Speaker's Highlight

• Don Sin University of British Columbia, St. Paul Hospital (Canada)
  Kenneth R. Chapman Toronto General Hospital Research Institute (Canada)
• Parameswaran Nair McMaster University (Canada)
  Carolyn Calfee UCSF (U.S.A.)
• Gregory P. Downey University of Colorado School of Medicine (U.S.A.)
  David A. Schwartz University of Colorado School of Medicine (U.S.A.)
• Neil Schluger Tuberculosis Control Branch, California Department of Public Health (U.S.A.)
  Nick Kim Critical Care & Sleep Medicine, University of California San Diego (U.S.A.)
• Nicola Hananiah Baylor College of Medicine (U.S.A.)
  Jae-Joon Yim Seoul National University College of Medicine (Republic of Korea)
• Koichiro Asano Tokai University School of Medicine (Japan)
  Diahn-Warng Perng Taipei Veterans General Hospital (Taiwan)
• Konstantinos Kostikas University of Ioannina (Greece)
  Karin Klooster University Medical Center Groningen (Kingdom of the Netherlands)

• Updates in Tuberculosis Diagnosis and Drug Resistance Patterns

  Tuberculosis (TB) remains a major cause of preventable illness and death, particularly where delayed diagnosis, limited laboratory capacity, and treatment interruptions allow transmission to continue. New diagnostic tools are changing how clinicians identify Mycobacterium tuberculosis, detect resistance, and select effective therapy sooner.

  The most important shift is from relying solely on sputum smear microscopy and culture toward rapid molecular testing. These methods can identify TB DNA and important resistance markers within hours, helping health services respond before a patient has experienced weeks of ineffective treatment or exposed household and community contacts.

  For respiratory specialists, interpreting results requires more than recognizing a positive or negative test. The clinical picture, specimen quality, HIV status, previous treatment, local epidemiology, and confirmatory drug-susceptibility testing all influence the safest management decision.

  Why Rapid Diagnosis Matters

  Sputum smear microscopy remains affordable and useful for identifying patients with a high bacillary burden, but it has limited sensitivity. It can miss people with paucibacillary disease, children, individuals living with HIV, and patients who cannot produce a good-quality sputum sample. A negative smear therefore does not exclude pulmonary TB.

  Culture is still an important reference method because it can confirm viable organisms and support phenotypic drug-susceptibility testing. Its major limitation is time: liquid culture may require several days or weeks, while solid culture takes longer. Molecular assays help bridge this gap by providing an early indication of TB infection and resistance.

  Molecular Tools In Current Practice

  The Xpert MTB/RIF and Xpert MTB/RIF Ultra assays detect TB complex DNA and mutations associated with rifampicin resistance. Ultra has improved analytical sensitivity and can be particularly valuable when the bacillary load is low. However, trace-positive results require careful interpretation, especially in people previously treated for TB, because residual DNA may remain after organisms have been cleared.

  Line-probe assays can identify resistance-associated mutations in the rpoB, katG, and inhA regions. They are useful for detecting rifampicin and isoniazid resistance directly from specimens or cultured isolates, although they may not capture every mechanism of resistance. Targeted next-generation sequencing and whole-genome sequencing provide a broader view of resistance mutations and may support surveillance when laboratory infrastructure is strong.

  Guidance, scientific sessions, and respiratory medicine updates associated with the APSR 2022 congress provide useful context for understanding how these tests fit into multidisciplinary clinical practice.

  Understanding Resistance Patterns

  Drug-resistant TB is not a single condition. Rifampicin-resistant TB (RR-TB) includes resistance to rifampicin with or without resistance to other medicines. Multidrug-resistant TB (MDR-TB) refers to resistance to at least isoniazid and rifampicin, the two key first-line drugs.

  The updated terminology for extensively drug-resistant TB (XDR-TB) is also important. XDR-TB is MDR/RR-TB with additional resistance to at least one fluoroquinolone and at least one of the group A drugs, such as bedaquiline or linezolid. Pre-XDR-TB refers to MDR/RR-TB with resistance to any fluoroquinolone. These definitions help clinicians and surveillance programs describe resistance consistently.

  Resistance patterns vary by geography, treatment history, transmission networks, and access to quality medicines. Rifampicin resistance often signals a high likelihood of additional resistance, but it should not automatically be treated as a complete resistance profile. Extended testing is needed to determine whether fluoroquinolones, bedaquiline, linezolid, and other agents remain active.

  Comparing Diagnostic Approaches

  No single test answers every clinical question. The best diagnostic pathway combines a rapid molecular assay with culture, phenotypic susceptibility testing, or sequencing when resistance is suspected or the initial result is unexpected.

  Method	Main value	Typical limitation	Best use
  Smear microscopy	Rapid assessment of bacillary burden	Lower sensitivity; no resistance information	Initial evaluation where resources are limited
  Xpert MTB/RIF Ultra	Rapid TB detection and rifampicin-resistance screening	Trace results can be difficult to interpret; limited resistance coverage	First-line molecular testing for suspected pulmonary TB
  Truenat MTB assays	Portable, near-patient molecular diagnosis	Requires trained operators and additional testing for broader resistance	Decentralized services and peripheral laboratories
  Line-probe assay	Detects selected resistance mutations	Cannot identify every mutation; technical requirements	Rapid isoniazid and rifampicin resistance assessment
  Liquid culture with DST	Confirms viable bacilli and tests drug activity	Slow and laboratory intensive	Confirmation and complex resistance investigation
  Whole-genome sequencing	Broad resistance and transmission analysis	Cost, infrastructure, and interpretation demands	Reference laboratories and surveillance

  Managing Discordant Results

  Discordant findings should trigger review rather than an automatic change in treatment. For example, a molecular test indicating rifampicin resistance may be followed by repeat testing, culture, sequencing, or referral to a reference laboratory. The urgency of starting an effective regimen must be balanced against the risk of exposing the patient to unnecessary toxic medicines.

  Clinical teams should also investigate specimen quality, contamination, prior TB therapy, and the possibility of mixed infection. A molecular result may detect DNA from nonviable organisms, while culture can be falsely negative after partial treatment. When the results do not align, consultation with a tuberculosis expert and review of the complete laboratory history are essential.

  Building Better Diagnostic Pathways

  Effective TB diagnosis depends on systems as much as equipment. Laboratories need reliable sample transport, uninterrupted electricity, internal quality control, external proficiency assessment, and clear procedures for reporting resistance results. Clinicians need rapid access to results and a defined pathway for patients whose tests indicate RR-TB or more advanced resistance.

  Patient-centered care also affects diagnostic accuracy. Clear instructions for sputum collection, infection-control measures, contact investigation, and support during treatment reduce missed cases and onward transmission. In children and people unable to produce sputum, gastric aspirates, induced sputum, nasopharyngeal specimens, or respiratory sampling through bronchoscopy may be considered according to local expertise and guidelines.

  Priorities For Clinical Teams

  A practical approach to modern TB diagnosis should include:

  • Use a rapid molecular assay as an initial test when pulmonary TB is suspected, rather than depending on smear microscopy alone.
  • Request expanded drug-susceptibility testing when rifampicin resistance, previous treatment, treatment failure, or contact with resistant TB is present.
  • Interpret trace-positive and discordant results alongside symptoms, imaging, treatment history, and specimen quality.
  • Refer complex resistance profiles to a specialized laboratory capable of sequencing or comprehensive susceptibility testing.
  • Record resistance data accurately to support individual care, infection control, and regional surveillance.

  The continuing development of molecular diagnostics is making tuberculosis care faster and more precise, but technology cannot replace clinical judgment or strong laboratory networks. Reviewing emerging evidence through professional respiratory medicine forums can help teams align local protocols with changing resistance patterns.

  Healthcare organizations can use the APSR 2022 website to explore congress information, scientific programming, and respiratory medicine resources relevant to diagnostic practice. Applying these insights through dependable testing pathways can shorten the time to effective treatment and improve outcomes for patients with drug-susceptible and drug-resistant TB.

  Richard Russell Nuffield Department of Clinical Medicine, University of Oxford (United Kingdom)
• Mona Bafadhel King’s College London (United Kingdom)
  David Jackson Guy’s and St Thomas’ Hospital, King’s College London (United Kingdom)
• James Chalmers University of Dundee (United Kingdom)
  David Price University of Aberdeen (United Kingdom)