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: Javier De la Serna, Isidro Jarque, Javier López-Jiménez, Jose María Fernández-Navarro, Valle Gómez, Manuel Jurado, Adriana Pascual, Josefina Serrano, Mónica Romero, Carlos Vallejo
• Journal: Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia (Rev Esp Quimioter) Vol. 26 Issue 1 Pg. 64-9 (Mar 2013) ISSN: 1988-9518 [Electronic] Spain
• PMID: 23546466 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antifungal Agents
• Triazoles
• Amphotericin B

Topics

• Adolescent
• Adult
• Aged
• Amphotericin B (therapeutic use)
• Antifungal Agents (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Aspergillosis (drug therapy, etiology)
• Candidiasis, Invasive (drug therapy, etiology)
• Child
• Child, Preschool
• Combined Modality Therapy
• Cross Infection (drug therapy)
• Drug Evaluation
• Female
• Fungemia (drug therapy)
• Hematologic Neoplasms (complications, drug therapy, surgery)
• Hematopoietic Stem Cell Transplantation
• Humans
• Immunocompromised Host
• Infant
• Male
• Middle Aged
• Myelodysplastic Syndromes (complications, drug therapy, surgery)
• Neutropenia (chemically induced, complications)
• Postoperative Complications (drug therapy, microbiology)
• Retrospective Studies
• Risk
• Transplantation, Homologous
• Treatment Outcome
• Triazoles (therapeutic use)
• Young Adult