that short courses of antibiotics for various infections are appropriate, with the same outcomes as longer courses,” he said.

One recent study looked specifically at neutropenic patients with gram-negative infections and found similar rates of mortality and relapse whether they got antibiotics for 10 days or less, 11 to 14 days, or 15 days or more. Results were published by Transplant Infectious Disease in 2023.

“For me, this gives some evidence it's safe to do shorter courses of antibiotics,” said Dr. Goese. “It fits along with some other literature, too.”

He wrapped up his talk by presenting research on newer concepts of neutropenic fever management. One study published in February 2025 by Transplantation and Cellular Therapy involved remote monitoring the temperatures of high-risk patients undergoing cancer treatment.

“Presumably, you can diagnose a fever faster and get someone to care faster,” he said. The trial, involving 25 patients, did diagnose and provide alerts about 22 fevers. In 12 cases, patients sought care that day, but the others delayed seeking care. “I just found this kind of amusing,” said Dr. Goese. “So 10 of the patients were just, ‘OK, I'm going to keep hanging out.’”

It goes to show the importance of testing new interventions before they are widely implemented, he noted. “What actually changes when we use this remote monitoring has yet to be determined, but it's an interesting application of a technology that theoretically might have some benefit,” Dr. Goese concluded.