title: Comparative clinical effectiveness of prophylactic voriconazole/posaconazole to fluconazole/itraconazole in patients with acute myeloid leukemia/myelodysplastic syndrome undergoing cytotoxic chemotherapy over a 12-year period.
abstract: Post-induction aplasia for acute myeloid leukemia/myelodysplastic syndrome is a high-risk period for invasive fungal diseases. The effectiveness of fluconazole, itraconazole solution, voriconazole and posaconazole prophylaxis used consecutively from December 1998 to January 2010 in patients with acute myeloid leukemia/myelodysplastic syndrome undergoing remission-induction chemotherapy was retrospectively evaluated. A total of 216 consecutive patients received 573 prophylaxis courses. Breakthrough-invasive fungal disease incidence in fluconazole, itraconazole, voriconazole, posaconazole recipients was 25%, 16%, 14% and 3%, respectively. Voriconazole/posconazole versus fluconazole/itraconazole combined was associated with significant reductions in breakthrough-invasive fungal disease incidence (20% vs. 8%, P=0.011), premature discontinuations (46% vs. 22% P<0.001) and empiric antifungal treatment (31% vs. 8.5%, P<0.001). Microbiologically confirmed infections were molds. Posaconazole compared to other drugs was associated with fewer courses requiring computed-tomography (43% vs. 26%, P<0.001). Adoption of voriconazole/posaconazole has decreased invasive fungal disease incidence, empiric antifungal treatment and for posaconazole, computed-tomography demand, with effectiveness of posaconazole comparable to clinical trial experience.
authors: Infectious Diseases Unit, Alfred Health Melbourne, Victoria 3004 Australia. m.ananda-rajah@alfred.org.au
authors: Michelle R
authors: MR
authors: Ananda-Rajah
authors: Andrew
authors: A
authors: Grigg
authors: Maria T
authors: MT
authors: Downey
authors: Ashish
authors: A
authors: Bajel
authors: Tim
authors: T
authors: Spelman
authors: Allen
authors: A
authors: Cheng
authors: Karin T
authors: KT
authors: Thursky
authors: Janette
authors: J
authors: Vincent
authors: Monica A
authors: MA
authors: Slavin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019072:Antibiotic Prophylaxis; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D015725:Fluconazole / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D017964:Itraconazole / Q000493:pharmacokinetics / Q000627:therapeutic use; D015470:Leukemia, Myeloid, Acute / Q000150:complications* / Q000188:drug therapy; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009181:Mycoses / Q000150:complications* / Q000517:prevention & control*; D009190:Myelodysplastic Syndromes / Q000150:complications* / Q000188:drug therapy; D011743:Pyrimidines / Q000493:pharmacokinetics / Q000627:therapeutic use; D012189:Retrospective Studies; D016896:Treatment Outcome; D014230:Triazoles / Q000493:pharmacokinetics / Q000627:therapeutic use; D065819:Voriconazole; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D017964:Itraconazole; C101425:posaconazole; D015725:Fluconazole; D065819:Voriconazole