Multidrug-resistant tuberculosis

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.

 

Comments

Post a Comment

Popular posts from this blog

Nutritional status in patients with TB and DM

Patel, D.G., Baral, T., Kurian, S.J., Malakapogu, P., Saravu, K. and Miraj, S.S., 2024. Nutritional status in patients with tuberculosis and diabetes mellitus: A comparative observational study.  Journal of Clinical Tuberculosis and Other Mycobacterial Diseases ,  35 , p.100428. Cardiovascular disease prevalence was highest in the DM group, followed by the TB-DM group. Anaemia was more prevalent in the TB-DM group. Smoking and alcohol use were most common in the TB group, followed by the TB-DM group. See also: TB and kidney function impairment In the TB-DM group, HbA1c levels indicated poor diabetic control (10.47%), higher than in the DM group (8.17%). FBS was also above normal in the TB-DM group, followed by the DM group. Although there were no significant differences in nutritional parameters like albumin, globulin, and total proteins, vitamin B12 levels were highest in the TB-DM group. Notably, 95.83% of patients in the TB-DM group had HbA1c > 6.5, with similarly high FBS and RB
Read more

Scientific advances and the end of tuberculosis

Reid, M., Agbassi, Y.J.P., Arinaminpathy, N., Bercasio, A., Bhargava, A., Bhargava, M., Bloom, A., Cattamanchi, A., Chaisson, R., Chin, D. and Churchyard, G., 2023. Scientific advances and the end of tuberculosis: a report from the Lancet Commission on Tuberculosis.  The Lancet ,  402 (10411), pp.1473-1498. Progress toward ending tuberculosis varies greatly across countries, with some achieving substantial improvements and others making minimal progress. Key challenges include frail health systems, underinvestment, and reliance on one-size-fits-all approaches. Insufficient case finding and diagnosis remain the most significant issues in high-burden countries, where only 38% of all tuberculosis cases were tested with WHO-recommended rapid molecular diagnostics in 2021. Two-thirds of tuberculosis deaths occurred in just eight countries, with over half of these in India, Indonesia, and Nigeria. Despite these challenges, some sub-Saharan African countries have seen improvements in tubercul
Read more

Impact of diabetes on tuberculosis and MDRTB susceptibility

There is a significant association between diabetes mellitus (DM) and multidrug-resistant tuberculosis (MDR-TB). TB patients without DM have a lower risk of developing MDR-TB compared to those with DM. Factors contributing to MDR-TB emergence in TB patients with DM include: Impaired immune function Altered microbial genomics Uncontrolled glucose levels, increasing susceptibility to MDR-TB Compromised phagocytic activity and reduced chemotactic response Increased oxidative species and microbe proliferation Altered drug disposition Higher likelihood of non-adherence to treatment TB patients with DM also experience higher treatment failure rates compared to those without DM. Most information on these associations is based on self-reported data or patient health records, which may introduce assessment errors Rehman Au, Khattak M, Mushtaq U, Latif M, Ahmad I, Rasool MF, Shakeel S, Hayat K, Hussain R, Alhazmi GA, Alshomrani AO, Alalawi MI, Alghamdi S, Imam MT, Almarzoky Abuhussain SS, Khayya
Read more