title: Treatment of invasive fungal infections in high risk hematological patients. The outcome with liposomal amphotericin B is not negatively affected by prior administration of mold-active azoles.
abstract: There are concerns of a reduced effect of liposomal amphotericin B (L-AmB) given sequentially after mold-active azoles due to a possible antagonism in their antifungal mechanism. To investigate this possible effect in the clinic, we retrospectively studied 182 high risk hematologic patients with invasive fungal infections (IFI) who were treated with L-AmB. Overall, 96 patients (52.7%) had possible, 52 (28.6%) probable and 34 (18.7%) proven IFI according to EORTC classification. Most had suspected or proven invasive aspergillosis. We compared patients with prior exposure to mold-active azoles (n=100) to those having not (n=82). The group with prior mold-active azoles included more patients with poor risk features for IFI as acute myeloid leukemia (p<0.05) and prolonged neutropenia (p<0.05). A favorable response in the IFI, defined as a complete or partial response, was achieved in 75% and 74.4% of patients in the whole cohort, and in 66% and 74.4% of patients with probable or proven IFI in the two groups. None of these differences were significant. Multivariate analysis showed that refractory baseline disease and renal dysfunction were adverse factors for response in the IFI (p<0.05). Survival was poorer for patients with prior broad spectrum azoles (p<0.05), and for those who did not recover from neutropenia (p<0.05). In conclusion, the effectiveness of treatment of breakthrough fungal infection with L-AmB is not likely to be affected by prior exposure to mold-active azoles prophylaxis, but survival largely depends on host and disease factors.
authors.affiliation: Hematology Dept., Hospital Universitario12 de Octubre, Madrid, Spain. drjdelaserna@gmail.com
authors.forename: Javier
authors.initials: J
authors.lastname: De la Serna
authors.forename: Isidro
authors.initials: I
authors.lastname: Jarque
authors.forename: Javier
authors.initials: J
authors.lastname: López-Jiménez
authors.forename: Jose María
authors.initials: JM
authors.lastname: Fernández-Navarro
authors.forename: Valle
authors.initials: V
authors.lastname: Gómez
authors.forename: Manuel
authors.initials: M
authors.lastname: Jurado
authors.forename: Adriana
authors.initials: A
authors.lastname: Pascual
authors.forename: Josefina
authors.initials: J
authors.lastname: Serrano
authors.forename: Mónica
authors.initials: M
authors.lastname: Romero
authors.forename: Carlos
authors.initials: C
authors.lastname: Vallejo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001228:Aspergillosis / Q000188:drug therapy / Q000209:etiology; D058365:Candidiasis, Invasive / Q000188:drug therapy / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003428:Cross Infection / Q000188:drug therapy; D004341:Drug Evaluation; D005260:Female; D016469:Fungemia / Q000188:drug therapy*; D019337:Hematologic Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000601:surgery; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016867:Immunocompromised Host; D007223:Infant; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000188:drug therapy / Q000601:surgery; D009503:Neutropenia / Q000139:chemically induced / Q000150:complications; D011183:Postoperative Complications / Q000188:drug therapy / Q000382:microbiology; D012189:Retrospective Studies; D012306:Risk; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; D000666:Amphotericin B