Flowers, C. R., Seidenfeld, J., Bow, E. J., Karten, C., Gleason, C., Hawley, D. K., . . . Ramsey, S. D. (2013). Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy. Journal of Clinical Oncology, 31, 794–810.

To provide guidelines for antimicrobial prophylaxis and management of febrile neutropenia (FN) for adult outpatients with neuropathy.

The resource was a consensus-based guideline. A literature search examined articles indexed in MEDLINE (January 1987–April 2011).  A systematic review of 47 articles from 43 studies were included in the analysis. Keywords included terms for malignant diseases; terms for neutropenia, infection, or fever; and terms for clinical guidelines, systematic reviews, meta-analyses, or clinical trials.

Articles were included if they were fully published English language reports on the topics of antimicrobials for the prevention of infection in neutropenic outpatient patients with cancer (with or without fever), direct comparisons of outcomes between inpatient and outpatient management of FN in patients with cancer, and methods to quantify risk of complications in patients with cancer and FN. Articles were excluded if they were meeting abstracts, commentaries, letters, editorials, case reports, and nonsystematic reviews.

Patients were undergoing the active treatment phase of care.

A table of recommendations addressed three main areas of concern: (a) preventing infection in patients at risk for neutropenia undergoing chemotherapy, (b) identifying which patients with cancer and FN may be safely treated as outpatients, and (c) identifying interventions for the outpatient management of FN.

• Patients should be systematically assessed for risk of FN and/or need for granulocyte colony-stimulating factor prophylaxis.
• Antimicrobial prophylaxis is recommended only if neutropenia is expected to be profound (absolute neutrophil count [ANC] <100) and more than seven days in duration.
• Annual influenza immunization is recommended for all patients undergoing chemotherapy and their family members.
• Drugs of choice are an oral fluoroquinolone for antibacterial prophylaxis and an oral triazole for antifungal prophylaxis.
• Patients with FN should be assessed using the Multinational Association for Supportive Care in Cancer (MASCC) score or Talcott’s rules to guide whether outpatient treatment is safe. In addition, patients should be compliant, live near the hospital, and have a caregiver and access to transportation at all times.
• If treating FN as an outpatient, it is recommended to begin empiric antimicrobial treatment within one hour and observe for four hours.
• Drugs of choice for outpatient empiric treatment of FN are an oral fluoroquinolone plus amoxicillin/clavulanate (or plus clindamycin for those allergic to penicillin).

• Limited data exist from randomized, controlled trials regarding health outcomes or comparing the efficacy and safety of alternative regimens of antimicrobial prophylaxis.
• The MASCC score revealed a high rate of false-positive results.

These guidelines help clinicians determine which patients require hospitalization and which can safely be treated in the outpatient setting. The guidelines also aid in selecting appropriate antimicrobial prophylaxis for neutropenic patients.