DOCSLIB.ORG

Evolution of Drug Resistance in Mycobacterium Tuberculosis: a Review on the Molecular Determinants of Resistance and Implications for Personalized Care

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Evolution of Drug Resistance in Mycobacterium Tuberculosis: a Review on the Molecular Determinants of Resistance and Implications for Personalized Care CORE Metadata, citation and similar papers at core.ac.uk Provided by ResearchSpace@UKZN J Antimicrob Chemother 2018; 73: 1138–1151 doi:10.1093/jac/dkx506 Advance Access publication 19 January 2018 Evolution of drug resistance in Mycobacterium tuberculosis: a review on the molecular determinants of resistance and implications for personalized care Navisha Dookie1*, Santhuri Rambaran1, Nesri Padayatchi1,2, Sharana Mahomed1 and Kogieleum Naidoo1,2 1Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa; 2South African Medical Research Council (SAMRC) - CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Durban, South Africa *Corresponding author. CAPRISA, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Private Bag X7, Congella, 4013 South Africa. Tel: !27 31 260 4703; Fax: !27 31 260 4549; E-mail: [email protected] Drug-resistant TB (DR-TB) remains a significant challenge in TB treatment and control programmes worldwide. Advances in sequencing technology have significantly increased our understanding of the mechanisms of resistance to anti-TB drugs. This review provides an update on advances in our understanding of drug resistance mechanisms to new, existing drugs and repurposed agents. Recent advances in WGS technology hold promise as a tool for rapid diagnosis and clinical management of TB. Although the standard approach to WGS of Mycobacterium tuberculosis is slow due to the requirement for organism culture, recent attempts to sequence directly from clinical specimens have improved the potential to diagnose and detect resistance within days. The introduction of new databases may be helpful, such as the Relational Sequencing TB Data Platform, which contains a collection of whole-genome sequences highlighting key drug resistance mutations and clinical outcomes. Taken together, these advances will help devise better molecular diagnostics for more effective DR-TB management enabling personalized treatment, and will facilitate the development of new drugs aimed at improving outcomes of patients with this disease. Introduction including treatment failure and mortality. The management of DR- TB is further compounded by the high cost, long duration and debili- Resistance to anti-TB drugs is an escalating global health crisis. tating toxicity of currently available second-line drugs.3 Current The global burden of TB remains alarmingly high, with 10.4 mil- treatment guidelines indicate standardized fixed dose 6 month reg- lion incident cases and 1.5 million deaths reported by the WHO imens for new treatment and re-treatment of drug-susceptible TB in 2015.1 Mycobacterium tuberculosis (MTB) strains displaying (DS-TB). In the case of DR-TB, the conventional 18–24 month treat- in vitro resistance to isoniazid and rifampicin accounted for ment regimen has been redesigned and now ranges between 9 480000 incident cases and 250000 deaths in 2015.1 XDR-TB and 24 months based on individual patient eligibility such as pre- strains display additional resistance to both the fluoroquinolones vious TB history and drug exposure. In addition to duration, complex and second-line injectable agents, and have been reported to 1,2 multidrug regimens and optimal medication adherence are cause disease in 106 countries to date. With high mortality 9,10 rates, XDR-TB poses a dire threat to public health, exacerbated by required for effective treatment of TB infection. Challenges its deadly interaction with the HIV/AIDS epidemic. of adherence are linked to complex dosing strategies, serious and Additional resistance beyond XDR has been described as totally often life-threatening drug side effects, and drug–drug interactions. drug-resistant TB, which displays further resistance to drugs used This review provides an update on scientific advances in under- to treat XDR-TB, resulting in programmatically untreatable forms standing drug resistance mechanisms in MTB, to new, existing and of TB.3 This, coupled with estimates from published studies that repurposed drugs. We also highlight developments in sequencing suggest that current treatment options for XDR-TB fail to cure technology and bioinformatics that enable personalized therapy 30%–75% of patients with XDR-TB, contributes to an emerging for DR-TB. public health crisis.4–8 New drugs such as bedaquiline and delama- nid, and repurposed drugs such as linezolid, have been introduced Implications for personalized therapy into drug-resistant TB (DR-TB) treatment regimens. Despite the for DR-TB availability of new drugs, limited access to these agents and/or the inability to construct an effective regimen containing at least four The diagnosis of DR-TB remains a challenge. Currently, the front- active drugs, contribute to ongoing poor outcomes in DR-TB, line molecular diagnostic assay for the detection of drug resistance VC The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] 1138 Review JAC is the Cepheid Xpert MTB/RIF (GeneXpert), which detects the pres- that the rate of mutations causing drug resistance varies according ence of MTB bacilli and simultaneously detects rifampicin resist- to the lineage to which the strain belongs. The Beijing strain family, ance.11 Whilst rapidly identifying patients eligible for MDR-TB which is strongly associated with DR-TB in many settings, has treatment, the test is limited to the detection of rifampicin resist- demonstrated increased mutation rates in vitro.32–34 ance. In addition to the GeneXpert, the WHO endorsed the use of The following section details the mutations mediating resist- the Hain line probe assay.12 Current versions include the Genotype ance to each of the anti-TB drugs. Table 1 summarizes the genes MTBDRplus and Genotype MTBDRsl-v2.0, which collectively detect associated with resistance, MICs and mutation frequencies to resistance to isoniazid, rifampicin, fluoroquinolones and second- existing anti-TB agents and new/repurposed agents, respectively. line injectable agents.13,14 However, analysis of published perform- 15,16 ance data of the tests shows suboptimal sensitivities. Thus, Mechanisms of resistance to first-line drugs WGS remains the most desirable platform to perform follow-on testing on rifampicin-resistant TB, which can accelerate the initia- Isoniazid tion of effective treatment. Isoniazid is a prodrug activated by the catalase/peroxidase The current gold standard for MTB drug susceptibility testing enzyme encoded by the katG gene. Once activated, isoniazid inhib- (DST) is culture on solid media, which takes several weeks to months its mycolic acid synthesis via the NADH-dependent enoyl-acyl owing to the slow growth rate of TB in vitro.Treatmentistherefore carrier protein reductase, encoded by the inhA gene.23,24 The often empirical, based on factors such as past medical or social his- molecular basis of isoniazid resistance is mediated by mutations in tory, or local prevalence of resistance. This results in delays in the ini- the katG, inhA gene or within the promoter region of the inhA gene. tiation of appropriate treatment.17 The use of empirical treatment The most common resistance mechanism has been identified as regimens often leads to overprescribing of drugs with adverse the katG S315T mutation, which leads to an inefficient isoniazid– effects including irreversible hearing loss, renal toxicity and hepato- NAD product inhibiting the antimicrobial action of isoniazid. This toxicity. In contrast, suboptimal treatment increases the potential mechanism is associated with high-level isoniazid resistance in for the development of drug resistance.18,19 MDR isolates.35–38 Mutations of the inhA promoter region, the most An additional challenge is the misdiagnosis of infection by non- common being found at position #15, result in an overexpression TB mycobacteria (NTM) as TB. Pulmonary infections caused by NTM of inhA. This mechanism is associated with low-level resistance in are gaining recognition for increasing isolation in clinical settings isoniazid monoresistant isolates and has been implicated in cross- worldwide.20 The presence of NTM as commensals in pulmonary resistance to a structural analogue, ethionamide. Mutations in the samples confounds MTB diagnosis, particularly in patients with a active region of the inhA gene result in a decreased affinity of the previous TB history and other chronic pulmonary conditions. isoniazid–NAD product. Such mutations are less frequent.38,39 Furthermore, the clinical signs and symptoms of NTM infection are clinically and radiologically indistinguishable from MTB infection, A recent study reported that mutations occurring in the inhA regu- 21 latory region and coding region resulted in high-level isoniazid underscoring the need for a reliable molecular-based diagnostic. 40 These factors clearly underscore the urgent need to detect rap- resistance and cross-resistance to ethionamide. Mutations in the idly the drug resistance and initiate personalized treatment for dfrA gene have recently been implicated in resistance to isoniazid. every patient presenting with DR-TB to prevent ongoing DR-TB
Load more

Recommended publications
  • Clofazimine As a Treatment for Multidrug-Resistant Tuberculosis: a Review
    Scientia Pharmaceutica Review Clofazimine as a Treatment for Multidrug-Resistant Tuberculosis: A Review Rhea Veda Nugraha 1 , Vycke Yunivita 2 , Prayudi Santoso 3, Rob E. Aarnoutse 4 and Rovina Ruslami 2,* 1 Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung 40161, Indonesia; [email protected] 2 Division of Pharmacology and Therapy, Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung 40161, Indonesia; [email protected] 3 Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran—Hasan Sadikin Hospital, Bandung 40161, Indonesia; [email protected] 4 Department of Pharmacy, Radboud University Medical Center, Radboud Institute for Health Sciences, 6255HB Nijmegen, The Netherlands; [email protected] * Correspondence: [email protected] Abstract: Multidrug-resistant tuberculosis (MDR-TB) is an infectious disease caused by Mycobac- terium tuberculosis which is resistant to at least isoniazid and rifampicin. This disease is a worldwide threat and complicates the control of tuberculosis (TB). Long treatment duration, a combination of several drugs, and the adverse effects of these drugs are the factors that play a role in the poor outcomes of MDR-TB patients. There have been many studies with repurposed drugs to improve MDR-TB outcomes, including clofazimine. Clofazimine recently moved from group 5 to group B of drugs that are used to treat MDR-TB. This drug belongs to the riminophenazine class, which has lipophilic characteristics and was previously discovered to treat TB and approved for leprosy. This review discusses the role of clofazimine as a treatment component in patients with MDR-TB, and Citation: Nugraha, R.V.; Yunivita, V.; the drug’s properties.
    [Show full text]
  • Inhaled Anti-Tubercular Therapy: Dry Powder Formulations, Device And
    UNI SYDNEY LOGO INHALED ANTI-TUBERCULAR THERAPY: DRY POWDER FORMULATIONS, DEVICE AND TOXICITY CHALLENGES Thaigarajan Parumasivam A thesis submitted in fulfillment of the requirements for the degree of Doctor of Philosophy Faculty of Pharmacy The University of Sydney 2017 STATEMENT OF AUTHENTICITY This thesis is submitted to the University of Sydney in fulfilment of the requirements for the Degree of Doctor of Philosophy. The work described was carried out in the Faculty of Pharmacy and Centenary Institute under the supervision of Professor Hak-Kim Chan and Professor Warwick Britton The work presented in this thesis, is to the best of my knowledge and belief, original except as acknowledged in the text. The contributions of all co-authors in publications included in the body of the thesis have been declared, signed by each co-author and attached as an appendix. I hereby declare that I have not previously or concurrently submitted this material, either in full or in part, for a degree at this or any other institution. Thaigarajan Parumasivam Oct 2016 ii CONTENTS Acknowledgement ................................................................................................................. viii Glossary .................................................................................................................................... x Thesis abstract .......................................................................................................................... 1 Chapter 1 .......................................................................................................................
    [Show full text]
  • Treatment of Drug-Resistant Tuberculosis an Official ATS/CDC/ERS/IDSA Clinical Practice Guideline Payam Nahid, Sundari R
    AMERICAN THORACIC SOCIETY DOCUMENTS Treatment of Drug-Resistant Tuberculosis An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline Payam Nahid, Sundari R. Mase, Giovanni Battista Migliori, Giovanni Sotgiu, Graham H. Bothamley, Jan L. Brozek, Adithya Cattamanchi, J. Peter Cegielski, Lisa Chen, Charles L. Daley, Tracy L. Dalton, Raquel Duarte, Federica Fregonese, C. Robert Horsburgh, Jr., Faiz Ahmad Khan, Fayez Kheir, Zhiyi Lan, Alfred Lardizabal, Michael Lauzardo, Joan M. Mangan, Suzanne M. Marks, Lindsay McKenna, Dick Menzies, Carole D. Mitnick, Diana M. Nilsen, Farah Parvez, Charles A. Peloquin, Ann Raftery, H. Simon Schaaf, Neha S. Shah, Jeffrey R. Starke, John W. Wilson, Jonathan M. Wortham, Terence Chorba, and Barbara Seaworth; on behalf of the American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America THIS OFFICIAL CLINICAL PRACTICE GUIDELINE WAS APPROVED BY THE AMERICAN THORACIC SOCIETY, THE EUROPEAN RESPIRATORY SOCIETY, AND THE INFECTIOUS DISEASES SOCIETY OF AMERICA SEPTEMBER 2019, AND WAS CLEARED BY THE U.S. CENTERS FOR DISEASE CONTROL AND PREVENTION SEPTEMBER 2019 Background: The American Thoracic Society, U.S. Centers for was judged to be very low, because the data came Disease Control and Prevention, European Respiratory Society, and from observational studies with significant loss to follow-up Infectious Diseases Society of America jointly sponsored this new and imbalance in background regimens between comparator practice guideline on the treatment of drug-resistant tuberculosis groups. Good practices in the management of MDR-TB are (DR-TB). The document includes recommendations on the described. On the basis of the evidence review, a clinical strategy treatment of multidrug-resistant TB (MDR-TB) as well as tool for building a treatment regimen for MDR-TB is also isoniazid-resistant but rifampin-susceptible TB.
    [Show full text]
  • Pretomanid Reference Number: CP.PMN.222 Effective Date: 03.01.20 Last Review Date: 02.20 Line of Business: Commercial, HIM, Medicaid Revision Log
    Clinical Policy: Pretomanid Reference Number: CP.PMN.222 Effective Date: 03.01.20 Last Review Date: 02.20 Line of Business: Commercial, HIM, Medicaid Revision Log See Important Reminder at the end of this policy for important regulatory and legal information. Description Pretomanid is a nitroimidazooxazine antimycobacterial drug. FDA Approved Indication(s) Pretomanid is indicated as part of a combination regimen with bedaquiline and linezolid for the treatment of adults with pulmonary extensively drug resistant (XDR), treatment-intolerant or nonresponsive multidrug-resistant (MDR) tuberculosis (TB). Approval of this indication is based on limited clinical safety and efficacy data. This drug is indicated for use in a limited and specific population of patients. Limitation(s) of use: • Pretomanid tablets are not indicated for patients with: o Drug-sensitive (DS) tuberculosis o Latent infection due to Mycobacterium tuberculosis o Extra-pulmonary infection due to Mycobacterium tuberculosis o MDR-TB that is not treatment-intolerant or nonresponsive to standard therapy • Safety and effectiveness of pretomanid tablets have not been established for its use in combination with drugs other than bedaquiline and linezolid as part of the recommended dosing regimen. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria. It is the policy of health plans affiliated with Centene Corporation® that pretomanid is medically necessary when the following criteria are met: I. Initial Approval Criteria A. Multi-Drug Resistant Tuberculosis (must meet all): 1. Diagnosis of pulmonary MDR-TB or XDR-TB; 2. Prescribed by or in consultation with an expert in the treatment of tuberculosis; 3.
    [Show full text]
  • Model-Informed Drug Discovery and Development Strategy for the Rapid Development of Anti-Tuberculosis Drug Combinations
    applied sciences Review Model-Informed Drug Discovery and Development Strategy for the Rapid Development of Anti-Tuberculosis Drug Combinations Rob C. van Wijk 1 , Rami Ayoun Alsoud 1, Hans Lennernäs 2 and Ulrika S. H. Simonsson 1,* 1 Department of Pharmaceutical Biosciences, Uppsala University, Uppsala 75123, Sweden; [email protected] (R.C.v.W.); [email protected] (R.A.A.) 2 Department of Pharmacy, Uppsala University, Uppsala 75123, Sweden; [email protected] * Correspondence: [email protected]; Tel.: +46-184-714-000 Received: 29 February 2020; Accepted: 25 March 2020; Published: 31 March 2020 Featured Application: Model-informed drug discovery and development (MID3) is proposed to be applied throughout the preclinical to clinical phases to provide an informative prediction of drug exposure and efficacy in humans in order to select novel anti-tuberculosis drug combinations for the treatment of tuberculosis. Abstract: The increasing emergence of drug-resistant tuberculosis requires new effective and safe drug regimens. However, drug discovery and development are challenging, lengthy and costly. The framework of model-informed drug discovery and development (MID3) is proposed to be applied throughout the preclinical to clinical phases to provide an informative prediction of drug exposure and efficacy in humans in order to select novel anti-tuberculosis drug combinations. The MID3 includes pharmacokinetic-pharmacodynamic and quantitative systems pharmacology models, machine learning and artificial intelligence, which integrates all the available knowledge related to disease and the compounds. A translational in vitro-in vivo link throughout modeling and simulation is crucial to optimize the selection of regimens with the highest probability of receiving approval from regulatory authorities.
    [Show full text]
  • Appraisal of NICE's Cost-Effectiveness Thresholds for Assessing Orphan
    Master's Degree Dissertation Appraisal of NICE’s cost-effectiveness thresholds for assessing orphan drugs Author: Ruodan Nan Master's Degree in Health Economics and Pharmacoeconomics UPF Barcelona School of Management Academic Year 2018 – 2021 Mentor: Laura Vallejo 1 Project performed within the framework of the Health Economics and Pharmacoeconomics program taught by Barcelona School of Management, a centre associated with Pompeu Fabra University 2 Abstract A rare disease is one that affects less than 1 in 2,000 in general population, and they are often chronic and life-threatening [1]. Due to the high cost to develop and small market for orphan drugs, historically manufacturers are reluctantly to explore the rare disease therapeutic areas. There is highly unmet need from patients with rare diseases. As the pharmaceutical expenditure rises, governments around the world are increasingly under pressure to contain the costs on drug reimbursement. Meanwhile patients with rare diseases need to be ensured for access to orphan drugs, and the industry needs to be incentivized to innovate. Health technology assessment and reimbursement bodies set out measures and policies for orphan drugs to be given market access. In this literature review, the landscape of health technology appraisals for orphan drugs in England UK is studied. The process for an orphan drug to gain marketing authorisation in the European Union (EU), the methods and criteria that used by National Institute for Health and Care Excellence (NICE) are reviewed. All orphan drugs with marketing authorisations from European Medicine Agency (EMA) are searched from the agency’s online database, whereas each of the authorised orphan drug is searched in NICE’s database for any technology appraisals and recommendations made for the orphan drug.
    [Show full text]
  • Orphan Maintenance Assessment Report
    31 July 2020 EMADOC-1700519818-446338 Correction1 EMA/OD/0000021750 Committee for Orphan Medicinal Products Orphan Maintenance Assessment Report Pretomanid FGK (pretomanid) Treatment of tuberculosis EU/3/07/513 Sponsor: FGK Representative Service GmbH Note COMP with all information of a commercially confidential nature deleted. 1 Significant benefit subheading: typographical corrections on pages 6 and 7 and addition of contextualisation sentence on page 6, adopted on 8 October 2020 Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 An agency of the European Union © European Medicines Agency, 2021. Reproduction is authorised provided the source is acknowledged. Table of contents 1. Product and administrative information .................................................. 3 2. Grounds for the COMP opinion ................................................................ 4 3. Review of criteria for orphan designation at the time of marketing authorisation .............................................................................................. 4 Article 3(1)(a) of Regulation (EC) No 141/2000 .............................................................. 4 Article 3(1)(b) of Regulation (EC) No 141/2000 .............................................................. 5 4. COMP list of issues .................................................................................
    [Show full text]
  • Full Text Article
    SJIF Impact Factor: 5.464 WORLD JOURNAL OF ADVANCE ISSN: 2457-0400 Swarna et al. World Journal of Advance HealthcareVolume: Research 5. HEALTHCARE RESEARCH Issue: 3. Page N. 425-437 Year: 2021 Review Article ww.wjahr.com PREDISPOSING FACTORS AND DEVELOPMENT OF RESISTANCE TO MYCOBACTERIUM TUBERCULI Swarna Priya B.*, Tharun Kanduri1 and P. Chetan Sai2 *Doctor of Pharmacy V year, Department of Pharmacy Practice, Jaya College of Pharmacy, Thiruninravur, Chennai, Tamil Nadu, India. 1,2Doctor of Pharmacy IV year, Department of Pharmacy Practice, Sri Venkateswara College of Pharmacy, Madhapur, Telangana, India. Received date: 03 April 2021 Revised date: 24 April 2021 Accepted date: 14 May 2021 *Corresponding author: Swarna Priya B. Doctor of Pharmacy V year, Department of Pharmacy Practice, Jaya College of Pharmacy, Thiruninravur, Chennai, Tamil Nadu, India. ABSTRACT Tuberculosis (TB) is one of the highly prevalent disease worldwide with the increase in severity and mortality as well. The disease is now a huge public health concern with the effect in association with resistance, resulting in poor health outcomes and huge community spread. The resistance formed makes it more vulnerable towards treatment regimens. This type of resistance can result in multiple drug intake and can poses a greater threat for major health complications as well in future. The current article is built on the different sequences in development of multi drug resistance in tuberculosis and also defines the strategies used to reduce the major public health concern of health outcomes in India. KEYWORDS: Tuberculosis, Highly Prevalent, Mortality, Community spread, Multi Drug resistance, Health Outcomes. INTRODUCTION ≥15) accounted for 56%, women (aged ≥15years) 32% and children (aged ≤15 years) 12%.
    [Show full text]
  • Mechanisms of Drug Resistance in Mycobacterium Tuberculosis: Update 2015
    INT J TUBERC LUNG DIS 19(11):1276–1289 STATE OF THE ART Q 2015 The Union http://dx.doi.org/10.5588/ijtld.15.0389 Mechanisms of drug resistance in Mycobacterium tuberculosis: update 2015 Y. Zhang,* W-W. Yew† *Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA; †Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong SAR, China SUMMARY Drug-resistant tuberculosis (DR-TB), including multi- resistance. However, further research is needed to and extensively drug-resistant TB, is posing a significant address the significance of newly discovered gene challenge to effective treatment and TB control world- mutations in causing drug resistance. Improved knowl- wide. New progress has been made in our understanding edge of drug resistance mechanisms will help understand of the mechanisms of resistance to anti-tuberculosis the mechanisms of action of the drugs, devise better drugs. This review provides an update on the major molecular diagnostic tests for more effective DR-TB advances in drug resistance mechanisms since the management (and for personalised treatment), and previous publication in 2009, as well as added informa- facilitate the development of new drugs to improve the tion on mechanisms of resistance to new drugs and treatment of this disease. repurposed agents. The recent application of whole KEY WORDS: antibiotics; drug resistance; mechanisms; genome sequencing technologies has provided new molecular diagnostics; new drugs insight into the mechanisms and complexity of drug The use of multiple-drug therapy, although defi- drug-resistant TB (DR-TB) epidemic thus remains nitely beneficial, is not an absolute guarantee an alarming problem, and is further aggravated by against the emergence of drug-resistant in- human immunodeficiency virus (HIV) coinfection.3 fections.
    [Show full text]
  • U.S. Food and Drug Administration (FDA) Approves Pretomanid
    U.S. Food and Drug Administration (FDA) Approves Pretomanid On August 14, 2019 the FDA granted approval for Pretomanid Tablets to the nonprofit Global Alliance for TB Drug Development (TB Alliance). Pretomanid is approved for use as part of a three-drug regimen with bedaquiline and linezolid to treat adults with pulmonary extensively drug-resistant (XDR), or to treat intolerant or nonresponsive multidrug-resistant (MDR) TB1. The three-drug, six-month, all oral regimen is also referred to as BPal (for bedaquiline, pretomanid and linezolid). As described in the FDA press release announcing the approval, “the safety and effectiveness of Pretomanid, taken orally in combination with bedaquiline and linezolid, was primarily demonstrated in a study of 109 patients with extensively drug-resistant, treatment intolerant or non-responsive multidrug-resistant pulmonary TB (of the lungs). Of the 107 patients who were evaluated six months after the end of therapy, 95 (89 percent) were successes, which significantly exceeded the historical success rates for treatment of extensively drug resistant TB.” In April 2019, TB Alliance granted a non-exclusive, worldwide license to pharmaceutical company Mylan for the manufacture and commercialization of Pretomanid. The drug is expected to be available in the U.S. by the end of calendar year 20192. Pretomanid is the second drug to be approved under the Limited Population for Antibacterial and Antifungal Drugs (LPAD) Pathway. This was added to the Federal Food, Drug and Cosmetic Act by Section 3042 of the 21st Century Cures Act enacted by the U.S. Congress in 2016. The intent of the LPAD Pathway is to facilitate the development of antibacterial (and antifungal) drug products that treat serious or life-threatening infections.
    [Show full text]
  • Perioperative Medication Management - Adult/Pediatric - Inpatient/Ambulatory Clinical Practice Guideline
    Effective 6/11/2020. Contact [email protected] for previous versions. Perioperative Medication Management - Adult/Pediatric - Inpatient/Ambulatory Clinical Practice Guideline Note: Active Table of Contents – Click to follow link INTRODUCTION........................................................................................................................... 3 SCOPE....................................................................................................................................... 3 DEFINITIONS .............................................................................................................................. 3 RECOMMENDATIONS ................................................................................................................... 4 METHODOLOGY .........................................................................................................................28 COLLATERAL TOOLS & RESOURCES..................................................................................................31 APPENDIX A: PERIOPERATIVE MEDICATION MANAGEMENT .................................................................32 APPENDIX B: TREATMENT ALGORITHM FOR THE TIMING OF ELECTIVE NONCARDIAC SURGERY IN PATIENTS WITH CORONARY STENTS .....................................................................................................................58 APPENDIX C: METHYLENE BLUE AND SEROTONIN SYNDROME ...............................................................59 APPENDIX D: AMINOLEVULINIC ACID AND PHOTOTOXICITY
    [Show full text]
  • Regimens to Treat Multidrug-Resistant Tuberculosis: Past, Present and Future Perspectives
    MINI-REVIEW TUBERCULOSIS Regimens to treat multidrug-resistant tuberculosis: past, present and future perspectives Emanuele Pontali1, Mario C. Raviglione2, Giovanni Battista Migliori 3 and the writing group members of the Global TB Network Clinical Trials Committee Affiliations: 1Dept of Infectious Diseases, Galliera Hospital, Genova, Italy. 2Global Health Programme, University of Milan, Milan, Italy. 3Servizio di Epidemiologia Clinica delle Malattie Respiratorie, Istituti Clinici Scientifici Maugeri IRCCS, Tradate, Italy. Correspondence: Giovanni Battista Migliori, Servizio di Epidemiologia Clinica delle Malattie Respiratorie, Istituti Clinici Scientifici Maugeri IRCCS, Via Roncaccio 16, 21049 Tradate, Italy. E-mail: [email protected] @ERSpublications The article reviews the evolution of the strategies and regimens to manage drug-resistant tuberculosis, opening a window on future perspectives. http://bit.ly/2Q1Rhx0 Cite this article as: Pontali E, Raviglione MC, Migliori GB, et al. Regimens to treat multidrug-resistant tuberculosis: past, present and future perspectives. Eur Respir Rev 2019; 28: 190035 [https://doi.org/ 10.1183/16000617.0035-2019]. ABSTRACT Over the past few decades, treatment of multidrug-resistant (MDR)/extensively drug- resistant (XDR) tuberculosis (TB) has been challenging because of its prolonged duration (up to 20– 24 months), toxicity, costs and sub-optimal outcomes. After over 40 years of neglect, two new drugs (bedaquiline and delamanid) have been made available to manage difficult-to-treat
    [Show full text]