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Meta-Analysis
. 2004;2004(3):CD004291.
doi: 10.1002/14651858.CD004291.pub2.

Antifungal agents for preventing fungal infections in solid organ transplant recipients

E G Playford  1 , A C Webster, T C Sorell, J C Craig
Affiliations
Meta-Analysis

Antifungal agents for preventing fungal infections in solid organ transplant recipients

E G Playford et al. Cochrane Database Syst Rev. 2004.

Abstract

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 (Issue 3, 2003), MEDLINE (1966-June 2003), and EMBASE (1980-June 2003) 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.

Reviewers' 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.

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Conflict of interest statement

  1. EGP: none declared

  2. ACW: none declared

  3. TCS: has advisory board involvement with Pfizer, has received unrelated project funding from Pfizer, Merck, and Gilead, and is a member of the Mycology Interest Group of the Australasian Society for Infectious Diseases, which is sponsored by Gilead.

  4. JCC: none declared

Figures

1
1
Search strategy results
2
2
Funnel plot for systemic antifungal agents versus placebo/no antifungal/nonabsorbable antifungal agent; outcome=proven invasive fungal infections
3
3
Funnel plot for systemic antifungal agents versus placebo/no antifungal/nonabsorbable antifungal agent; outcome=mortality
1.1
1.1. Analysis
Comparison 1 Systemic antifungal agent versus placebo/no antifungal/nonabsorbable antifungal agent, Outcome 1 Mortality.
1.2
1.2. Analysis
Comparison 1 Systemic antifungal agent versus placebo/no antifungal/nonabsorbable antifungal agent, Outcome 2 Proven invasive fungal infection.
1.3
1.3. Analysis
Comparison 1 Systemic antifungal agent versus placebo/no antifungal/nonabsorbable antifungal agent, Outcome 3 Proven invasive fungal infection (azole‐resistant Candida species).
1.4
1.4. Analysis
Comparison 1 Systemic antifungal agent versus placebo/no antifungal/nonabsorbable antifungal agent, Outcome 4 Proven invasive fungal infection (moulds).
1.5
1.5. Analysis
Comparison 1 Systemic antifungal agent versus placebo/no antifungal/nonabsorbable antifungal agent, Outcome 5 Proven invasive fungal infection (azole‐resistant Candida species or moulds).
1.6
1.6. Analysis
Comparison 1 Systemic antifungal agent versus placebo/no antifungal/nonabsorbable antifungal agent, Outcome 6 Suspected invasive fungal infection.
1.7
1.7. Analysis
Comparison 1 Systemic antifungal agent versus placebo/no antifungal/nonabsorbable antifungal agent, Outcome 7 Proven or suspected invasive fungal infection.
1.8
1.8. Analysis
Comparison 1 Systemic antifungal agent versus placebo/no antifungal/nonabsorbable antifungal agent, Outcome 8 Superficial fungal infection.
1.9
1.9. Analysis
Comparison 1 Systemic antifungal agent versus placebo/no antifungal/nonabsorbable antifungal agent, Outcome 9 Fungal colonisation.
1.10
1.10. Analysis
Comparison 1 Systemic antifungal agent versus placebo/no antifungal/nonabsorbable antifungal agent, Outcome 10 Fungal colonisation (azole‐resistant Candida species).
1.11
1.11. Analysis
Comparison 1 Systemic antifungal agent versus placebo/no antifungal/nonabsorbable antifungal agent, Outcome 11 Adverse effects requiring cessation.
2.1
2.1. Analysis
Comparison 2 Systemic antifungal agent versus another systemic antifungal agent, Outcome 1 Mortality.
2.2
2.2. Analysis
Comparison 2 Systemic antifungal agent versus another systemic antifungal agent, Outcome 2 Proven invasive fungal infection.
2.3
2.3. Analysis
Comparison 2 Systemic antifungal agent versus another systemic antifungal agent, Outcome 3 Proven invasive fungal infection (azole‐resistant Candida species).
2.4
2.4. Analysis
Comparison 2 Systemic antifungal agent versus another systemic antifungal agent, Outcome 4 Proven invasive fungal infection (moulds).
2.5
2.5. Analysis
Comparison 2 Systemic antifungal agent versus another systemic antifungal agent, Outcome 5 Proven invasive fungal infection (moulds or azole‐resistant Candida species).
2.6
2.6. Analysis
Comparison 2 Systemic antifungal agent versus another systemic antifungal agent, Outcome 6 Suspected invasive fungal infection.
2.7
2.7. Analysis
Comparison 2 Systemic antifungal agent versus another systemic antifungal agent, Outcome 7 Proven or suspected invasive fungal infection.
2.8
2.8. Analysis
Comparison 2 Systemic antifungal agent versus another systemic antifungal agent, Outcome 8 Superficial fungal infection.
2.9
2.9. Analysis
Comparison 2 Systemic antifungal agent versus another systemic antifungal agent, Outcome 9 Fungal colonisation.
2.10
2.10. Analysis
Comparison 2 Systemic antifungal agent versus another systemic antifungal agent, Outcome 10 Fungal colonisation (azole‐resistant Candida species).
2.11
2.11. Analysis
Comparison 2 Systemic antifungal agent versus another systemic antifungal agent, Outcome 11 Adverse effects requiring cessation.
3.2
3.2. Analysis
Comparison 3 Nonabsorbable antifungal agent versus no antifungal agent, Outcome 2 Proven invasive fungal infection.
3.3
3.3. Analysis
Comparison 3 Nonabsorbable antifungal agent versus no antifungal agent, Outcome 3 Proven invasive fungal infections (azole‐resistant Candida species).
3.4
3.4. Analysis
Comparison 3 Nonabsorbable antifungal agent versus no antifungal agent, Outcome 4 Proven invasive fungal infection (moulds).
3.5
3.5. Analysis
Comparison 3 Nonabsorbable antifungal agent versus no antifungal agent, Outcome 5 Proven invasive fungal infection (azole‐resistant Candida species and moulds).
3.8
3.8. Analysis
Comparison 3 Nonabsorbable antifungal agent versus no antifungal agent, Outcome 8 Superficial fungal infection.
3.11
3.11. Analysis
Comparison 3 Nonabsorbable antifungal agent versus no antifungal agent, Outcome 11 Adverse effects requiring cessation.
4.8
4.8. Analysis
Comparison 4 Nonabsorbable antifungal agent versus another nonabsorbable antifungal agent, Outcome 8 Superficial fungal infection.
4.9
4.9. Analysis
Comparison 4 Nonabsorbable antifungal agent versus another nonabsorbable antifungal agent, Outcome 9 Fungal colonisation.
4.11
4.11. Analysis
Comparison 4 Nonabsorbable antifungal agent versus another nonabsorbable antifungal agent, Outcome 11 Adverse effects requiring cessation.
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Update of

  • doi: 10.1002/14651858.CD004291

References

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Playford 2003
    1. Playford EG, Webster AC, Sorell TC, Craig JC. Antifungal agents for preventing fungal infections in solid organ transplant recipients. Cochrane Database of Systematic Reviews 2003, Issue 3. [DOI: 10.1002/14651858.CD004291] - DOI - PMC - PubMed

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