- Delayed diagnosis and treatment of infectious MDRTB patients
- Higher population density or more respiratory contacts
- Circulation of particularly transmissible MDR strains
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Wulandari, D.A., Hartati, Y.W., Ibrahim, A.U. and Pitaloka, D.A.E., 2024. Multidrug-resistant tuberculosis. Clinica Chimica Acta, 559, p.119701.
- Multidrug-resistant tuberculosis (MDR-TB) is defined by resistance to at least rifampicin (RIF) and isoniazid (INH).
- MDR-TB arises from inadequate treatment practices, such as incomplete treatment, insufficient drug doses and durations, poor drug quality, and transmission from individuals with drug-resistant TB.
- Resistance in MTB (Mycobacterium tuberculosis) results from spontaneous chromosomal mutations. There are ten gene variants linked to resistance against first-line anti-TB medications, including katG, inhA, ahpC, kasA, and Ndh for INH, and rpoB for RIF.
- Drug resistance occurs primarily through two mechanisms: primary resistance from exposure to a resistant MTB strain and secondary resistance due to poor treatment adherence.
Classification of Drug-Resistant TB
- Mono-resistant TB: Resistant to one first-line anti-TB drug only.
- Isoniazid-resistant TB: Resistant to Isoniazid, but susceptible to Rifampicin.
- Poly-resistant TB: Resistant to more than one first-line anti-TB drug, excluding both Isoniazid and Rifampicin.
- Rifampicin-resistant TB (RR): Resistance to rifampicin detected using phenotypic or genotypic methods, with or without resistance to other anti-TB drugs. Includes mono-resistance, poly-resistance, MDR, or XDR.
- Multidrug-resistant TB (MDR-TB): Resistant to at least both Isoniazid and Rifampicin.
- Pre-extensively drug-resistant TB: Resistant to Rifampicin, Isoniazid, and either Fluoroquinolones or one injectable drug (Amikacin or Kanamycin).
- Extensively drug-resistant TB (XDR-TB): Resistance to any fluoroquinolone, and at least one of three second-line injectable drugs (capreomycin, kanamycin, or amikacin), in addition to being multidrug-resistant.
Rifampicin:
- A lipophilic antibiotic that inhibits RNA synthesis by binding to the β-subunit of DNA-dependent RNA polymerase, blocking RNA transcription.
- Common side effects include hepatotoxicity, immunological allergies, skin syndromes, gastrointestinal issues, influenza-like symptoms, hemolytic anaemia, shock, and acute renal failure.
Isoniazid:
- Requires activation by the mycobacterial enzyme katG to inhibit mycolic acid synthesis essential for the mycobacterial cell wall.
- Side effects include peripheral neuropathy, seizures from overdose, lupus erythematosus, rheumatoid-like syndrome, and various hematological disorders.
Ethambutol:
- Inhibits mycobacterial arabinosyltransferase, crucial for bacterial cell wall biosynthesis.
- It mimics arabinofuranosyl, disrupting the cell wall synthesis process and causing bacterial aggregation and morphological changes.
Pyrazinamide:
- A prodrug activated in acidic conditions to pyrazinoic acid, which inhibits fatty acid synthesis in MTB.
MDR-TB Detection:
- Phenotypic testing: Culture-based method using solid (Lowenstein Jensen) or liquid media (mycobacterium growth indicator tube, MGIT), taking 2-3 months for results.
- Genotypic testing: Faster molecular tests identify mutations causing drug resistance, including probe-based assays and sequence-based assays.
- The GeneXpert test, a NAAT, detects TB and RIF resistance in about 2 hours using real-time PCR with molecular beacons.
- Despite advancements, culture-based methods remain the gold standard for their high identification sensitivity.
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