Summary
Objective
A meta-analysis was performed to compare mold-active triazoles or lipid
amphotericin B plus an echinocandin to non-echinocandin monotherapy for acute invasive
aspergillosis (IA).
Methods
We searched PubMed, EMBASE, and other databases through May 2013 unrestricted
by language. We included observational and experimental studies wherein patients with
proven or probable IA by EORTC/MSG criteria underwent our comparative intervention.
PRISMA and MOOSE guidelines were followed and quality was assessed using the Jadad and
Newcastle–Ottawa criteria. Meta-regression with fixed and random effects and
sensitivity analyses were performed. The primary study outcome measure was 12-week
overall mortality. The secondary outcome assessed was complete and partial response.
Results
Only observational studies of primary 12-week survival showed heterogeneity
(I2 = 48.96%, p = 0.05). For salvage IA
therapy, fixed effects models demonstrated improved 12-week survival (Peto odds ratio
(OR) 1.80, 95% confidence interval (CI) 1.08–3.01) and success (Peto OR 2.17, 95%
CI 1.21–3.91) of combination therapy. Significance remained after applying random
effects as a sensitivity analysis (12-week survival: Peto OR 1.90, 95% CI
1.04–3.46, and unchanged value for success). Restriction to high quality studies
and including echinocandins as the comparator for refractory IA revealed an adjusted OR
of 1.72 (95% CI 0.96–3.09; p = 0.07) for global success, while
the survival endpoint remained unaltered.
Conclusions
Combination antifungals for IA demonstrate improved outcomes over monotherapy
in the salvage setting. Clinicians should consider this approach in certain
situations.