Drug-Resistant Tuberculosis
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Direct answer
Drug-resistant tuberculosis is infection with Mycobacterium tuberculosis strains resistant to one or more first-line drugs. Multidrug-resistant tuberculosis means resistance to at least isoniazid and rifampicin, the two most important first-line drugs, while extensive resistance adds fluoroquinolone and second-line injectable resistance. Treatment now favours short all-oral regimens such as BPaLM, chosen according to the susceptibility profile.
What you must remember
- MDR-TB: resistance to at least isoniazid and rifampicin, the two most potent first-line drugs.
- XDR-TB, older definition: MDR-TB with resistance to any fluoroquinolone and to at least one second-line injectable such as amikacin, kanamycin or capreomycin.
- XDR-TB, newer framework: MDR-TB with fluoroquinolone resistance plus resistance to bedaquiline or linezolid.
- Key genes: rpoB for rifampicin, katG and inhA for isoniazid, embB for ethambutol, pncA for pyrazinamide, gyrA for fluoroquinolones and rrs for injectables.
- Acquisition: resistance mainly arises from selection during incomplete, monotherapy or poorly supervised treatment, although some strains are transmitted with resistance already present.
- BPaLM regimen: bedaquiline, pretomanid, linezolid and moxifloxacin given for six months as an all-oral regimen for eligible patients.
- Linezolid toxicity: myelosuppression, peripheral and optic neuropathy and lactic acidosis limit its prolonged use.
A pathway from resistance detection to a safe regimen
A patient treated previously for tuberculosis has positive sputum at two months and a rifampicin-resistant result on CBNAAT. The steps follow the pathway from detecting resistance to choosing a regimen that is safe to give.
- Confirm the resistance pattern: rifampicin resistance on CBNAAT triggers the drug-resistant pathway, and line probe assay or phenotypic testing confirms isoniazid and fluoroquinolone resistance.
- Classify the pattern: isoniazid plus rifampicin resistance defines MDR, and further resistance defines pre-XDR or XDR, using the older injectable-based or newer fluoroquinolone and bedaquiline or linezolid-based framework.
- Review the history: prior treatment, interrupted regimens and contact with known resistant cases raise the likelihood of acquired resistance.
- Select the regimen: BPaLM is considered for eligible patients with MDR/RR-TB (BPaL if fluoroquinolone resistance is confirmed), and otherwise an individualised regimen is built from second-line drugs guided by susceptibility.
- Monitor toxicity: linezolid is watched for myelosuppression, neuropathy and visual symptoms, bedaquiline is checked for QT prolongation, and liver function is tested regularly.
- Support adherence: directly observed therapy and nutritional and psychosocial support are provided, because interrupted treatment drives further resistance.
Where the exam tries to catch you
Drug-resistant tuberculosis questions often hinge on which definition the question uses and which drugs remain usable.
- Trap: treating MDR-TB with first-line drugs alone Correct: isoniazid and rifampicin are already ineffective, so the regimen needs second-line drugs such as fluoroquinolones, bedaquiline or linezolid.
- Trap: applying one XDR definition to every question Correct: older definitions use second-line injectables, while newer frameworks use bedaquiline or linezolid resistance, so check which framework the question names.
- Trap: assuming resistant strains spread far more easily Correct: they do not spread much more readily than susceptible strains, and resistance mainly arises from incomplete or poorly supervised treatment.
Frequently asked questions
What is the definition of multidrug-resistant tuberculosis?
Multidrug-resistant tuberculosis is defined as resistance to at least isoniazid and rifampicin, the two most effective first-line drugs. Rifampicin resistance alone is often used to trigger drug-resistant treatment pathways in national programmes.
What is the older definition of extensively drug-resistant tuberculosis?
Under the older definition, extensively drug-resistant tuberculosis is MDR-TB with resistance to any fluoroquinolone and to at least one second-line injectable such as amikacin, kanamycin or capreomycin. Newer frameworks instead use resistance to bedaquiline or linezolid in the definition.
Which gene mutation is most often linked to rifampicin resistance?
Mutations in the rpoB gene, which encodes the beta subunit of RNA polymerase, are the main cause of rifampicin resistance in Mycobacterium tuberculosis. This is the mutation that CBNAAT detects for rapid screening of rifampicin resistance.
What is the BPaLM regimen used for in drug-resistant tuberculosis?
The BPaLM regimen combines bedaquiline, pretomanid, linezolid and moxifloxacin, given for six months as an all-oral regimen for eligible patients with MDR-TB. Fluoroquinolone susceptibility is checked before starting, because moxifloxacin is dropped (BPaL) when the isolate is fluoroquinolone resistant, and linezolid toxicity is monitored throughout.
Why does linezolid need monitoring in drug-resistant tuberculosis?
Linezolid can cause myelosuppression, peripheral and optic neuropathy, and lactic acidosis during prolonged use. Regular blood counts and visual and neurological checks are therefore needed when linezolid forms part of a drug-resistant tuberculosis regimen.