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

Abstract

Objectives: 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.Patients and methods: 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.Results: 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 5 0.88. Peritoneal amphotericin B level was inversely correlated with C-reactive protein level on the same day (r 2 5 0.30).Conclusions: 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.

Penetration of Amphotericin B Lipid Formulations into Pleural Effusion

“…Median intraperitoneal levels of AMB previously amounted to 0.12 g/ml in samples from critically ill patients during intravenous treatment with AMB deoxycholate (18), which is comparable to our results for pleural effusion samples. In noninfected rabbits, total AMB concentrations were much lower in alveolar epithelial lining fluid than in lung tissue (7).…”

Anidulafungin Pharmacokinetics in Ascites Fluid and Pleural Effusion of Critically Ill Patients

“…Micafungin achieved mean concentrations of 0.7 and 1.0 g/ml in pleural effusion and in ascites fluid, respectively (12)(13)(14). Amphotericin B concentrations of Ͻ0.5 g/ml were recovered from ascites fluid and from pleural effusion during treatment with different amphotericin B formulations (15)(16)(17). Flucytosine levels in peritoneal fluid were comparable to the simultaneous levels in plasma (15).…”

Tissue Penetration of Antifungal Agents

“…Furthermore, in adults or children undergoing peritoneal dialysis, dialysate concentrations of fluconazole (following systemic administration) are similar to or exceed those in the plasma (193,194). Limited clinical data suggest that the peritoneal concentrations of 5FC in humans are approximately 65% to 100% of those in serum (195,196).…”

“…The peritoneal concentrations of amphotericin B following AmBd administration are variable and less than 50% of serum concentrations (91,195,198) and, on occasion, are undetectable (196). Weiler and colleagues (199) have demonstrated that similar amphotericin B ascitic fluid concentrations are attained following administration of either L-AMB or ABLC for 7 to 13 days at 3 to 5 mg/kg/day.…”