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Danger in the Water. University of Toronto & University Health Network. Theodore Marras MD FRCPC. Declarations. Potential conflicts of interest Financial – none Other – clinical and academic interest in pulmonary NTM disease (especially epidemiology, long term outcomes)
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Danger in the Water University of Toronto & University Health Network Theodore Marras MD FRCPC
Declarations Potential conflicts of interest Financial – none Other – clinical and academic interest in pulmonary NTM disease (especially epidemiology, long term outcomes) Off label use of therapies None of the medications mentioned have a formal indication for the treatment of pulmonary NTM disease
Objectives - Pulmonary Mycobacterium avium complex (pMAC) • Identify relevant potential infective exposures • Review management of pMAC: • Recommended drug treatment • Approach to comprehensive management • Review data on treatment outcomes • Combining knowledge of: • Environment / interventions (relevance, uncertainty) • Treatment outcomes … to better inform clinical decisions
Pulmonary NTM - Microbiology
Pulmonary NTM - Microbiology
Pulmonary NTM - Microbiology
Pulmonary NTM - Microbiology
Pulmonary NTM - Microbiology
Pulmonary NTM - Microbiology
Pulmonary NTM Disease - ATS / IDSA 2007
Increasingly common disease of the elderly in Ontario
The Water we Drink - MAC • Moist environments • Natural and treated water • Soils • Very disinfectant resistant
Pulmonary NTM Source of infection Study Design Hypersensitivity Pneumonitis Reaction to Mycobacterium avium in Household Water* Theodore K. Marras, MD; Richard J. Wallace, Jr., MD, FCCP; Laura L. Koth, MD; Michael S. Stulbarg, MD;† Clayton T. Cowl, MD, FCCP; and Charles L. Daley, MD … Multiple respiratory samples and shower and bathtub specimens grew MAC, with matching PFGE patterns… (CHEST 2005; 127:664–671)
Pulmonary NTM Source of infection Mycobacterium avium in a shower linked to pulmonary disease Joseph O. Falkinham III, Michael D. Iseman, Petra de Haas and Dick van Soolingen … M. avium isolated from showerhead water and biofilm in the home of a woman with M. avium disease. DNA fingerprinting demonstrated identical M. avium isolates from showerhead and patient… J Water Health 06(2):209–213
MAC skin testing - Soil exposure Study Design Occupational soil exposure - risk factor for MAC skin test reactivity
MAC skin testing - Soil exposure Study Design Occupational soil exposure - risk factor for MAC skin test reactivity
MAC skin testing - Soil exposure Study Design Occupational soil exposure - risk factor for MAC skin test reactivity
MAC skin testing - Soil exposure Study Design Occupational soil exposure - risk factor for MAC skin test reactivity
Pulmonary NTM Source of infection High numbers of … M. avium, M.intracellulare, and M. chelonae, recovered from aerosols produced by pouring commercialpotting soil and potting soil samples provided by patients with pulmonary mycobacterialinfections. Dominant mycobacteria in soil samples corresponded to dominant species implicatedclinically. Pulsed-field gel electrophoresis demonstrated a closely related pair of M. avium isolates recovered from a patient and from that patient’s own potting soil. App Env Microbiol 2006; 72:7602-6.
ATS / IDSA guidelines - Diagnosis Treatment “Making the diagnosis of NTM lung disease does not, per se, necessitate the institution of therapy, which is a decision based on potential risks and benefits of therapy for individual patients” - ATS / IDSA 2007 Symptoms + Imaging + Cultures = NTM Disease
ATS / IDSA guidelines - Diagnosis Treatment “Making the diagnosis of NTM lung disease does not, per se, necessitate the institution of therapy, which is a decision based on potential risks and benefits of therapy for individual patients” - ATS / IDSA 2007 Symptoms + Imaging + Cultures = NTM Disease
Pulmonary NTM - Diagnosis Treatment When to treat? Micro • Repeated isolates / AFB smear + Symptoms • Systemic* – fatigue, fever/sweat, weight loss • Local – cough, sputum, hemoptysis, dyspnea Significant burden on imaging • Consolidation, nodules, cavities … • Progression
Pulmonary MAC - Goals of treatment Non-destructive infection • Cure Localized destruction • Cure (?) Diffuse destruction • Suppress Severe drug intolerance • Suppress Recurrence • Cure or Suppress?
Pulmonary MAC - Goals of treatment Non-destructive infection • Cure Localized destruction • Cure (?) Diffuse destruction • Suppress Severe drug intolerance • Suppress Recurrence • Cure or Suppress?
Pulmonary MAC - Goals of treatment Non-destructive infection • Cure Localized destruction • Cure (?) Diffuse destruction • Suppress Severe drug intolerance • Suppress Recurrence • Cure or Suppress?
Pulmonary MAC - Goals of treatment Non-destructive infection • Cure Localized destruction • Cure (?) Diffuse destruction • Suppress Severe drug intolerance • Suppress Recurrence • Cure or Suppress?
Pulmonary MAC - Goals of treatment Non-destructive infection • Cure Localized destruction • Cure (?) Diffuse destruction • Suppress Severe drug intolerance • Suppress Recurrence • Cure or Suppress?
ATS / IDSA guidelines - Drug treatment – MAC
ATS / IDSA guidelines - Drug treatment – MAC Other agents - Fluoroquinolones, clofazimine, linezolid
Pulmonary NTM - Treatment duration When to stop? Sputum cultures negative for 12 months
Pulmonary MAC - Drugs • Start with guidelines • Expect drug intolerance (staggered start) • Macrolides whenever possible • Amikacin for advanced cases* • Fluoroquinolones, clofazimine, linezolid as needed / tolerated • Aim for >3 drugs* • More drugs, higher doses greater efficacy • Tailor therapy • Switch drugs to minimize AE’s • Re-evaluate objectives based on response, toxicity * When treating intensively
Pulmonary MAC - Treatment – Other • Other interventions • Nutrition • Bronchodilators / Inhaled steroids? • Pulmonary hygiene • Surgery • Avoid exposure • Hot tubs • Shower?
Pulmonary MAC - Treatment – Other • Other interventions • Nutrition • Bronchodilators / Inhaled steroids? • Pulmonary hygiene • Surgery • Avoid exposure • Hot tubs • Shower?
Pulmonary MAC - Treatment – Other • Other interventions • Nutrition • Bronchodilators / Inhaled steroids? • Pulmonary hygiene • Surgery • Avoid exposure • Hot tubs • Shower?
Pulmonary MAC - Treatment – Other • Other interventions • Nutrition • Bronchodilators / Inhaled steroids? • Pulmonary hygiene • Surgery (?)
Pulmonary MAC - Following patients on therapy Assess response Microbiologic – sputum q 2-4 months Clinical – periodic Radiographic – LDCT scan 4-6 mo, then q 6-12 mo Follow for drug toxicities • Education important toxicity stop drugs • Clinical • Rifamycin CBC, liver tests • Ethambutol visual acuity, colour etc. • Amikacin ‘lytes, creatinine, serum level, audiograms
pNTM – a chronic disease? - Clinical practice Clinical practice (geographic region) • Leeds, UK; MAC 1999-2001 • 41% disease recurrence or mortality at 2 years post treatment Henry, ERJ 2004
pNTM – a chronic disease? - Clinical practice Clinical practice (specialty clinic) • 50% didn’t achieve sputum culture conversion • 60% didn’t tolerate initial antibiotics • 85% remain symptomatic Huang, Chest 1999