Management of Neutropenic Fever

Febrile neutropenia is a frequent complication in hematology-oncology, BMT, and solid organ transplantation. Approximately 50% of those who develop febrile neutropenia have a documented or occult infection. Febrile patients with severe neutropenia (<100/mm3) have bacteremia in up to 20% of cases. Initial evaluation should include careful history and physical examination with particular attention to the upper and lower respiratory tract, skin, IV sites, abdomen and perianal area. Choice of initial antibacterial therapy must be individualized and depends upon: clinical findings; most frequent pathogens and resistance profiles for the hospital; use of any recent antibacterials (e.g. prophylaxis), and anticipated duration of neutropenia (i.e. low-risk if expected to be ≤10 days). Low risk patients who also meet other criteria may be suitable for outpatient oral therapy. Inpatient management options include: monotherapy (imipenem, meropenem, ceftazidime, or cefepime), duotherapy (aminoglycoside plus antipseudomonal beta-lactam), or the combination of vancomycin plus one or two drugs for selected patients at particular risk of serious gram positive bacterial infections. Many centres have observed an increasing proportion of infections due to gram positive bacteria in recent years, particularly coagulase negative and positive staphylococci, and alpha-hemolytic streptococci. The presence of polymicrobial infection at some sites (e.g. lower respiratory tract) has been increasingly recognized. Further investigations should be considered for patients who have persistent fevers including CT scan of the chest, ultrasound ± CT scan of the abdomen; and possibly serologic studies (e.g. Aspergillus galactomannan, β-1, 3-glucan). Various adjustments to the initial regimen are more often required in high-risk patients and are dependent upon: the duration of fever and general condition of the patient; development of clinical or culture proven sites of infection, including susceptibility patterns; and drug toxicities. Adjustments to the regimen may include: the addition of vancomycin; addition of second drug for gram negative bacterial coverage: addition of empiric antifungal therapy: and consideration of other interventions (e.g. removal of central venous cathethers, or surgical resection of a localized site of invasive fungal infection encroaching upon a major pulmonary vessel). The duration of therapy is dependent upon specific diagnostic findings, and the duration of neutropenia and fever.