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Ann Microbiol Antimicrob.
2009 August 25; 8: 25,
PMCID: PMC2713200
Antifungal Treatment for Invasive
Candida Infections: A Mixed
Treatment Comparison Meta-Analysis.
Edward J Mills, Dan Perri, Curtis
Cooper, Jean B Nachega, Ping Wu,
Imad Tleyjeh, Peter Phillips.
The purpose of this study was to
quantify the effects of antifungal
therapy on confirmed systemic fungal
infection response rates, associated
mortality and safety. Invasive
fungal infections are a major cause
of mortality among at risk patients
including those with hematologic
cancers, recent transplants,
autoimmune disorders, and critical
illness. The most common fungal
pathogen is
Candida.
Early and accurate diagnosis of
invasive fungal infections is often
difficult; antifungal treatment for
confirmed cases is challenging and
evaluations of therapeutic
interventions are limited. Several
choices of antifungal agents exist
that differ greatly with respect to
both toxicity and cost. There have
been many studies done on the use of
antifungal agents in patients with
candidemia. Previous systematic
reviews of the available literature
have not looked at the relative
effectiveness of interventions of
confirmed infections.
This study was a systematic
literature review of the using
meta-analytic techniques. The
reviewers conducted independent,
comprehensive searches of the
MEDLINE, EMBASE, Cochrane CENTRAL,
AMED, CINAHL, TOXNET, Development
and Reproductive Toxicology,
Hazardous Substances Databank,
Psych-info and Web of Science
databases. They identified
randomized trials of antifungal
therapies for confirmed cases of
invasive candidiasis in adults that
reported on: clinical response,
all-cause mortality;
fungal-attributable death, adverse
events and disseminated disease
rather than single site fungal
infections.
The literature search identified
forty two clinical trials of which
eleven met the inclusion criteria.
These trials enrolled a total of 965
patients (median age of fifty seven
years) and were predominantly
conducted in populations dominated
by patients with hematologic cancers
experiencing infection with
Candida
species. Seven of the studies
assessed azole-class drugs (fluconazole,
itraconazole, voriconazole) compared
to amphotericin B. The other studies
compared: anidulafungin to
fluconazole; micafungin to
amphotericin B; caspofungin to
amphotericin B; and micafungin to
caspofungin. The reviewers collected
and analyzed data on the antifungal
therapy and type of interventions
tested, the population studied (age,
setting, underlying conditions), the
treatment effect on specified
outcomes, adverse events, and
general methodological quality
features of the trial. Their mixed
treatment comparison analysis found
similar within-class effects across
all interventions. Adverse event
profiles differed, with amphotericin
B exhibiting a greater number of
adverse event effects.
The reviewers concluded that azoles
and echinocandins are equally
effective interventions for treating
invasive candidiasis, confirming the
Infectious Disease Society of
America (IDSA) guidelines that
recommend azoles or echinocandins as
the first line treatment for
Candida
infections. The effects within
each class of drug were found to be
similar. Amphotericin B offers an
effective, but more toxic
alternative.
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