Inadequate therapeutic response to a recommended antituberculosis fixed-dose combination regimen in an overweight patient with Mycobacterium bovis infection

Ann Pharmacother. 2013 Jan;47(1):e4. doi: 10.1345/aph.1R452. Epub 2013 Jan 16.

Abstract

Objective: To report a case of an overweight man with lymph node tuberculosis due to Mycobacterium bovis, a part of the Mycobacterium tuberculosis complex, treated with fixed-dose combination (FDC) chemotherapy.

Case report: Following guidelines, according to the patient's weight (92 kg), we prescribed the maximum recommended doses of isoniazid-rifampin-pyrazinamide FDC. It led initially to underdosing, with a poor clinical outcome, justifying increased doses and a complex regimen using separate drugs (isoniazid 600 mg, rifampin 1200 mg, and levofloxacin 1000 mg) to achieve therapeutic drug concentrations and clinical response.

Discussion: Usually recommended doses of FDC chemotherapies may be inappropriate in overweight patients. We discuss here the different factors that may be involved in poor clinical outcomes, particularly the consequences of excess weight on drug metabolism: drug-drug interaction, FDC use, generic formulation use, intestinal malabsorption, and acetylation profile.

Conclusions: Therapeutic drug monitoring in overweight patients may be useful in the clinical setting to help clinicians individualize drug therapeutic regimens and optimize drug response, adherence, and safety.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Antitubercular Agents / administration & dosage
  • Antitubercular Agents / therapeutic use*
  • Drug Combinations
  • Drug Monitoring
  • Drug Therapy, Combination
  • Humans
  • Isoniazid / administration & dosage
  • Isoniazid / therapeutic use
  • Levofloxacin
  • Male
  • Mycobacterium bovis / isolation & purification*
  • Ofloxacin / administration & dosage
  • Ofloxacin / therapeutic use
  • Overweight*
  • Practice Guidelines as Topic
  • Pyrazinamide / administration & dosage
  • Pyrazinamide / therapeutic use
  • Rifampin / administration & dosage
  • Rifampin / therapeutic use
  • Treatment Outcome
  • Tuberculosis, Lymph Node / drug therapy*
  • Tuberculosis, Lymph Node / microbiology

Substances

  • Antitubercular Agents
  • Drug Combinations
  • Pyrazinamide
  • Levofloxacin
  • Ofloxacin
  • Isoniazid
  • Rifampin