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Treatment of Slow Growing NTM

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Treatment of Slow Growing NTM TreatmentPresenter of Slow Growing NTM of Reproduction for Property Not Charles L. Daley, MD UniversityNational of Colorado, Jewish DenverHealth Disclosures • Research Grant – Insmed – Spero Presenter • Advisory Board: of – Insmed Reproduction – Johnson and Johnson for – Spero PharmaceuticalsProperty – Horizon PharmaceuticalsNot – Paratek – Meiji Objectives • After participating in this lecture, you should be able to: – Describe an approach to deciding whom to Presenter treatment with NTM ofpulmonary infections – Describe how to treat Reproductionthe most common slow growing mycobacteriafor Property Not NTM That Have Been Reported to Cause Lung Disease Slowly Growing Mycobacteria Rapidly Growing Mycobacteria* M. arupense M. kubicae M. abscessus M. holsaticum M asiaticum M. lentiflavum M. alvei M. fortuitum M. avium M. malmoense PresenterM. boenickei M. mageritense M. branderi M. palustre of M. bolletii M. massiliense M. celatum M. saskatchewanse M. brumae M. mucogenicum Reproduction M. chimaera M. scrofulaceum M. chelonae M. peregrinum for M. florentinum M.Property shimodei M. confluentis M. phocaicum M. heckeshornense M. simiaeNot M. elephantis M. septicum M. intermedium M. szulgai M. goodii M. thermoresistible M. interjectum M. terrae M. intracellulare M. triplex M. kansasii M. xenopi * Growth in subculture within 7 days NTM That Have Been Reported to Cause Lung Disease Slowly Growing Mycobacteria Rapidly Growing Mycobacteria* M. arupense M. kubicae M. abscessus M. holsaticum M asiaticum M. lentiflavum M. alvei M. fortuitum M. avium M. malmoense PresenterM. boenickei M. mageritense M. branderi M. palustre of M. bolletii M. massiliense M. celatum M. saskatchewanse M. brumae M. mucogenicum Reproduction M. chimaera M. scrofulaceum M. chelonae M. peregrinum for M. florentinum M.Property shimodei M. confluentis M. phocaicum M. heckeshornense M. simiaeNot M. elephantis M. septicum M. intermedium M. szulgai M. goodii M. thermoresistible M. interjectum M. terrae M. intracellulare M. triplex M. kansasii M. xenopi * Growth in subculture within 7 days NTM That Have Been Reported to Cause Lung Disease Slowly Growing Mycobacteria Rapidly Growing Mycobacteria* M. arupense M. kubicae M. abscessus M. holsaticum M asiaticum M. lentiflavum M. alvei M. fortuitum M. avium M. malmoense PresenterM. boenickei M. mageritense M. branderi M. palustre of M. bolletii M. massiliense M. celatum M. saskatchewanse M. brumae M. mucogenicum Reproduction M. chimaera M. scrofulaceum M. chelonae M. peregrinum for M. florentinum M.Property shimodei M. confluentis M. phocaicum M. heckeshornense M. simiaeNot M. elephantis M. septicum M. intermedium M. szulgai M. goodii M. thermoresistible M. interjectum M. terrae M. intracellulare M. triplex M. kansasii M. xenopi * Growth in subculture within 7 days ATS Diagnostic Criteria For NTM Lung Disease Clinical Radiographs Bacteriology Presenter of Reproduction Cough for ≥ 2 positive Property sputum cultures Fatigue Not Weight Loss ATS/IDSA AJRCCM 2007;175:367 Progression of NTM Pulmonary Disease in Those Who Meet ATS/IDSA Diagnostic Criteria 488 with MAC-PD 551 with MAC-PD 1001 with NTM-PD (per ATS) (per ATS) (per ATS) Presenter 41.4% 45.0% 62.5% 23.6% 58.6% of 55.0% No No Progressed Stable Treated Treated Reproductiontreatment treatment for Spontaneously 51.6% Property 52.2% 35.0% culture converted Not Hwang JA, et al. Byoung, et al. Moon SM, et al. Eur Respir J 2017;49:1600537 Resp Med 2019;150:45-50 Resp Med 2019;151:1-7. WHO to Treat? Risk Factors Associated with Progression Host/Demographic Laboratory Radiographic Microbial Factors Factors Factors Factors • Male gender • Elevated Presenter• Fibrocavitary • Bacterial load • Older age inflammatory of • Extent of • Species • Presence of co- indices (ESR, CRP) disease morbidities • Anemia Reproduction • Low body mass • Hypoalbuminemiafor index Property Not Hwang JA, et al. Eur Respir J 2017;49:1600537 Byoung, et al. Resp Med 2019;150:45-50 Moon SM, et al. Resp Med 2019;151:1-7. Question #1 Which of the following infections is associated with the lowest culture conversion rate? A. Extensively drug resistantPresenter TB (XDR -TB) B. Macrolide resistant Mycobacteriumof avium complex Reproduction for C. MycobacteriumProperty abscessus subspecies abscessus Not D. Mycobacterium simiae Treatment of MAC • 65 year old Caucasian woman treated for Mycobacterium avium complex on two previous occasions with macrolide, Presenter rifampin, and ethambutol of • Now with AFB smear Reproduction positive sputum specimen for and culture positive forProperty M. intracellulare Not Mycobacterium avium Complex 12 Species Presenter MAC of M. paraintracellulare Reproduction M. lepraemurium for Property Not Tortoli E, et al. J System Evol Micro 2004;54:1277-1285. van Ingen J, et al. Int J Syst Evol Microb 2018;68:36666 Tortoli E. Clin Micro Rev 2014;27:727-752 Distribution and Clinical Significance of MAC Species, S. Korea Mycobacterium • Phenotypic intracellulare (n=91) identification 82% M. intracellularePresenter of 9% M. chimaera • Multilocus 4% M. “indicusReproduction pranii” sequencing 4% M. yongonense for Property M. intracellulare 72% Not M. chimaera 38% • Met ATS M. “indicus pranii” 75% criteria M. yongonese 50% Kim SY et al. Diag Micro Infect Dis 2017;88:125 Treatment of Pulmonary M. avium complex MAC Duration : Duration Macrolide Yes sensitive No Presenter 12 mos Cavities Present of Clofazimine DAILY culture negativity MoxifloxacinReproduction Rifampin No Yes forCiprofloxacin Ethambutol Property Bedaquiline Other drug 3X/WEEK DAILY Not Inh. amikacin Azithromycin Azithromycin Other drugs? Rifampin Rifampin Ethambutol Ethambutol Add IV Amikacin Treatment Outcomes of M. avium complex Systematic Review and Meta-analysis • 42 studies (2,748 patients) – 18 retrospective, 18 prospective, 6 randomized • Treatment success - sputumPresenter culture conversions after subtractingof posttreatment microbiologic recurrenceReproduction for • Treatment successProperty Not – Overall for macrolide containing regimen – 52.8% – 3-drug ATS regimen – 61.4% – Above taken for at least a year – 65.7% Diel R, et al. Chest 2018;153:888-921 Treatment Outcomes for MAC Macrolide Resistant Culture Conversion Macrolide resistant No surgery/aminoglycoside Presenter 5% Some surgery/aminoglycosideof 15% Surgery + prolonged Reproduction80% aminoglycoside* for * ≥ 6 months IV aminoglycosideProperty Not Griffith DE, et al. AJRCCM 2006;174:928 Wallace R, et al. Chest 2014;146:276-282 Jeong BH, et al. AJRCCM 2015;191:96-103 Koh WJ, et al. Eur Respir J 2017;50 Moon SM, et al. Antimicrob Agents Chemother; 2016 Morimoto K, et al. Ann ATS 2016;11:1904 MAC Recurrences After Completion of Therapy: Relapse vs reinfection University of Texas, Northwestern, Samsung, Tyler 1 Chicago, IL 2 Seoul, Korea3 Number of 155 190 402 patients Presenter of Microbiologic 48% 25% 29% recurrence Reproduction New infection 75%* 46%* 74%** for *Determined by pulse field electrophoresisProperty **Determined by rep-PCR Not 1. Wallace R, et al. Chest 2014;146:276-282 2. Boyle DP, et al. Ann Am Thorac Soc 2016 3. Koh WJ, et al. ERJ 2017;50 epub Treatment Failures Strengthen the Treatment Regimen Intermittent to Daily Dosing ∼ Presenter conversion 30% of Repurposed Drugs (moxifloxacin, Reproductionamikacin, clofazimine) Regimen for Property Not New Drugs (bedaquiline, delamanid) Presenter of ReproductionCONVERT STUDY Phasefor 3 Randomized, Controlled Trial of Liposomal Amikacin Inhalation PropertySuspension (ALIS) + GBT vs GBT alone in treatment refractory MAC lung disease Not Griffith D, et al. AJRCCM 2018 epub Phase 3 – Randomized Controlled Trial of ALIS + GBT vs GBT alone in Treatment Refractory MAC Proportion of Patients With Negative Sputum Cultures for NTM Presenter of Reproduction for Property Microbiologic response up Not to MIC ≤64 Griffith D, et al. AJRCCM, 2018. CONVERT STUDY Treatment Emergent Adverse Events (TEAE) Adverse Event GBT + ALIS GBT Respiratory-related AEs Dysphonia 45.7% 0.9% Cough 37.2% 15.2% Dyspnea 21.5%Presenter 8.9%) Hemoptysis of 17.5% 13.4% Oropharyngeal pain Reproduction10.8% 1.8% Audiological AEs for Tinnitus Property 7.6% 0.9% Dizziness Not 6.3% 2.7% Hearing loss 4.5% 6.3% Serious adverse events 20.2% 17.9% Discontinuation of ALIS 17.5% – Griffith D, et al. AJRCCM, 2018. Mixed Infection with Different MAC Species 62 y/o woman with fatigue and chronic cough Presenter of Treatment: azi/rif/embReproduction Cultures for Property Not Mycobacterium avium complex Summary • MAC pulmonary disease responds well to therapy with azithromycin, rifampin, and ethambutol • Culture conversion as high as 80% in macrolide susceptible disease but as lowPresenter as 5% in macrolide resistant disease of • Amikacin liposome inhaled suspension is indicated for Reproduction treatment refractory disease for • Duration of therapyProperty – treatment should continue for at least 12 months beyondNot culture conversion • Recurrence occurs in 25-50% of patients with reinfection in 50-75% Case 2 45 year old Caucasian woman with chronic cough Chest x-ray - abnormal Presenter Three sputum specimens of obtained Reproduction She was started on a 4-drug for TB treatment regimenProperty Not Sputum cultures grew M. kansasii Mycobacterium kansasii • First described by Buhler and Pollack as the Presenter“yellow bacilli” in 1953 of and later named in 1955 Reproductionby Hauduroy. for Property • Most cases are Not associated with progressive disease Treatment Regimen M. kansasii M. kansasii Duration : Duration Rifampin Yes sensitive No Presenter 12 mos
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