Objective: Invasive fungal infection is one of the major complications, contributing to high mortality and morbidity among lung transplant (LTx) patients. Data for voriconazole use in pre-emptive/targeted prophylactic setting remain scant. This study aimed to investigate the efficacy and safety of voriconazole pre-emptive/targeted prophylaxis among LTx patients once airway fungal colonisation was confirmed. Methods: A retrospective, single-centre, observational cohort study was conducted. All adult LTx patients who received voriconazole preemptive/ targeted prophylaxis for the first time between July 2003 and June 2010 were followed up for 1 year. Outcomes were determined at 6 months (primary end-point) and at 12 months after initiation of voriconazole prophylaxis. Chi-square test was used to assess the relationships between variables and outcomes (i.e. fungal infection, Aspergillus colonisation, death and drug-related hepatotoxicity). Cumulative survival rate at 12-month after initiation of prophylaxis were estimated using the Kaplan-Meier method. Results: A total of 62 LTx patients were included. A. fumigatus (75.8%) was the most common colonising isolate. Median duration of voriconazole prophylaxis was 84 days. At the 6-month end-point, one (1.6%) had developed probable fungal pneumonia, 48 (77.5%) had successful eradication of colonisation, three (4.8%) had persistent colonisation, six (9.7%) had recurrent colonisation, two (3.2%) had aspergilloma and two (3.2%) were clinically unstable but no culture was performed. Sixteen (25.8%) had died by the 12-month end-point, half due to Bronchiolitis Obliterans Syndrome. Ten (16.1%) had drugrelated hepatotoxicity. Patients with diabetes mellitus within 30 days before commencing voriconazole prophylaxis (OR: 8.4, 95% CI: 2.1- 33.4, p = 0.003) were at higher risk for Aspergillus colonisation at 12- month end-point. Preliminary analyses suggest that acute rejection (OR: 4.9, 95% CI: 1.2-19.4, p = 0.026) and chronic rejection (OR: 6.5, 95% CI: 1.3-31.5, p = 0.022) within 30 days prior to voriconazole prophylaxis were significantly associated with 12-month mortality. LTx patients older than 55 years old were 5.9 times more likely to have hepatotoxicity after initiation of prophylaxis (95% CI: 1.1-30.6; p = 0.036).
Full conference title:
22nd European Congress of Clinical Microbiology and Infectious Diseases
- ECCMID 22nd (2012)