Institutional experience with voriconazole compared with liposomal amphotericin B as empiric therapy for febrile neutropenia.
OBJECTIVE
To assess the effectiveness, safety, and cost of empiric treatment of febrile neutropenia before and after implementing an algorithm in which voriconazole was substituted for liposomal amphotericin B (L-AmB).


METHODS
Retrospective cohort analysis.


METHODS
An 850-bed tertiary care hospital, which is also a referral site for patients with acute leukemia.


METHODS
Fifty-five adult patients who started empiric antifungal therapy for febrile neutropenia between January 1, 2002, and December 31, 2003, encompassing 58 treatment episodes (defined as a hospitalization during which empiric antifungal therapy was administered).


RESULTS
Medical charts, including patients' pharmacy and laboratory data, were reviewed. Twenty-six and 32 episodes of L-AmB and voriconazole use, respectively, were identified. No significant differences between the L-AmB and voriconazole groups were noted at baseline. Rates of fever resolution (54% vs 59%, p=0.791) and breakthrough invasive fungal infections (11% vs 12%, p>0.999) were similar for the L-AmB and voriconazole episodes. Premature drug discontinuation due to the prescriber's perceived lack of efficacy occurred most frequently in the voriconazole group (25% vs 8%, p=0.160). Survival was significantly higher in the voriconazole than in the L-AmB group (100% vs 77%, p=0.006). Adverse effects that were significantly more common in the L-AmB group than in the voriconazole group were elevated serum creatinine levels (27% vs 3%, p=0.017) and electrolyte disturbances (19% vs 0%, p=0.014). Adverse effects reported more frequently in the voriconazole group than in the L-AmB group were visual disturbances (9% vs 0%, p=0.245) and elevated hepatic enzyme levels (9% vs 8%, p>0.999). Mean drug expenditures/episode for initial empiric antifungal therapy were lower for voriconazole than for L-AmB ($1593 vs $4144, or $153 vs $380/day).


CONCLUSIONS
Our institution's algorithm incorporating voriconazole into the empiric management of febrile neutropenia was associated with effectiveness outcomes comparable to those observed with L-AmB as well as a lower frequency of adverse effects and overall expenditures for antifungal drugs.
Shehab
Nadine
N
Department of Clinical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA.
DePestel
Daryl D
DD
Mackler
Emily R
ER
Collins
Curtis D
CD
Welch
Kathleen
K
Erba
Harry P
HP
D000666:Amphotericin B / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D005260:Female; D005334:Fever / Q000188:drug therapy / Q000191:economics; D017048:Health Care Costs; D006760:Hospitalization / Q000191:economics / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000188:drug therapy* / Q000191:economics; D011743:Pyrimidines / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D065819:Voriconazole
D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; C068538:liposomal amphotericin B; D000666:Amphotericin B; D065819:Voriconazole