Outpatient management of febrile neutropenia is appropriate for carefully selected low-risk patients, according to Ashley Morris Engemann, PharmD, Duke University Medical Center, who spoke at the 2012 Pharmacy Program held in Hollywood, Florida, during the 17th Annual Conference of the National Comprehensive Cancer Network (NCCN). Engemann noted that treating patients at home is clearly the patient’s preference and is cost saving. Risk assessment is the first step, as outpatient management is not appropriate for high-risk patients but can be considered in low-risk patients. High-risk patients are those with a score <21 on the MASCC (Multinational Association for Supportive Care in Cancer) index, which generally includes patients expected to have prolonged neutropenia (>7 days) or profound neutropenia (absolute neutrophil count ≤100 cells/mm3) following chemotherapy, and those with significant medical comorbidities or hepatic or renal insufficiency.
“In general, we recommend hospitalization for IV antibiotics in these cases,” she said. Low-risk patients (MASCC score ≥21) are anticipated to have a brief (≤7 days) neutropenic period or no or few comorbidities. “These patients may be treated with oral and/or outpatient empirical antibiotic therapy,”1 Engemann said. The 2012 NCCN Guidelines allow selected low-risk patients who are not already on fluoroquinolone prophylaxis to be considered for initial therapy with oral broad-spectrum antibiotics, most commonly with the following:
- Ciprofloxacin 500 mg PO q8h plus amoxicillin/clavulanate 50 mg PO q8h
- Ciprofloxacin plus clindamycin if allergic to penicillin
While not part of the NCCN Guidelines, there is supporting literature for levofloxacin 750 mg PO daily in selected patients.2
Recent Study Supportive but Underpowered
Two key studies have evaluated the outpatient treatment of febrile neutropenia.3,4 A study from 2006 identified 178 outpatients who presented to the hospital with a first febrile neutropenia episode and who were deemed to be at low risk for complications.3 They were treated with oral ciprofloxacin and amoxicillin/clavulanate and observed over 24 hours while hospitalized. Of these, 79 subjects (44%) were discharged early (median hospitalization time of 26 hours), while the other 56% remained hospitalized. No difference in complication rates was observed. Three patients in the early discharge group were readmitted for various reasons. The success rate for outpatient treatment was 96%.
In 2011, Talcott and colleagues also reported success with early discharge in a study of 121 patients who developed postchemotherapy fever and neutro - penia and were deemed at low risk.4 Patients were either discharged for home treatment (n = 50) or continued on hospital treatment (n = 71) with the same IV antibiotic regimen (penicillin/aminoglycoside combination or ceftazidime alone; imipenem- or aztreonam-based regimen if; vancomycin added at the discretion of physician). Oral antibiotic therapy was not standard at the time.
“Unfortunately, this study was closed early due to poor accrual so we cannot draw significant conclusions,” Engemann said, “but it showed the feasibility of outpatient treatment.” The median duration of fever was 3 days; of neutropenia, 4 days; and of febrile neutropenia, 4 days. Subsequent antibiotic changes were more common in hospitalized patients (24% vs 9%; P = .04). Four outpatient episodes (9%) resulted in hospital readmission. Major medical complications occurred in 8% of hospitalized patients and 9% of outpatients. Quality-of-life measures slightly favored the outpatient treatment, but most measures were equivalent.
Home Treatment Is Less Expensive
“It’s no surprise the cost of home management is much less,” she added. This was confirmed by a study published in 2011 in which investigators collected direct medical and self-reported indirect costs for 57 inpatient and 35 outpatient episodes (2008 dollars).5 In the hospitalized group versus the home treatment group, mean total charges were 49% higher ($16,341 vs $10,977; P <.01), mean estimated total costs were 30% higher ($10,143 vs $7830; P <.01), and patient/caregiver out-of-pocket costs were higher (mean, $201 vs $74; P <.01). Informal caregivers in both groups reported similar time caring for patients and time lost from work.
“The study concluded that home IV antibiotic treatment was less costly than continued inpatient care for carefully selected patients,” Engemann said. “At this point, it’s not known whether oral and IV therapy are equally effective, but we do know that early discharge following evaluation is a strategy we can use and it has cost savings.”
- Freifeld AG, Bow EJ, Sepkowitz KA, et al. 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:e56-e93.
- Freifeld A, Sankaranarayanan J, Ullrich F, et al. Clinical practice patterns of managing low-risk adult febrile neutropenia during cancer chemotherapy in the USA. Support Care Cancer. 2008;16:181-191.
- Klastersky J, Paesmans M, Georgala A, et al. Outpatient oral antibiotics for febrile neutropenic cancer patients using a score predictive for complications. J Clin Oncol. 2006;24:4129-4134.
- Talcott JA, Yeap BY, Clark JA, et al. Safety of early discharge for low-risk patients with febrile neutropenia: a multicenter randomized controlled trial. J Clin Oncol. 2011;29:3977-3983.
- Hendricks AM, Loggers ET, Talcott JA. Costs of home versus inpatient treatment for fever and neutropenia: analysis of a multicenter randomized trial. J Clin Oncol. 2011;29:3984-3989.