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Febrile Neutropenia

Febrile neutropenia is defined as an absolute neutrophil count <1000 cells/μL and temperature ≥38.3°C by oral or tympanic thermometry. It occurs in 10% to 50% of patients with solid cancers and more than 80% with hematologic cancers. The initial laboratory evaluation of all patients with febrile neutropenia includes a complete blood cell count with differential leukocyte count, renal and hepatic function tests, and at least 2 sets of blood cultures.

The Infectious Diseases Society of America and the American Society of Clinical Oncology promote the use of the Multinational Association for Supportive Care in Cancer (MASCC) score to identify low-risk patients with febrile neutropenia for whom outpatient treatment with oral antibiotics may be appropriate.

Characteristic Points
Burden of symptoms  
No or mild symptoms 5
Moderate symptoms 3
Severe or morbid symptoms 0
No hypotension (SBP >90) 5
Solid or hematologic cancer w/o previous fungal infection 4
No dehydration requiring parenteral fluiids 3
Outpatient status at onset of fever 3
Age <60 years 2


Severe symptoms include tachypnea (respiratory rate >24/min), tachycardia (heart rate >120 bpm), and hypoxemia (oxygen saturation <90% breathing room air). The maximum MASCC score is 26. A score of 21 or greater is considered low risk and a score less than 21 is considered high risk.

After a period of observation of 4 hours in the emergency department or clinic, low-risk patients can be treated as outpatients with oral fluoroquinolones plus amoxicillin-clavulanate (or clindamycin if penicillin allergic) with close monitoring.

In high-risk patients with febrile neutropenia, hospitalization and intravenous monotherapy with an antipseudomonal β-lactam agent is recommended. Guidelines recommend against the routine initial use of vancomycin, even in high-risk patients, with consideration if patients have suspected catheter-related infection, skin or soft-tissue infection, pneumonia, or hemodynamic instability.

Despite this guideline, hospitalization and inappropriate intravenous antibiotic use in low-risk patients are common. A 5-year study from an academic US medical center found that 98% of low-risk patients with febrile neutropenia received guideline-discordant care. Unnecessary hospitalization and antibiotic use are associated with the emergence of multidrug-resistant organisms in these patients who are susceptible to infection. Outpatient management and close follow-up is a validated treatment strategy in low-risk patients with a MASCC score ≥21.


Bergstrom C. et al. Management of Patients with Febrile Neutropenia: A teachable moment. JAMA Intern Med. Published online February 12, 2018. doi:10.1001/jamainternmed.2017.8386.

Freifeld AG, Bow EJ, Sepkowitz KA, et al; Infectious Diseases Society of America.  Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America.  Clin Infect Dis. 2011;52(4):427-431.

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