Multidrug Resistant Tuberculosis

Updated Nov 28, 2022

NCCID Disease Debriefs provide Canadian public health practitioners and clinicians with up-to-date reviews of essential information on prominent infectious diseases for Canadian public health practice. While not a formal literature review, information is gathered from key sources including the Public Health Agency of Canada (PHAC), the USA Centers for Disease Control and Prevention (CDC), the World Health Organization (WHO) and peer-reviewed literature.

This disease debrief was prepared by Nancy Bedingfield. Questions, comments, and suggestions regarding this disease brief are most welcome and can be sent to

What are Disease Debriefs? To find out more about how information is collected, see our page dedicated to the Disease Debriefs.

Questions Addressed in this debrief:

  1. What are the important characteristics of Multidrug Resistant TB?
  2. What is the current state of MDR TB globally?
  3. What is the current risk to Canadians from MDR TB?
  4. What should be done when a patient may be sick with MDR TB?

What are the important characteristics of Multidrug Resistant TB?


Multidrug resistant TB (MDR TB) is a disease caused by any strain of Mycobacterium tuberculosis which is not effectively killed by both isoniazid and rifampin, two of the first-line, safest and most effective anti-TB medications. Bacteria which cause MDR TB may also be resistant to other commonly used TB medications. Both the Canadian and World Health Organization (WHO) MDR treatment guidelines group TB disease caused by bacteria resistant only to rifampin (and not isoniazid) together with MDR TB because of the importance of rifampin to successful TB treatment. In WHO documents, this category is referred to as multidrug resistant/rifampin resistant TB (MDR/RR TB).

MDR TB develops at the population level when people with TB are not adequately treated. When TB treatment is not adequate, bacteria which have not been killed by the medications survive, continue to grow, and spread to others. Inadequate TB treatment can happen for many reasons including poor access to mycobacterial lab testing; inappropriate prescription of TB medications; problems at all stages of the medication supply chain; drug side effects; and structural barriers to treatment completion, for example when patients and families face catastrophic costs associated with TB. [1]

Individuals develop MDR TB through either primary or acquired drug resistance. People who contract primary MDR TB have never been treated for TB before but develop resistant disease because of contact with someone else with infectious MDR TB.  Only a small percentage of people who have such contacts will become ill themselves. People living with HIV and other immunosuppressive conditions are at higher risk of becoming ill post-exposure. People who have recently become infected with MDR TB may be candidates for preventative treatment depending on the susceptibility profile of the source strain.

Acquired MDR TB refers to TB disease which develops after a previous course of TB treatment has been unsuccessful. In these cases, the disease which recurs is resistant to previously used medications. Patients with acquired MDR TB may need retreatment soon after the first treatment or decades later.

Centers for Disease Control and Prevention: Multidrug-Resistant Tuberculosis Fact Sheet

Centers for Disease Control and Prevention: Drug-Resistant TB

Signs and symptoms

MDR TB has the same symptoms as drug susceptible TB. Symptoms of drug susceptible TB include fever, night sweats, and weight loss. Persistent cough is a symptom of pulmonary TB; however, TB can occur in other body systems including the lymphatic system, the nervous system (e.g., brain and spine), the gut, and the reproductive tract. When TB occurs outside of the lungs, coughing is not a prominent symptom, but a patient may experience pain and swelling in the affected areas.

Public Health Agency of Canada: Tuberculosis Symptoms and Treatment

WHO: Tuberculosis Symptoms

Centers for Disease Control and Prevention: Multidrug-Resistant Tuberculosis Fact Sheet

Severity and complications

As with drug susceptible TB, MDR TB disease can be mild or advanced. The extent of the disease is measured using the same indicators used for active TB. These indicators include acid fast bacilli smear results, diagnostic imaging, and patient symptoms. The severity of MDR TB disease is also determined by the resistance profile of the bacteria. When the bacteria are resistant to many drugs, fewer treatment options are available, making the disease more difficult to treat. TB bacteria which are considered extremely drug resistant TB are resistant to more medications than MDR TB; extremely drug resistant TB is the category of drug resistant TB most difficult to treat.

WHO: Types of Drug Resistant TB

Complications related to MDR TB are often caused by treatment rather than disease. Complications occur because the safest and most effective anti-TB antibiotics cannot be used and more toxic, less effective medications must be used instead. Patients taking MDR treatment often need support to manage the cumulative medication-related side effects. These often include cardiovascular problems, muscle and tendon pain, peripheral neuropathy, nausea, depression, psychosis, and hearing loss.

Many patients are not able to complete a full course of MDR TB treatment and as a result, they are at increased risk of disease recurrence. Best global estimates indicate that 60% of those starting MDR TB treatment complete a full course, compared to 86% of those who start treatment for active TB disease. [2]

Infectiousness of MDR TB

The infectiousness of a person with TB is determined by the site and burden of disease, and stage of treatment. This is also true for people with MDR TB because the resistance profile of the bacteria is not thought to influence infectiousness.

Centers for Disease Control and Prevention: Multidrug Resistant Tuberculosis Fact Sheet

Nevertheless, isolation requirements for people with MDR TB are often more extensive compared to those with drug susceptible TB. People with MDR TB are often asked to follow more rigorous isolation precautions (e.g., isolation in hospital as opposed to at home) because of the serious consequences for others who may become infected with MDR TB.  People with MDR TB can also be isolated for longer periods because of difficulties obtaining the medications required to help them become non-infectious.


MDR TB diagnosis disease follows the diagnosis of active TB. Active TB diagnoses are based on positive findings from lab tests (e.g., acid fast bacilli smear and culture sample from the affected site), diagnostic imaging (e.g., chest x-ray and computed tomography scans), patient history, and symptoms. Lab cultures are critical in the diagnosis of active TB because the cultured bacteria (i.e., TB isolate) can be tested for drug susceptibility (DST) and these results are used to guide treatment. In Canada it is recommended that all TB isolates undergo DST. However, implementation of this recommendation may vary from province to province.

MDR TB is diagnosed when DST results demonstrate resistance to isoniazid, rifampin, and possibly other antibiotics.

Although other tests (e.g., whole genome sequencing) show promising results, there is currently no substitute for DST which takes several weeks to complete. Long waits for DST results often cause delays in the initiation of effective treatment for MDR TB patients.

Two molecular tests have been approved by the WHO and Health Canada to rapidly predict drug resistance and provide information while waiting for DST results. The Geno Type MTBDR plus line probe assay and the Gene Xpert nucleic acid amplification test may be requested by ordering physicians; however, the availability of these tests varies from province to province across Canada.

Public Health Agency of Canada: Tuberculosis for Health Professionals:

Canadian TB Standards 8th Edition: Chapter 3: Diagnosis of tuberculosis disease and drug-resistant tuberculosis disease


The same strategies used to prevent drug susceptible TB are effective to prevent MDR TB. These strategies include rapid diagnosis of patients with TB disease and effective airborne isolation of infectious patients.

Additionally, many stakeholders in TB care have an important role to play in preventing MDR TB. Practitioners can minimize the need for re-treatment by making every effort to obtain a culture-based diagnosis, avoiding the use of TB drugs for non-TB purposes, and treating TB according to current standards. Provincial and Territorial health systems can build TB lab capacity to make DST and rapid molecular testing accessible to practitioners. TB programs can carefully monitor their medication supply, work with partners to reduce barriers, and increase supports to completing TB treatment. Targeted supports may reduce the impact of structural barriers which affect patients and their families and could include accessible hours and locations for medication dispensing, translated patient education materials, and income support programs. 

WHO: Tuberculosis: Multidrug Resistant Tuberculosis

Public Health Agency of Canada: Tuberculosis for Health Professionals

Centers for Disease Control and Prevention: Multidrug Resistant Tuberculosis Fact Sheet

Centers for Disease Control and Prevention: Drug Resistant TB


Bacillus Calmette–Guérin (BCG) vaccine is used to prevent serious illness and death in young children exposed to TB. However, BCG vaccine does not prevent adults from developing TB (including MDR TB) and potentially spreading bacteria to others. The availability of BCG vaccine varies among different regions in Canada.

Centers for Disease Control and Prevention: Multidrug Resistant Tuberculosis Fact Sheet


Physicians should screen all patients with active TB for MDR TB risk factors before starting treatment. Important risk factors for MDR TB include history of previous TB treatment, history of residence or travel to a country with high rates of MDR TB, and significant exposure to a person with infectious MDR TB. If MDR TB is likely, the patient should be initiated on MDR TB treatment rather than standard treatment [3] while waiting for the results of rapid molecular or traditional drug susceptibility testing.

Authors of the most recent WHO MDR treatment guidelines endorse a standardized and individualized treatment regimen that practitioners may select based on program and patient circumstances. In the first regimen, standardized drugs are used and treatment is 9-12 months in duration. In the second regimen, the selection of drugs is based on patients’ susceptibility profile and treatment typically lasts 18- 20 months.

The authors of the most recent Canadian TB Standards on MDR TB treatment recommend the individualized regimen based on the results of meta-analyses demonstrating improved patient outcomes with individualized treatment and good access to DST in Canada.  According to Canadian recommendations, baseline MDR TB treatment should consist of a floroquinolone, bedaquiline, linezolid, clofazimine, and cycloserine, and then be tailored to patients’ tolerance and drug susceptibility profile. Several medications used to treat MDR TB must be requested through Health Canada’s Special Access Program.

Patients on MDR TB treatment should be monitored closely for both improvement and medication side effects. Imaging and acid fast bacilli culture conversion can be used to monitor for improvement. If there is no improvement, drug susceptibility testing should be repeated. Monitoring for the cumulative toxicity of 5 or more antibiotics is critical. General practitioners may wish to consult available TB and/or public health experts for support when managing a patient with MDR TB.

Canadian Tuberculosis Standards (8th Ed): Chapter 8: Drug resistant tuberculosis

WHO Consolidated Guidelines on drug resistant tuberculosis treatment

American Thoracic Society: Treatment of Drug-Resistant Tuberculosis: An Official ATS/CDC/ERS/IDSA Clinical Practice Guidelines

What is the current state of MDR TB globally?

According to the WHO, the global MDR TB burden is currently stable at 3.6% of people newly diagnosed with TB, and 18% of those requiring re-treatment.[4] However, there is cause for concern. The WHO set a target for 1.5 million people to be enrolled in MDR TB treatment between 2018 and 2022 as part of the END TB Strategy. Unfortunately, only 649 000 people have been enrolled on MDR TB treatment since 2018.[5] Thus, it is likely that many people who need MDR TB treatment are not receiving it and may be capable of spreading this serious infection to others.

The shortfall in global MDR TB treatment enrollments is, in part, related to the COVID-19 pandemic. The COVID-19 pandemic has resulted in considerable setbacks in the overall effort to eliminate TB. There are many reasons that these occurred but the large-scale diversion of resources away from TB care and toward the COVID-19 response and reduced health seeking behaviour on the part of patients were important factors. 

The burden of MDR TB is much greater in some countries compared to others. The WHO maintains a list of 30 countries with a high burden of MDR/Rifampin resistant TB. This list is comprised of both countries with a high MDR/Rifampin resistant TB incidence rate, and countries with a lower incidence rate, but a large absolute number of patients with MDR/Rifampin resistant TB. Countries in Eastern Europe (i.e., Russia, Ukraine, Kazakhstan) have the highest rates, with MDR/Rifampin resistant TB being diagnosed in approximately one third of new cases. However, countries in Asia (e.g., India, Pakistan, Philippines) and Africa (e.g., Nigeria, South Africa, Somalia) are also on the list of high burden countries.   

WHO Multidrug Resistant Tuberculosis Overview

WHO Surveillance of Drug Resistant TB

WHO Global List of High Burden Countries

WHO Global TB Report (2022)

What is the current risk to Canadians from MDR TB?

Canada has a low burden of MDR TB; in 2018, 21 (1.4%) of the 1475 TB isolates tested for drug resistance in Canada were categorized as multidrug resistant.

Public Health Agency of Canada: Tuberculosis drug resistance in Canada: 2018

However, rates of MDR TB in Canada may increase with increased migration from high MDR TB burden countries affected by conflict, famine, and natural disaster. Regions in Canada with traditionally low rates of TB could experience increases in TB and MDR TB associated with immigration. Practitioners in such regions should maintain vigilance by promptly assessing patients with TB symptoms using chest x-ray and sputum testing to prevent secondary spread.

What should be done when a patient may be sick with MDR TB?

Practitioners must first determine the likelihood that a patient’s symptoms are related to active TB and take steps to diagnose TB [6]. When TB is likely, practitioners should inquire about MDR TB risk factors (i.e., previous TB treatment, residence or travel to a high MDR burden country, or significant exposure to a person with infectious MDR TB). Practitioners who believe MDR TB is likely should contact local or provincial TB experts and/or public health officials for guidance on the safe isolation of the patient.

Patients with confirmed or possible MDR TB may be isolated at home or in the hospital. Isolation in hospital may be required if there are others in the home who are at high risk of progressing to active TB (e.g., young children or those with immune suppressive conditions). Regardless of where it occurs, isolation comes at a significant cost to patients and family members. The Canadian Tuberculosis Standards recommends that public health officials and practitioners must take steps to ensure that patients are de-isolated as soon as it is safe, and the patient and family members’ physical and psychosocial needs are met during the often-lengthy isolation period.

Practitioners who believe a patient may have infectious TB should inquire if the patient has any close contacts with pulmonary symptoms so others who may be infectious can be diagnosed and treated without delay.

Public Health Agency of Canada: Tuberculosis for Health Professionals

Canadian TB Standards 8th Edition: Chapter 3: Diagnosis of tuberculosis disease and drug-resistant tuberculosis disease

Canadian Tuberculosis Standards (8th Ed): Appendix B: De-isolation review and recommendations

[1] The WHO defines catastrophic costs as 20% of household income which is lost as result of treatment or the ability to generate income. Retrieved Nov 14, 2022 from:

[2] World Health Organization. (2022). Global Tuberculosis Report 2022.  Retrieved Nov 8, 2022, from:

[3] The medications used for drug susceptible TB treatment include rifampin, isoniazid, ethambutol, and pyrazinamide.

[4] World Health Organization. (2022). Global Tuberculosis Report 2022.  Retrieved Nov 8, 2022, from:

[5] World Health Organization. (2022). Global Tuberculosis Report 2022.  Retrieved Nov 8, 2022, from:

[6] Assessment for active TB should include a detailed history of present symptoms, previous TB exposures and treatments, countries of residence and travel, and underlying comorbidities. Verbal assessment could then be followed by imaging of affected site and testing samples for acid fast bacilli smear and culture.