title: Use of rifabutin for the treatment of a latent tuberculosis infection in a patient after solid organ transplantation.
abstract: Latent tuberculosis infection is an important problem for solid organ transplant recipients because of the frequency of its occurrence and its potential for reactivation. Because of the high mortality rate associated with active tuberculosis infections in transplant recipients, guidelines from the American Thoracic Society recommend treatment for latent tuberculosis in this population. However, the choice of treatments is often difficult because liver transplant recipients may be more sensitive to isoniazid hepatotoxicity, and rifampin has significant drug interactions with the calcineurin inhibitors used for immunosuppression. Two prior case reports described success with the use of rifabutin, a rifampin alternative, as part of a multidrug treatment regimen for active tuberculosis in posttransplant patients; however, there is no prior literature describing any experience with rifabutin for the treatment of latent tuberculosis in the posttransplant setting. We present a summary of tacrolimus drug levels and corresponding dose requirements for a single posttransplant patient during the administration of 3 different latent tuberculosis drug regimens: rifampin alone, rifampin plus ketoconazole, and rifabutin. In this patient's case, rifabutin allowed the maintenance of adequate tacrolimus levels, although an approximate 2.5-fold increase in the dose was required. Rifampin alone was associated with inadequate immunosuppressant levels, and rifampin plus ketoconazole was associated with a problematically prolonged QT interval and concerns about inadequate tuberculosis treatment.
authors.affiliation: School of Medicine, University of California San Francisco, San Francisco, CA 94143-0454, USA. matt.hickey@ucsf.edu
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Hickey
authors.forename: David J
authors.initials: DJ
authors.lastname: Quan
authors.forename: Peter V
authors.initials: PV
authors.lastname: Chin-Hong
authors.forename: John P
authors.initials: JP
authors.lastname: Roberts
mesh_terms: D000293:Adolescent; D000904:Antibiotics, Antitubercular / Q000009:adverse effects / Q000627:therapeutic use*; D004347:Drug Interactions; D016903:Drug Monitoring; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007654:Ketoconazole / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology; D055985:Latent Tuberculosis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D016031:Liver Transplantation / Q000009:adverse effects* / Q000276:immunology; D008133:Long QT Syndrome / Q000139:chemically induced; D008297:Male; D017828:Rifabutin / Q000009:adverse effects / Q000627:therapeutic use*; D012293:Rifampin / Q000627:therapeutic use; D016559:Tacrolimus / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000904:Antibiotics, Antitubercular; D007166:Immunosuppressive Agents; D017828:Rifabutin; D007654:Ketoconazole; D012293:Rifampin; D016559:Tacrolimus