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Antifungal treatment for invasive Candida infections: a mixed treatment comparison meta-analysis.

Mills EJ, Perri D, Cooper C, Nachega JB, Wu P, Tleyjeh I, Phillips P - Ann. Clin. Microbiol. Antimicrob. (2009)

Bottom Line: Our mixed treatment comparison analysis found similar within-class effects across all interventions.Adverse event profiles differed, with amphotericin B exhibiting larger adverse event effects.Treatment options appear to offer preferential effects on response rates and mortality.

View Article: PubMed Central - HTML - PubMed

Affiliation: Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada. emills@cfenet.ubc.ca

ABSTRACT

Objectives: Invasive fungal infections are a major cause of mortality among patients at risk. Treatment guidelines vary on optimal treatment strategies. We aimed to determine the effects of different antifungal therapies on global response rates, mortality and safety.

Methods: We searched independently and in duplicate 10 electronic databases from inception to May 2009. We selected any randomized trial assessing established antifungal therapies for confirmed cases of invasive candidiasis among predominantly adult populations. We performed a meta-analysis and then conducted a Bayesian mixed treatment comparison to differentiate treatment effectiveness. Sensitivity analyses included dosage forms of amphotericin B and fluconazole compared to other azoles.

Results: Our analysis included 11 studies enrolling a total of 965 patients. For our primary analysis of global response rates, we pooled 7 trials comparing azoles to amphotericin B, Relative Risk [RR] 0.87 (95% Confidence Interval [CI], 0.78-0.96, P = 0.007, I2 = 43%, P = 0.09. We also pooled 2 trials of echinocandins versus amphotericin B and found a pooled RR of 1.10 (95% CI, 0.99-1.23, P = 0.08). One study compared anidulafungin to fluconazole and yielded a RR of 1.26 (95% CI, 1.06-1.51) in favor of anidulafungin. We pooled 7 trials assessing azoles versus amphotericin B for all-cause mortality, resulting in a pooled RR of 0.88 (95% CI, 0.74-1.05, P = 0.17, I2 = 0%, P = 0.96). Echinocandins versus amphotericin B (2 trials) for all-cause mortality resulted in a pooled RR of 1.01 (95% CI, 0.84-1.20, P = 0.93). Anidulafungin versus fluconazole resulted in a RR of 0.73 (95% CI, 0.48-1.10, P = 0.34). Our mixed treatment comparison analysis found similar within-class effects across all interventions. Adverse event profiles differed, with amphotericin B exhibiting larger adverse event effects.

Conclusion: Treatment options appear to offer preferential effects on response rates and mortality. When mycologic data are available, therapy should be tailored.

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Related in: MedlinePlus

Caterpillar plots of the odds ratios and 95% CrIs for mixed treatment comparisons, all-cause mortality.
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Related In: Results  -  Collection

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Figure 6: Caterpillar plots of the odds ratios and 95% CrIs for mixed treatment comparisons, all-cause mortality.

Mentions: Figure 4 displays the geometric distribution of the mixed treatment comparison. Figures 5 and 6 display the caterpillar plots. Table 1 reports the odds ratios of response rates for all the pairwise comparisons of the antifungal treatment regimens and table 2 presents estimates of the absolute efficacy for each treatment, along with the estimated probability that each treatment is best (response rate).


Antifungal treatment for invasive Candida infections: a mixed treatment comparison meta-analysis.

Mills EJ, Perri D, Cooper C, Nachega JB, Wu P, Tleyjeh I, Phillips P - Ann. Clin. Microbiol. Antimicrob. (2009)

Caterpillar plots of the odds ratios and 95% CrIs for mixed treatment comparisons, all-cause mortality.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2713200&req=5

Figure 6: Caterpillar plots of the odds ratios and 95% CrIs for mixed treatment comparisons, all-cause mortality.
Mentions: Figure 4 displays the geometric distribution of the mixed treatment comparison. Figures 5 and 6 display the caterpillar plots. Table 1 reports the odds ratios of response rates for all the pairwise comparisons of the antifungal treatment regimens and table 2 presents estimates of the absolute efficacy for each treatment, along with the estimated probability that each treatment is best (response rate).

Bottom Line: Our mixed treatment comparison analysis found similar within-class effects across all interventions.Adverse event profiles differed, with amphotericin B exhibiting larger adverse event effects.Treatment options appear to offer preferential effects on response rates and mortality.

View Article: PubMed Central - HTML - PubMed

Affiliation: Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada. emills@cfenet.ubc.ca

ABSTRACT

Objectives: Invasive fungal infections are a major cause of mortality among patients at risk. Treatment guidelines vary on optimal treatment strategies. We aimed to determine the effects of different antifungal therapies on global response rates, mortality and safety.

Methods: We searched independently and in duplicate 10 electronic databases from inception to May 2009. We selected any randomized trial assessing established antifungal therapies for confirmed cases of invasive candidiasis among predominantly adult populations. We performed a meta-analysis and then conducted a Bayesian mixed treatment comparison to differentiate treatment effectiveness. Sensitivity analyses included dosage forms of amphotericin B and fluconazole compared to other azoles.

Results: Our analysis included 11 studies enrolling a total of 965 patients. For our primary analysis of global response rates, we pooled 7 trials comparing azoles to amphotericin B, Relative Risk [RR] 0.87 (95% Confidence Interval [CI], 0.78-0.96, P = 0.007, I2 = 43%, P = 0.09. We also pooled 2 trials of echinocandins versus amphotericin B and found a pooled RR of 1.10 (95% CI, 0.99-1.23, P = 0.08). One study compared anidulafungin to fluconazole and yielded a RR of 1.26 (95% CI, 1.06-1.51) in favor of anidulafungin. We pooled 7 trials assessing azoles versus amphotericin B for all-cause mortality, resulting in a pooled RR of 0.88 (95% CI, 0.74-1.05, P = 0.17, I2 = 0%, P = 0.96). Echinocandins versus amphotericin B (2 trials) for all-cause mortality resulted in a pooled RR of 1.01 (95% CI, 0.84-1.20, P = 0.93). Anidulafungin versus fluconazole resulted in a RR of 0.73 (95% CI, 0.48-1.10, P = 0.34). Our mixed treatment comparison analysis found similar within-class effects across all interventions. Adverse event profiles differed, with amphotericin B exhibiting larger adverse event effects.

Conclusion: Treatment options appear to offer preferential effects on response rates and mortality. When mycologic data are available, therapy should be tailored.

Show MeSH
Related in: MedlinePlus