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Safety & Wellness

First-Line Drug Resistance in Tuberculosis

November 06, 2023

Tuberculosis is a lung infection caused by Mycobacterium tuberculosis (MTB). Although it mainly affects the lungs, it can also affect other body organs, such as the brain, joints, bones, etc. It is very contagious and can be transmitted to others by inhaling droplets from an infected person. Tuberculosis (TB) can be treated by using first-line anti-tubercular drugs. These are known to be the most effective and least toxic drugs. However, a few times bacteria develop resistance to these drugs which is termed first-line 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.



The first-line anti-tubercular drugs are known to be most effective towards Mycobacterium tuberculosis bacteria and are usually less toxic when compared to other anti-tubercular treatments.

The first-line anti-tubercular drugs include:

• Isoniazid

• Rifampicin

• Pyrazinamide

• Streptomycin

• Ethambutol



Isoniazid is a hydrazide of isonicotinic acid which is highly bactericidal against replicating tuberculosis bacteria. It is normally taken orally but may also be administered through intramuscular (into the muscle) or intravenous (in a vein) route to a critically ill patient.


Side effects: Sleepiness, anaemia, joint pains, rashes, etc.



Rifampicin is a semi-synthetic derivative of rifamycin. It serves as a complex macro-lytic antibiotic that inhibits a broad range of microbial pathogens. It has bactericidal and potent sterilizing effects against Mycobacterium tuberculosis in both cellular and extracellular locations. It is administered orally.


Side effects: Abdominal pain, nausea, vomiting, etc., pruritis (itchy skin) – with or without rash. 



It is weakly bactericidal in nature but possesses strong sterilizing effects against Mycobacterium tuberculosis, particularly in the acidic environment of macrophages and in areas of acute inflammation. It is highly effective and is recommended during the first two months of the treatment. It has enabled shorter treatment regimen plans alongside reducing the risk of relapse. It is given orally.


Side effects: Gastrointestinal intolerance, flushing of skin, anemia, photosensitive dermatitis, etc.



Streptomycin, an antibiotic derived from Streptomyces griseus, is used effectively in tuberculosis treatment and in sensitive gram-negative infections. It is usually administered by deep intramuscular injections since it cannot be absorbed through the gastrointestinal route. 


Side effects:

Numbness and tingling around the mouth, pain at the injection site with rash or sterile abscess, skin hypersensitivity reactions, etc.



Ethambutol is active against different bacteria of the Mycobacterium genus such as Mycobacterium tuberculosis, Mycobacterium bovis, etc., along with some other nonspecific Mycobacterium.  It is used in addition to other antitubercular drugs to prevent or delay the emergence of resistant strains. It is given orally.


Side effects

Headache, blurred vision, and pain in one or both eyes. Other rare adverse reactions include hepatitis (inflammation of the liver), skin lesions, etc.



Antitubercular drugs are often effective against Mycobacterium tuberculosis bacteria. However, a few times the bacteria may develop spontaneous gene mutations that may render bacterial resistance to the most commonly used antitubercular drugs, i.e., first-line antitubercular drugs. 



A few reasons that may cause drug resistance include:

• Non-compliant nature of the individual taking antitubercular drugs

• Wrong medication prescribed by the healthcare provider

• Drugs of poor quality

• Unavailability of drugs for proper treatment

• Taking antitubercular medications irregularly

• Not completing the full course of medications prescribed

• Abruptly stopping the medications without the doctor’s advice


Despite all the advancements made in the treatment and management of tuberculosis, it still remains one of the main public health concerns worldwide. It is due to the resistance that the bacteria develop over time due to the challenges posed by Mycobacterium tuberculosis infection. It may be through its interaction with the individual’s immune system or its mechanism of evasion that it may require many more breakthroughs to make a significant impact on the worldwide tuberculosis problem. GeneXpert MTB/RIF is a new revolutionary tuberculosis test that can help with both TB diagnosis and its associated drug resistance, allowing healthcare professionals to plan treatment regimens for such individuals.

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