Itraconazole added to a lipid formulation of amphotericin B does not improve outcome of primary treatment of invasive aspergillosis.
BACKGROUND
Invasive aspergillosis (IA) is associated with poor outcome in patients with hematologic malignancy treated with amphotericin B (AMB)-based therapy. Itraconazole (ITC), a triazole with activity against Aspergillus, has been used in combination with AMB or lipid formulations of AMB (LipoAMB) in the treatment of IA, although the efficacy of this strategy is uncertain.


METHODS
To determine whether the addition of ITC to LipoAMB improves outcome of IA, the authors retrospectively studied 179 consecutive patients with hematologic malignancies and definite or probable IA who received primary antifungal therapy with either LipoAMB (n = 146), or lipoAMB plus ITC (n = 33) between June 1993 and June 2003. In view of the erratic absorption of ITC tablets, only patients who received either intravenous or liquid ITC were analyzed. Patients who received < 1 week of treatment were excluded.


RESULTS
Evaluable patients in both groups (LipoAMB: n =101; ITC and LipoAMB: n = 11) had comparable distribution of risk factors of poor outcome such as neutropenia at onset of IA, persistent neutropenia, systemic steroids, previous antifungal prophylaxis, admission to the intensive care unit, disseminated IA, previous bone marrow transplant, and IA due to infection by a non-fumigatus Aspergillus species. Response to primary antifungal therapy was equally poor in both groups (LipoAMB group: 10%; ITC and LipoAMB group: 0%; P = not significant).


CONCLUSIONS
In the authors' 10-year study of patients with hematologic malignancy and IA, the response rate to LipoAMB given as primary therapy was very poor. In a comparable group of patients, the addition of ITC did not result in a therapeutic benefit.
Kontoyiannis
Dimitrios P
DP
Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. dkontoyi@mdanderson.org
Boktour
Maha
M
Hanna
Hend
H
Torres
Harrys A
HA
Hachem
Ray
R
Raad
Issam I
II
D000666:Amphotericin B / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D007275:Injections, Intravenous; D017964:Itraconazole / Q000627:therapeutic use*; D008055:Lipids / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D004364:Pharmaceutical Preparations; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
D000935:Antifungal Agents; D008055:Lipids; D004364:Pharmaceutical Preparations; D017964:Itraconazole; D000666:Amphotericin B