Antifungal prophylaxis in chemotherapy-associated neutropenia: a retrospective, observational study.
BACKGROUND
In August 2002, the antifungal prophylaxis algorithm for neutropenic hematology/oncology (NHO) patients at the Medical Center was changed from conventional amphotericin (AMB) to an azole (AZ) based regimen (fluconazole [FLU] in low-risk and voriconazole [VOR] in high-risk patients). The aim of our study was to compare outcomes associated with the two regimens, including breakthrough fungal infection, adverse drug events, and costs.


METHODS
Adult, non-febrile, NHO patients who received prophylactic AMB from 01 August 2001-30 July 2002 or AZ from 01 August 2002-30 July 2003 were retrospectively evaluated.


RESULTS
A total of 370 patients (AMB: n = 181; AZ: n = 216) associated with 580 hospitalizations (AMB: n = 259; AZ: n = 321) were included. The incidence of probable/definite breakthrough Aspergillus infections was similar among regimens (AMB: 1.9% vs AZ: 0.6%; p=0.19). A greater incidence of mild/moderate (24.7% vs. 5.3%; p < 0.0001) and severe renal dysfunction (13.5% vs. 4.4%; p < 0.0012) was observed with AMB. In contrast, patients treated with VOR were found to have an increased rate of severe hepatic toxicity (32.5%) compared with patients treated with either AMB (22.6%) or FLU (21.4%) (p = 0.05). While the AZ period was associated with a >$9,000 increase in mean total costs/hospitalization, the mean acquisition cost associated with AZ was only $947/hospitalization more than AMB.


CONCLUSIONS
While an AZ-based regimen is associated with increased cost, the reduced rate of nephrotoxicity and availability of oral dosage forms, suggests that azoles be used preferentially over AMB. However, an increased rate of severe hepatic toxicity may be associated with VOR.
Riedel
Amy
A
Department of Clinical Pharmacy, School of Pharmacy, University of California San Francisco, San Francisco, USA. amyoriedel@yahoo.com
Choe
Lan
L
Inciardi
John
J
Yuen
Courtney
C
Martin
Thomas
T
Guglielmo
B Joseph
BJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000666:Amphotericin B / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis / Q000009:adverse effects / Q000191:economics; D000935:Antifungal Agents / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D015725:Fluconazole / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000517:prevention & control*; D009503:Neutropenia / Q000382:microbiology*; D011743:Pyrimidines / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D012189:Retrospective Studies; D014230:Triazoles / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D065819:Voriconazole
D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D000666:Amphotericin B; D015725:Fluconazole; D065819:Voriconazole