Tuberculosis is a bacterial lung infection caused by Mycobacterium tuberculosis (MTB). It can be fatal if not treated on time. It primarily affects the lungs but can also affect other body organs such as the brain, bones, etc. It is very contagious and can be transmitted to others by inhaling droplets from an infected person. It is treated using antitubercular drugs. However, a few times bacteria can develop resistance to these drugs, thereby slowing or stopping the treatment efficacy in individuals.

SIGNS & SYMPTOMS OF TUBERCULOSIS

Individuals with active TB show the following symptoms:

• Persistent cough

• Coughing up blood

• Weight loss

• Pain in the chest

• Fatigue or weakness

• Loss of appetite

• Fever

• Chills

• Night sweats

TYPES OF DRUG-RESISTANCE IN TUBERCULOSIS

Mono-resistance – It refers to resistance to only one first-line antitubercular drug.

Poly-resistance – It refers to resistance to more than one first-line antitubercular drug, except for isoniazid and rifampicin.

Multidrug-resistance (MDR) – It refers to resistance to both isoniazid and rifampicin drugs of first-line antitubercular drugs. 

Extensive drug resistance (XDR) – In addition to multidrug resistance, it includes resistance to at least one of the three second-line antitubercular injectable drugs.

Rifampicin resistance (RR) – It refers to resistance towards rifampicin with or without resistance to other anti-tubercular drugs. It includes resistance to rifampicin in any form of mono-resistance, poly-resistance, MDR, or XDR.

RISK FACTORS FOR XDR-TB (Extensively Drug-Resistant Tuberculosis):

• Failure to respond to first-line antitubercular drugs.

• Relapse after a full course of treatment with first-line antitubercular drugs.

• Long exposure to a known case of MDR-TB.

• Living in places with a high prevalence of MDR-TB.

• HIV co-infection.

SECOND-LINE ANTITUBERCULAR DRUGS:

The XDR-TB treatment is comparatively difficult as the second-line drugs are mostly weak and toxic at the same time. Because of the weak sterilizing activity of second-line antitubercular drugs, it takes longer to achieve the outcomes of the treatment. 

Based on their efficacy, safety, experience of use, and drug class, the second-line antitubercular drugs are further classified into the following five groups:

GROUP-1 

Fluoroquinolones are drugs that serve as broad-spectrum antibiotics against a wide range of bacterial infections of the respiratory, gastrointestinal, urinary tract, and sexually transmitted diseases. These have excellent antimicrobial activity against Mycobacterium tuberculosis. These are currently used in the treatment of tuberculosis in individuals who are drug-resistant to first-line antitubercular agents.

Side effects: Gastrointestinal intolerance, rashes, dizziness, and headache.  

GROUP 2

These include drugs such as Linezolid, delamanid, and bedaquiline. These are antibacterial, antifungal and anti-mycobacterial in function. These work either by inhibiting ATP synthesis or by interfering with bacterial protein synthesis. 

per week

Side effects: Gastrointestinal distress (nausea, vomiting, abdominal pain, loss of appetite), joint pain, headache, etc.

GROUP 3 

These include drugs such as amikacin, kanamycin, and capreomycin. These are injectable forms of antitubercular drugs given in the treatment of multidrug-resistant tuberculosis. These work by interfering with the protein translation of Mycobacterium tuberculosis.

Side effects: Hearing loss, nephrotoxicity, electrolyte abnormalities, pain and local injection site complications, etc.

GROUP 4

These include drugs such as clofazimine, ethionamide, and carbapenems. These affect by either causing bactericidal or bacteriostatic effects depending upon the susceptibility and concentrations attained at the infection site. 

Side effects: Diarrhoea, nausea, vomiting, discolouration of skin, conjunctiva, cornea, and body fluids, dry skin, etc.

GROUP 5

These include drugs such as cycloserine, para-aminosalicylic acid, and amoxicillin/clavulanate. These are bacteriostatic in nature and work by interfering with the cell wall synthesis of the tuberculosis bacterium. 

Side effects: Gastrointestinal distress such as nausea, vomiting, diarrhoea, hypothyroidism (rare), hepatitis, neurologic and psychiatric disturbances, sleep disturbances, etc.

RESISTANCE TO ANTI-TUBERCULAR DRUGS:

Antitubercular drugs are often effective against Mycobacterium tuberculosis bacteria. However, a few times the bacteria may develop spontaneous gene alterations that may render bacterial resistance to antitubercular drugs.

REASONS TO DEVELOP RESISTANCE AGAINST DRUGS:

A few reasons that may cause drug resistance may include:

• Non-compliant nature of the individual taking antitubercular drugs.

• Taking antitubercular medications irregularly.

• Not completing the full course of medications prescribed.

• Abruptly stopping the medications without the doctor’s advice.

• Wrong medication prescribed by the healthcare provider.

• Drugs of poor quality.

• Unavailability of drugs for proper treatment.

The treatment of resistant tuberculosis (resistance to first-line antitubercular drugs) involves the use of second-line antitubercular drugs. Individuals who live in areas with a high prevalence of drug-resistant tuberculosis (MDR-TB) or who are exposed to MDR-TB can develop XDR-TB. Several second-line drugs from various categories function in different ways to overcome bacterial resistance. However, because these treatment alternatives are often weak and toxic when compared to other classes of antitubercular drugs, medication adherence by affected individuals may become difficult.

Xpert MTB/XDR is a rapid nucleic acid amplification test for tuberculosis and drug resistance detection that can be used in lower-level and intermediate laboratories.