Multidrug-resistant Tuberculosis (MDR TB)

Background

• MDR TB is defined as TB caused by Mycobacterium tuberculosis resistant to at least isoniazid and rifampin.
• An estimated 460,000 cases of MDR TB emerged globally in 2017.
• In the United States in 2015, of all culture-positive TB cases with drug-susceptibility testing results, 1.2% (89 cases) were MDR TB.
• Risk factors for MDR TB include:
  • exposure to persons with MDR TB
  • a history of TB with treatment failure or relapse
  • poor adherence to or not completing anti-TB medications during previous TB treatment
  • positive sputum smears after 2 months of standard anti-TB combination therapy
  • residence in or travel to area with a high prevalence of drug resistance
• With proper management, cure rates are > 60%.

Evaluation

• The clinical presentation of MDR TB does not differ from that of drug-susceptible TB.
• MDR TB diagnosis is traditionally confirmed with culture and drug-susceptibility testing.
• The addition of molecular testing can rapidly identify resistance to rifampin and isoniazid and is preferred to conventional testing for initial management.
• When molecular testing is not performed, MDR TB may be suspected prior to receipt of drug susceptibility results if 1 or more of the following:
  • risk factors for MDR TB are present
  • there are persistently positive sputum smears and/or serial cultures despite adherence to standard anti-TB treatment
  • there is little improvement in signs and symptoms of TB despite adherence to standard anti-TB treatment

Management

• Any hospitalized patient with suspected TB or who has acid-fast bacilli (AFB) smear-positive sputum should be placed in airborne infection isolation with appropriate infection control measures for providers and visitors.
• TB is a reportable illness in the United States. Report all cases of suspected or confirmed TB and MDR TB promptly to local health authorities.
• MDR TB should be managed by experts with experience in the treatment of drug-resistant TB.
• Prior to receipt of drug-susceptibility testing results, empiric treatment for MDR TB should be started in those in whom MDR TB is suspected.
• World Health Organization (WHO) 2020 recommendations on treatment of drug-resistant TB.
  • Consider 9-12 month all-oral bedaquiline-containing regimen as preferred option only if (Weak recommendation):
    • fluoroquinolone resistance is ruled out.
    • < 1 month exposure to previous treatment with second-line medicines in the regimen.
    • no resistance to or suspected ineffectiveness of medicines in the regimen (except isoniazid resistance).
    • no extensive disease or severe extrapulmonary TB.
    • the patient is ≥ 6 years old and not pregnant.
  • Longer regimens appropriate for all patients with drug-resistant TB, but preferred for those ineligible for shorter all-oral regimens and patients with quinolone resistance.
• American Thoracic Society/Centers for Disease Control and Prevention/European Respiratory Society/Infectious Diseases Society of America (ATS/CDC/ERS/IDSA) 2019 practice guideline on treatment of drug-resistant TB.
  • Consider using ≥ 5 drugs in intensive phase of treatment and 4 drugs in continuation phase of treatment (Weak recommendation).
  • Suggested duration of treatment:
    • Consider intensive-phase duration of 5-7 months after culture conversion (Weak recommendation).
    • Recommended total treatment duration is 15-21 months after culture conversion for most patients (Weak recommendation), but 15-24 months after culture conversion for patients with pre-extensive drug-resistant tuberculosis (XDR TB) and XDR TB (Weak recommendation).
• Treatment for latent TB infection in contacts of MDR TB patients should be guided by drug-susceptibility results in the source patient, when possible.