Antifungal drugs used for prevention can significantly reduce the number of invasive fungal infections in liver transplant patients

Playford EG, Webster AC, Craig JC, Sorrell TC

Published Online:

July 8, 2009

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.

Abstract (click to read)

Background:

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.

This record should be cited as:

Playford EG, Webster AC, Craig JC, Sorrell TC. Antifungal agents for preventing fungal infections in solid organ transplant recipients. Cochrane Database of Systematic Reviews 2004, Issue 3. Art. No.: CD004291. DOI: 10.1002/14651858.CD004291.pub2

Assessed as up to date:

November 22, 2005

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Primary Review Group:

Renal Group

Health topics:

Gastroenterology > Transplantation > Solid organ

Heart & circulation > Transplantation > Solid organ

Kidney disease > Kidney transplant > Complications & co-interventions

Kidney disease > Kidney-pancreas transplant > Complications & co-interventions

Lungs & airways > Transplantation > Solid organ

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Antifungal drugs used for prevention can significantly reduce the number of invasive fungal infections in liver transplant patients

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