Extensively Drug-resistant Tuberculosis (XDR TB)

Background

• XDR TB is defined as TB caused by Mycobacterium tuberculosis resistant to isoniazid, rifampin, any fluoroquinolone, and at least 1 of 3 injectable second-line drugs (amikacin, kanamycin, or capreomycin).
• In 2017, the average proportion of multidrug-resistant (MDR) TB cases with XDR TB was 8.5% (95% CI 6.2%-11%).
• 15 countries reported ≥ 10 cases of XDR TB during the most recent year data were available. Countries with the highest number of cases included Lithuania, Kazakhstan, Latvia, Tajikistan, and Georgia.
• XDR TB is rare in the United States with ≤ 10 cases reported each year during 1993-2013.
• In the United States for 1993-2006, 49 cases of XDR TB, representing 3% of MDR TB cases had drug-susceptibility testing results reported for ≥ 1 fluoroquinolone and 1 injectable second-line drug.
• Risk factors for MDR and XDR TB:
  • prior TB treatment (> 1 month)
  • failure of a TB treatment regimen containing second-line drugs including an injectable agent and a fluoroquinolone
  • close contact with a patient with MDR TB, XDR TB, or with a patient whose treatment regimen including second-line drugs is failing or has failed
  • delayed treatment
  • HIV
  • foreign birth
  • younger age
  • female sex
  • previous imprisonment

Evaluation

• Clinical presentation of XDR TB does not differ from that of drug-susceptible TB.
• XDR TB diagnosis is confirmed with culture and drug-susceptibility testing.
• XDR TB may be suspected prior to receipt of culture results if risk factors for multidrug-resistant (MDR) TB are present or there are persistently positive sputum smears and/or cultures or little/no improvement in signs and symptoms of TB, despite standard anti-TB treatment.
• Molecular testing can rapidly identify resistance to rifampin and isoniazid and is preferred to conventional testing (Weak recommendation).

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 XDR TB promptly to local health authorities.
• XDR TB should be managed by only those expert in the treatment of drug-resistant TB.
• Prior to receipt of drug-susceptibility testing results, empiric treatment for XDR TB should be started in those in whom XDR TB is suspected.
• WHO 2020 recommendations on treatment of multidrug-resistant TB
  • Start treatment with ≥ 4 effective TB drugs and ensure ≥ 3 effective TB drugs are included if bedaquiline is stopped after 6 months (Weak recommendation).
  • Suggested duration of treatment:
    • Total treatment duration of 18-20 months (15-17 months after culture conversion) suggested for most patients, which may be modified depending on treatment response (Weak recommendation).
    • 6-7 month intensive phase suggested for most patients on regimens containing amikacin or streptomycin, which may be modified depending on treatment response (Weak recommendation).
  • Elective partial lung resection (lobectomy or wedge resection) may be used alongside recommended regimen (Weak recommendation).
  • Provide health education and counselling on disease and treatment adherence (Strong recommendation)
• 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).
    • Total treatment duration 15-24 months after culture conversion for patients with pre-extensive drug-resistant tuberculosis (XDR TB) and XDR TB (Weak recommendation).
  • Elective partial lung resection (lobectomy or wedge resection) may be used alongside recommended drug regimen.
• Treatment for latent TB infection in contacts of MDR TB patients should be guided by drug-susceptibility results in the source patient, when possible.