Combination antifungal therapy for invasive aspergillosis.
BACKGROUND
Aspergillosis therapy with amphotericin, azoles, or echinocandins is associated with substantial mortality, ranging from 30% to 80%, depending on the stage of infection and the host's underlying disease. The results of in vitro studies and animal models suggest that combination therapy with azoles and echinocandins may have additive activity against Aspergillus species.


METHODS
We evaluated the outcomes of patients with aspergillosis who experienced failure of initial therapy with amphotericin B formulations and received either voriconazole (n=31) or a combination of voriconazole and caspofungin (n=16) for salvage therapy.


RESULTS
The combination of voriconazole and caspofungin was associated with improved 3-month survival rate, compared with voriconazole alone (hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.17-1.1; P=.048). In multivariable models, salvage therapy with the combination of voriconazole and caspofungin was associated with reduced mortality, compared with therapy with voriconazole (HR, 0.28; 95% CI, 0.28-0.92; P=.011), independent of other prognostic variables (e.g., receipt of transplant and type of conditioning therapy). The probability of death due to aspergillosis was lowest in patients who received the combination regimen.


CONCLUSIONS
Randomized trials are warranted to determine whether this combination should be used as primary therapy for aspergillosis.
Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. kmarr@fhcrc.org
Kieren A
KA
Marr
Michael
M
Boeckh
Rachel A
RA
Carter
Hyung Woo
HW
Kim
Lawrence
L
Corey
D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy*; D000077336:Caspofungin; D004359:Drug Therapy, Combination; D054714:Echinocandins; D005260:Female; D006801:Humans; D055666:Lipopeptides; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000188:drug therapy*; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012189:Retrospective Studies; D016879:Salvage Therapy; D016019:Survival Analysis; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D065819:Voriconazole
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D010456:Peptides, Cyclic; D011743:Pyrimidines; D014230:Triazoles; D000077336:Caspofungin; D065819:Voriconazole