- Paper Report
- Open Access
Empiric antifungal therapy in febrile neutropenia
- Naresh Ramakrishnan1
© Current Science Ltd 2000
- Published: 10 May 2000
- Amphotericin B
- antifungal therapy
- febrile neutropenia
- fungal infection
Invasive fungal infections are on the increase and are a challenge to the clinician. Until recently, there have been very few systemic antifungal agents available. amphotericin B was considered standard treatment, but its well-known side effects have made physicians reluctant to use it. Recently, triazoles have been developed, among them fluconazole, which is available for both oral and intravenous administration and is much better tolerated than amphotericin. This forms the rationale of this trial comparing fluconazole with amphotericin B for the empiric treatment of febrile neutropenics, with suspected invasive fungal infections.
A prospective, randomized unblinded study
Total of 317 febrile neutropenics (Absolute neutrophil count < 500 cells/mm3)
Persistent fever > 4 days duration; undergoing treatment with antibacterial agents
Fluconazole 800 mg iv on day 1, followed by 400 mg/day iv or amphotericin B 0.5 mg/kg/day, with dose increased to 1.0 - 1.5 mg/kg/day, if evidence of invasive fungal infection is found
Response was defined satisfactory if patient was afebrile (< 38°C). No clinical/microbiological incidence of fungal infection
Mean age 47 years (SD± 15) and both groups were well matched for other demographics
There were equal number of successors (68% vs 67%) and failures (8% vs 6%) in both arms; however, neither reached statistical significance. The incidence of drug withdrawal due to toxicity was higher in the amphotericin group (7% vs 1%; P = 0.005). Interestingly 13% of the patients treated with the fluconazole needed to have treatment changed to amphotericin B for lack of clinical improvement, as opposed to 2% treated with amphotericin b (P < 0.001).
Candida species are the prominent fungal pathogens, followed by Aspergillus species and occasionally other opportunistic fungi in febrile neutropenics. In patients without neutropenia, fluconazole has been shown to be as effective as amphotericin B in the treatment of Candidemia.