Invasive fungal infections - infections of the bloodstream and organs within the body (e.g. meningitis, pneumonia, peritonitis) - are important causes of morbidity and mortality in liver, pancreas, heart, kidney and lung (i.e. solid organ) transplant recipients. This review found that fluconazole, used as a preventive drug, significantly reduced the number of invasive fungal infections in liver transplant patients. More studies are needed to determine how effective antifungal drugs are for pancreas, heart, kidney and lung transplant patients.
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Invasive fungal infections (IFIs) are important causes of morbidity and mortality in solid organ transplant recipients.
Objectives
This study aims to systematically identify and summarise the effects of antifungal prophylaxis in solid organ transplant recipients.
Search strategy
The Cochrane Central Register of Controlled Trials, MEDLINE (from 1966), and EMBASE (from 1980) were searched. Reference lists, abstracts of conference proceedings and scientific meetings (1998-2003) were handsearched. Authors of included studies and pharmaceutical manufacturers were contacted.
Selection criteria
Randomised controlled trials (RCTs) in all languages comparing the prophylactic use of any antifungal agent or regimen with placebo, no antifungal, or another antifungal agent or regimen.
Data collection and analysis
Two reviewers independently applied selection criteria, performed quality assessment, and extracted data using an intention-to-treat approach. Differences were resolved by discussion. Data were synthesised using the random effects model and expressed as relative risk (RR) with 95% confidence intervals (95% CI).
Main results
Fourteen unique trials with 1497 randomised participants were included. Antifungal prophylaxis did not reduce mortality (RR 0.90, 95% CI 0.57 to 1.44). In liver transplant recipients, a significant reduction in IFIs was demonstrated for fluconazole (RR 0.28, 95% CI 0.13 to 0.57). Although less data were available for itraconazole and liposomal amphotericin B, indirect comparisons and one direct comparative trial suggested similar efficacy. Fluconazole prophylaxis did not significantly increase invasive infections or colonisation with fluconazole-resistant fungi. In renal and cardiac transplant recipients, neither ketoconazole nor clotrimazole significantly reduced invasive infections. Overall, the strength and precision of comparisons however were limited by a paucity of data.
Authors' conclusions
For liver transplant recipients, antifungal prophylaxis with fluconazole significantly reduces the incidence of IFIs with no definite mortality benefit. Given a 10% incidence of IFI, 14 liver transplant recipients would require fluconazole prophylaxis to prevent one infection. In transplant centres where the incidence of IFIs is high, or in situations where the individual risk is great, antifungal prophylaxis should be considered.
