NEW DRUGS FOR TUBERCULOSIS: THE NEED, THE HOPE AND THE REALITY
|
|
- Elwin Berry
- 6 years ago
- Views:
Transcription
1 NEW DRUGS FOR TUBERCULOSIS: THE NEED, THE HOPE AND THE REALITY Neil W. Schluger, M.D. Professor of Medicine, Epidemiology and Environmental Health Sciences Columbia University Global tuberculosis incidence Overall: 2 2 billion with with latent infection million prevalent cases/year million incident cases/year million deaths/year deaths 8-9 million new cases/year WHO, Global Report 2012 December 12,
2 HIV prevalence among new cases of TB WHO, Global Report 2012 Distribution and prevalence of MDR-TB Total MDR cases: Total MDR 500,000 cases >500,000 Zignol WHO et 2010 al. Bull Global WHO 2012; Report 90: D December 12,
3 Why do we need new drugs to treat TB? Shorter overall treatment duration Lower relapse rates Development of regimens with fewer adverse effects, particularly less hepatotoxicity Development of regimens that can be given easily and safely in combination with antiretroviral therapy Development of regimens that are effective in treating MDR TB/XDR TB Current therapy for tuberculosis 2HRZE/4HR Induction phase: 2 months isoniazid, rifampin, pyrazinamide, ethambutol Continuation phase: 4 months isoniazid, rifampin Advantages: 100% effective Low relapse rate (3 4%) Inexpensive Universally available Can be given intermittently Disadvantages 6 months duration High relapse rate (15%) Adverse effects common Interactions with HIV treatment Not useful against MDR strains December 12,
4 drug discovery/development and its impact on treatment Pyrazinamide Ethionamide Streptomycin Kanamycin/amikacin Capreomycin Isoniazid PAS Thioacetazone Cycloserine Rifampin EMB The evolution of treatment for active TB months HS months 2HRZE/4HR 250 regimens tested in 25,000 patients in order to determine optimal: drug combinations doses dosing intervals treatment duration December 12,
5 TB drugs in clinical development Sponsor Drug Stage Sanofi-Aventis Rifapentine Phase 4 Bayer/GA Moxifloxacin Phase 2/3 EU, WHO Gatifloxacin Phase 2/3 Tibotec TMC207 Phase 2 Otsuka OPC67683 Phase 2 Global Alliance PA-824 Phase 2 Sequella SQ-109 Phase 2 Lupin LL-3858 Phase 2 Pfizer PNU Phase 2 AstraZeneca AZD-5847 Phase 1 December 12,
6 RMZ has greater sterilizing activity than RHZ or RHZM in murine TB Nuermberger, AJRCCM, 2004;169:421 RHZ RHZM RMZ Activity of enhanced-dose rifapentine in the mouse model R 10 HZ (5/7) R 10 MZ (5/7) P 10 HZ (5/7) PLoS Medicine 2007: 4: e344 December 12,
7 TBTC Phase 2 study design Hypothesis: Addition or substitution of DRUG X during intensive phase will result in a significantly greater proportion of patients whose sputum is culture negative at 2 months, compared with the standard regimen Smear positive tuberculosis STANDARD REGIMEN NOVEL REGIMEN 8 WEEKS SPUTUM CULTURE 8 WEEKS 4HR 4HR TBTC trials of novel regimens for active tuberculosis TBTC Study Patients enrolled Novel regimen Standard regimen Improvement in 2 month culture conversion HRZM HRZE 0% MRZE HRZE 5.5% HRptZE 10 mg/kg) 29X 334 HRptZE (15-20 mg/kg) HRZE 3.0% HRZE? 1. AJRCCM 2006; 174: AJRCCM 2009; 180: J Infect Dis. 2012; 206: December 12,
8 Resistance to quinolones among TB cases: a growing problem? Ramachandran R et al. Int J Tuberc Lung Dis 2009; 13(9): REMOX TB Trial Three arm trial sponsored by the MRC and the TB Alliance Treatment shortening, moxifloxacin based Arms: 2HRZE/4HR 2EMRZ/4HR 2MHRZ/2MHR Enrollment completed 2/12 Results expected in months December 12,
9 High dose rifamycin based treatment shortening trials Rifaquin Sponsored by the EDCTP Study arms 2EHRZ/4HR 2EMRZ/2P2M2 (moxi 400 mg b.i.w.; Rpt 900 mg b.i.w) 2EMRZ/4P1M1 (moxi 400 mg. q.w.; Rpt 1200 q.w.) Enrollment completed, currently in follow up Utility of linezolid in the treatment of MDR and XDR TB: New York City experience All patients resistant to H/R; 10/16 resistant to injectables; 6/16 resistant to quinolones Anger et al. J Antimicrob Chemother 2010; 65: December 12,
10 Adverse effects associated with administration of linezolid for tuberculosis Lee et al. N Engl J Med 2012;367: TB drugs in clinical development Sponsor Drug Stage Sanofi-Aventis Rifapentine Phase 4 Bayer/GA Moxifloxacin Phase 2/3 EU, WHO Gatifloxacin Phase 2/3 Tibotec TMC207 Phase 2 Otsuka OPC67683 Phase 2 Global Alliance PA-824 Phase 2 Sequella SQ-109 Phase 2 Lupin LL-3858 Phase 2 Pfizer PNU Phase 2 AstraZeneca AZD-5847 Phase 1 December 12,
11 Mice inoculated i.v. with M. tuberculosis 12 days later, drug treatment started Mice killed 1 (yellow) or 2 (blue) months later Surviving bacteria in lungs counted Science 2005; 307: Activity of TMC207 in a murine model of therapy: daily therapy Tibotec data presented at ICAAC, December 2005 December 12,
12 Activity of TMC207 in a murine model of therapy: weekly therapy Log 10 CFU Tibotec data presented at ICAAC, December 2005 Bedaquiline (TMC207), an ATP synthase inhibitor, in the treatment of MDR-TB Diacon et al. N Engl J Med 2009; ;360: December 12,
13 Time to culture conversion in patients with MDR Tb treated with bedaquiline: C208 trial Source: Janssen briefing document prepared for FDA hearing, Nov. 28, 2012 Excess deaths in experimental arm of C208, bedaquiline clinical trial in MDR TB Source: Janssen briefing document prepared for FDA hearing, Nov. 28, 2012 December 12,
14 Chemical Structure of OPC N O O N O OCF 3 O 2 N N OPC : (R) 2 Methyl 6 nitro 2 {4 [4 (4 trifluoromethoxyphenoxy) piperidin 1 yl]phenoxymethyl} 2,3 dihydroimidazo[2,1 b]oxazole December 12,
15 Effects of OPC on Mycolic Acid Biosynthesis Compound Subclass mycolic acid IC50 (µg/ml) 95% CI (µg/ml) OPC Fatty acid α Methoxy Keto >0.25 > INH Fatty acid α Methoxy Keto > PNAS 2012; 109: December 12,
16 Three drug combination containing OPC vs. standard regimen Infection 1M Start of treatment 0 1M 2M 3M 4M 5M 6M CFU CFU CFU CFU CFU CFU Compound Dose (mg/kg) mouse Cmax (µg/ml) human Cmax (µg/ml) OPC RFP /6 0/6 4/5 INH EB PZA Vehicle : 5% Gum Acacia ; RHEZ : 2RHEZ + 4RH ; ORZ : 2ORZ + 2OR Sputum culture conversion in patients with MDR-TB treated with delaminid (OPC-67683) Gler et al. N Engl J Med 2012;366: December 12,
17 Early bactericidal activity using novel drugs and combinations DS-TB patients Diacon et al. Lancet 2012; 380: December 12,
18 Combining novel agents in the treatment of TB in a murine model Taseen R et al. Antimicrob Agents Chemother 2011; 55: The challenge of tuberculosis clinical trials Type Endpoint Size Duration of study What is being studied? Phase 1 Safety/tolerability small days-weeks drug Phase 1 PK/PD PK/PD data; drug interactions small days-weeks drug(s) Phase 2a EBA small days-weeks drug Phase 2b 2-month culture conversion medium months regimen Phase 3 Failure/relapse large years regimen Phase 4 Detection of uncommon side effects large years regimen December 12,
19 COMPANION GRAPHS December 12,
20 Annual Global Plan Research Funding Targets vs Investments $800,000,000 $740,000,000 $600,000,000 $400,000,000 $420,000,000 $340,000,000 $380,000,000 $200,000,000 $250,038,877 $0 $120,361,419 Fundamental research $55,043,541 New diagnostics New drugs New vaccines $80,000,000 $95,446,326 $84,140,175 Operational research Global Plan Annual Targets 2011 Investments Total TB R&D Funding: $700,000,000 $649,648,183 $619,209,536 $630,446,462 $525,000,000 $350,000,000 $473,920,682 $491,476,917 $417,824,708 $357,426,170 $175,000,000 $ TB R&D investments witnessed an 82% increase over 2005 levels, but only 3% growth since December 12,
21 NIH funding for AIDS research Source: Treatment Action Group Report on TB Research Funding New drugs for TB: conclusions More drugs in clinical development than at any time in the last 40 years Bedaquiline on the verge of approval the first new TB drug since rifampin Multiple challenges in TB drug development Combining novel agents Clinical trials capacity Length of trials Funding December 12,
Hot Issues in Tuberculosis: Treatment of Latent TB Infection and New TB Drugs
Slide 1 Hot Issues in Tuberculosis: Treatment of Latent TB Infection and New TB Drugs Constance A. Benson, M.D. Professor of Medicine Division of Infectious Diseases University of California, San Diego
More informationShorter TB regimens What is in de pipeline? Martin Boeree, Associate Professor Radboudumc, Nijmegen, the Netherlands Tuesday, 23 September, 2014
Shorter TB regimens What is in de pipeline? Martin Boeree, Associate Professor Radboudumc, Nijmegen, the Netherlands Tuesday, 23 September, 2014 Disclosures Clinical trials and studies funded by EDCTP,
More informationImproving Translation in TB Drug Development Through Quantitative Modeling. CPTR Workshop 2016, Washington DC
Improving Translation in TB Drug Development Through Quantitative Modeling Lessons from Recent Phase III TB Trials CPTR Workshop 2016, Washington DC Christian Lienhardt Global TB Programme WHO, Geneva,
More informationDevelopment of New Regimens for Tuberculosis Zhenkun Ma, Ph.D.
Development of New Regimens for Tuberculosis Chief Scientific Officer Global Alliance for TB Drug Development 40 Wall Street, 24th Floor New York, NY 10005 USA 1 Outline What are the unmet needs in TB
More informationNew TB Medications. National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention New TB Medications Neha Shah MD MPH Field Medical Officer Tuberculosis Control Branch California Department of Public Health Centers
More informationTB Updates for the Physician Rochester, Minnesota June 19, 2009
TB Updates for the Physician Rochester, Minnesota June 19, 2009 Recent Findings & Activities of the Tuberculosis Trials Consortium (TBTC) Bill Burman Denver TBTC Unit & Denver Public Health Recent findings
More informationMultiple Drug-resistant Tuberculosis: a Threat to Global - and Local - Public Health
Multiple Drug-resistant Tuberculosis: a Threat to Global - and Local - Public Health C. Robert Horsburgh, Jr. Boston University School of Public Health Background Outline Why does drug resistance threaten
More informationNewer anti-tb drugs and regimens. DM Seminar
Newer anti-tb drugs and regimens DM Seminar 31-10-14 Why are newer drugs/regimens needed? Problems with current drugs/regimens Drug resistance Drug interaction of anti-tubercular drugs with ART Long duration
More informationSirturo: a new treatment against multidrug resistant tuberculosis
Sirturo: a new treatment against multidrug resistant tuberculosis TB is an on-going problem WHO estimated incidence of new TB cases 2009 Global Tuberculosis Control: WHO report 2010. Available at: http://www.who.int/tb/publications/global_report/2010/en/index.html
More informationTBTC research update: are we ready for 3 month treatment? 2009 TBTC Recompetition. NTCA presentation outline
TBTC research update: are we ready for 3 month treatment? Stefan Goldberg, MD Project officer, TBTC Studies 27, 28, 29 Tuberculosis Trials Consortium (TBTC) CDC Division of TB Elimination NTCA breakout
More informationHA Convention 2016 : Special Topic Session 3 May 2016
HA Convention 2016 : Special Topic Session 3 May 2016 Diagnosis and Management of TB in Adults Dr. Thomas Mok COS(RMD), KH Tuberculosis An airborne infectious disease caused by Mycobacterium tuberculosis
More informationNon-rifampin rifamycins in TB/HIV
Non-rifampin rifamycins in TB/HIV Richard E. Chaisson, MD Johns Hopkins University Center for TB Research Consortium to Respond Effectively to the AIDS-TB Epidemic Rifamycins for TB Inhibit bacterial DNA-dependent
More informationPharmacology and Pharmacokinetics of TB Drugs Part I
Pharmacology and Pharmacokinetics of TB Drugs Part I Charles A. Peloquin, Pharm. D. Professor, and Director Infectious Disease Pharmacokinetics Laboratory College of Pharmacy and The Emerging Pathogens
More informationCurrent Status in the Development of the New Anti-Tuberculosis Drugs
National Scientific Meeting TB UPDATE IX 2017 WORKSHOP AND SYMPOSIUM Novel Management to End TB Hotel Bumi Surabaya 29-30 April 2017 Current Status in the Development of the New Anti-Tuberculosis Drugs
More informationResearch Excellence to Stop TB Resistance. Plan for MDR-TB Clinical Trials: An Overview March 9, 2010
RESIST-TB: Summary Research Excellence to Stop TB Resistance Plan for MDR-TB Clinical Trials: An Overview March 9, 2010 The current epidemic of Multidrug-Resistant Tuberculosis (MDR-TB) is a major threat
More informationActivity of PNU and its major metabolite in whole blood and broth culture models of TB
Activity of PNU 100480 and its major metabolite in whole blood and broth culture models of TB Paul Converse 1, Jin Lee 1, Kathy Williams 1, Opokua Amoabeng 1, Kim Dionne 1, Nicole Parish 1, Robert Wallis
More informationProblems, progress and evaluation of agents in clinical development ACCEPTED. Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
AAC Accepts, published online ahead of print on 15 December 2008 Antimicrob. Agents Chemother. doi:10.1128/aac.00749-08 Copyright 2008, American Society for Microbiology and/or the Listed Authors/Institutions.
More informationACCESS TO MEDICINES. Update on tuberculosis field activities
ACCESS TO MEDICINES Update on tuberculosis field activities Update on clinical activities 1/3 Latent TB Prevent study (S26) main study (8053 patients) PK substudy construction of a POPPK model Paediatric
More informationGlobal epidemiology of drug-resistant tuberculosis. Factors contributing to the epidemic of MDR/XDR-TB. CHIANG Chen-Yuan MD, MPH, DrPhilos
Global epidemiology of drug-resistant tuberculosis Factors contributing to the epidemic of MDR/XDR-TB CHIANG Chen-Yuan MD, MPH, DrPhilos By the end of this presentation, participants would be able to describe
More informationAuthors Schluger, N; Karunakara, U; Lienhardt, C; Nyirenda, T E; Chaisson, R
MSF Field Research Building clinical trials capacity for tuberculosis drugs in highburden countries Item type Article Authors Schluger, N; Karunakara, U; Lienhardt, C; Nyirenda, T E; Chaisson, R Citation
More informationShort Course Treatment for MDR TB
Objectives Short Course Treatment for MDR TB Barbara J Seaworth M.D. Medical Director Heartland National TB Center Professor of Medicine, University of Texas Health Northeast Participants will utilize
More informationIssues in TB Drug Development for Sensitive Disease - Clinical Development
Issues in TB Drug Development for Sensitive Disease - Clinical Development GATB Open Forum New Delhi, 5-6 May 2008 Christian Lienhardt, MD, DTM, MSc, PhD IRD, Paris, France & International Union Against
More informationTreatment of Tuberculosis
Treatment of Tuberculosis Marcos Burgos, MD April 5, 2016 TB Intensive April 5 8, 2016 San Antonio, TX EXCELLENCE EXPERTISE INNOVATION Marcos Burgos, MD has the following disclosures to make: No conflict
More informationElizabeth A. Talbot MD Assoc Professor, ID and Int l Health Deputy State Epidemiologist, NH GEISELMED.DARTMOUTH.EDU GEISELMED.DARTMOUTH.
The image part with relationship ID rid2 was not found in the file. MDR TB Management Review of the Evolution (or Revolution?) Elizabeth A. Talbot MD Assoc Professor, ID and Int l Health Deputy State Epidemiologist,
More informationTB Prevention in PLHIV: Options Other Than Isoniazid. Johns Hopkins Center for Tuberculosis. Research. Richard E. Chaisson, MD
TB Prevention in PLHIV: Options Other Than Isoniazid Johns Hopkins Center for Tuberculosis Richard E. Chaisson, MD Research Johns Hopkins University Center for Tuberculosis Research Consortium to Respond
More informationSupplementary Appendix
Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Zumla A, Raviglione M, Hafner R, von Reyn CF. Tuberculosis.
More informationMULTIDRUG- RESISTANT TUBERCULOSIS. Dean Tsukayama Hennepin County Medical Center Hennepin County Public Health Clinic
MULTIDRUG- RESISTANT TUBERCULOSIS Dean Tsukayama Hennepin County Medical Center Hennepin County Public Health Clinic I have no relevant financial relationships. Discussion includes off label use of: amikacin
More informationThe treatment of patients with initial isoniazid resistance
The treatment of patients with initial isoniazid resistance 2011 INTERTB Meeting, St George s, London Patrick Phillips, MRC Clinical Trials Unit DA Mitchison, AJ Nunn. 21 st October 2011 Outline Background
More informationMarcos Burgos, MD has the following disclosures to make:
Guidelines for the Treatment of Tuberculosis Marcos Burgos, MD May 13, 2015 TB for Pulmonologist March 13, 2015 Phoenix, AZ EXCELLENCE EXPERTISE INNOVATION Marcos Burgos, MD has the following disclosures
More informationManagement of MDR TB. Dr Priscilla Rupali MD; DTM&H Professor and Head Department of Infectious Diseases Christian Medical College Vellore
Management of MDR TB Dr Priscilla Rupali MD; DTM&H Professor and Head Department of Infectious Diseases Christian Medical College Vellore Outline Global epidemiology of Tuberculosis Epidemiology of Tuberculosis
More informationTreatment of Tuberculosis
TB Clinical i l Intensive Seattle Treatment of Tuberculosis June 16, 2016 Masa Narita, MD Public Health Seattle & King County; Firland Northwest TB Center, University of Washington Outline Unique features
More informationChapter 5 Treatment. 5.1 First-Line Antituberculous Treatment
Chapter 5 Treatment Abstract In this chapter the treatment of drug sensitive and drug resistant TB and timing of antiretroviral treatment for HIV infected patients will be reviewed. Emphasis is placed
More informationUpcoming TB Alliance Studies. CPRT DST Review September, 2014
Upcoming TB Alliance Studies CPRT DST Review September, 2014 STAND PaMZ Ph 3 STAND: Phase 3 Trial of the Pa-M-Z Regimen Participants with newly diagnosed smear positive DS- and MDR-TB DS Pa(100mg)-M-Z
More informationWhat He Said: Rifampin versus Rifapentine
What He Said: Rifampin versus Rifapentine Charles A. Peloquin, Pharm.D. Director Infectious Disease Pharmacokinetics Laboratory Professor, College of Pharmacy & The Emerging Pathogens Institute University
More informationNew Drugs, New Treatments, Shorter Regimens
New Drugs, New Treatments, Shorter Regimens Sarah K. Brode, MD MPH FRCP(C) West Park Healthcare Centre, University Health Network, University of Toronto TB Elimination: Back to Basics November 16, 2016
More informationNIAID TB Therapeutic Clinical Research Priorities. Prognostic biomarkers for disease progression, treatment response/relapse
NIAID TB Therapeutic Clinical Research Priorities New drugs and combinations for DS and DR TB: Efficient Phase I and II evaluations Phase III Killing Persisters Sterilizing activity is crucial Prognostic
More informationDrug Interactions with ART and New TB drugs: What Do We Know?
Drug Interactions with ART and New TB drugs: What Do We Know? HIV/TB Research Frontiers Meeting 20 th Conference on Retroviruses and Opportunistic Infections 3 March 2013 Presented by: Kelly Dooley MD,
More informationDrug Interactions Lisa Armitige, MD, PhD November 17, 2010
Substance Abuse and Tuberculosis Oklahoma City, Oklahoma November 17, 2010 Drug Interactions Lisa Armitige, MD, PhD November 17, 2010 Drug Interactions Lisa Y. Armitige, M.D., Ph.D. Medical Consultant
More informationTreatment of Active Tuberculosis
Treatment of Active Tuberculosis Jeremy Clain, MD Pulmonary & Critical Care Medicine Mayo Clinic October 16, 2017 2014 MFMER slide-1 Disclosures No relevant financial relationships No conflicts of interest
More informationTreatment of Tuberculosis. Dr Sarabjit Chadha The Union
Treatment of Tuberculosis Dr Sarabjit Chadha The Union History of treatment of TB. Believed to be as old as mankind Spinal TB has been diagnosed in Egyptian mummies dating 2400 BC Egyptian medical treatise
More informationPrinciples and practice of treating drug-sensitive TB
Principles and practice of treating drug-sensitive TB Brian Eley Paediatric Infectious Diseases Unit Red Cross War Memorial Children s Hospital Department of Paediatrics and Child Health University of
More informationPerspectives for new treatments for MDR-TB
Perspectives for new treatments for MDR-TB Life cycle of M. tuberculosis Active TB in 2015 10.4 million cases >1.4 million deaths Latent TB >2 billion cases Switzerland 564 cases (18 MDR) 2 Koul et al.
More informationTreatment of Tuberculosis, 2017
Treatment of Tuberculosis, 2017 Charles L. Daley, MD National Jewish Health University of Colorado Health Sciences Center Treatment of Tuberculosis Disclosures Advisory Board Horizon, Johnson and Johnson,
More informationTreatment of XDR-TB. Focus on the Nix-TB and ZeNix Trials. RESIST-TB Webinar 11 January 2018 Daniel Everitt, MD
Treatment of XDR-TB Focus on the Nix-TB and ZeNix Trials RESIST-TB Webinar 11 January 2018 Daniel Everitt, MD Global Alliance for TB Drug Development Outline of Discussion TB Alliance Approach to Treatment
More informationMultidrug-resistant tuberculosis in children
Multidrug-resistant tuberculosis in children James Seddon Clinical Lecturer Imperial College London UCL-TB and LSHTM TB Centre World TB Day 2015 24th March 2015 Outline Burden Recent studies Preventive
More informationMoving Past the Basics of Tuberculosis Phoenix, Arizona May 8-10, 2012
Moving Past the Basics of Tuberculosis Phoenix, Arizona May 8-10, 2012 LTBI and TB Disease Treatment Cara Christ, MD, MS May 8, 2012 Cara Christ, MD, MS has the following disclosures to make: No conflict
More informationTuberculosis Intensive November 17 20, 2015 San Antonio, TX
Treatment of Tuberculosis Elizabeth S. Guy, MD November 17, 2015 Tuberculosis Intensive November 17 20, 2015 San Antonio, TX EXCELLENCE EXPERTISE INNOVATION Elizabeth S. Guy, MD has the following disclosures
More informationTuberculosis. New TB diagnostics. New drugs.new vaccines. Dr: Hussein M. Jumaah CABM Mosul College of Medicine 23/12/2012
Tuberculosis New TB diagnostics. New drugs.new vaccines Dr: Hussein M. Jumaah CABM Mosul College of Medicine 23/12/2012 Tuberculosis (TB )is a bacterial disease caused by Mycobacterium tuberculosis (occasionally
More informationPediatric TB Intensive San Antonio, Texas October 14, 2013
Pediatric TB Intensive San Antonio, Texas October 14, 2013 Treatment of Tuberculosis in Children Jeffrey R. Starke, M.D. Professor of Pediatrics October 14, 2013 Jeffrey R. Starke, M.D. has the following
More informationPharmacokinetics and doses of antituberculosis drugs in children
Pharmacokinetics and doses of antituberculosis drugs in children HS Schaaf Desmond Tutu TB Centre Department of Paediatrics and Child Health Stellenbosch University Declarations I have no conflict of interest
More informationAPSR RESPIRATORY UPDATES
APSR RESPIRATORY UPDATES Volume 5, Issue 2 Newsletter Date: February 2013 APSR EDUCATION PUBLICATION Inside this issue: Tuberculosis Multidrug-resistant pulmonary tuberculosis treatment regimens and patient
More informationDiagnosis and Treatment of Tuberculosis, 2011
Diagnosis of TB Diagnosis and Treatment of Tuberculosis, 2011 Alfred Lardizabal, MD NJMS Global Tuberculosis Institute Diagnosis of TB, 2011 Diagnosis follows Suspicion When should we Think TB? Who is
More informationSterilizing Activity of Novel TMC207- and PA-824-Containing Regimens in a Murine Model of Tuberculosis
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Dec. 2011, p. 5485 5492 Vol. 55, No. 12 0066-4804/11/$12.00 doi:10.1128/aac.05293-11 Copyright 2011, American Society for Microbiology. All Rights Reserved. Sterilizing
More informationStatus of the TB Drug Pipeline: Clinical Candidates
Status of the TB Drug Pipeline: Clinical Candidates Ann M. Ginsberg, MD, PhD Global Alliance for TB Drug Development Open Forum III Delhi, India Global TB Drug Portfolio: 7 clinical candidates gatifloxacin
More informationWhat is drug resistance? Musings of a clinician
What is drug resistance? Musings of a clinician William Burman MD Denver Public Health Tuberculosis Trials Consortium Financial disclosures Tibotec (developer of TMC207 and several antiretroviral drugs)
More informationPreventing TB: Recent Research Results and Novel Short Course Therapy for LTBI
Preventing TB: Recent Research Results and Novel Short Course Therapy for LTBI Constance A. Benson, M.D. Professor of Medicine Director, UCSD AntiViral Research Unit PI, CD4 Collaborative HIV Clinical
More informationTreatment: First Line Drugs TUBERCULOSIS TREATMENT: MEDICATIONS & REGIMENS TREATMENT: GENERAL PRINCIPLES MECHANISM OF ACTION MID 27
TUBERCULOSIS TREATMENT: MEDICATIONS & REGIMENS Treatment: First Line Drugs 1. ISONIAZID = INH Bacteriocidal against dividing organisms Dose = 300mg = one pill = well absorbed Good CNS penetration Can be
More informationTreatment of Tuberculosis
TB Intensive Tyler, Texas June 1-3, 2009 Treatment of Tuberculosis Barbara Seaworth, MD June 3, 2009 Treatment of Tuberculosis Barbara J Seaworth MD Medical Director Heartland National TB Center 1 Purpose
More informationClinical Trials Lecture 4: Data analysis
Clinical Trials Lecture 4: Data analysis Dick Menzies, MD Respiratory Epidemiology and Clinical Research Unit Montreal Chest Institute TB Research methods course July 17, 2014 Lecture 4: Data analysis
More informationPharmacokinetics (PK) and Pharmacodynamics (PD) in the Treatment of Tuberculosis
Pharmacokinetics (PK) and Pharmacodynamics (PD) in the Treatment of Tuberculosis Shaun E. Gleason, PharmD, MGS Associate Professor, Department of Clinical Pharmacy Director, Distance Degrees and Programs
More informationImpact of the interaction of R with rifampin on the. treatment of tuberculosis studied in the mouse model ACCEPTED
AAC Accepts, published online ahead of print on 21 July 2008 Antimicrob. Agents Chemother. doi:10.1128/aac.00566-08 Copyright 2008, American Society for Microbiology and/or the Listed Authors/Institutions.
More informationThe clinical pharmacology and drug interactions of bedaquiline
7 TH FIDSSA 2017 The clinical pharmacology and drug interactions of bedaquiline Helen McIlleron Division of Clinical Pharmacology University of Cape Town 20 years 2 drugs conditional approval based on
More information"Sterilization of TB disease in
11/1/1 "Sterilization of TB disease in mice " Jacques Grosset Pharmacodynamics of daily rifapentine and rifampin in mice Free rifam mycin Concentrati ion/mic 1 1 Rifapentine (1mg/kg) Free rifam mycin Concentrati
More informationThe innovation gaps and challenges for MDR-TB. Blessina Kumar TB/ HIV Activist Community Representative & Vice Chair STBP Coordinating Board
The innovation gaps and challenges for the diagnostic and treatment of TB and MDR-TB Blessina Kumar TB/ HIV Activist Community Representative & Vice Chair STBP Coordinating Board Diagnosis Overview of
More informationTB ReFLECT Meta-Analysis of Fluoroquinolone-Containing Regimens for the Treatment of Drug-Susceptible TB
TB ReFLECT Meta-Analysis of Fluoroquinolone-Containing Regimens for the Treatment of Drug-Susceptible TB Rada Savic, PhD Medical Consultant Meeting San Antonio, TX November 29-30, 2018 1 EXCELLENCE EXPERTISE
More informationPAEDIATRIC TB TRIAL UPDATE
PAEDIATRIC TB TRIAL UPDATE ANNEKE C. HESSELING PROFESSOR IN PAEDIATRICS AND CHILD HEALTH DIRECTOR: DESMOND TUTU TB CENTRE DEPARTMENT OF PAEDIATRICS AND CHILD HEALTH STELLENBOSCH UNIVERSITY, SOUTH AFRICA
More informationRECENT ADVANCES OF TUBERCULOSIS MANAGEMENT. Qais Abdulmajeed Haddad Consultant ID & IC Security Forces Hospital Program Riyadh - Saudi Arabia
RECENT ADVANCES OF TUBERCULOSIS MANAGEMENT Qais Abdulmajeed Haddad Consultant ID & IC Security Forces Hospital Program Riyadh - Saudi Arabia RECENT ADVANCES OF TUBERCULOSIS MANAGEMENT History Epidemiology
More informationTherapeutic TB vaccines Shortening Treatment for (DS- and) DR-TB?
Therapeutic TB vaccines Shortening Treatment for (DS- and) DR-TB? Mark Hatherill South African Tuberculosis Vaccine Initiative (SATVI) University of Cape Town, South Africa 1 1. The need for a therapeutic
More informationA Review of the Sutezolid (PNU ) Patent Landscape
2014 A Review of the Sutezolid (PNU-100480) Patent Landscape A scoping report JANUARY 2014 A Review of the Sutezolid (PNU-100480) Patent Landscape UNITAID Secretariat World Health Organization Avenue Appia
More informationTB Intensive San Antonio, Texas
TB Intensive San Antonio, Texas April 6-8, 2011 TB Disease: ATS/CDC/IDSA Guidelines Barbara Seaworth, MD Thursday April 7, 2011 Barbara Seaworth, MD has the following disclosures to make: Has received
More informationDosage and Administration
SIRTURO product information for healthcare providers 2 WARNINGS: An increased risk of death was seen in the SIRTURO (bedaquiline) treatment group (9/79, 11.4%) compared to the placebo treatment group (2/81,
More informationTherapeutic Drug Monitoring for Improving TB Treatment Outcomes: A Concept for a Randomized Clinical Trial before Clinical Implementation
Therapeutic Drug Monitoring for Improving TB Treatment Outcomes: A Concept for a Randomized Clinical Trial before Clinical Implementation Randall Reves, MD, MSc TB Consultant Professor of Medicine and
More informationUpdate on Tuberculosis Botswana, March 2017
Update on Tuberculosis Botswana, March 2017 Zelalem Temesgen, MD FIDSA AAHIVS Professor of Medicine Executive Director, Mayo Clinic Center for Tuberculosis Director, HIV Program Regional Training and
More informationHigh-dose rifampin: potential for treatment shortening
High-dose rifampin: potential for treatment shortening Martin Boeree, MD, PhD Associate Professor Radboud University Nijmegen Medical Centre Rob Aarnoutse, Georgette Plemper van Balen, Andreas Diacon,
More informationSoedarsono Department of Pulmonology and Respiratory Medicine Faculty of Medicine, Universitas Airlangga Dr. Soetomo General Hospital
Soedarsono Department of Pulmonology and Respiratory Medicine Faculty of Medicine, Universitas Airlangga Dr. Soetomo General Hospital MDR-TB is a public health crisis 480 000 people developed MDR-TB in
More informationClinical spectrum and standard treatment of tuberculosis
Clinical spectrum and standard treatment of tuberculosis Graham Bothamley Homerton University Hospital, London, UK 2 nd European Advanced Course in Clinical Tuberculosis 1 Plan of talk Why is there a clinical
More informationCDC's Tuberculosis Trials Consortium
CDC's Tuberculosis Trials Consortium Kayla Laserson, Andrew Vernon, Erin Bliven, Neil Schluger, William Burman, Fred Gordin, Tim Sterling, Carol Dukes Hamilton, Debra Benator, Donna Conwell, Nancy Dianis,
More informationSynergistic Activity of R Combined with Pyrazinamide against Murine Tuberculosis
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Mar. 2007, p. 1011 1015 Vol. 51, No. 3 0066-4804/07/$08.00 0 doi:10.1128/aac.00898-06 Copyright 2007, American Society for Microbiology. All Rights Reserved. Synergistic
More informationThe shorter regimen for MDR-TB: evidence and pitfalls
The shorter regimen for MDR-TB: evidence and pitfalls Helen Cox 10 November 2017 What is the shortened regimen? Current conventional regimen (SA): Intensive Phase (at least 6 months): PZA / (EMB) / Kana
More informationSupplementary Appendix
Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Mitnick CD, Shin SS, Seung KJ, et al. Comprehensive treatment
More informationWeekly Moxifloxacin and Rifapentine Is More Active Than the Denver Regimen in Murine Tuberculosis
Weekly Moxifloxacin and Rifapentine Is More Active Than the Denver Regimen in Murine Tuberculosis Ian M. Rosenthal, Kathy Williams, Sandeep Tyagi, Andrew A. Vernon, Charles A. Peloquin, William R. Bishai,
More informationStandard TB Treatment
Standard TB Treatment Chris Keh, MD TB Controller, TB Prevention and Control Program, San Francisco Department of Public Health Assistant Clinical Professor, Division of Infectious Diseases, University
More informationPZA: A New Look Based on RNASeq, the Hollow Fiber System, and Patient Level Data. Tawanda Gumbo
PZA: A New Look Based on RNASeq, the Hollow Fiber System, and Patient Level Data Tawanda Gumbo Office of Global Health University of Texas Southwestern Medical Center, Dallas, Texas The team: this work
More informationTuberculosis: update 2013
Tuberculosis: update 2013 William R. Bishai, MD, PhD Center for TB Research Division of Infectious Diseases Department of Medicine Johns Hopkins School of Medicine Question 1 A TB speaker at a major conference
More informationDr Devendra S. Dadhwal NEW DRUGS FOR TUBERCULOSIS
Dr Devendra S. Dadhwal 08 03 2013 NEW DRUGS FOR TUBERCULOSIS Introduction Mycobacterium tuberculosis has been present in the human since antiquity fragments of the spinal column from Egyptian mummies from
More informationAnti-Infective Drugs Advisory Committee Meeting. Briefing Document. TMC207 (bedaquiline) Treatment of Patients with MDR-TB NDA
ADVISORY COMMITTEE BRIEFING MATERIALS: AVAILABLE FOR PUBLIC RELEASE 1 Anti-Infective Drugs Advisory Committee Meeting Briefing Document TMC207 (bedaquiline) Treatment of Patients with MDR-TB NDA 204-384
More informationThe contribution of bedaquiline to the treatment of MDRTB
WHO/STB Expert Group Meeting Geneva, 29-30 January 2013 The contribution of bedaquiline to the treatment of MDRTB Synthesis of publicly available evidence Prepared by Bernard Fourie, PhD Commissioned by
More informationThe Role of Rifampin for the Treatment of Latent TB Infection. Introduction. Introduction
The Role of Rifampin for the Treatment of Latent TB Infection March 26, 2008 Alfred A. Lardizabal, MD Associate Professor of Medicine New Jersey Medical School Global Tuberculosis institute Treatment of
More informationTreatment of Tuberculosis
Treatment of Tuberculosis, 1940 s Treatment of Tuberculosis ATS/CDC/IDSA Joint Statement 2003 Saskatchewan Lung Association Outline, 2012 Treatment of Tuberculosis Principles of treatment of tuberculosis
More informationBedaquiline: 10 years later, the drug susceptibility testing protocol is still pending
EDITORIAL TUBERCULOSIS Bedaquiline: 10 years later, the drug susceptibility testing protocol is still pending Max Salfinger 1 and Giovanni Battista Migliori 2 Affiliations: 1 Dept of Medicine, National
More informationResearch in Tuberculosis: Translation into Practice
Case History Research in Tuberculosis: Translation into Practice This is a 6-year6 year-old Bosnian male, who presented to ER with one-week history of fever and occasional vomiting. No cough, difficulty
More informationWhat is the recommended shorter treatment regimen for MDR-TB?
DRTB STAT + TAG BRIEF Is shorter better? Is shorter better? Understanding the shorter regimen for treating drugresistant tuberculosis by Safiqa Khimani Edited by Vivian Cox, Mike Frick, Jennifer Furin,
More informationPHARMACOTHERAPY OF TUBERCULOSIS MANAGEMENT
PHARMACOTHERAPY OF TUBERCULOSIS MANAGEMENT Rahela Ambaras Khan BPharm (USM), MPharm (Clin.)(UKM), BCPS(US) PhD Student Faculty of Medicine University Malaya OUTLINE Introduction to Tuberculosis Management
More informationRecognizing MDR-TB in Children. Ma. Cecilia G. Ama, MD 23 rd PIDSP Annual Convention February 2016
Recognizing MDR-TB in Children Ma. Cecilia G. Ama, MD 23 rd PIDSP Annual Convention 17-18 February 2016 Objectives Review the definitions and categorization of drugresistant tuberculosis Understand the
More informationOverview: TB Alliance Drug Development Pipeline
Overview: TB Alliance Drug Development Pipeline Mengchun Li, MD Head of Pharmacovigilance, TB Alliance Mar 26, 2018 TB Alliance is a not for profit organization dedicated to the discovery and development
More information6/8/2018 TB TREATMENT. Bijan Ghassemieh, MD Seattle TB Clinical Intensive Disclosures. None
TB TREATMENT Bijan Ghassemieh, MD Seattle TB Clinical Intensive 2018 Disclosures None 1 Objectives Understand the following Rationale and goals for standard TB regimen When to initiate TB treatment Standard
More informationSurgery for MDR/XDR Tuberculosis
Surgery for MDR/XDR Tuberculosis John D. Mitchell, M.D. Davis Endowed Chair in Thoracic Surgery Professor and Chief, General Thoracic Surgery Department of Surgery University of Colorado School of Medicine
More informationFinal Results from Stage 1 of a Double-Blind, Placebo- Controlled Trial with TMC207 in Patients with Multi- Drug Resistant (MDR)
Final Results from Stage 1 of a Double-Blind, Placebo- Controlled Trial with TMC207 in Patients with Multi- Drug Resistant (MDR) Tuberculosis (TB). AH Diacon*, A Pym**, MP Grobusch, G. Churchyard, T De
More informationDiagnosis of drug resistant TB
Diagnosis of drug resistant TB Megan Murray, MD, ScD Harvard School of Public Health Brigham and Women s Hospital Harvard Medical School Broad Institute Global burden of TB 9 million new cases year 2 million
More informationPhase III Clinical Trial Results at the 48 th Union World Conference on Lung Health: Implications for the Field 1
Phase III Clinical Trial Results at the 48 th Union World Conference on Lung Health: Implications for the Field 1 Preliminary results from two phase III drug-resistant TB (DR-TB) clinical trials were presented
More information