Extensively Drug-Resistant Tuberculosis

Tuberculosis resistant to ISONIAZID and RIFAMPIN and at least three of the six main classes of second-line drugs (AMINOGLYCOSIDES; polypeptide agents; FLUOROQUINOLONES; THIOAMIDES; CYCLOSERINE; and PARA-AMINOSALICYLIC ACID) as defined by the CDC.

Also Known As:

Extremely Drug-Resistant Tuberculosis; Tuberculosis, Extremely Drug-Resistant; XDR-TB; Drug-Resistant Tuberculoses, Extensively; Drug-Resistant Tuberculoses, Extremely; Drug-Resistant Tuberculosis, Extensively; Drug-Resistant Tuberculosis, Extremely; Extensively Drug Resistant Tuberculosis; Extensively Drug-Resistant Tuberculoses; Extremely Drug Resistant Tuberculosis; Extremely Drug-Resistant Tuberculoses; Tuberculoses, Extensively Drug-Resistant; Tuberculoses, Extremely Drug-Resistant; Tuberculosis, Extensively Drug Resistant; Tuberculosis, Extremely Drug Resistant; Tuberculosis, Extensively Drug-Resistant

Networked: 712 relevant articles (59 outcomes, 94 trials/studies)

Relationship Network

Disease Context: Research Results

Infections: 526564
- Bacterial Infections and Mycoses: 1
  - Bacterial Infections: 24368
    - Gram-Positive Bacterial Infections: 348
      - Actinomycetales Infections: 1
        Mycobacterium Infections: 93
        Tuberculosis: 48666
        Multidrug-Resistant Tuberculosis: 2430
        Extensively Drug-Resistant Tuberculosis: 712

Related Diseases

1.	Tuberculosis (Tuberculoses)
2.	Multidrug-Resistant Tuberculosis (Drug-Resistant Tuberculosis)
3.	Extensively Drug-Resistant Tuberculosis
4.	Infections
5.	Latent Infection

Experts

1.	Migliori, Giovanni Battista: 42 articles (01/2020 - 01/2007)
2.	Centis, Rosella: 34 articles (03/2022 - 10/2007)
3.	D'Ambrosio, Lia: 28 articles (03/2022 - 12/2012)
4.	Sotgiu, Giovanni: 26 articles (01/2021 - 11/2008)
5.	Dheda, Keertan: 23 articles (01/2022 - 12/2009)
6.	Tiberi, Simon: 22 articles (03/2022 - 06/2013)
7.	Zumla, Alimuddin: 18 articles (03/2022 - 05/2010)
8.	Skrahina, Alena: 16 articles (01/2021 - 02/2012)
9.	Lange, Christoph: 15 articles (01/2021 - 12/2007)
10.	Spanevello, Antonio: 15 articles (01/2019 - 10/2009)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Extensively Drug-Resistant Tuberculosis:

1.	Linezolid (Zyvox)FDA Link 06/01/2012 - "Our findings suggest that linezolid at a daily dose of 300 mg is effective against intractable MDR/XDR-TB, and may be associated with fewer neuropathic side effects than a daily dose of 600 or 1200 mg." 09/30/2020 - "The aim of this review was to present the efficacy of linezolid as an agent against multidrug and extensively drug-resistant tuberculosis as gathered from many recent research studies. " 08/01/2010 - "Larger numbers of patients should be studied to confirm the efficacy of the linezolid 300 mg twice-daily dosage in MDR-TB or XDR-TB treatment." 08/01/2009 - "We describe a young child with pulmonary XDR-TB who did not respond to an aggressive multidrug-resistant TB treatment regimen, but was cured with linezolid in combination with other reserve antituberculous drugs. " 05/01/2009 - "Adjunctive surgical treatment and linezolid improved the outcome for selected patients with XDR-TB."
2.	bedaquiline (R207910)IBA 01/01/2019 - "The use of bedaquiline in MDR and XDR TB treatment regimens appears to be effective and safe across different settings, although the certainty of evidence was assessed as very low." 01/01/2022 - "Recent clinical findings reported improved treatment outcomes of XDR-TB with the bedaquiline (BDQ)-based regimens. " 04/01/2021 - "Early outcome and safety of bedaquiline-containing regimens for treatment of MDR- and XDR-TB in China: a multicentre study." 03/19/2021 - "The aim of the study is to evaluate the frequency and severity of adverse events (AEs) of bedaquiline-containing regimen in a cohort of Chinese patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-TB based on active drug safety monitoring (aDSM) system of New Drug Introduction and Protection Program (NDIP). " 01/01/2020 - "The aim of the study was to determine the incidence of adverse effects caused by bedaquiline in patients diagnosed with XDR-TB. "
3.	VaccinesIBA 01/01/2017 - "This vaccine provided remarkable protective efficacy and strong therapeutic efficacy against MDR-TB and XDR-TB in murine models. " 01/01/2011 - "This vaccine also provided therapeutic efficacy against multi-drug resistant TB (MDR-TB) and extremely drug resistant TB (XDR-TB) in murine models. " 06/01/2010 - "This vaccine also provided therapeutic efficacy against multidrug resistant TB (MDR-TB) and extremely drug resistant TB (XDR-TB) in murine models. " 01/01/2010 - "This vaccine also provided therapeutic efficacy against multi-drug resistant TB (MDR-TB) and extremely drug resistant TB (XDR-TB) (prolongation of survival time and the decrease in the number of TB in the lung) in murine models. " 05/26/2009 - "This vaccine provided therapeutic efficacy as well as remarkable protective efficacy via CD8(+) T and CD4(+) T cells in murine models compared with the saline controls, on the basis of CFU of number of multi-drug resistant TB (MDR-TB), and survival of extremely drug resistant TB (XDR-TB) challenged mice. "
4.	pretomanidIBA 12/03/2021 - "BPaL for XDR-TB is likely to be cost saving in all study settings when pretomanid is priced at the Global Drug Facility list price. " 01/01/2022 - "These data support the use of pretomanid as part of the 6-month BPaL regimen for treating XDR-TB and MDR-TB." 02/01/2021 - "Pretomanid (PA-824) is the recently (2019) approved drug for the treatment of extensively drug-resistant (XDR) TB and the multidrug-resistant (MDR) TB by US FDA. " 11/17/2021 - "The newly approved regimen combining BDQ with pretomanid and linezolid is the first 6-month oral regimen proven to be effective against MDR/XDR-TB. " 01/01/2023 - "A newly approved regimen combining LZD with bedaquiline (BDQ) and pretomanid (PMD) (BPaL regimen) is the first 6-month oral regimen that is effective against multidrug- and extensively drug-resistant tuberculosis. "
5.	Thioridazine (Mellaril)FDA LinkGeneric 05/01/2011 - "Safety and efficacy of thioridazine as salvage therapy in Indian patients with XDR-TB." 03/01/2012 - "Potential therapy of multidrug-resistant and extremely drug-resistant tuberculosis with thioridazine." 06/01/2010 - "Although thioridazine is beyond patent protection, its use for the therapy of XDR TB is new and therefore, a patent may be sought for "use as an anti-XDR TB agent"." 06/01/2010 - "Therapy Of XDR TB with thioridazine a drug beyond patent protection but eligible for patent "as new use"." 09/01/2008 - "Promising therapy of XDR-TB/MDR-TB with thioridazine an inhibitor of bacterial efflux pumps."
6.	Drug CombinationsIBA 12/25/2022 - "In recent years, the use of new anti-TB drugs, repurposed drugs, and their drug combinations has greatly improved treatment outcomes in patients with both drug-susceptible TB and MDR/XDR-TB. " 01/01/2014 - "The efficacy of PAS-GR appears equivalent to that of PAS, and its tolerance improved over earlier PAS formulations, thus supporting the use of PAS-GR as part of drug combinations for the treatment of MDR and XDR-TB." 04/01/2019 - "Effective drug combinations and appropriate use of new drugs may improve treatment outcomes of FQ-R MDR and XDR TB. " 01/01/2020 - "We evaluated the safety and efficacy of the drug combination for 26 weeks in patients with extensively drug-resistant tuberculosis and patients with multidrug-resistant tuberculosis that was not responsive to treatment or for which a second-line regimen had been discontinued because of side effects. " 08/01/2019 - "Our in vitro data demonstrate no observed synergistic effects against XDR-TB for drug combinations that included BDQ in combination with MFX, GAT, LZD, or CLO."
7.	FluoroquinolonesIBA 04/01/2019 - "Improved Fluoroquinolone-Resistant and Extensively Drug-Resistant Tuberculosis Treatment Outcomes." 10/17/2017 - "Overall, studies from Western states of India reported highest prevalence of DR-TB (57.8% [95% CI = 37.4; 78.2], n = 6) and MDR-TB (39.9% [95% CI = 21.7; 58.0], n = 6) during decade 2. Prevalence of pre-XDR TB was 7.9% (95% CI = 4.4; 11.4, n = 5) with resistance to fluoroquinolone (66.3% [95% CI = 58.2; 74.4], n = 5) being the highest. " 09/08/2016 - "Extensively drug-resistant tuberculosis: indirect testing, MTBDRsl pooled sensitivity and specificity were 70.9% (42.9% to 88.8%) and 98.8% (96.1% to 99.6%), (eight studies, 880 participants); direct testing (smear-positive specimen), pooled sensitivity and specificity were 69.4% (38.8% to 89.0%) and 99.4% (95.0% to 99.3%), (six studies, 1420 participants, low quality evidence).Similar to the original Cochrane review, we found no evidence of a significant difference in MTBDRsl version 1.0 accuracy between indirect and direct testing for fluoroquinolone resistance, SLID resistance, and extensively drug-resistant tuberculosis. " 07/01/2010 - "These results suggest that the addition of later-generation fluoroquinolones to XDR TB regimens may improve treatment outcomes and should be systematically evaluated in well-designed clinical studies." 09/30/2022 - "Moreover, the resistance to fluoroquinolones is also on the rise, a characteristic of extensively drug-resistant TB (XDR TB). "
8.	OPC-67683IBA 01/14/2021 - "In this study, we assessed cardiovascular safety and effectiveness (culture conversion, treatment outcomes and post-treatment recurrence) of delamanid-containing regimens among adults (>18 years) with MDR-TB or XDR-TB from June 2016 to February 2018. " 01/01/2018 - "In addition, recent results outside clinical studies show favourable responses in highly resistant TB patients including extensively drug resistant (XDR)-TB when treated with delamanid-containing regimens in routine programmatic settings. " 01/01/2018 - "The purpose of this study was to evaluate the efficacy as well as the safety and tolerability of a delamanid-containing regimen for 24 weeks in the treatment of MDR- and XDR-TB. " 07/01/2017 - "One of the studies retrieved reported evidence on 19 M/XDR-TB children, 16 of them treated under compassionate use with delamanid (13 achieving consistent bacteriological conversion) and 3 candidates for the drug. " 01/14/2021 - "Effectiveness and cardiovascular safety of delamanid-containing regimens in adults with multidrug-resistant or extensively drug-resistant tuberculosis: A nationwide cohort study from Belarus, 2016-18."
9.	Clofazimine (Lamprene)FDA Link 11/01/2014 - "Clofazimine was associated with improved culture conversion in the treatment of XDR-TB/HIV. " 11/01/2014 - "Based on these preliminary data, further study of clofazimine in XDR-TB/HIV treatment is warranted. " 11/01/2014 - "Given the present low rates of culture conversion in XDR-TB treatment, we recommend empirical inclusion of clofazimine in treatment regimens for XDR-TB." 11/01/2014 - "This was a retrospective cohort study of adult XDR-TB patients in KwaZulu-Natal, South Africa, treated with either a clofazimine- or non-clofazimine-containing XDR-TB treatment regimen. " 01/02/2014 - "Safety and availability of clofazimine in the treatment of multidrug and extensively drug-resistant tuberculosis: analysis of published guidance and meta-analysis of cohort studies."
10.	Anti-Bacterial Agents (Antibiotics)IBA 06/01/2015 - "This study confirms that primary transmission of drug-resistant TB, including MDR/XDR-TB, is a real threat to achieving effective control of drug-resistant TB in the Guizhou Province and indicates the necessity to determine antibiotic susceptibility patterns in patients with TB to improve treatment outcomes. " 01/01/2022 - "The outstanding genetic arsenal of this geographically widespread M/XDR strain clade represents a "perfect storm" that jeopardizes the successful introduction of new anti-M/XDR-TB antibiotic regimens." 05/16/2019 - "Multidrug-resistant TB (MDR-TB) was found in 2 cases (0.28%) (95% CI: 0.08-1.02), 1.68% were resistant to only one antibiotic, 0.14% had rifampicine-resistant TB (RR-TB), 0.28% had MDR-TB, and 0.14% had extensively drug-resistant TB (XDR-TB). " 01/01/2019 - "Azaaurones as Potent Antimycobacterial Agents Active against MDR- and XDR-TB." 08/29/2018 - "Our results showed evolutionary changes in the serial genetic characteristics of the pre-XDR TB patients due to accumulation of the fixed drug-resistant related mutations, and the transient mutations under continuous antibiotics pressure over several years."

Therapies and Procedures

1.	Therapeutics 09/01/2007 - "Once no reliable therapy is available, the best way to prevent XDR-Tb is to ensure the efficacy of national TB control programs. " 04/01/2019 - "Our findings highlight the need for improved adherence, better-tolerated and shorter therapies, and enhanced posttreatment surveillance among patients treated for XDR-TB." 10/01/2010 - "Concurrent XDR-TB and HIV therapy is feasible and effective in children, although more research is needed into potential overlapping toxicities. " 09/01/2013 - "This study illustrates the growing epidemic of MDR and XDR-TB, it emphasizes the importance of proper diagnosis and adequate management of TB in patients at risk for resistance and stresses the need for new therapies." 06/01/2010 - "Because XDR-TB is essentially a terminal disease in many areas of the world and no new effective agents have yet to yield successful clinical trials, global clinical trials for the therapy of XDR-TB are urgently required."
2.	Duration of Therapy 01/01/2021 - "Due to the commencement of MDR-TB (multi-drug resistance) and XDR-TB (extensively drug resistance), there is a crucial need for the development of novel anti-tubercular agents with improved characteristics such as low toxicity, enhanced inhibitory activity and short duration of treatment. " 04/01/2018 - "Various trials and studies have recently been undertaken (some already published and others ongoing), all aimed at improving outcomes of M/XDR-TB treatment by changing the overall approach, shortening treatment duration, and developing a universal regimen. " 11/01/2018 - "These new targets bring with them the aspiration of shortening treatment duration as well as a pipeline of effective regimens against XDR-TB, positioning Mtb drug discovery to become a model for anti-infective discovery." 04/01/2018 - "Treating M/XDR-TB continues to be a difficult task, because of the high incidence of adverse events, the long duration of treatment, the high cost of the regimens used, and the drain on health care resources. " 01/01/2016 - "Our results indicated that a small fraction of people knew the exact definition and treatment duration of MDR TB and XDR TB in our society. "
3.	Drug Therapy (Chemotherapy) 12/01/2008 - "Pulmonary resection under cover of state-of-the-art chemotherapy is safe and effective for patients with localized extensively drug-resistant tuberculosis." 08/01/2012 - "With appropriate chemotherapy and timely adjuvant surgery, patients with XDR-TB localized to lobe or lung may achieve a "cure" with low morbidity and mortality. " 03/01/2020 - "It can be used for molecular diagnosis of MDR- and XDR-TB to rapidly initiate appropriate anti-TB drug therapy." 03/01/2017 - "XDR-TB should be suspected if there is clinical and/or radiological progression of TB in spite of chemotherapy or a prior history of treatment for TB. " 03/01/2017 - "We present a case of spinal XDR-TB in a child, managed with extended second-line antitubercular chemotherapy (ATT). "
4.	Salvage Therapy 05/01/2011 - "Safety and efficacy of thioridazine as salvage therapy in Indian patients with XDR-TB."
5.	Thoracotomy 03/01/2016 - "In the XDR-TB/HIV-negative group, 1 patient was cured, 3 converted and 1 patient developed a post-thoracotomy superficial wound infection. "