Four RCTs (n=626) were included in the review. Two additional RCTs (n=143) were included in the sensitivity analysis.
The studies were of a high quality (median Jadad score 6); the authors of the review did not report the range of possible scores for their scoring system. All four RCTs and two additional RCTs were double-blinded. Inter-rater agreement for the quality assessment was good (kappa 0.95).
There was no evidence of publication bias from either the funnel plot or Begg's statistic (p=0.734).
The meta-analysis showed that prophylactic fluconazole significantly reduced the risk of fungal infection compared with placebo (OR 0.44, 95% CI: 0.27, 0.72, p<0.001). No statistically significant heterogeneity was detected (p=0.692).
There was no significant difference between treatments in terms of candidaemia, although there were few actual cases of candidaemia (14 cases in 626 patients: 11 cases in fluconazole-treated groups and 3 cases in placebo-treated groups).
Prophylactic fluconazole was associated with a significant reduction in the risk of candida albicans (OR 0.51, 95% CI: 0.30, 0.87, p=0.014) but there was no significant difference between treatments in terms of nonalbicans candida infections (p=0.10).
There was no significant difference between treatments in terms of mortality (OR 0.87, 95% CI: 0.59, 1.28). The meta-analysis that included two additional studies also showed no significant difference between treatments.
Neither of the two studies assessing ICU length of stay reported any significant difference between treatments.
Three studies assessed adverse events and reported that fluconazole was generally well-tolerated with no difference between fluconazole and placebo in rates of laboratory abnormalities. No deaths were attributed to fluconazole and few patients had treatments discontinued due to suspected toxicity (two receiving fluconazole and three receiving placebo).