Purpose: Prevention of invasive fungal infections (IFI) in HSCT recipients remains an important challenge; expansion of antifungal activity to include mould infections has become crucial in the choice of a prophylactic agent. In consideration of its antifungal spectrum, M has emerged as an attractive alternative to fluconazole. Additional experience in pediatric settings will further inform the decision regarding appropriate prophylaxis. Methods: Retrospective evaluation of patients receiving M for prophylaxis in allogeneic HSCT recipients at CHLA was undertaken. Data pertaining to demographics, microbiologic surveillance, new IFIs, adverse effects and mortality were collected. Results: M (1mg/kg/day) has been the standard antifungal prophylactic agent for HSCT recipients at CHLA since August 2007. A total of 41 patients receiving M were identified; evaluation of medical records was completed for 20 to date. The median age of patients was 7 years (range 7 months-17 years), the median duration of M prophylaxis was 40.5 days (11-249 days). 3/20 patients developed new G.I. colonization with candidal species while on M, all C. parapsilosis. IFIs were identified in 3 patients while on M prophylaxis: 1 patient with prior possible IFI developed probable aspergillosis (BAL galactomannan positive) at day +7; 1 patient developed possible IFI at day +20; and 1 patient developed C. parapsilosis fungemia at day +239. No patient developed adverse drug effects attributed to M necessitating its discontinuation or substitution of another antifungal. 1 patient died of severe VOD while on M prophylaxis. 16 patients who did not develop an IFI on M were transitioned to oral prophylaxis with various agents (4-fluconazole, 10-voriconazole, 1-clotrimazole, 1-nystatin). 6 of these 16 patients subsequently developed an IFI (4 probable Aspergillus, 1 probable candida, and 1 possible mucor/Aspergillus) at a median of 163 days post-transplant (135-326 days). 15/20 patients developed GVHD at median of 51 days (4-425 days).; 8/9 patients with IFI developed GVHD. Overall, 10/20 patients have died at a median of 278.5 days post-transplant (18-394 days), and 8 of these 10 patients had IFIs. Conclusions: In this pediatric experience, M prophylaxis appeared to be well tolerated and may have offered benefit to recipients of HSCT within the early post transplantation period. IFIs remain an important cause of morbidity and mortality in this patient population. The potential for emergence of C. parapsilosis under selective pressure from echinocandins is of concern and merits further investigation. The high prevalence of late onset IFI indicates the need for rethinking prophylactic strategies, including consideration of extended duration of a mould active agent.
Full conference title:
4th Advances Against Aspergillosis
- AAA 4th (2010)