Effective antibiotic treatment results in palliation of fever-associated constitutional symptoms, as well as palliation of site-specific symptoms such as cough secondary to pneumonia or localized pain due to abscess formation. For febrile neutropenic patients (granulocyte count <500), immediate initiation of broad-spectrum antibiotic treatment is imperative, as the mortality rate is 70% for patients not receiving antibiotics within 48 hours. For the purposes of neutropenia, fever is defined as a single temperature elevation above 38.5°C or three elevations above 38°C in a 24-hour period.
Since the cause of neutropenic fever is not documented in 50% to 70% of patients, antibiotic use is guided by knowledge of the treating institution's antimicrobial spectrum and antibiotic resistance pattern, as well as the suspected cause. There is no consensus on the particular antibiotic or combination of antibiotics to be used, but empiric antibiotic therapy generally falls into one of four protocols:
- Aminoglycoside plus antipseudomonal beta-lactam.
- Combination of two beta-lactams.
- Vancomycin plus aminoglycoside and antipseudomonal beta-lactam.
When multiple-lumen catheters are present, antibiotic therapy should be rotated through each lumen. Bacteriostatic antibiotics (i.e., tetracycline, erythromycin, chloramphenicol) are not beneficial in the absence of granulocytes, which, when given concomitantly, reduce the efficacy of the bactericidal antibiotics.[4,11]
Treatment regimens are further modified by the duration of fever and individual patient risk factors such as the presence of central lines or other artificial devices, history of steroid use, and history of injection drug use. Various investigators have developed models predicting risk groups of febrile neutropenia, with implications for management strategies. Therapeutic options under evaluation include early hospital discharge, home intravenous antibiotic therapy, and oral antibiotic regimens. A subset of these studies focus on the pediatric population. Because of rapid changes in the field, the reader is directed to specialized sources for specific management recommendations of febrile neutropenia.[12,13,14]
After a specific pathogen is isolated, antibiotic therapy is modified to provide optimal therapeutic response with minimal toxicity. Broad-spectrum coverage must be maintained to prevent secondary bacterial and fungal infections. Antibiotic therapy is usually discontinued after 5 to 7 days provided that the patient's granulocyte count exceeds 500 and the patient remains free of fever and infection. There is no consensus as to appropriate management in cases of persistent granulocytopenia when the patient is afebrile. Some advocate continued therapy, whereas others favor discontinuing antibiotics once the patient stabilizes. Empirical antifungal therapy is often added if a neutropenic patient remains febrile after 1 week of broad-spectrum antibiotics or has recurrent fever, since continued granulocytopenia is usually associated with the development of nonbacterial opportunistic infections, particularly those caused by Candida and Aspergillus. Prolonged therapy (>10–14 days) is indicated in the patient with a residual focus of bacterial or mycotic infection. Amphotericin B is usually the agent of choice. Alternative antifungal agents (5-fluorocytosine, miconazole, fluconazole, or itraconazole) are indicated when organisms develop resistance to amphotericin B.