title: Retrospective study of the renal effects of amphotericin B lipid complex when used at higher-than-recommended dosages and longer durations compared with lower dosages and shorter durations in patients with systemic fungal infections.
abstract: BACKGROUND
  Patients with fungal infections who are treated with amphotericin B lipid complex (ABLC) often receive dosages less than that recommended in the product information (5 mg/kg.d). This occurs despite the described safety and increased efficacy in select patients treated with higher ABLC dosages.
  
  
  OBJECTIVE
  The purpose of this study was to compare the renal effects of high-dosage/long-duration (HDos/LDur) ABLC therapy (>5 mg/kg.d for >12 days) with those of low-dosage/short-duration (LDos/SDur) ABLC therapy (<or=5 mg/kg.d for <or=12 days).
  
  
  METHODS
  Male and female ABLC-treated patients of all ages were prospectively enrolled, and data were retrospectively collected for those who had received >or=4 ABLC doses according to a large, multicenter patient database, the Collaborative Exchange of Antifungal Research (CLEAR) registry. The safety profile of each dosage was evaluated using serum creatinine concentration (S-Cr) and calculated creatinine clearance (CCcr).
  
  
  RESULTS
  A total of 1726 patients were studied. The HDos/LDur group included 309 patients and theLDos/SDur group included 1417 patients. The median ages of the HDos/LDur and LDos/SDur groups were 42 and 48 years, respectively (ranges, <1 to 83 and <1 to 95 years; P < 0.001); females comprised 51% and 42% of the 2 populations (P = 0.004); and 6% and 12% had solid tumors (P = 0.002). The HDos/LDur group was more likely than the LDos/SDur group to have been treated for multiple systemic fungal pathogen infections (16% and 9%, respectively) and for mold infections (28% and 12%, respectively) (both, P < 0.001). The median change in S-Cr from baseline was 0.1 mg/dL in both groups (range, -4.9 to 5 mg/dL in the HDos/LDur group and -3.96 to 4.7 mg/dL in the LDos/SDur group). No increased risk for renal dysfunction, as reflected in the median change from baseline in CCcr, was observed in either cohort (-3 mL/min [range, -118.65 to 69.03 mL/min] in the HDos/LDur group; -2.17 mL/min [range, -107.48 to 104.45 mL/min] in the LDos/SDur group).
  
  
  CONCLUSIONS
  These data suggest that higher ABLC dosages appear to be as well tolerated as lower dosages, warranting further study of ABLC dosages >5 mg/kg.d for >12 days in the treatment of systemic fungal infections.
authors.affiliation: ProSanos Corporation, 7590 Fay Avenue, Suite 204, La Jolla, CA 92037, USA. roya.hooshmand-rad@prosanos.com
authors.forename: Roya
authors.initials: R
authors.lastname: Hooshmand-Rad
authors.forename: Michael D
authors.initials: MD
authors.lastname: Reed
authors.forename: Alice
authors.initials: A
authors.lastname: Chu
authors.forename: Vincent
authors.initials: V
authors.lastname: Gotz
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Morris
authors.forename: John
authors.initials: J
authors.lastname: Weinberg
authors.forename: Edward A
authors.initials: EA
authors.lastname: Dominguez
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000617:Aminoglycosides / Q000627:therapeutic use; D000666:Amphotericin B / Q000008:administration & dosage*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000935:Antifungal Agents / Q000008:administration & dosage*; D065095:Calcineurin Inhibitors; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy*; D010713:Phosphatidylcholines / Q000008:administration & dosage*; D010715:Phosphatidylglycerols / Q000008:administration & dosage*; D011446:Prospective Studies; D012042:Registries; D012189:Retrospective Studies; D014640:Vancomycin / Q000627:therapeutic use
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D065095:Calcineurin Inhibitors; D004338:Drug Combinations; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C068538:liposomal amphotericin B; D014640:Vancomycin; D000666:Amphotericin B; D003404:Creatinine