The pharmacokinetics and antifungal activity of the
echinocandins anidulafungin (AFG),
micafungin (MFG), and
caspofungin (CAS) were assessed in
ascites fluid and plasma of
critically ill adults treated for suspected or proven
invasive candidiasis.
Ascites fluid was obtained from
ascites drains or during paracentesis. The antifungal activity of the
echinocandins in
ascites fluid was assessed by incubation of Candida albicans and Candida glabrata at concentrations of 0.03 to 16.00 μg/ml. In addition,
ascites fluid samples obtained from our study patients were inoculated with the same isolates and evaluated for fungal growth. These patient samples had to be spiked with
echinocandins to restore the original concentrations because
echinocandins had been lost during sterile filtration. In
ascites fluid specimens of 29 patients,
echinocandin concentrations were below the simultaneous plasma levels. Serial sampling in 20 patients revealed a slower rise and decline of
echinocandin concentrations in
ascites fluid than in plasma. Proliferation of C. albicans in
ascites fluid was slower than in culture medium and growth of C. glabrata was lacking, even in the absence of antifungals. In CAS-spiked
ascites fluid samples, fungal CFU counts moderately declined, whereas spiking with AFG or MFG had no relevant effect. In
ascites fluid of our study patients,
echinocandin concentrations achieved by therapeutic doses did not result in a consistent eradication of C. albicans or C. glabrata. Thus, therapeutic doses of AFG, MFG, or CAS may result in
ascites fluid concentrations preventing relevant proliferation of C. albicans and C. glabrata, but do not warrant reliable eradication.