Prospective, Multicenter Study of Caspofungin (CAS) for Prophylaxis in High Risk Liver Transplantation (LT).

J. FORTUN1, P. MUí‘OZ 1, P. MARTIN-DAVILA 1, M. FOGEDA 1, M. MONTEJO 1, J. M. CISNEROS 1, A. RAMOS 1, J. GAVALDA 1, C. ARAGON 1, M. BLANES 1, C. SANZ-RODRIGUEZ 2;

Author address: 

1GESITRA (Spanish Transplantation: Infection Study Group), Madrid, Spain, 2Merck Sharp & DHOME of Spain, Madrid, Spain.

Abstract: 

Background: Prevention of invasive fungal infections (IFI) in patients (pts) undergoing LT remains elusive. The aim of this study was to evaluate the prophylactic use of CAS in adult LT recipients at high risk of developing IFI (HR-LT) (study sponsored by GESITRA, funded by MSD Spain). Methods: HR-LT included second LT due to primary dysfunction of previous graft, renal failure or kidney replacement techniques, LT post-fulminant hepatitis, or the coincidence of ≥ 2 of the following: all-other-cause second LT, fungal colonization, high transfusion requirements, Roux-en-Y, biliary leak, or reintervention. Pts were expected to receive CAS at 50 mg qD (with 70 mg LD) for 21 days. The primary efficacy endpoint was overall response (OR) 100 days post-CAS onset. Favourable OR required the absence of breakthrough IFI (proven or probable per EORTC/MSG criteria) with no premature CAS discontinuation because of toxicity or lack of efficacy. Results: An interim analysis was performed on the first 32 pts enrolled in the study (enrollment plan: 70 pts). The median duration of CAS prophylaxis was 21 days (range, 5-54). The dose of CAS was lowered to 35 mg qD due to LT-related liver dysfunction in 12 (38%) pts. Two (6%) more pts discontinued CAS due to drug-related altered liver function tests after 16 and 19 days of therapy. CAS was otherwise well tolerated. Four (13%) pts died of CAS-unrelated, LT-related complications other than IFI. Among survivors (up to 100-day follow-up), one (3%) pt experienced an invasive Mucor surgical wound infection 41 days post-CAS prophylaxis. No other pt met diagnostic criteria for possible, probable or proven IFI. Conclusions: In this interim analysis, the favourable OR rate was 91% (29/32), with an overall incidence of documented IFI of 3% (1/32). These results suggest promise for the prophylactic use of CAS in HR-LT.
2006

abstract No: 

K-272

Full conference title: 

46th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 46th