Therapeutic Drug Monitoring of Amphotericin-B in Plasma and Peritoneal Fluid of Pediatric Patients after Liver Transplantation: A Case Series

Abstract

Fungal infections represent a serious complication during the post-liver transplantation period. Abdominal infections can occur following pre-existing colonization, surgical procedures, and permanence of abdominal tubes. In our center, liposomal amphotericin-B is used as antifungal prophylaxis in pediatric patients undergoing liver transplantation. The aim of this study is to evaluate peritoneal levels of amphotericin-B following intravenous administration. Six liver recipients received liposomal amphotericin-B. Three of them were treated as prophylaxis; meanwhile, three patients received liposomal amphotericin-B to treat Candida albicans infection. Plasma and peritoneal amphotericin-B levels were measured by LC-MS/MS in two consecutive samplings. Cmin (pre-dose) and Cmax (2 h after the end of infusion) were evaluated as drug exposure parameters for both plasma and peritoneum. Our results showed that peritoneal amphotericin-B levels were significantly lower than plasma and that the correlation coefficient was 0.72 (p = 0.03) between plasma and peritoneal Cmin. Moreover, although peritoneal levels were within the therapeutic range, they never reached the PK/PD target (Cmax/MIC > 4.5). In conclusion, PK exposure parameters could be differently used to analyze amphotericin-B concentrations in plasma and peritoneum. However, liposomal amphotericin-B should be preferred in these patients as prophylactic rather than therapeutic treatment for fungal infections.

Therapeutic drug monitoring of liposomal amphotericin B in children. Are we there yet? A systematic review

“…The differences between the PK/PD of L-amb and DamB are underemphasized, such that a lower DamB C max /MIC ratio of 5–10 is improperly applied to studies using L-amb. One L-amb paediatric TDM study by Tortora et al , 34 which was excluded due to the paediatric patient numbers (<5), and another adult multicentre study currently underway by Roberts et al , 35 use a lower C max /MIC target of >4.5 for L-amb.…”

Critical appraisal beyond clinical guidelines for intraabdominal candidiasis

“…For amphotericin desoxycholate, some years ago a good linear correlation was found between serum and peritoneal levels [ 92 ], but no data are available for liposomal amphotericin B. A published case series in paediatric patients concluded that peritoneal liposomal amphotericin B concentrations were significantly lower than in plasma, hampering to attain the Cmax/MIC target value [ 93 ]. Considering MIC 90 values for the different Candida species (MICs of 0.5–1 mg/L) [ 41 , 52 , 53 ], Cmax of liposomal amphotericin B in peritoneum should be at least 4.5 mg/L.…”

“…In one case, a much higher concentration of amphotericin B was observed in the infected lung lesion than in uninfected lung tissue which support the hypothesis that liposomal amphotericin B accumulates in lesions of fungal infection [ 88 , 91 , 95 ]. In the peritoneal study, half of the patients received liposomal amphotericin B as prophylaxis [ 93 ], making it difficult to draw conclusions. According to the literature, liposomal amphotericin B attains fungicidal activity concentrations in difficult-to-reach compartments, as peritoneum, among others [ 68 ].…”