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


CONCLUSIONS
Treatment options appear to offer preferential effects on response rates and mortality. When mycologic data are available, therapy should be tailored.
Mills
Edward J
EJ
Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada. emills@cfenet.ubc.ca
Perri
Dan
D
Cooper
Curtis
C
Nachega
Jean B
JB
Wu
Ping
P
Tleyjeh
Imad
I
Phillips
Peter
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000666:Amphotericin B / Q000009:adverse effects / Q000627:therapeutic use; D000077612:Anidulafungin; D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001393:Azoles / Q000009:adverse effects / Q000627:therapeutic use; D002177:Candidiasis / Q000188:drug therapy* / Q000401:mortality; D054714:Echinocandins / Q000009:adverse effects / Q000627:therapeutic use; D015725:Fluconazole / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D055815:Young Adult
D000935:Antifungal Agents; D001393:Azoles; D054714:Echinocandins; D000666:Amphotericin B; D015725:Fluconazole; D000077612:Anidulafungin