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Antifungal Prevention of Systemic Candidiasis in Immunocompetent ICU Adults: Systematic Review and Meta-Analysis of Clinical Trials

Dupont, Hervé MD, PhD1,2; Mahjoub, Yazine MD, PhD1,2; Chouaki, Taieb PharmD3; Lorne, Emmanuel MD, PhD1,2; Zogheib, Elie MD1,2

doi: 10.1097/CCM.0000000000002698
Review Article

Objectives: The aim of this study was to identify the impact of antifungal prevention in critically ill immunocompetent adult patients on mortality and subsequent infection.

Data Sources: A systematic review and meta-analysis of randomized controlled trials comparing any antifungal use versus placebo to prevent candidiasis in ICU patients were performed.

Study Selection: Searches were performed on PubMed, Embase, Scopus, main conference proceedings, and, as well as reference lists.

Data Extraction: The primary outcomes were mortality and invasive candidiasis. The secondary outcome was the rate of Candida albicans and nonalbicans strains after treatment. A random effect model was used, and sensitivity analysis was performed for both outcomes. Results are expressed as risk ratios and their 95% CIs.

Data Synthesis: Nineteen trials (10 with fluconazole, four with ketoconazole, one with itraconazole, three with micafungin, and one with caspofungin) including 2,792 patients were identified. No individual trial showed a decreased mortality rate. Combined analysis showed that preventive antifungal did not decrease mortality (risk ratio, 0.88; 95% CI, 0.74–1.04; p = 0.14) but significantly decreased secondary fungal infections by 50% (risk ratio, 0.49; 95% CI, 0.35–0.68; p = 0.0001). No shift across nonalbicans strains was observed during treatment (risk ratio, 0.62; 95% CI, 0.19–1.97; p = 0.42). However, publication biases preclude any definite conclusions for prevention of infection.

Conclusions: Antifungal prevention of systemic candidiasis in immunocompetent critically ill adults did not reduce mortality and may have decreased secondary fungal infection rates. However, significant publication bias was present.

1Department of Anesthesiology and Critical Care Medicine, CHU Amiens Picardie, Amiens, France.

2INSERM UMR 1088, University of Picardy Jules Verne, Amiens, France.

3Mycology Laboratory, CHU Amiens Picardie, Amiens, France.

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Drs. Dupont, Mahjoub, and Zogheib designed the study. Drs. Dupont and Mahjoub performed the literature search. Drs. Dupont and Zogheib extracted the date and classified the studies. Discrepancies were resolved with Dr. Mahjoub, Mr. Chouaki, and Dr. Lorne. Dr. Dupont performed statistical analysis. Drs. Dupont, Mahjoub, Mr. Chouaki, and Drs. Lorne and Zogheib interpreted the results. Drs. Dupont, Mahjoub, and Zogheib wrote the first draft of the article, which all authors critically revised for important intellectual content. Dr. Dupont wrote the final version, which all the authors approved for publication.

Dr. Dupont has been a consultant and member of the boards for Astellas, Pfizer, Gilead, Basilea, and Merck Sharp and Dohme (MSD). Dr. Zogheib has received conference and congress fees from Astellas, MSD, and Pfizer. Mr. Chouaki has received conference and congress fees from Astellas, MSD, Gilead, and Pfizer. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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