Efficacy of micafungin alone or in combination against systemic murine aspergillosis

Abstract

We tested the efficacy of micafungin (FK) alone or in combination with other antifungals against systemic murine aspergillosis. FK alone at 10 mg/kg of body weight/dose prolonged survival (P = 0.01) and reduced CFU in the brain and kidney. Combination therapy that used suboptimal FK with amphotericin B or itraconazole prolonged survival. Although no survivors were free of infection, no antagonism was seen. Nikkomycin Z with FK showed significantly greater potency (P < 0.01) than either alone.

FIG. 1.

Cumulative mortality of mice infected systemically with A. fumigatus given one of the indicated treatments. All treatments began on day 1 postinfection and continued for 12 days. Treatments were twice daily at the dosage (milligrams per kilogram) indicated. An asterisk indicates a P value of 0.011 versus untreated controls and a P value of 0.046 versus diluent controls. No other comparisons were significant at the P = 0.05 level.

FIG. 2.

Cumulative mortality of mice infected systemically with A. fumigatus given one of the indicated treatments. All treatments began on day 1 postinfection and continued for 12 days. (A) Treatments with FK and AMB. (B) Treatments with FK and ICZ. (C) Treatments with FK and NIK. BID, twice daily; QD, once a day.

FIG. 3.

Scattergram of the CFU recovered from the brains and kidneys of surviving mice in the combination therapy study. Animals succumbing to infection were assigned a log₁₀ value of 5 for each organ, and organs with no detectable infection were assigned a log₁₀ value of 0. The bar represents the median value for the group. No surviving mouse was free of infection in both organs.