title: Targeted prophylaxis with amphotericin B lipid complex in liver transplantation.
abstract: The purpose of this study is to prospectively evaluate a strategy in which prophylaxis with amphotericin B lipid complex at 3 different dosages was targeted to liver transplant recipients at high risk for the development of invasive fungal infection (IFI). High risk was defined as a postoperative requirement for prolonged (>/=5 days) intensive care unit (ICU) treatment. Consecutive high-risk patients were administered prophylaxis with amphotericin B lipid complex from day 5 after orthotopic liver transplantation (OLT) until ICU discharge or death. The first 10 eligible patients were administered 5 mg/kg/d, the next 10 patients were administered 2.5 mg/kg/d, and a final 10 patients were administered 1 mg/kg/d. Drug safety and efficacy were assessed before each dosage reduction. During the study period, 130 adult patients underwent 137 OLTs. Thirty patients fulfilled the entry criteria and were administered prophylaxis with amphotericin B lipid complex. No patient developed proven IFI during prophylaxis. Cultures from normally sterile sites (blood and abdominal drain fluid) always showed negative results. All fungal isolates were sensitive in vitro to amphotericin B. There was no significant difference in colonization scores among the groups of patients administered different dosages of amphotericin B lipid complex. No death, serious adverse reaction, or nephrotoxicity was attributed to amphotericin B lipid complex. We conclude that prophylaxis with amphotericin B lipid complex targeted to patients requiring prolonged ICU treatment after OLT appears to be well tolerated and may prevent IFI. Our current policy is to use amphotericin B lipid complex, 1 mg/kg/d, as antifungal prophylaxis in this high-risk group.
authors.affiliation: Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Edgbaston, Birmingham, UK. saket@singhal.freeserve.co.uk
authors.forename: S
authors.initials: S
authors.lastname: Singhal
authors.forename: R W
authors.initials: RW
authors.lastname: Ellis
authors.forename: S G
authors.initials: SG
authors.lastname: Jones
authors.forename: S J
authors.initials: SJ
authors.lastname: Miller
authors.forename: N C
authors.initials: NC
authors.lastname: Fisher
authors.forename: J G
authors.initials: JG
authors.lastname: Hastings
authors.forename: D J
authors.initials: DJ
authors.lastname: Mutimer
mesh_terms: D000328:Adult; D000666:Amphotericin B / Q000009:adverse effects / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use*; D001232:Aspergillus fumigatus / Q000302:isolation & purification / Q000502:physiology; D002175:Candida / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology; D002176:Candida albicans / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology; D004338:Drug Combinations; D004352:Drug Resistance, Microbial; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008485:Medical Audit; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000382:microbiology / Q000517:prevention & control*; D010713:Phosphatidylcholines / Q000009:adverse effects / Q000627:therapeutic use*; D010715:Phosphatidylglycerols / Q000009:adverse effects / Q000627:therapeutic use*; D011182:Postoperative Care; D011183:Postoperative Complications / Q000517:prevention & control*; D011446:Prospective Studies
chemical_list: D000935:Antifungal Agents; D004338:Drug Combinations; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C068538:liposomal amphotericin B; D000666:Amphotericin B; D015725:Fluconazole