Antifungal agents for preventing fungal infections in non-neutropenic critically ill and surgical patients: Systematic review and meta-analysis of randomized clinical trials

Playford, E. Geoffrey, Webster, Angela C., Sorrell, Tania C. and Craig, Jonathan, C. (2006) Antifungal agents for preventing fungal infections in non-neutropenic critically ill and surgical patients: Systematic review and meta-analysis of randomized clinical trials. Journal of Antimicrobial Chemotherapy, 57 4: 628-638. doi:10.1093/jac/dkl491


Author Playford, E. Geoffrey
Webster, Angela C.
Sorrell, Tania C.
Craig, Jonathan, C.
Title Antifungal agents for preventing fungal infections in non-neutropenic critically ill and surgical patients: Systematic review and meta-analysis of randomized clinical trials
Journal name Journal of Antimicrobial Chemotherapy   Check publisher's open access policy
ISSN 1460-2091
0305-7453
Publication date 2006-04-01
Sub-type Article (original research)
DOI 10.1093/jac/dkl491
Volume 57
Issue 4
Start page 628
End page 638
Total pages 11
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Subject 1103 Clinical Sciences
11 Medical and Health Sciences
Formatted abstract
Objectives: This study aims to systematically identify and summarize the effects of antifungal prophylaxis in non-neutropenic critically ill adult patients on all-cause mortality and the incidence of invasive fungal infections.

Methods:
Systematic review and meta-analysis of randomized controlled trials in all languages comparing the prophylactic use of any antifungal agent or regimen with placebo, no antifungal or another antifungal agent or regimen in non-neutropenic critically ill adult patients. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2005), MEDLINE (1966 to 2 September 2005) and EMBASE (1980 to week 36, 2005). We also hand-searched reference lists, abstracts of conference proceedings and scientific meetings (1998–2004) and contacted authors of included studies and pharmaceutical manufacturers. The primary outcomes assessed were all-cause mortality and proven invasive fungal infections. Two reviewers independently applied selection criteria, performed quality assessment and extracted data using an intention-to-treat approach. Data were synthesized using the random effects model and expressed as relative risk with 95% confidence intervals.

Results: Twelve unique trials (eight comparing fluconazole and four ketoconazole with no antifungal or a non-absorbable agent) involving 1606 randomized patients were included. For both outcomes of total mortality and invasive fungal infections, almost all trials of fluconazole and ketoconazole separately showed a non-significant risk reduction with prophylaxis. When combined, fluconazole/ketoconazole reduced total mortality by one-quarter (relative risk 0.76, 95% confidence interval 0.59–0.97) and invasive fungal infections by about one-half (relative risk 0.46, 95% confidence interval 0.31–0.68). No significant increase in the incidence of infection or colonization with the azole-resistant fungal pathogens Candida glabrata or Candida krusei was demonstrated, although the confidence intervals of the summary effect measures were wide. Adverse effects requiring treatment discontinuation were not more common amongst patients receiving prophylaxis. Results across all trials were homogeneous despite considerable heterogeneity in clinical and methodological characteristics.

Conclusions: Prophylaxis with fluconazole or ketoconazole in critically ill patients reduces invasive fungal infections by one-half and total mortality by one-quarter. Although no significant increase in azole-resistant Candida species associated with prophylaxis was demonstrated, trials were not powered to exclude such an effect. In patients at increased risk of invasive fungal infections, antifungal prophylaxis with fluconazole should be considered.
Keyword Mycoses
Candidiasis
Fungaemia
Antifungals
Fluconazole
Ketoconazole
Intensive care
Critical Care
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 95 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 21 Dec 2009, 22:43:51 EST by Elissa Saffery on behalf of School of Medicine