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Prospective, multicentre study of caspofungin for prophylaxis in high-risk liver transplantation

Abstract number: 1733_463

Fortún J., Montejo M., Martín-Dávila P., Muñoz P., Cisneros J.M., Aragón C., Blanes M., Ramos A., Gavaldá J., San Juan R., Llinares on behalf of the Spanish Transplantation Infection Study Group P.

Objective: There is significant morbidity and mortality related to invasive fungal infections (IFI) in patients undergoing liver transplantation (LT). Prevention remains elusive, especially for IFI caused by moulds. The aim of this study was to evaluate the efficacy and safety of caspofungin (CAS) as prophylaxis for IFI in the subset of LT recipients at high risk of developing IFI (HR-LT) (study sponsored by GESITRA, funded by MSD Spain).

Methods: A prospective, non-comparative, open label trial was conducted in HR-LT adult patients who received CAS prophylaxis. HR-LT included second LT due to primary dysfunction of a previous graft, renal failure and/or kidney replacement techniques, LT post-fulminant hepatitis, or the coincidence of ≥2 of the following: all-other-cause second LT, fungal colonisation, high transfusion requirements, choledocojejunostomy, biliary leak, or reintervention. Patients were expected to receive CAS at 50 mg qD (with 70 mg load) for 21 days. A succesful treatment outcome was defined as the absence of breakthrough IFI (proven or probable per EORTC/MSG criteria) during the first 100 days after the onset of caspofungin in the absence of premature discontinuation of prophylaxis because of toxicity or lack of efficacy.

Results: An interim analysis was performed on the first 41 patients enrolled in the study (enrollment plan: 70 patients). 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 16 (39.0%) patients. Four (9.8%) more patients discontinued CAS due to drug-related altered liver function tests after 8 to 19 days of therapy. CAS was otherwise well tolerated. Eight (19.5%) patients died of CAS-unrelated, LT-related complications other than IFI. Among survivors (up to 100-day follow-up), one (2.4%) patient experienced an invasive Mucor surgical wound infection 41 days post-CAS prophylaxis. No other patient met diagnostic criteria for possible, probable or proven IFI during CAS therapy or during the predefined 100-day follow-up period post-CAS discontinuation. Thus, the overall incidence of documented IFI was 1/41 (2.4%). Overall, CAS prophylaxis was successful in 36 patients (87.8%).

Conclusion: In this interim analysis, the outcome of CAS prophylaxis was successful in 87.8% (36/41) of the patients, with an overall incidence of documented IFI of 2.4% (1/41). These results suggest promise for the prophylactic use of CAS in HR-LT recipients.

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Subject:
Location: ICC, Munich, Germany
Presentation type:
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