View source for Multidrug-resistant tuberculosis

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{{update|inaccurate=yes|part=Pretomanid, delamanid, bedaquiline approval & current clinical experience (if any)|date=November 2023}}

'''Multidrug-resistant tuberculosis''' ('''MDR-TB''') is a form of [[tuberculosis]] (TB) infection caused by bacteria that are [[Antimicrobial resistance|resistant]] to treatment with at least two of the most powerful first-line [[Tuberculosis management|anti-TB medications]] (drugs): [[isoniazid]] and [[rifampicin]]. Some forms of TB are also resistant to [[Tuberculosis management|second-line]] medications, and are called extensively drug-resistant TB ([[Extensively drug-resistant tuberculosis|XDR-TB]]).<ref name="who.int">{{cite web|url=https://www.who.int/tb/challenges/mdr/mdr_tb_factsheet.pdf|archive-url=https://web.archive.org/web/20131025074305/http://www.who.int/tb/challenges/mdr/MDR_TB_FactSheet.pdf|url-status=dead|archive-date=25 October 2013|publisher=[[World Health Organization]] (WHO) |title=Diagnosis and notification of multidrug-resistant TB|access-date=7 December 2016}}</ref>

Tuberculosis is caused by infection with the bacterium ''[[Mycobacterium tuberculosis]]''. Almost one in four people in the world are infected with TB bacteria.<ref name="who.int" /> 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 (medical)|immunity]], such as HIV, advancing age, diabetes or other immunocompromising illnesses. TB can usually be treated with a course of four standard, or [[Therapy#Lines of therapy|first-line]], anti-TB drugs (i.e., [[isoniazid]], [[rifampicin]], [[pyrazinamide]] and [[ethambutol]]).<ref name="McGraw Hill">{{cite book|url=http://accessmedicine.mhmedical.com/content.aspx?bookid=331&Sectionid=40726917|title=Harrison's Principles of Internal Medicine|date=2012|publisher=McGraw Hill|edition=18th|location=New York|pages=Chapter 165: Tuberculosis|display-authors=etal|last1=Longo, Fausci|access-date=7 Dec 2016}}</ref><ref>{{cite journal |last1=Sileshi |first1=Tesemma |last2=Tadesse |first2=Esayas |last3=Makonnen |first3=Eyasu |last4=Aklillu |first4=Eleni |title=The Impact of First-Line Anti-Tubercular Drugs' Pharmacokinetics on Treatment Outcome: A Systematic Review |journal=Clinical Pharmacology: Advances and Applications |date=2021 |volume=13 |pages=1–12 |doi=10.2147/CPAA.S289714 |pmc=7811439 |pmid=33469389 |doi-access=free }}</ref>

However, beginning with the first antibiotic [[Tuberculosis management|treatment]] for TB in 1943, some strains of the TB bacteria developed resistance to the standard drugs through genetic changes (see [[Multidrug-resistant tuberculosis#Mechanism of M. tuberculosis drug resistance|mechanisms]].)<ref name="McGraw Hill" /><ref>{{Cite web|url=http://accessmedicine.mhmedical.com/content.aspx?bookid=331&Sectionid=40726917|title=Chapter 168. Antimycobacterial Agents {{!}} Harrison's Principles of Internal Medicine, 18e |publisher=AccessMedicine {{!}} McGraw-Hill Medical |access-date=2016-12-07}}</ref><ref name="Iseman1993" /> 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).<ref name="Millard et al" /><ref name="accessmedicine.mhmedical.com">{{cite book|url=http://accessmedicine.mhmedical.com/content.aspx?bookid=710&Sectionid=46796911|title=Understanding Global Health. Chapter 10: TB and HIV/AIDS|date=2014|publisher=McGraw Hill|edition=12th|last1=Adams and Woelke|access-date=9 May 2015}}</ref><ref>{{Cite journal|last1=Keshavjee|first1=Salmaan|last2=Farmer|first2=Paul E.|date=2012-09-06|title=Tuberculosis, Drug Resistance, and the History of Modern Medicine|journal=New England Journal of Medicine |volume=367 |issue=10 |pages=931–936 |doi=10.1056/NEJMra1205429 |issn=0028-4793 |pmid=22931261|doi-access=free}}</ref> 

Treatment of MDR-TB requires treatment with [[Tuberculosis management#Second line|second-line drugs]],  (i.e., [[fluoroquinolones]], [[aminoglycoside]]s, and others), which in general are less effective, more toxic and much more expensive than first-line drugs.<ref name="Millard et al" /> Treatment regimes can run for two years, compared to the six months of first-line drug treatment.<ref>Kaplan, Jeffrey. 2017. "Tuberculosis" American University. Lecture.</ref><ref name="accessmedicine.mhmedical.com" />  If these second-line drugs are prescribed or taken incorrectly, further resistance can develop leading to XDR-TB.{{Cn|date=April 2025}}

MDR-TB can be directly [[Tuberculosis#Mechanism|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.<ref>{{Cite journal|last1=Nathanson|first1=Eva|last2=Nunn|first2=Paul|last3=Uplekar|first3=Mukund|last4=Floyd|first4=Katherine|last5=Jaramillo|first5=Ernesto|last6=Lönnroth|first6=Knut|last7=Weil|first7=Diana|last8=Raviglione|first8=Mario|date=2010-09-09|title=MDR Tuberculosis — Critical Steps for Prevention and Control|journal=New England Journal of Medicine|volume=363|issue=11|pages=1050–1058|doi=10.1056/NEJMra0908076|issn=0028-4793|pmid=20825317|url=http://whqlibdoc.who.int/publications/2010/9789241599191_eng.pdf}}</ref> 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.<ref name="Iseman1993" /><ref name="Millard et al">{{Cite journal|last1=Millard|first1=James|last2=Ugarte-Gil|first2=Cesar|last3=Moore|first3=David A. J.|date=2015-02-26|title=Multidrug resistant tuberculosis|url=http://www.bmj.com/content/350/bmj.h882|journal=BMJ|volume=350|pages=h882|doi=10.1136/bmj.h882|issn=1756-1833|pmid=25721508|s2cid=11683912}}</ref>

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.<ref>{{Cite web|url=https://www.who.int/tb/areas-of-work/drug-resistant-tb/en/|title=Drug-resistant tuberculosis|website=World Health Organization|language=en-GB|access-date=2018-10-02}}</ref> Globally, most MDR-TB cases occur in South America, Southern Africa, India, China, and the former Soviet Union.<ref>{{cite web|url=https://extranet.who.int/sree/Reports?op=vs&path=/WHO_HQ_Reports/G2/PROD/EXT/MDRTB_Indicators_map|archive-url=https://web.archive.org/web/20130918203951/https://extranet.who.int/sree/Reports?op=vs&path=/WHO_HQ_Reports/G2/PROD/EXT/MDRTB_Indicators_map|url-status=dead|archive-date=18 September 2013|title=Multi-drug-resistant tuberculosis (MDR-TB) – 2015 Update |publisher=[[World Health Organization]] (WHO) |access-date=7 December 2016}}</ref>{{TOC limit|3}}

== Origin ==
Researchers hypothesize that an ancestor of ''Mycobacterium tuberculosis'' first originated in the East African region approximately 3 million years ago, with modern strains mutating and arising 20,000 years ago.<ref>{{Cite journal |last=Daniel |first=Thomas M. |date=2006-11-01 |title=The history of tuberculosis |url=https://www.resmedjournal.com/article/S0954-6111(06)00401-X/abstract |journal=Respiratory Medicine |language=English |volume=100 |issue=11 |pages=1862–1870 |doi=10.1016/j.rmed.2006.08.006 |issn=0954-6111 |pmid=16949809|doi-access=free }}</ref> As migration out of East Africa increased, so did the spread of the disease, starting in Asia and then spreading towards the West and South America. Multidrug-resistant tuberculosis has a variety of causes, but resistance is usually due to treatment failure, drug combinations, coinfections, prior use of anti-TB medications, inadequate absorption of medication, underlying disease, and noncompliance with anti-TB drugs.<ref name=":02">{{Cite journal |last1=Ahmad |first1=Suhail |last2=Mokaddas |first2=Eiman |date=2010-01-01 |title=Recent advances in the diagnosis and treatment of multidrug-resistant tuberculosis |url=https://www.sciencedirect.com/science/article/pii/S175500171000028X |journal=Respiratory Medicine CME |language=en |volume=3 |issue=2 |pages=51–61 |doi=10.1016/j.rmedc.2010.08.001 |issn=1755-0017|url-access=subscription }}</ref>

== Mechanism of drug resistance ==
The TB bacterium has natural defenses against some drugs, and can acquire drug resistance through genetic mutations. The bacterium does not have the ability to transfer genes for resistance between organisms through [[plasmid]]s ([[Horizontal gene transfer|see horizontal transfer]]). Some mechanisms of drug resistance include:<ref>{{cite journal|last1=Sandhu|first1=P|last2=Akhter|first2=Y|title=Evolution of structural fitness and multifunctional aspects of mycobacterial RND family transporters.|journal=Archives of Microbiology|volume=200|issue=1|pages=19–31|date=26 September 2017|doi=10.1007/s00203-017-1434-6|pmid=28951954|s2cid=13656026}}</ref>
# [[Cell wall]]: The cell wall of ''M. tuberculosis'' (TB) contains complex [[lipid]] molecules which act as a barrier to stop drugs from entering the cell. In order to lessen its vulnerability, M. tuberculosis can also stop medications from penetrating its cells. RIF resistance is linked to numerous genes and proteins that are involved in the formation of cell walls. Maintaining the M. tuberculosis cell wall is a major function of the PE11 protein. It is hypothesized that upregulating the production of PE11 protein can decrease the quantity of antibiotics that enter M. tuberculosis. The expression of M. tuberculosis PE11 protein in M. smegmatis can generate raised resistance levels to several antibiotics, including RIF.
# Drug modifying & inactivating [[enzyme]]s: The TB genome codes for enzymes ([[protein]]s) that inactivate drug molecules. These enzymes are usually phosphorylate, acetylate, or adenylate drug compounds.
# [[Efflux (microbiology)|Drug efflux]] systems: The TB cell contains molecular systems that actively pump drug molecules out of the cell.
# [[Mutation]]s: Spontaneous mutations in the TB genome can alter proteins which are the target of drugs, making the bacteria drug-resistant.<ref>{{cite journal|last2=Warren|first2=R. M.|last3=Gey Van Pittius|first3=N. C.|last4=McEvoy|first4=C. R. E.|last5=Van Helden|first5=P. D.|last6=Victor|first6=T. C.|year=2009|title=A Balancing Act: Efflux/Influx in Mycobacterial Drug Resistance|journal=Antimicrobial Agents and Chemotherapy|volume=53|issue=8|pages=3181–9|doi=10.1128/AAC.01577-08|pmc=2715638|pmid=19451293|last1=Louw|first1=G. E.}}</ref>

One example is a mutation in the ''rpoB'' gene, which encodes the beta subunit of the bacterium's RNA polymerase enzyme. In non-resistant TB, rifampin binds the beta subunit of RNA polymerase and disrupts transcription elongation. Mutation in the ''rpoB'' gene changes the sequence of amino acids and eventual conformation, or arrangement, of the beta subunit. In this case, rifampin can no longer bind or prevent transcription, and the bacterium is resistant.<ref>{{Cite journal |last1=Zaw |first1=Myo T. |last2=Emran |first2=Nor A. |last3=Lin |first3=Zaw |date=2018-09-01 |title=Mutations inside rifampicin-resistance determining region of rpoB gene associated with rifampicin-resistance in Mycobacterium tuberculosis |journal=Journal of Infection and Public Health |language=en |volume=11 |issue=5 |pages=605–610 |doi=10.1016/j.jiph.2018.04.005 |pmid=29706316 |s2cid=14058414 |issn=1876-0341|doi-access=free }}</ref><ref>{{cite journal |last1=Mousavi-Sagharchi |first1=Seyyed Mohammad Amin |last2=Afrazeh |first2=Elina |last3=Seyyedian-Nikjeh |first3=Seyyedeh Fatemeh |last4=Meskini |first4=Maryam |last5=Doroud |first5=Delaram |last6=Siadat |first6=Seyed Davar |title=New insight in molecular detection of Mycobacterium tuberculosis |journal=AMB Express |date=21 June 2024 |volume=14 |issue=1 |pages=74 |doi=10.1186/s13568-024-01730-3 |doi-access=free |pmid=38907086 |pmc=11192714 |issn=2191-0855}}</ref>

Other mutations make the bacterium resistant to other drugs. For example, there are many mutations that confer resistance to isoniazid (INH), including in the genes ''katG'', ''inhA'', ''ahpC'' and others. Amino acid replacements in the NADH binding site of InhA apparently result in INH resistance by preventing the inhibition of mycolic acid biosynthesis, which the bacterium uses in its cell wall. Mutations in the ''katG'' gene make the enzyme catalase peroxidase unable to convert INH to its biologically active form. Hence, INH is ineffective and the bacterium is resistant.'''<ref>{{cite journal |doi=10.1128/AAC.46.2.267-274.2002 |title=Evolution of Drug Resistance in Mycobacterium tuberculosis: Clinical and Molecular Perspective |year=2002 |last1=Gillespie |first1=S. H. |journal=Antimicrobial Agents and Chemotherapy |volume=46 |issue=2 |pages=267–74 |pmid=11796329 |pmc=127054}}</ref><ref>{{cite journal |pmid=10645439 |year=1998 |last1=Ramaswamy |first1=S |last2=Musser |first2=JM |title=Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update |volume=79 |issue=1 |pages=3–29 |doi=10.1054/tuld.1998.0002 |journal=Tubercle and Lung Disease}}</ref>''' The discovery of new molecular targets is essential to overcome drug-resistance problems.<ref>{{Cite journal|last1=Baptista|first1=Rafael|last2=Bhowmick|first2=Sumana|last3=Nash|first3=Robert J|last4=Baillie|first4=Les|last5=Mur|first5=Luis AJ|date=2018-03-23|title=Target discovery focused approaches to overcome bottlenecks in the exploitation of antimycobacterial natural products|journal=[[Future Medicinal Chemistry]]|volume=10|issue=7|pages=811–822|language=EN|doi=10.4155/fmc-2017-0273|pmid=29569936|s2cid=4145657 |url=http://orca.cf.ac.uk/110455/8/Target%20discovery%20focused%20approaches%20to%20overcome%20bottlenecks%20in%20the%20exploitation%20of%20antimycobacterial%20natural%20products.pdf}}</ref>

In some TB bacteria, the acquisition of these mutations can be explained by other mutations in the DNA recombination, recognition and repair machinery.<ref>{{Cite journal|last1=Hanekom|first1=M.|last2=Pittius|first2=N.C. Gey van|last3=McEvoy|first3=C.|last4=Victor|first4=T.C.|last5=Helden|first5=P.D. Van|last6=Warren|first6=R.M.|title=Mycobacterium tuberculosis Beijing genotype: A template for success|journal=Tuberculosis|volume=91|issue=6|pages=510–523|doi=10.1016/j.tube.2011.07.005|pmid=21835699|year=2011}}</ref> Mutations in these genes allow the bacteria to have a higher overall mutation rate and to accumulate mutations that cause drug resistance more quickly.<ref>{{Cite journal|last1=Ford|first1=Christopher B.|last2=Shah|first2=Rupal R.|last3=Maeda|first3=Midori Kato|last4=Gagneux|first4=Sebastien|last5=Murray|first5=Megan B.|last6=Cohen|first6=Ted|last7=Johnston|first7=James C.|last8=Gardy|first8=Jennifer|last9=Lipsitch|first9=Marc|date=July 2013|title=Mycobacterium tuberculosis mutation rate estimates from different lineages predict substantial differences in the emergence of drug resistant tuberculosis|journal=Nature Genetics|volume=45|issue=7|pages=784–790|doi=10.1038/ng.2656|issn=1061-4036|pmc=3777616|pmid=23749189}}</ref><ref>{{Cite journal|last1=Mestre|first1=Olga|last2=Luo|first2=Tao|last3=Vultos|first3=Tiago Dos|last4=Kremer|first4=Kristin|last5=Murray|first5=Alan|last6=Namouchi|first6=Amine|last7=Jackson|first7=Céline|last8=Rauzier|first8=Jean|last9=Bifani|first9=Pablo|date=2011-01-20|title=Phylogeny of Mycobacterium tuberculosis Beijing Strains Constructed from Polymorphisms in Genes Involved in DNA Replication, Recombination and Repair|journal=PLOS ONE|volume=6|issue=1|pages=e16020|doi=10.1371/journal.pone.0016020|pmid=21283803|pmc=3024326|bibcode=2011PLoSO...616020M|issn=1932-6203|doi-access=free}}</ref>

==Extensively drug-resistant TB==
{{Main|Extensively drug-resistant tuberculosis}}
MDR-TB can become resistant to the major [[Tuberculosis management|second-line]] TB drug groups: [[Quinolone antibiotic|fluoroquinolone]]s ([[moxifloxacin]], [[ofloxacin]]) and injectable [[aminoglycoside]] or polypeptide drugs ([[amikacin]], [[capreomycin]], [[Kanamycin A|kanamycin]]). When MDR-TB is resistant to at least one drug from each group, it is classified as [[extensively drug-resistant tuberculosis]] (XDR-TB).<ref name="Millard et al" />

WHO has revised the definitions of pre-XDR-TB and XDR-TB in 2021 as following:<ref>{{Cite journal|last1=Viney|first1=Kerri|last2=Linh|first2=Nguyen Nhat|last3=Gegia|first3=Medea|last4=Zignol|first4=Matteo|last5=Glaziou|first5=Philippe|last6=Ismail|first6=Nazir|last7=Kasaeva|first7=Tereza|last8=Mirzayev|first8=Fuad|date=2021|title=New definitions of pre-extensively and extensively drug-resistant tuberculosis: update from the World Health Organization|journal=The European Respiratory Journal|volume=57|issue=4|pages=2100361|doi=10.1183/13993003.00361-2021|issn=1399-3003|pmid=33833074|s2cid=233192729 |doi-access=free}}</ref>

'''''Pre-XDR-TB:''''' ''TB caused by Mycobacterium tuberculosis (M. tuberculosis) strains that fulfill the definition of MDR/RR-TB and which are also resistant to any fluoroquinolone.''

'''''XDR-TB:''''' ''TB caused by Mycobacterium tuberculosis (M. tuberculosis) strains that fulfill the definition of MDR/RR-TB and which are also resistant to any fluoroquinolone and at least one additional Group A drug.''

The Group A drugs are currently levofloxacin or moxifloxacin, bedaquiline and linezolid, therefore XDR-TB is MDR/RR-TB that is resistant to a fluoroquinolone and at least one of bedaquiline or linezolid (or both).

In a study of MDR-TB patients from 2005 to 2008 in various countries, 43.7% had resistance to at least one second-line drug.<ref name=dalton>{{cite journal |doi=10.1016/S0140-6736(12)60734-X |title=Prevalence of and risk factors for resistance to second-line drugs in people with multidrug-resistant tuberculosis in eight countries: A prospective cohort study |year=2012 |last1=Dalton |first1=Tracy |last2=Cegielski |first2=Peter |last3=Akksilp |first3=Somsak |last4=Asencios |first4=Luis |last5=Caoili |first5=Janice Campos |last6=Cho |first6=Sang-Nae |last7=Erokhin |first7=Vladislav V |last8=Ershova |first8=Julia |last9=Gler |first9=Ma Tarcela |last10=Kazennyy |first10=Boris Y |last11=Kim |first11=Hee Jin |last12=Kliiman |first12=Kai |last13=Kurbatova |first13=Ekaterina |last14=Kvasnovsky |first14=Charlotte |last15=Leimane |first15=Vaira |last16=Van Der Walt |first16=Martie |last17=Via |first17=Laura E |last18=Volchenkov |first18=Grigory V |last19=Yagui |first19=Martin A |last20=Kang |first20=Hyungseok |journal=The Lancet |volume=380 |issue=9851 |pages=1406–17 |pmid=22938757 |last21=Global Petts |first21=Investigators |last22=Akksilp |first22=R |last23=Sitti |first23=W |last24=Wattanaamornkiet |first24=W |last25=Andreevskaya |first25=SN |last26=Chernousova |first26=LN |last27=Demikhova |first27=OV |last28=Larionova |first28=EE |last29=Smirnova |first29=TG |last30=Vasilieva |first30=IA |s2cid=10446754 |pmc=11019390 }}</ref> About 9% of MDR-TB cases are resistant to a drug from both classes and classified as XDR-TB.<ref name="who.int" /><ref name=WHO/>

In the past 10 years{{When|date=April 2025}} TB strains have emerged in Italy, Iran, India, and South Africa which are resistant to all available first and second line TB drugs, classified as totally drug-resistant tuberculosis, though there is some controversy over this term.<ref>{{cite journal|last1=Velayati|first1=A|author2=Farnia P|author3=Masjedi M|title=The totally drug resistant tuberculosis (TDR-TB)|journal=International Journal of Clinical and Experimental Medicine|date=2013|volume=6|issue=4|pages=307–309|pmid=23641309|pmc=3631557}}</ref><ref name="Zumla et al">{{Cite journal|last1=Zumla|first1=Alimuddin|last2=Abubakar|first2=Ibrahim|last3=Raviglione|first3=Mario|last4=Hoelscher|first4=Michael|last5=Ditiu|first5=Lucica|last6=Mchugh|first6=Timothy D.|last7=Squire|first7=S. Bertel|last8=Cox|first8=Helen|last9=Ford|first9=Nathan|date=2012-05-15|title=Drug-Resistant Tuberculosis—Current Dilemmas, Unanswered Questions, Challenges, and Priority Needs|journal=Journal of Infectious Diseases|volume=205|issue=suppl 2|pages=S228–S240|doi=10.1093/infdis/jir858|issn=0022-1899|pmid=22476720|doi-access=free}}</ref><ref>{{Cite journal|last1=Parida|first1=S. K.|last2=Axelsson-Robertson|first2=R.|last3=Rao|first3=M. V.|last4=Singh|first4=N.|last5=Master|first5=I.|last6=Lutckii|first6=A.|last7=Keshavjee|first7=S.|last8=Andersson|first8=J.|last9=Zumla|first9=A.|date=2015-04-01|title=Totally drug-resistant tuberculosis and adjunct therapies|journal=Journal of Internal Medicine|volume=277|issue=4|pages=388–405|doi=10.1111/joim.12264|pmid=24809736|s2cid=43844933|issn=1365-2796|doi-access=}}</ref> Increasing levels of resistance in TB strains threaten to complicate the current global public health approaches to TB control. New drugs are being developed to treat extensively resistant forms but major improvements in detection, diagnosis, and treatment will be needed.<ref name="Zumla et al" />

There have been reports of [[totally drug-resistant tuberculosis]], but such strains of TB are not recognized by the WHO.<ref>{{Cite web |date=2015-12-11 |title=WHO {{!}} Drug-resistant TB: Totally drug-resistant TB FAQ |url=http://www.who.int/tb/areas-of-work/drug-resistant-tb/totally-drug-resistant-tb-faq/en/ |access-date=2022-12-07 |archive-url=https://web.archive.org/web/20151211171235/http://www.who.int/tb/areas-of-work/drug-resistant-tb/totally-drug-resistant-tb-faq/en/ |archive-date=11 December 2015 }}</ref>

==Prevention==
There are several ways that drug resistance to TB, and drug resistance in general, can be prevented:<ref>{{cite journal |doi=10.1016/j.ddmec.2010.09.006 |title=Transmission of MDR tuberculosis |year=2010 |last1=Gao |first1=Qian |last2=Li |first2=Xia |journal=Drug Discovery Today: Disease Mechanisms |volume=7 |pages=e61–5}}</ref><ref>{{cite journal |doi=10.1097/QCO.0b013e3283229fab |title=Extensively drug-resistant tuberculosis |year=2009 |last1=Lobue |first1=Philip |journal=Current Opinion in Infectious Diseases |volume=22 |issue=2 |pages=167–73 |pmid=19283912|s2cid=24995375 |url=https://zenodo.org/record/1234905 }}</ref>
# Rapid diagnosis & treatment of TB: One of the greatest risk factors for drug-resistant TB is problems in treatment and diagnosis, especially in developing countries. If TB is identified and treated soon, drug resistance can be avoided.
# Completion of treatment: Previous treatment of TB is an indicator of MDR TB. If the patient does not complete their antibiotic treatment, or if the physician does not prescribe the proper antibiotic regimen, resistance can develop. Also, drugs that are of poor quality or less in quantity, especially in developing countries, contribute to MDR TB.
# Identifying and diagnosing patients with HIV/AIDS as soon as possible. They lack the immunity to fight the TB infection and are at great risk of developing drug resistance.
# Identifying contacts who could have contracted TB: family members, people in close contact, etc.
# Research: Much research and funding is needed in the diagnosis, prevention and treatment of TB and MDR TB.

"Opponents of a universal tuberculosis treatment, reasoning from misguided notions of cost-effectiveness, fail to acknowledge that MDRTB is not a disease of poor people in distant places. The disease is infectious and airborne. Treating only one group of patients looks inexpensive in the short run, but will prove disastrous for all in the long run." Paul Farmer {{sfn|Farmer|2005|p=133}}

===DOTS-Plus===
Community-based treatment programs such as DOTS-Plus, a MDR-TB-specialized treatment using the popular [[Directly Observed Therapy – Short Course]] (DOTS) initiative, have shown considerable success in the world. In these locales, these programs have proven to be a good option for proper treatment of MDR-TB in poor, rural areas. A successful example has been in [[Lima]], Peru, where the program has seen cure rates of over 80%.<ref>{{cite journal |doi=10.1016/j.socscimed.2004.01.027 |title=Community-based treatment of multidrug-resistant tuberculosis in Lima, Peru: 7 years of experience |year=2004 |last1=Shin |first1=Sonya |last2=Furin |first2=Jennifer |last3=Bayona |first3=Jaime |last4=Mate |first4=Kedar |last5=Kim |first5=Jim Yong | author5-link =Jim Yong Kim |last6=Farmer |first6=Paul | author6-link =Paul Farmer|journal=[[Social Science & Medicine]] |volume=59 |issue=7 |pages=1529–39 |pmid=15246180}}</ref>

However, the DOTS program administered in the [[Georgia (country)|Republic of Georgia]] uses passive case finding. This means that the system depends on patients coming to health care providers, without conducting compulsory screenings. As medical anthropologists like Erin Koch have shown, this form of implementation does not suit all cultural structures. They urge that the DOTS protocol be constantly reformed in the context of local practices, forms of knowledge and everyday life.<ref>{{cite journal |doi=10.1080/01459740.2010.531064 |title=Local Microbiologies of Tuberculosis: Insights from the Republic of Georgia |year=2011 |last1=Koch |first1=Erin |journal=Medical Anthropology |volume=30 |pages=81–101 |pmid=21218357 |issue=1|s2cid=27735359 }}</ref>

==Treatment==
{{See also|Tuberculosis treatment}}{{Technical|date=April 2025|section}}
Usually, multidrug-resistant tuberculosis can be cured with long treatments of second-line drugs, but these are more expensive than [[first-line treatment|first-line]] drugs and have more adverse effects.<ref name="greenfacts2008">{{cite web | title=Scientific Facts on Drug-resistant Tuberculosis| publisher=GreenFacts | date=2008-12-18 | access-date=2009-03-26 | url= http://www.greenfacts.org/en/tuberculosis/l-2/1-mdr-tb-xdr.htm}}</ref> The treatment and prognosis of MDR-TB are much more akin to those for cancer than to those for infection. MDR-TB has a mortality rate of about 15% with treatment, which further depends on a number of factors, including:<ref>{{Cite web |title=Global tuberculosis report 2019 |url=https://www.who.int/publications-detail-redirect/9789241565714 |access-date=2022-09-24 |website=www.who.int |language=en}}</ref>
# How many drugs the organism is resistant to (the fewer the better)
# How many drugs the patient is given (patients treated with five or more drugs do better)
# The expertise and experience of the physician responsible
# How co-operative the patient is with treatment (treatment is arduous and long, and requires persistence and determination on the part of the patient)
# Whether the patient is [[HIV-positive]] or not (HIV co-infection is associated with increased mortality).

The majority of patients with multidrug-resistant tuberculosis do not receive treatment, as they are found in underdeveloped countries or in poverty. Denial of treatment remains a difficult [[human rights]] issue, as the high cost of second-line medications often precludes those who cannot afford therapy.<ref name="Farmer, Paul 2001"/>

A study of cost-effective strategies for tuberculosis control supported three major policies. First, the treatment of smear-positive cases in DOTS programs must be the foundation of any tuberculosis control approach, and should be a basic practice for all control programs. Second, there is a powerful economic case for treating smear-negative and extra-pulmonary cases in DOTS programs along with treating smear-negative and extra-pulmonary cases in DOTS programs as a new WHO "STOP TB" approach and the second global plan for tuberculosis control. Last but not least, the study shows that a significant scaling-up of all interventions is needed in the next 10 years if the millennium development goal and related goals for tuberculosis control are to be achieved. If the case detection rate can be improved, this will guarantee that people who gain access to treatment facilities are covered and that coverage is widely distributed to people who do not now have access.<ref>{{cite journal |doi=10.1136/bmj.38645.660093.68 |title=Cost effectiveness analysis of strategies for tuberculosis control in developing countries |year=2005 |last1=Baltussen |first1=R. |journal=BMJ |volume=331 |issue=7529 |pages=1364 |pmid=16282379 |last2=Floyd |first2=K |last3=Dye |first3=C |pmc=1309642}}</ref>

In general, treatment courses are measured in months to years; MDR-TB may require surgery, and death rates remain high despite optimal treatment. However, good outcomes for patients are still possible.<ref name="Mitnick2003">{{cite journal |doi=10.1056/NEJMoa022928 |title=Community-Based Therapy for Multidrug-Resistant Tuberculosis in Lima, Peru |year=2003 |last1=Mitnick |first1=Carole |last2=Bayona |first2=Jaime |last3=Palacios |first3=Eda |last4=Shin |first4=Sonya |last5=Furin |first5=Jennifer |last6=Alcántara |first6=Felix |last7=Sánchez |first7=Epifanio |last8=Sarria |first8=Madeleny |last9=Becerra |first9=Mercedes |last10=Fawzi |first10=Mary C. Smith |last11=Kapiga |first11=Saidi |last12=Neuberg |first12=Donna |last13=Maguire |first13=James H. |last14=Kim |first14=Jim Yong |last15=Farmer |first15=Paul |journal=New England Journal of Medicine |volume=348 |issue=2 |pages=119–28 |pmid=12519922|url=https://researchonline.lshtm.ac.uk/9891/1/nejmoa022928.pdf }}</ref>

The treatment of MDR-TB must be undertaken by physicians experienced in the treatment of MDR-TB. Mortality and morbidity in patients treated in non-specialist centers are significantly higher than those of patients treated in specialist centers. Treatment of MDR-TB must be done on the basis of sensitivity testing: it is impossible to treat such patients without this information. When treating a patient with suspected MDR-TB, pending the result of laboratory sensitivity testing, the patient could be started on SHREZ ([[Streptomycin]]+ [[isoniazid|isonicotinyl Hydrazine]]+ [[Rifampicin]]+[[Ethambutol]]+ [[pyrazinamide|pyraZinamide]]) and [[moxifloxacin]] with [[cycloserine]]. There is evidence that previous therapy with a drug for more than a month is associated with diminished efficacy of that drug regardless of ''in vitro'' tests indicating susceptibility.<ref>{{cite journal |doi=10.1056/NEJM199302253280802 |title=Treatment of 171 Patients with Pulmonary Tuberculosis Resistant to Isoniazid and Rifampin |year=1993 |last1=Goble |first1=Marian |last2=Iseman |first2=Michael D. |last3=Madsen |first3=Lorie A. |last4=Waite |first4=Dennis |last5=Ackerson |first5=Lynn |last6=Horsburgh Jr |first6=C. Robert |journal=New England Journal of Medicine |volume=328 |issue=8 |pages=527–32 |pmid=8426619|doi-access=free }}</ref> Hence, a detailed knowledge of the treatment history of each patient is essential. In addition to the obvious risks (i.e., known exposure to a patient with MDR-TB), risk factors for MDR-TB include HIV infection, previous incarceration, failed TB treatment, failure to respond to standard TB treatment, and relapse following standard TB treatment.{{cn|date=March 2023}}

A gene probe for ''[[rpoB]]'' is available in some countries. This serves as a useful marker for MDR-TB, because isolated RMP resistance is rare (except when patients have a history of being treated with rifampicin alone). If the results of a gene probe (''rpoB'') are known to be positive, then it is reasonable to omit RMP and to use SHEZ+[[moxifloxacin|MXF]]+[[cycloserine]]. The reason for maintaining the patient on INH is that INH is so potent in treating TB that it is foolish to omit it until there is microbiological proof that it is ineffective (even though isoniazid resistance so commonly occurs with rifampicin resistance).{{cn|date=March 2023}}

For treatment of RR- and MDT-TB, WHO treatment guidelines are as follows: "a regimen with at least five effective TB medicines during the intensive phase is recommended, including pyrazinamide and four core second-line TB medicines – one chosen from Group A, one from Group B, and at least two from Group C3 (conditional recommendation, very low certainty in the evidence). If the minimum number of effective TB medicines cannot be composed as given above, an agent from Group D2 and other agents from Group D3 may be added to bring the total to five. It is recommended that the regimen be further strengthened with high-dose isoniazid and/or ethambutol (conditional recommendation, very low certainty in the evidence)."<ref>{{Cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK390455/|title=WHO Treatment Guidelines for Drug-Resistant Tuberculosis, 2016 Update|date=2016|publisher=World Health Organization|isbn=9789241549639|series=WHO Guidelines Approved by the Guidelines Review Committee|location=Geneva|pmid=27748093}}</ref> Medicines recommended are the following:
* Group A: Fluoroquinolones (levofloxacin, moxifloxicin), linezolid, bedaquiline
* Group B: Clofazimine, cycloserine/terizidone
* Group C: Other core second-line agents (ethambutol, delamanid, pyrazinamide, imipenem-cilastatin/meropenem, amikacin/streptomycin, ethionamide/prothionamide, p-aminosalicylic acid)

For patients with RR-TB or MDR-TB, "not previously treated with second-line drugs and in whom resistance to fluoroquinolones and second-line injectable agents was excluded or is considered highly unlikely, a shorter MDR-TB regimen of 9–12 months may be used instead of the longer regimens (conditional recommendation, very low certainty in the evidence)."<ref>{{Cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK390455/|title=WHO Treatment Guidelines for Drug-Resistant Tuberculosis, 2016 Update|date=2016|publisher=World Health Organization|isbn=9789241549639|series=WHO Guidelines Approved by the Guidelines Review Committee|location=Geneva|pmid=27748093}}</ref>

In general, resistance to one drug within a class means resistance to all drugs within that class, but a notable exception is rifabutin: Rifampicin-resistance does not always mean rifabutin-resistance, and the laboratory should be asked to test for it. It is possible to use only one drug within each drug class. If it is difficult finding five drugs to treat then the clinician can request that high-level INH-resistance be looked for. If the strain has only low-level INH-resistance (resistance at 0.2&nbsp;mg/L INH, but sensitive at 1.0&nbsp;mg/L INH), then high dose INH can be used as part of the regimen. When counting drugs, PZA and interferon count as zero; that is to say, when adding PZA to a four-drug regimen, another drug must be chosen to make five. It is not possible to use more than one injectable (STM, capreomycin or amikacin), because the toxic effect of these drugs is additive: If possible, the aminoglycoside should be given daily for a minimum of three months (and perhaps thrice weekly thereafter). Ciprofloxacin should not be used in the treatment of tuberculosis if other fluoroquinolones are available. As of 2008, Cochrane reports that trials of other fluoroquinolones are ongoing.<ref>{{Cite journal |last1=Ziganshina |first1=L. E. |last2=Squire |first2=S. B. |date=2008-01-23 |editor1-last=Ziganshina |editor1-first=Lilia E |title=Fluoroquinolones for treating tuberculosis |journal=The Cochrane Database of Systematic Reviews |issue=1 |pages=CD004795 |doi=10.1002/14651858.CD004795.pub3 |issn=1469-493X |pmid=18254061}}</ref> While Rifampin is an effective drug, lack of adherence has led to relapse. This is why the use of various first-line drugs, along with developing new drugs that are specific towards drug-resistant strains, is essential.<ref name=":02"/> {{Update span|text=There are a number of new anti-TB medications that are currently|date=April 2025}} in the developmental stage that are directed to treat drug resistant strains; a few of these drugs are PA-824 (now [[pretomanid]]), OPC-67683 (now [[delamanid]]), and R207910 (now [[bedaquiline]]), all of which are in Phase II of development.<ref name=":02"/> Pretomanid and delamanid are both in the nitroimidazole class and have mechanisms involving bioactive reductive activation.<ref>{{Cite journal |last1=Nuermberger |first1=Eric |last2=Tyagi |first2=Sandeep |last3=Tasneen |first3=Rokeya |last4=Williams |first4=Kathy N. |last5=Almeida |first5=Deepak |last6=Rosenthal |first6=Ian |last7=Grosset |first7=Jacques H. |date=April 2008 |title=Powerful Bactericidal and Sterilizing Activity of a Regimen Containing PA-824, Moxifloxacin, and Pyrazinamide in a Murine Model of Tuberculosis |journal=Antimicrobial Agents and Chemotherapy |language=en |volume=52 |issue=4 |pages=1522–1524 |doi=10.1128/AAC.00074-08 |issn=0066-4804 |pmc=2292539 |pmid=18285479}}</ref>{{failed verification|date=November 2023}} Bedaquiline is a diarylquinoline that has a different mechanism; this drug directly inhibits energy production, so this drug may be a better option because it may not require as long of a treatment course as other drugs.<ref>{{Cite journal |last1=Andries |first1=Koen |last2=Verhasselt |first2=Peter |last3=Guillemont |first3=Jerome |last4=Göhlmann |first4=Hinrich W. H. |last5=Neefs |first5=Jean-Marc |last6=Winkler |first6=Hans |last7=Van Gestel |first7=Jef |last8=Timmerman |first8=Philip |last9=Zhu |first9=Min |last10=Lee |first10=Ennis |last11=Williams |first11=Peter |last12=de Chaffoy |first12=Didier |last13=Huitric |first13=Emma |last14=Hoffner |first14=Sven |last15=Cambau |first15=Emmanuelle |date=2005-01-14 |title=A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis |journal=Science |language=en |volume=307 |issue=5707 |pages=223–227 |doi=10.1126/science.1106753 |pmid=15591164 |bibcode=2005Sci...307..223A |s2cid=33219841 |issn=0036-8075|doi-access=free }}</ref>

When it is not possible to find five drugs from the lists above; the drugs
[[imipenem]],<ref>{{cite journal |last1=Chambers |first1=H. F. |last2=Turner |first2=J. |last3=Schecter |first3=G. F. |last4=Kawamura |first4=M. |last5=Hopewell |first5=P. C. |year=2005 |title=Imipenem for Treatment of Tuberculosis in Mice and Humans |journal=Antimicrobial Agents and Chemotherapy |volume=49 |issue=7 |pages=2816–21 |doi=10.1128/AAC.49.7.2816-2821.2005 |pmc=1168716 |pmid=15980354}}</ref>
[[co-amoxiclav]],<ref>{{cite journal |last1=Chambers |first1=Henry F. |last2=Kocagöz |first2=Tanil |last3=Sipit |first3=Tugrul |last4=Turner |first4=Joan |last5=Hopewell |first5=Philip C. |year=1998 |title=Activity of Amoxicillin/Clavulanate in Patients with Tuberculosis |journal=Clinical Infectious Diseases |volume=26 |issue=4 |pages=874–7 |doi=10.1086/513945 |pmid=9564467 |doi-access=}}</ref><ref>{{cite journal |last1=Peter r. Donald |first1=Frederick a. Sirge |last2=Sirgel |first2=FA |last3=Venter |first3=A |last4=Parkin |first4=DP |last5=Van De Wal |first5=BW |last6=Barendse |first6=A |last7=Smit |first7=E |last8=Carman |first8=D |last9=Talent |first9=J |last10=Maritz |first10=J |year=2001 |title=Early Bactericidal Activity of Amoxicillin in Combination with Clavulanic Acid in Patients with Sputum Smear-positive Pulmonary Tuberculosis |journal=Scandinavian Journal of Infectious Diseases |volume=33 |issue=6 |pages=466–9 |doi=10.1080/00365540152029954 |pmid=11450868 |s2cid=218876137}}</ref>
[[clofazimine]],<ref>{{cite journal |last1=Jagannath |first1=C |last2=Reddy |first2=M V |last3=Kailasam |first3=S |last4=O'Sullivan |first4=J F |last5=Gangadharam |first5=P R |year=1995 |title=Chemotherapeutic activity of clofazimine and its analogues against Mycobacterium tuberculosis. In vitro, intracellular, and in vivo studies |journal=American Journal of Respiratory and Critical Care Medicine |volume=151 |issue=4 |pages=1083–6 |doi=10.1164/ajrccm.151.4.7697235 |pmid=7697235}}</ref><ref>{{cite journal |last1=Adams |first1=Linda B. |last2=Sinha |first2=Indu |last3=Franzblau |first3=Scott G. |last4=Krahenbuhl |first4=James L. Krahenbuhl |last5=Mehta |first5=Reeta T. Mehta |year=1999 |title=Effective Treatment of Acute and Chronic Murine Tuberculosis with Liposome-Encapsulated Clofazimine |journal=Antimicrobial Agents and Chemotherapy |volume=43 |issue=7 |pages=1638–43 |doi=10.1128/AAC.43.7.1638 |pmc=89336 |pmid=10390215}}</ref><ref>{{cite journal |last1=Janulionis |first1=E. |last2=Sofer |first2=C. |last3=Song |first3=H.-Y. |last4=Wallis |first4=R. S. |year=2004 |title=Lack of Activity of Orally Administered Clofazimine against Intracellular Mycobacterium tuberculosis in Whole-Blood Culture |journal=Antimicrobial Agents and Chemotherapy |volume=48 |issue=8 |pages=3133–5 |doi=10.1128/AAC.48.8.3133-3135.2004 |pmc=478499 |pmid=15273133}}</ref>
[[prochlorperazine]],<ref>{{cite journal |last1=Shubin |first1=H |last2=Sherson |first2=J |last3=Pennes |first3=E |last4=Glaskin |first4=A |last5=Sokmensuer |first5=A |year=1958 |title=Prochlorperazine (compazine) as an aid in the treatment of pulmonary tuberculosis |journal=Antibiotic Medicine and Clinical Therapy |volume=5 |issue=5 |pages=305–9 |pmid=13521769}}</ref>
[[metronidazole]]<ref>{{cite journal |last1=Wayne |first1=L G |last2=Sramek |first2=H A |year=1994 |title=Metronidazole is bactericidal to dormant cells of Mycobacterium tuberculosis |journal=Antimicrobial Agents and Chemotherapy |volume=38 |issue=9 |pages=2054–8 |doi=10.1128/AAC.38.9.2054 |pmc=284683 |pmid=7811018}}</ref> have been used in desperation, though it is not certain whether they are effective at all.

There is no intermittent regimen validated for use in MDR-TB, but clinical experience is that giving injectable drugs for five days a week (because there is no-one available to give the drug at weekends) does not seem to result in inferior results. Directly observed therapy helps to improve outcomes in MDR-TB and should be considered an integral part of the treatment of MDR-TB.<ref name="Leimane2005">{{cite journal |doi=10.1016/S0140-6736(05)17786-1 |title=Clinical outcome of individualised treatment of multidrug-resistant tuberculosis in Latvia: A retrospective cohort study |year=2005 |last1=Leimane |first1=Vaira |last2=Riekstina |first2=Vija |last3=Holtz |first3=Timothy H |last4=Zarovska |first4=Evija |last5=Skripconoka |first5=Vija |last6=Thorpe |first6=Lorna E |last7=Laserson |first7=Kayla F |last8=Wells |first8=Charles D |author-link7=Kayla Laserson|journal=The Lancet |volume=365 |issue=9456 |pages=318–26 |pmid=15664227|s2cid=32752884 }}</ref>

Patients with MDR-TB should be isolated in negative-pressure rooms, if possible. Patients with MDR-TB should not be accommodated on the same ward as immunosuppressed patients (HIV-infected patients, or patients on immunosuppressive drugs). Careful monitoring of compliance with treatment is crucial to the management of MDR-TB (and some physicians insist on hospitalisation if only for this reason). Some physicians will insist that these patients remain isolated until their sputum is smear-negative, or even culture-negative (which may take many months, or even years). Keeping these patients in hospital for weeks (or months) on end may be a practical or physical impossibility, and the final decision depends on the clinical judgement of the physician treating that patient. The attending physician should make full use of [[therapeutic drug monitoring]] (in particular, of the aminoglycosides) both to monitor compliance and to avoid toxic effects. Response to treatment must be obtained by repeated sputum cultures (monthly if possible).<ref>{{Cite web |last=Wisconsin DHS |date=2022-08-12 |title=TB Fact Sheet Series: Sputum Collection During TB Treatment |url=https://www.dhs.wisconsin.gov/publications/p4/p47131.pdf |url-status=live |archive-url=https://web.archive.org/web/20220812213836/https://www.dhs.wisconsin.gov/publications/p4/p47131.pdf |archive-date=2022-08-12 |access-date=2022-12-07 }}</ref>

Some supplements may be useful as adjuncts in the treatment of tuberculosis, but, for the purposes of counting drugs for MDR-TB, they count as zero (if four drugs are already in the regimen, it may be beneficial to add arginine or vitamin D or both, but another drug will be needed to make five). Supplements include:
[[arginine]] (peanuts are a good source),<ref>{{cite journal |doi=10.1183/09031936.03.00090702 |title=Arginine as an adjuvant to chemotherapy improves clinical outcome in active tuberculosis |year=2003 |last1=Schon |first1=T. |last2=Elias |first2=D. |last3=Moges |first3=F. |last4=Melese |first4=E. |last5=Tessema |first5=T. |last6=Stendahl |first6=O. |last7=Britton |first7=S. |last8=Sundqvist |first8=T. |journal=European Respiratory Journal |volume=21 |issue=3 |pages=483–8 |pmid=12662006|doi-access=free }}</ref>
[[vitamin D]],<ref>{{cite journal |first1=Kirk A. |last1=Rockett |first2=Roger |last2=Brookes |first3=Irina |last3=Udalova |first4=Vincent |last4=Vidal |first5=Adrian V. S. |last5=Hill |first6=Dominic |last6=Kwiatkowski |title=1,25-Dihydroxyvitamin D3 Induces Nitric Oxide Synthase and Suppresses Growth of ''Mycobacterium tuberculosis'' in a Human Macrophage-Like Cell Line |journal=Infection and Immunity |pmid=9784538 |year=1998 |volume=66 |issue=11 |pages=5314–21 |pmc=108664 |doi=10.1128/iai.66.11.5314-5321.1998}}</ref>
[[Dzherelo]],<ref>{{cite journal |doi=10.1111/j.1469-0691.2009.02760.x |title=Treatment of cavitary and infiltrating pulmonary tuberculosis with and without the immunomodulator Dzherelo |year=2009 |last1=Zaitzeva |first1=S. I. |last2=Matveeva |first2=S. L. |last3=Gerasimova |first3=T. G. |last4=Pashkov |first4=Y. N. |last5=Butov |first5=D. A. |last6=Pylypchuk |first6=V. S. |last7=Frolov |first7=V. M. |last8=Kutsyna |first8=G. A. |journal=Clinical Microbiology and Infection |volume=15 |issue=12 |pages=1154–62 |pmid=19456829|doi-access=free }}</ref>
[[V5 Immunitor]].<ref>{{cite journal |doi=10.1186/1476-8518-9-3 |title=Phase IIb randomized trial of adjunct immunotherapy in patients with first-diagnosed tuberculosis, relapsed and multi-drug-resistant (MDR) TB |year=2011 |last1=Butov |first1=Dmitry A |last2=Pashkov |first2=Yuri N |last3=Stepanenko |first3=Anna L |last4=Choporova |first4=Aleksandra I |last5=Butova |first5=Tanya S |last6=Batdelger |first6=Dendev |last7=Jirathitikal |first7=Vichai |last8=Bourinbaiar |first8=Aldar S |last9=Zaitzeva |first9=Svetlana I |journal=Journal of Immune Based Therapies and Vaccines |volume=9 |pages=3 |pmid=21244690 |pmc=3031205 |doi-access=free }}</ref>

On 28 December 2012, the U.S. [[Food and Drug Administration]] (FDA) approved [[bedaquiline]] (marketed as Sirturo by [[Johnson & Johnson]]) to treat multidrug-resistant tuberculosis, the first new treatment in 40 years. Sirturo is to be used in a combination therapy for patients who have failed standard treatment and have no other options. Sirturo is an [[adenosine triphosphate]] synthase ([[ATP synthase]]) inhibitor.<ref>{{cite web|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm333695.htm|archive-url=https://web.archive.org/web/20130102232413/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm333695.htm?|url-status=dead|archive-date=2 January 2013|title=FDA Press Release|publisher=U.S. [[Food and Drug Administration]]|date=31 December 2012}}</ref><ref>{{cite web|url=http://www.fiercebiotech.com/story/jj-wins-accelerated-ok-first-new-tb-drug-40-years/2012-12-31|title=J&J wins accelerated OK for first new TB drug in 40 years|author=Carroll, John|publisher=fiercebiotech.com|date=31 December 2012|access-date=3 January 2013}}</ref>

The resurgence of tuberculosis in the United States, the advent of HIV-related tuberculosis, and the development of strains of TB resistant to the first-line therapies developed in recent decades serve to reinforce the thesis that ''Mycobacterium tuberculosis'', the causative organism, makes its own preferential option for the poor.{{sfn|Farmer|1999|p={{page needed|date=November 2013}}}} The simple truth is that almost all tuberculosis deaths result from a lack of access to existing effective therapy.{{sfn|Farmer|2005|p=148}}

Treatment success rates remain unacceptably low globally with variation between regions. 2016 data published by the WHO<ref name="apps.who.int">{{Cite book |last=World Health Organization |url=https://apps.who.int/iris/bitstream/handle/10665/329368/9789241565714-eng.pdf?ua=1 |title=Global Tuberculosis Report 2019 |year=2019 | publisher=World Health Organization |isbn=978-92-4-156571-4 |language=en |author-link=World Health Organization}}</ref> reported treatment success rates of multidrug-resistant TB globally. For those started on treatment for multidrug-resistant TB 56% successfully completed treatment, either treatment course completion or eradication of disease; 15% of those died while in treatment; 15% were lost to follow-up; 8% had treatment failure and there was no data on the remaining 6%. Treatment success rate was highest in the World Health Organization Mediterranean region at 65%. Treatment success rates were lower than 50% in Ukraine, Mozambique, Indonesia and India. Areas with poor TB surveillance infrastructure had higher rates of loss to follow-up of treatment.<ref name="apps.who.int"/>
[[File:Pneumothorax apparatus, London, England, 1901-1930 Wellcome L0058223.jpg|alt=Pneumothorax apparatus, London, England, 1901-1930|thumb|Before the discovery of effective antibiotics in the early 1940s, a collapsed lung might be triggered deliberately as a treatment for tuberculosis. Gases such as nitrogen and oxygen would be injected into the chest cavity, collapsing the lung and so allowing it to heal more easily. This Pneumothorax apparatus was made by the Genito-Urinary Manufacturing Co Ltd and would have been used in hospitals, especially those dedicated to treating tuberculosis patients.]]
57 countries reported outcomes for patients started on extreme-drug resistant TB, this included 9258 patients. 39% completed treatment successfully, 26% of patients died and treatment failed for 18%. 84% of the extreme drug resistant cohort was made up of only three countries; India, Russian Federation and Ukraine. Shorter treatment regimes for MDR-TB have been found to be beneficial having higher treatment success rates.<ref name="apps.who.int" />

=== Surgery ===
In cases of extremely resistant disease, surgery to remove infection portions of the lung is, in general, the final option. Early surgical treatments beginning in the 19th century include inducing lung collapse, as standing tissue heals faster than tissue in use, called artificial pneumothorax. Shrinking the lung cavity, thoracoplasty, to fill void space caused by tuberculosis damage was done by either removing ribs, raising the diaphragm, or implanting fluids or solid materials into lung cavity as a less invasive alternative to artificial pneumothorax.<ref name=":1">{{Cite journal |last=Molnar |first=Tamas F. |date=August 2018 |title=Tuberculosis: mother of thoracic surgery then and now, past and prospectives: a review |journal=Journal of Thoracic Disease |language=en |volume=1 |issue=1 |pages=S2628–S2642 |doi=10.21037/jtd.2018.04.131 |pmid=30345099 |pmc=6178290 |issn=2077-6624 |doi-access=free }}</ref> These treatments fell out of favor with the invention anti-tuberculosis drugs in the mid-20th century and have not seen a revival with MDR-TB, except for thoracoplasty done with implanted muscle tissue. Surgically removing portions of the lung, called lung resectioning, was a mostly theoretical possibility until the improved surgical tools and techniques of the mid-20th century.<ref name=":1" /> As of 2016, surgery is typically performed after 6–8 months of unsuccessful anti-TB treatment by other means.<ref name=":2">{{Cite journal |last1=Subotic |first1=Dragan |last2=Yablonskiy |first2=Piotr |last3=Sulis |first3=Giorgia |last4=Cordos |first4=Ioan |last5=Petrov |first5=Danail |last6=Centis |first6=Rosella |last7=D'Ambrosio |first7=Lia |last8=Sotgiu |first8=Giovanni |last9=Migliori |first9=Giovanni Battista |date=July 2016 |title=Surgery and pleuro-pulmonary tuberculosis: a scientific literature review |journal=Journal of Thoracic Disease |language=en |volume=8 |issue=7 |pages=E474–E485 |doi=10.21037/jtd.2016.05.59 |pmid=27499980 |pmc=4958807 |issn=2077-6624 |doi-access=free }}</ref> Surgical treatment has a high success rate, upwards of 80%, but a similarly high failure rate of upwards of 10% including the risk of death. Surgery is first focused on stabilizing cavities, or "destroyed lung", caused by the disease, followed by the removal of [[tuberculoma]]s, and then the removal of fluid and pus build up.<ref name=":2" /> Tuberculosis and lung cancer can coexist in patients as a possible complication, however the surgical therapies are similar as lung cancer surgery has its roots in aforementioned tuberculosis treatments.<ref name=":1" /><ref name=":2" />

==Epidemiology==
Cases of MDR tuberculosis have been reported in every country surveyed.<ref name="Farmer, Paul 2001">{{cite journal |doi=10.1056/NEJM200107193450310 |title=The Major Infectious Diseases in the World — to Treat or Not to Treat? |year=2001 |last1=Farmer |first1=Paul |journal=New England Journal of Medicine |volume=345 |issue=3 |pages=208–10 |pmid=11463018}}</ref> MDR-TB most commonly develops in the course of TB treatment,<ref name=Iseman1993>{{cite journal |doi=10.1056/NEJM199309093291108 |title=Treatment of Multidrug-Resistant Tuberculosis |year=1993 |last1=Wood |first1=Alastair J.J. |last2=Iseman |first2=Michael D. |journal=New England Journal of Medicine |volume=329 |issue=11 |pages=784–91 |pmid=8350889}}</ref> and is most commonly due to doctors giving inappropriate treatment, or patients missing doses or failing to complete their treatment. Because MDR tuberculosis is an airborne pathogen, persons with active, pulmonary tuberculosis caused by a multidrug-resistant strain can transmit the disease through coughing.<ref name="Farmer, Paul 2001" /> TB strains are often less fit and less transmissible, and outbreaks occur more readily in people with weakened immune systems (e.g., patients with [[HIV]]).<ref>{{cite journal |title=Nosocomial transmission of multidrug-resistant tuberculosis among HIV-infected persons—Florida and New York, 1988–1991 |journal=[[Morbidity and Mortality Weekly Report]] |volume=40 |issue=34 |pages=585–91 |date=August 1991 |pmid=1870559
 |author1=Centers for Disease Control (CDC) }}</ref><ref>{{cite journal |doi=10.1056/NEJM199206043262302 |title=An Outbreak of Multidrug-Resistant Tuberculosis among Hospitalized Patients with the Acquired Immunodeficiency Syndrome |year=1992 |last1=Edlin |first1=Brian R. |last2=Tokars |first2=Jerome I. |last3=Grieco |first3=Michael H. |last4=Crawford |first4=Jack T. |last5=Williams |first5=Julie |last6=Sordillo |first6=Emelia M. |last7=Ong |first7=Kenneth R. |last8=Kilburn |first8=James O. |last9=Dooley |first9=Samuel W. |last10=Castro |first10=Kenneth G. |last11=Jarvis |first11=William R. |last12=Holmberg |first12=Scott D. |journal=New England Journal of Medicine |volume=326 |issue=23 |pages=1514–21 |pmid=1304721|doi-access=free }}</ref><ref>{{cite journal |doi=10.1016/0140-6736(90)91987-L |title=Outbreaks of drug-resistant tuberculosis at AIDS centre |year=1990 |last1=Pitchenik |first1=Arthure |last2=Burr |first2=Janice |last3=Laufer |first3=Marla |last4=Miller |first4=Gary |last5=Cacciatore |first5=Robert |last6=Bigler |first6=Williamj. |last7=Witte |first7=Johnj. |last8=Cleary |first8=Timothy |journal=The Lancet |volume=336 |issue=8712 |pages=440–1 |pmid=1974967|s2cid=39041093 |doi-access=free }}</ref><ref>{{cite journal
 |title=Transmission of multidrug-resistant tuberculosis from an HIV-positive client in a residential substance-abuse treatment facility—Michigan |journal=[[Morbidity and Mortality Weekly Report]] |volume=40 |issue=8 |pages=129–31 |date=March 1991 |pmid=1900098
 |author1=Centers for Disease Control (CDC) }}</ref><ref>{{cite journal |doi=10.7326/0003-4819-117-3-177 |title=An Outbreak of Tuberculosis Caused by Multiple-Drug-resistant Tubercle Bacilli among Patients with HIV Infection |year=1992 |last1=Fischl |first1=Margaret A. |journal=Annals of Internal Medicine |volume=117 |issue=3 |pages=177–83 |pmid=1616211 |last2=Uttamchandani |first2=RB |last3=Daikos |first3=GL |last4=Poblete |first4=RB |last5=Moreno |first5=JN |last6=Reyes |first6=RR |last7=Boota |first7=AM |last8=Thompson |first8=LM |last9=Cleary |first9=TJ |last10=Lai |first10=S|s2cid=45415966 }}</ref> Outbreaks among non-immunocompromised healthy people do occur,<ref>{{cite journal
 |journal=[[Morbidity and Mortality Weekly Report]] |year=1990 |volume=39 |issue=22 |pages=369–72 |title=Outbreak of multidrug-resistant tuberculosis—Texas, California, and Pennsylvania |author=Centers for Disease Control |pmid=2111434 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/00001636.htm }}</ref> but are less common.<ref name=Iseman1993/>

As of 2013, 3.7% of new tuberculosis cases have MDR-TB. Levels are much higher in those previously treated for tuberculosis – about 20%. WHO estimates that there were about 0.5 million new MDR-TB cases in the world in 2011. About 60% of these cases occurred in Brazil, China, India, the Russian Federation and South Africa alone.<ref name=WHO>{{cite web|last=WHO|title=Multidrug-resistant tuberculosis (MDR-TB) 2013 Update|url=https://www.who.int/tb/challenges/mdr/MDR_TB_FactSheet.pdf|publisher=World Health Organization|access-date=14 June 2013}}</ref> In [[Moldova]], the crumbling health system has led to the rise of MDR-TB.<ref>{{cite web |last=Rochkind |first=David |title=Moldova: Fighting a Deadly Disease |url=http://pulitzercenter.org/projects/eastern-europe/moldova-fighting-deadly-disease |publisher=Pulitzer Center on Crisis Reporting |access-date=23 September 2012 |date=2010-08-09 |archive-date=11 September 2012 |archive-url=https://web.archive.org/web/20120911004034/http://pulitzercenter.org/projects/eastern-europe/moldova-fighting-deadly-disease |url-status=dead }}</ref> In 2013, the [[Mexico–United States border]] was noted to be "a very hot region for drug resistant TB", though the number of cases remained small.<ref name=mckay2013>{{cite news  |title=Risk of Deadly TB Exposure Grows Along U.S.—Mexico Border |first=Betsy |last=McKay |type=paper |page=A1 |newspaper=[[The Wall Street Journal]] |date=March 9–10, 2013 }}</ref>

A study in Los Angeles, California, found that only 6% of cases of MDR-TB were clustered. Likewise, the appearance of high rates of MDR-TB in New York City in the early 1990s was associated with the explosion of [[AIDS]] in that area.<ref>{{cite journal |doi=10.1056/NEJM199302253280801 |title=The Emergence of Drug-Resistant Tuberculosis in New York City |year=1993 |last1=Frieden |first1=Thomas R. |last2=Sterling |first2=Timothy |last3=Pablos-Mendez |first3=Ariel |last4=Kilburn |first4=James O. |last5=Cauthen |first5=George M. |last6=Dooley |first6=Samuel W. |journal=New England Journal of Medicine |volume=328 |issue=8 |pages=521–6 |pmid=8381207|doi-access=free }}</ref>{{sfn|Garrett|2000|p=266ff}} In New York City, a report issued by city health authorities states that fully 80 percent of all MDR-TB cases could be traced back to prisons and homeless shelters.{{sfn|Garrett|1994|p=524}} When patients have MDR-TB, they require longer periods of treatment. Several of the less powerful second-line drugs, which are required to treat MDR-TB, are also more toxic, with side effects such as nausea, abdominal pain, and even psychosis. The Partners in Health team had treated patients in Peru who were sick with strains that were resistant to ten and even twelve drugs. Most such patients require adjuvant surgery for any hope of a cure.{{sfn|Farmer|2005|p=118}}

=== Somalia ===
MDR-TB is widespread in Somalia, where 8.7% of newly discovered TB cases are resistant to Rifampicin and Isoniazid, in patients which were treated previously the share was 47%.<ref name="Ärzteblatt">{{Cite web|url=https://www.aerzteblatt.de/nachrichten/72186/MDR-Tuberkulose-unter-Migranten-aus-Somalia|title=MDR-Tuberkulose unter Migranten aus Somalia|last=Ärzteblatt|first=Deutscher Ärzteverlag GmbH, Redaktion Deutsches|date=2016-12-27|website=Deutsches Ärzteblatt|language=de|access-date=2019-09-27}}</ref>

Refugees from Somalia brought an until then unknown variant of MDR tuberculosis with them to Europe. A few number of cases in four different countries were considered by the [[European Centre for Disease Prevention and Control]] to pose no risk to the native population.<ref name="Ärzteblatt"/>

===Russian prisons===
One of the so-called "hot-spots" of drug-resistant tuberculosis is within the [[Russian prisons|Russian prison system]]. Infectious disease researchers Nachega & Chaisson report that 10% of the one million prisoners within the system have active TB.<ref name="Nachega">{{cite journal | author = Nachega J., Chaisson R. | year = 2003 | title = Tuberculosis Drug Resistance: A Global Threat | journal = Clinical Infectious Diseases | volume = 36 | issue = 1| pages = S24–S30 | doi=10.1086/344657| pmid = 12516027 | doi-access = free }}</ref> One of their studies found that 75% of newly diagnosed inmates with TB are resistant to at least one drug; 40% of new cases are multidrug-resistant.<ref name="Nachega"/> In 1997, TB accounted for almost half of all Russian prison deaths, and as Bobrik et al. point out in their public health study, the 90% reduction in TB incidence contributed to a consequential fall in the prisoner death rate in the years following 1997.<ref name="Bobrik">{{cite journal |author1=Bobrik A. |author2=Danishevski K. |author3=Eroshina K. |author4=McKee M. | year = 2005 | title = Prison Health in Russia: The Larger Picture | journal = Journal of Public Health Policy | volume = 26 | issue = 1| pages = 30–59 | doi=10.1057/palgrave.jphp.3200002|pmid=15906874 |s2cid=2102820 }}</ref> Baussano et al. articulate that concerning statistics like these are especially worrisome because spikes in TB incidence in prisons are linked to corresponding outbreaks in surrounding communities.<ref name="Bassauno">{{cite journal |author1=Baussano I. |author2=Williams B. |author3=Nunn P. |author4=Beggiato M. |author5=Fedeli U. | year = 2010 | title = Tuberculosis Incidence in Prisons: A Systematic Review | journal = PLOS Medicine | volume = 7 | issue = 12| page = e1000381 | doi = 10.1371/journal.pmed.1000381 |pmid=21203587 |pmc=3006353 |doi-access=free }}</ref> Additionally, rising rates of incarceration, especially in Central Asian and Eastern European countries like Russia, have been correlated with higher TB rates in civilian populations.<ref name="Bobrik" /> Even as the [[DOTS|DOTS program]] is expanded throughout Russian prisons, researchers such as Shin et al. have noted that wide-scale interventions have not had their desired effect, especially with regard to the spread of drug-resistant strains of TB.<ref name="Shin">{{cite journal |author1=Shin S. S. |author2=Pasechnikov A. |author3=Gelmanova I. |author4=Peremitin G. |author5=Strelis A. |author6=Andreev Y. |author7=Golubchikova V. |author8=Tonkel T. |author9=Yanova G. |author10=Nikiforov M. |author11=Yedilbayev A. |author12=Mukherjee J. |author13=Furin J. |author14=Barry D. |author15=Farmer P. |author16=Rich M. |author17=Keshavjee S. | year = 2006 | title = Treatment outcomes in an integrated civilian and prison MDR-TB treatment program in Russia | journal = The International Journal of Tuberculosis and Lung Disease | volume = 10 | issue = 4| pages = 402–407 |pmid=16602404 }}</ref>

====Contributing factors====
There are several elements of the Russian prison system that enable the spread of MDR-TB and heighten its severity. Overcrowding in prisons is especially conducive to the spread of tuberculosis; an inmate in a prison hospital has (on average) 3 meters of personal space, and an inmate in a correctional colony has 2 meters.<ref name="Bobrik"/> Specialized hospitals and treatment facilities within the prison system, known as TB colonies, are intended to isolate infected prisoners to prevent transmission; however, as Ruddy et al. demonstrate, there are not enough of these colonies to sufficiently protect staff and other inmates.<ref name="Ruddy"/> Additionally, many cells lack adequate ventilation, which increases likelihood of transmission. Bobrik et al. have also noted food shortages within prisons, which deprive inmates of the nutrition necessary for healthy functioning.<ref name="Bobrik"/>

Comorbidity of [[HIV]] within prison populations has also been shown to worsen health outcomes. Nachega & Chaisson articulate that while HIV-infected prisoners are not more susceptible MDR-TB infection, they are more likely to progress to serious clinical illness if infected.<ref name="Nachega"/> According to Stern, HIV infection is 75 times more prevalent in Russian prison populations than in the civilian population.<ref name="Stern"/> Therefore, prison inmates are both more likely to become infected with MDR-TB initially and to experience severe symptoms because of previous exposure to HIV.{{cn|date=March 2023}}

Shin et al. emphasize another factor in MDR-TB prevalence in Russian prisons: alcohol and substance use.<ref name="Shin"/> Ruddy et al. showed that risk for MDR-TB is three times higher among recreational drug users than non-users.<ref name="Ruddy"/> Shin et al.'s study demonstrated that alcohol usage was linked to poorer outcomes in MDR-TB treatment; they also noted that a majority of subjects within their study (many of whom regularly used alcohol) were nevertheless cured by their aggressive treatment regimen.<ref name="Shin"/>

Non-compliance with treatment plans is often cited as a contributor to MDR-TB transmission and mortality. Indeed, of the 80 newly released TB-infected inmates in Fry et al.'s study, 73.8% did not report visiting a community dispensary for further treatment.<ref name="Fry">{{cite journal |author1=Fry R. |author2=Khoshnood K. |author3=Vdovichenko E. |author4=Granskaya J. |author5=Sazhin V. |author6=Shpakovskaya L |author7=Zhemkov V. |author8=Zhemkova M. |author9=Rowhani-Rahbar A. |author10=Funk M. |author11=Kozlov A. | year = 2005 | title = Barriers to completion of tuberculosis treatment among prisoners and former prisoners in St. Petersburg, Russia | journal = The International Journal of Tuberculosis and Lung Disease | volume = 9 | issue = 9| pages = 1027–1033 |pmid=16158896 }}</ref> Ruddy et al. cite release from facilities as one of the main causes of interruption in prisoner's TB treatment, in addition to non-compliance within the prison and upon reintegration into civilian life.<ref name="Ruddy"/> Fry et al.'s study also listed side effects of TB treatment medications (especially in HIV positive individuals), financial worries, housing insecurities, family problems, and fear of arrest as factors that prevented some prisoners from properly adhering to TB treatment.<ref name="Fry"/> They also note that some researchers have argued that the short-term gains TB-positive prisoners receive, such as better food or work exclusion, may dis-incentivize becoming cured.<ref name="Fry"/> In their World Health Organization article, Gelmanova et al. posit that non-adherence to TB treatment indirectly contributes to bacterial resistance.<ref name="Gelmanova">{{cite journal |author1=Gelmanova I. |author2=Keshavjee S. |author3=Golubchikova V. |author4=Berezina V. |author5=Strelis A. |author6=Yanova G. |author7=Atwood S. |author8=Murray M. | year = 2007 | title = Barriers to successful tuberculosis treatment in Tomsk, Russian Federation: non-adherence, default and the acquisition of multidrug resistance | journal = Bulletin of the World Health Organization | volume = 85 | issue = 9|pages=703–11 |doi=10.2471/BLT.06.038331 |pmid=18026627 |pmc=2636414 }}</ref> Although ineffective or inconsistent treatment does not "create" resistant strains, mutations within the high bacterial load in non-adherent prisoners can cause resistance.

Nachega & Chaisson argue that inadequate TB control programs are the strongest driver of MDR-TB incidence.<ref name="Nachega"/> They note that prevalence of MDR-TB is 2.5 times higher in areas of poorly controlled TB.<ref name="Nachega"/> Russian-based therapy (i.e., not DOTS) has been criticized by Kimerling et al. as "inadequate" in properly controlling TB incidence and transmission.<ref name="Kimerling">{{cite journal |author1=Kimerling M.E. |author2=Kluge H. |author3=Vezhnina N. |author4=Iacovazzi T. |author5=Demeulenaere T. |author6=Portaels F. |author7=Matthys F. | year = 1999 | title = Inadequacy of the current WHO re-treatment regimen in a central Siberian prison: treatment failure and MDR-TB. | journal = The International Journal of Tuberculosis and Lung Disease | volume = 3 | issue = 5| pages = 451–453 |title-link=WHO |pmid=10331736 }}</ref> Bobrik et al. note that treatment for MDR-TB is equally inconsistent; the second-line drugs used to treat the prisoners lack specific treatment guidelines, infrastructure, training, or follow-up protocols for prisoners reentering civilian life.<ref name="Bobrik"/>

====Policy impacts====

As Ruddy et al. note, Russia's early 2000s penal reforms could greatly reduce the number of inmates inside prison facilities and thus increase the number of ex-convicts integrated into civilian populations.<ref name="Ruddy">{{cite journal |author1=Ruddy M. |author2=Balabanova Y. |author3=Graham C. |author4=Fedorin I. |author5=Malomanova N. |author6=Elisarova E. |author7=Kuznetznov S. |author8=Gusarova G. |author9=Zakharova S. |author10=Melentyev A. |author11=Krukova E. |author12=Golishevskaya V. |author13=Erokhin V. |author14=Dorozhkova I. |author15=Drobniewski F. | year = 2005 | title = Rates of drug resistance and risk factor analysis in civilian and prison patients with tuberculosis in Samar Region, Russia | journal = Thorax | volume = 60 | issue = 2| pages = 130–135 | doi=10.1136/thx.2004.026922|pmid=15681501 |pmc=1747303 }}</ref> Because the incidence of MDR-TB is strongly predicted by past imprisonment, the health of Russian society will be greatly impacted by this change.<ref name="Ruddy"/> Formerly incarcerated Russians will re-enter civilian life and remain within that sphere; as they live as civilians, they will infect others with the contagions they were exposed to in prison. Researcher Vivian Stern argues that the risk of transmission from prison populations to the general public calls for an integration of prison healthcare and national health services to better control both TB and MDR-TB.<ref name="Stern">Stern, V. (2001). Problems in Prisons Worldwide, with a Particular Focus on Russia. ''Annals of the New York Academy of Sciences'', 953b, 113-119.</ref> While second-line drugs necessary for treating MDR-TB are arguably more expensive than a typical regimen of DOTS therapy, infectious disease specialist [[Paul Farmer]] posits that the outcome of leaving infected prisoners untreated could cause a massive outbreak of MDR-TB in civilian populations, thereby inflicting a heavy toll on society.<ref name="Farmer">{{cite journal | author = Farmer P | year = 1999 | title = Pathologies of power: rethinking health and human rights | journal = American Journal of Public Health | volume = 89 | issue = 10| pages = 1486–1496 | doi=10.2105/ajph.89.10.1486| pmid = 10511828 | pmc = 1508789}}</ref> Additionally, as MDR-TB spreads, the threat of the emergence of [[Totally-drug-resistant tuberculosis|totally-drug-resistant TB]] becomes increasingly apparent.{{cn|date=March 2023}}

==See also==
* [[2007 tuberculosis scare]]
* [[Drug resistance]]
* [[Methicillin-resistant Staphylococcus aureus|MRSA]]
* [[Vancomycin-resistant enterococcus]] (VRE)
* [[Totally drug-resistant tuberculosis]] (TDR-TB)
* [[Medicines Patent Pool]]

==References==
{{Reflist}}

;Notes
* {{cite book |last1=Farmer |first1=Paul |title=Infections and inequalities : the modern plagues |url=https://archive.org/details/infectionsinequa0000farm |url-access=registration |publisher=[[University of California Press]] |location=Berkeley, California, United States |year=1999 |isbn=978-0-520-22913-6 }}
* {{cite book |last1=Farmer |first1=Paul |title=Pathologies of Power: health, human rights, and the new war on the poor |publisher=[[University of California Press]] |location=Berkeley, California, United States |year=2005 |isbn=978-0-520-93147-3 }}
* {{cite book |last1=Garrett |first1=Laurie |title=The coming plague : newly emerging diseases in a world out of balance |publisher=[[Farrar, Straus and Giroux]] |location=New York, New York, United States |year=1994 |isbn=978-0-374-12646-9 |url=https://archive.org/details/comingplaguenew000garr }}
* {{cite book |last1=Garrett |first1=Laurie |title=Betrayal of trust: the collapse of global public health |publisher=[[Hachette Books|Hyperion Books]] |location=New York, New York, United States |year=2000 |isbn=978-0-7868-6522-2 |url=https://archive.org/details/betrayaloftrustc00garr_0 }}

==Further reading==
* {{cite web|author=American Lung Association|author-link=American Lung Association|date=April 2007|title=Multidrug Resistant Tuberculosis Fact Sheet|url=http://www.lungusa.org/site/pp.aspx?c=dvLUK9O0E&b=35815|access-date=29 November 2007|url-status=dead|archive-url=https://web.archive.org/web/20061130122651/http://www.lungusa.org/site/pp.aspx?c=dvLUK9O0E&b=35815|archive-date=30 November 2006}}

==External links==
{{Medical resources
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|  ICD10          = {{ICD10|Z16.24}}
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* [https://web.archive.org/web/20110605111631/http://www.wilsoncenter.org/index.cfm?topic_id=116811&fuseaction=topics.event_summary&event_id=239772 Video: Drug-Resistant TB in Russia] 24 July 2007, [[Woodrow Wilson Center]] event featuring Salmaan Keshavjee and [[Murray Feshbach]]
* [https://web.archive.org/web/20111111155206/http://www.tbcindia.org/pdfs/DOTS_Plus_Guidelines_Jan2010.pdf MDR-TB (DOTS Plus) protocol followed under RNTCP in India (PDF)]
* [https://www.buzzfeed.com/natalieshure/you-never-think-about-tuberculosis-until-you-lose-two-years "The Strange, Isolated Life of a Tuberculosis Patient in the 21st Century"], Buzzfeed

{{Gram-positive actinobacteria diseases}}
{{Tuberculosis}}
{{Authority control}}

{{DEFAULTSORT:Multidrug-Resistant Tuberculosis}}
[[Category:Antibiotic-resistant bacteria]]
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[[Category:Tuberculosis]]