From Tuberculosis Wiki

Treatment of tuberculosis (TB) varies depending on factors including level of drug resistance, HIV status, and the patient's age and weight. Treatment regimes are mostly drug-based, but some regimes include surgery.

Drug-susceptible TB[edit | edit source]

Drug susceptible TB importantly means that all 4 first-line medications are susceptible, but particularly, that both isoniazid and rifampin are effective at treating that strain of disease. Typically, regimens for uncomplicated pulmonary TB is treated for 6 months, which consists of a 2-month intensive phase of 3-4 drugs (rifampin, isoniazid, pyrazinamide and/or ethambutol), followed by 4 months of dual therapy (isoniazid and rifampin).[1] There are a number of complicating factors that can lead to prolongation of TB therapy up to 12 months, including TB meningitis and drug resistance. Drug susceptibility testing should be done shortly after diagnosis for all patients with TB disease. Resistance to isoniazid alone leads to a small modification in regimen (ie. adding a fluoroquinolone such as levofloxacin or moxifloxacin) while resistance to rifampin can be more complex. Rapid molecular testing is recommended as part of evaluation and testing of the treatment regimen.[2]

In recent years, there has been some research done to better understand whether shorter treatment durations are safe and effective, as well as whether higher doses of rifampin in particular can be adequately tolerated. However, the 6-month regimen described above remains the mainstay of treatment worldwide. Work has been done internationally to ensure that fixed-dose combination tablets (ie. multiple drugs in one tablet) are available in low- and middle-income countries with a high burden of TB disease.

Multidrug-resistant TB[edit | edit source]

Multidrug-resistant tuberculosis (MDR-TB) is both more complicated and more expensive to diagnose and treat than drug-susceptible TB. There are three types of drug resistant TB.[2]

  • Multidrug-resistant TB (MDR-TB) is caused by TB bacteria that are resistant to at least isoniazid and rifampin
  • Pre-Extensively drug-resistant TB (pre-XDR-TB) is a type of MDR-TB caused by TB bacteria that are resistant to isoniazid, rifampin, and a fluroquinolone OR by TB bacteria that are resistant to isoniazid, rifampin, and a second-line injectable (amikacin, capreomycin, and kanamycin).
  • Extensively drug-resistant TB (XDR-TB) is a rare type of MDR TB caused by TB bacteria that are resistant to isoniazid and rifampin, a fluroquinolone, and a second-line injectable (amikacin, capreomycin, and kanamycin) OR by TB bacteria that are resistant to isoniazid, rifampin, a fluroquinolone, and bedaquiline or linezolid.

Treatment of MDR-TB can follow multiple pathways.

  • Fluoroquinolones have become a mainstay of regimens used to treat MDR-TB, as their mechanism of action is distinct from both isoniazid and rifampicin.[3] The US FDA recommends restricting fluoroquinolones to only cases where there are no other options, due to adverse side effects.[4] Levofloxacin and Moxifloxacin are the two most frequently recommended fluoroquinolones, and the WHO has recommended the use of these drugs for the treatment of MDR-TB.
  • Linezolid was discovered in the 1990s and approved for commercial use in 2000. It has been shown to have neurological and Myelosuppression effects, leading to 16.3% of patients stopping treatment before the end of the 6 month regimen.[5]
  • Bedaquiline (BDQ) became available in 2012. It has been used for treatment of MDR-TB and XDR-TB.
  • Delamanid was introduced in 2014. It can be used as a substitute for BDQ,[5], or in conjunction with BDQ.[6] It is particularly useful for children, who are not eligible for some treatment plans that use BDQ.

References[edit | edit source]

  1. ^ Nahid, P; Dorman, SE; Alipanah, N; Barry, PM; Brozek, JL; Cattamanchi, A; Chaisson, LH; Chaisson, RE; Daley, CL; Grzemska, M; Higashi, JM; Ho, CS; Hopewell, PC; Keshavjee, SA; Lienhardt, C; Menzies, R; Merrifield, C; Narita, M; O'Brien, R; Peloquin, CA; Raftery, A; Saukkonen, J; Schaaf, HS; Sotgiu, G; Starke, JR; Migliori, GB; Vernon, A (1 October 2016). "Executive Summary: Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis". Clin Infect Dis. 63 (7): 853–867. doi:10.1093/cid/ciw566. PMC 6366011. PMID 27621353.
  2. ^ a b "Treatment for TB Disease". U.S. Centers for Disease Control and Prevention. 22 March 2023.
  3. ^ Migliori, GB; Langendam, MW; D’Ambrosio, L; Centis, R; Blasi, F; Huitric, E (2012). "Protecting the tuberculosis drug pipeline: stating the case for the rational use of fluoroquinolones". Eur Respir J. 40: 814–822. doi:10.1183/09031936.00036812. PMC 3461345. PMID 22653774.
  4. ^ "FDA Drug Safety Communication: FDA updates warnings for oral and injectable fluoroquinolone antibiotics due to disabling side effects". U.S. Food and Drug Administration. 26 July 2016.
  5. ^ a b Jang, JG; Chung, JH (October 2020). "Diagnosis and treatment of multidrug-resistant tuberculosis". Yeungnam Univ J Med. 37 (4): 277–285. doi:10.12701/yujm.2020.00626. PMC 7606956. PMID 32883054.
  6. ^ Krishnan, Vidya (February 2022). Phantom Plague: How Tuberculosis Shaped History. New York: PublicAffairs. pp. Chapter 6.