Serum and intraperitoneal levels of amphotericin B and flucytosine during intravenous treatment of critically ill patients with Candida peritonitis

Abstract

To study the relation between serum and peritoneal levels of amphotericin B and flucytosine during intravenous treatment in patients with abdominal sepsis due to a perforated gut. Included were consecutive patients with abdominal sepsis due to a perforated gut, who were treated intravenously with amphotericin B and/or flucytosine after surgery if an abdominal drain was present. Amphotericin B and flucytosine were measured from simultaneously collected serum and abdominal fluid samples. Twenty-one consecutive patients were included. Five repeated samples were taken from three patients. The time interval between the start of the medication and the first sampling was median 4.0 days (range 2-7 days). The correlation coefficient (r(2)) between serum and peritoneal levels of amphotericin B was 0.79. In nine patients (43%) with a maximum serum level of 0.28 mg/L, amphotericin B in the peritoneal fluid was undetectable. The lowest serum level that was present with a detectable peritoneal level was 0.16 mg/L. A short duration of treatment (2 days) was associated with low serum and undetectable peritoneal levels. In seven patients, flucytosine levels were measured. Peritoneal flucytosine levels did not differ significantly from serum levels. Serum and peritoneal flucytosine levels correlated well with r(2)=0.88. Peritoneal amphotericin B level was inversely correlated with C-reactive protein level on the same day (r(2)=0.30). It is shown, during continuous infusion, that peritoneal levels of amphotericin B are lower than serum levels. The amphotericin B serum levels should exceed 0.5 mg/L to obtain peritoneal levels above MIC values. Flucytosine levels in the abdominal fluid are comparable to serum levels and within MIC ranges.