Multidrug-resistant tuberculosis

Multidrug-resistance tuberculosis
Mycobacterium tuberculosis bacteria seen by microscope
SpecialtyInfectious disease

Multidrug-resistant tuberculosis (MDR-TB) is a form of tuberculosis (TB) infection caused by bacteria that are resistant to treatment with at least two of the most powerful first-line anti-TB medications (drugs): isoniazid and rifampicin. Some forms of TB are also resistant to second-line medications, and are called extensively drug-resistant TB (XDR-TB).[1]

Tuberculosis is caused by infection with the bacterium Mycobacterium tuberculosis. Almost one in four people in the world are infected with TB bacteria.[1] Only when the bacteria become active do people become ill with TB. Bacteria become active as a result of anything that can reduce the person's immunity, such as HIV, advancing age, diabetes or other immunocompromising illnesses. TB can usually be treated with a course of four standard, or first-line, anti-TB drugs (i.e., isoniazid, rifampicin, pyrazinamide and ethambutol).[2][3]

However, beginning with the first antibiotic treatment for TB in 1943, some strains of the TB bacteria developed resistance to the standard drugs through genetic changes (see mechanisms.)[2][4][5] Currently the majority of multidrug-resistant cases of TB are due to one strain of TB bacteria called the Beijing lineage.[6][7] This process accelerates if incorrect or inadequate treatments are used, leading to the development and spread of multidrug-resistant TB (MDR-TB). Incorrect or inadequate treatment may be due to use of the wrong medications, use of only one medication (standard treatment is at least two drugs), or not taking medication consistently or for the full treatment period (treatment is required for several months).[8][9][10] Treatment of MDR-TB requires second-line drugs (i.e., fluoroquinolones, aminoglycosides, and others), which in general are less effective, more toxic and much more expensive than first-line drugs.[8] Treatment schedules for MDR-TB involving fluoroquinolones and aminoglycosides can run for two years, compared to the six months of first-line drug treatment, and cost over US$100,000.[11] If these second-line drugs are prescribed or taken incorrectly, further resistance can develop leading to XDR-TB.

Resistant strains of TB are already present in the population, so MDR-TB can be directly transmitted from an infected person to an uninfected person. In this case a previously untreated person develops a new case of MDR-TB. This is known as primary MDR-TB, and is responsible for up to 75% of cases.[12] Acquired MDR-TB develops when a person with a non-resistant strain of TB is treated inadequately, resulting in the development of antibiotic resistance in the TB bacteria infecting them. These people can in turn infect other people with MDR-TB.[5][8]

MDR-TB caused an estimated 600,000 new TB cases and 240,000 deaths in 2016 and MDR-TB accounts for 4.1% of all new TB cases and 19% of previously treated cases worldwide.[13] Globally, most MDR-TB cases occur in South America, Southern Africa, India, China, and the former Soviet Union.[14]

Treatment of MDR-TB requires treatment with second-line drugs, usually four or more anti-TB drugs for a minimum of 6 months, and possibly extending for 18–24 months if rifampin resistance has been identified in the specific strain of TB with which the patient has been infected.[9] Under ideal program conditions, MDR-TB cure rates can approach 70%.[9]

  1. ^ a b "Diagnosis and notification of multidrug-resistant TB" (PDF). World Health Organization (WHO). Archived from the original (PDF) on 25 October 2013. Retrieved 7 December 2016.
  2. ^ a b Longo, Fausci; et al. (2012). Harrison's Principles of Internal Medicine (18th ed.). New York: McGraw Hill. pp. Chapter 165: Tuberculosis. Retrieved 7 December 2016.
  3. ^ Sileshi, Tesemma; Tadesse, Esayas; Makonnen, Eyasu; Aklillu, Eleni (2021). "The Impact of First-Line Anti-Tubercular Drugs' Pharmacokinetics on Treatment Outcome: A Systematic Review". Clinical Pharmacology: Advances and Applications. 13: 1–12. doi:10.2147/CPAA.S289714. PMC 7811439. PMID 33469389.
  4. ^ "Chapter 168. Antimycobacterial Agents | Harrison's Principles of Internal Medicine, 18e". AccessMedicine | McGraw-Hill Medical. Retrieved 7 December 2016.
  5. ^ a b Cite error: The named reference Iseman1993 was invoked but never defined (see the help page).
  6. ^ Stoffels, Karolien; Allix-Béguec, Caroline; Groenen, Guido; Wanlin, Maryse; Berkvens, Dirk; Mathys, Vanessa; Supply, Philip; Fauville-Dufaux, Maryse (9 May 2013). "From Multidrug- to Extensively Drug-Resistant Tuberculosis: Upward Trends as Seen from a 15-Year Nationwide Study". PLOS ONE. 8 (5): e63128. Bibcode:2013PLoSO...863128S. doi:10.1371/journal.pone.0063128. ISSN 1932-6203. PMC 3650045. PMID 23671662.
  7. ^ Parwati, Ida; Crevel, Reinout van; Soolingen, Dick van (February 2010). "Possible underlying mechanisms for successful emergence of the Mycobacterium tuberculosis Beijing genotype strains". The Lancet Infectious Diseases. 10 (2): 103–111. doi:10.1016/s1473-3099(09)70330-5. PMID 20113979.
  8. ^ a b c Millard, James; Ugarte-Gil, Cesar; Moore, David A. J. (26 February 2015). "Multidrug resistant tuberculosis". BMJ. 350: h882. doi:10.1136/bmj.h882. ISSN 1756-1833. PMID 25721508. S2CID 11683912.
  9. ^ a b c Adams and Woelke (2014). Understanding Global Health. Chapter 10: TB and HIV/AIDS (12th ed.). McGraw Hill. Retrieved 9 May 2015.
  10. ^ Keshavjee, Salmaan; Farmer, Paul E. (6 September 2012). "Tuberculosis, Drug Resistance, and the History of Modern Medicine". New England Journal of Medicine. 367 (10): 931–936. doi:10.1056/NEJMra1205429. ISSN 0028-4793. PMID 22931261.
  11. ^ Kaplan, Jeffrey. 2017. "Tuberculosis" American University. Lecture.
  12. ^ Nathanson, Eva; Nunn, Paul; Uplekar, Mukund; Floyd, Katherine; Jaramillo, Ernesto; Lönnroth, Knut; Weil, Diana; Raviglione, Mario (9 September 2010). "MDR Tuberculosis — Critical Steps for Prevention and Control" (PDF). New England Journal of Medicine. 363 (11): 1050–1058. doi:10.1056/NEJMra0908076. ISSN 0028-4793. PMID 20825317.
  13. ^ "Drug-resistant tuberculosis". World Health Organization. Retrieved 2 October 2018.
  14. ^ "Multi-drug-resistant tuberculosis (MDR-TB) – 2015 Update". World Health Organization (WHO). Archived from the original on 18 September 2013. Retrieved 7 December 2016.