What is drug-resistant tuberculosis?

There are different types of drug-resistant TB.
There are different types of drug-resistant TB.

Usually, anti-tuberculosis (anti-TB) drugs have been divided into 

Most people with TB are cured by following a strict six-month, four-standard anti-TB drug regimen. However, sometimes the bacteria that cause TB, namely Mycobacterium tuberculosis, becomes more resistant to treatment and due to mismanagement leads to misuse of anti-TB drugs and reduced patient  immunity. Further, when anti-TB drugs that are used to cure the disease fail to eradicate microbial activity, it is known as drug-resistant TB. 

Types of drug-resistant TB are as follows

  • Monoresistance: This is when one of the first-line anti-TB drugs fails to work against TB infection.
  • Polydrug resistance: This is when more than one first-line anti-TB drugs (except both isoniazid and rifampicin) fail to work against TB infection.
  • Multidrug resistance (MDR): This is when both isoniazid and rifampicin fail to work against TB infection.
  • Extensive drug resistance (XDR): Extensively drug-resistant TB (XDR-TB) is a form of TB that is resistant to at least four of the core anti-TB drugs. XDR-TB involves resistance to the two most powerful anti-TB drugs, namely isoniazid and rifampicin. This is also known as multidrug-resistant TB (MDR-TB). MDR-TB also involves resistance to any of the fluoroquinolones (such as levofloxacin and moxifloxacin) and to at least one of the three injectable second-line drugs (amikacin, capreomycin or kanamycin).
  • Rifampicin resistance (RR): This is when rifampicin, alone or with other drugs (whether with mono-resistance, MDR, polydrug resistance or XDR), fails to work against TB infection.

What is multidrug-resistant TB (MDR-TB)?

In multidrug-resistant tuberculosis (MDR-TB), certain strains of TB bacteria fail to respond to first-line drugs, which include two of the most powerful anti-TB drugs (isoniazid and rifampicin).

Your risk of MDR-TB is higher if you

  • Have first-line drugs and they fail to work against TB infection.
  • Have an infection that relapses even after completing a full course of a first-line regimen.
  • Are exposed to a person infected with MDR-TB.
  • Are exposed to a high prevalence of MDR-TB areas, such as a prison, hospital or a particular country.
  • Got treatment after treatment default (treatment interruption for at least two consecutive months) with a first-line regimen.
  • Have human immunodeficiency virus (HIV) infection. 

What is extensively drug-resistant TB (XDR-TB)?

Extensively drug-resistant tuberculosis (XDR-TB) is a rare type of multidrug-resistant tuberculosis (MDR-TB) in which several of the most effective (at least four) and core anti-TB drugs fail to work against microbial activity. These drugs include 

  • Isoniazid
  • Rifampicin
  • Levofloxacin or moxifloxacin
  • At least one injectable second-line drug (amikacin, capreomycin or kanamycin)

What is the difference between multidrug-resistant TB and extensively drug-resistant TB?

  • Multidrug-resistant tuberculosis (MDR-TB) is a type (strain) of TB bacteria that cannot be treated with the two most powerful first-line anti-TB drugs (isoniazid and rifampicin). Extensively drug-resistant tuberculosis (XDR-TB) is a form of MDR-TB infection where several of the most effective anti-TB drugs (levofloxacin or moxifloxacin and at least one of three second-line drugs such as capreomycin, kanamycin and amikacin, in addition to isoniazid and rifampicin) fail to work. 
  • Prevalence: According to the 2013 World Health Organization (WHO) report, about 9.6 percent of people with MDR-TB worldwide fo on to develop XDR-TB. The global cure rate for XDR-TB is much lower at 20 percent and it is associated with a 44 percent death rate.
  • Diagnosis: Poor access to second-line drug susceptibility testing (DST) in many parts of the world leads to undiagnosed XDR-TB. All patients who are diagnosed with MDR-TB should be tested for XDR-TB. DST (culture or molecular method) is necessary for early diagnosis and treatment of MDR-TB or XDR-TB. The molecular methods (Xpert test) have now revolutionized the diagnosis of MDR-TB involving testing for resistance to three second-line injectable drugs (kanamycin, amikacin and capreomycin) and at least one from the group of ciprofloxacin, levofloxacin and moxifloxacin. This technique can provide results within hours.
  • Treatment: Both MDR-TB and XDR-TB infections take substantially longer time to treat than ordinary TB infection, which responds well to drugs. 

Are MDR-TB and XDR-TB curable?

Multidrug-resistant tuberculosis (MDR-TB) is practically incurable by standard first-line treatment. However, extensively drug-resistant tuberculosis (XDR-TB) is resistant to both first- and second-line drugs due to drug misuse and mismanagement. Therefore, XDR-TB treatment becomes even harder. It is therefore very important to manage and control TB infection properly at the initial stage itself.

MDR-TB takes longer than an ordinary TB infection and is difficult to treat because treatment options are limited. Early and accurate diagnosis is very important for effective treatment of MDR-TB. Effective treatment includes a selection of perfect second-line drugs that are available to a doctor who is an expert in treating such cases. 

MDR-TB treatment with second-line drugs is more expensive, weaker and is  associated with more side effects than first-line drugs, which are used for ordinary drug-responsive TB. Many times, the recommended medicines are not available. Most of these second-line drugs were developed years ago, but they are hardly ever used because they are associated with side effects. 

Microbial-killing activity of second-line TB drugs is very weak. Therefore, MDR-TB generally takes 18 to 24 months to be cured completely. The cure rate for MDR-TB is much lower globally. Sometimes, even more severe drug non-responsive (resistant) TB infection may develop. Coinfections such as human immunodeficiency virus (HIV) may increase death rates in patients with MDR-TB. 

XDR-TB treatment options are very seriously limited and patients may respond to even fewer available other medicines. Patients with XDR-TB can still be cured, but with the currently available drugs, the possibility of complete cure becomes lower than in those with ordinary TB or even MDR-TB. Cure of XDR-TB infection depends on the extent of drug responsiveness, disease severity and a person’s immunity. XDR-TB is a highly drug-resistant strain that has significantly worse outcomes and can even be deadly.

Although MDR and XDR-TB infection treatments are very challenging and difficult, a cure is often possible with early identification and proper drug management. Proper infection control measures also require prevention of bacterial spread. Your healthcare professional will support the patient in addressing obstacles in adherence to TB treatment.

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Medically Reviewed on 11/18/2020
References
Medscape Medical Reference

WHO




CDC




Cold Spring Harbor Perspectives in Medicine