Mycobacterial Disease (Student) 2023 (1).pptx

Mycobacterial Disease Tuberculosis (TB) Sachi Patel, PA-C, MSPAS Assistant Professor, Master of Physician Assistant Studies November 2023 Plan • To provide historical and epidemiological perspectives on TB • To describe clinical presentation, diagnosis, treatment, prevention of TB • Types of T...

Mycobacterial Disease Tuberculosis (TB) Sachi Patel, PA-C, MSPAS Assistant Professor, Master of Physician Assistant Studies November 2023 Plan • To provide historical and epidemiological perspectives on TB • To describe clinical presentation, diagnosis, treatment, prevention of TB • Types of TB • To review future directions in prevention, diagnosis, treatment of TB     History     7000 BC – Ancient disease Was called “Consumption” in the 1800s (Gr. phthisis) Was also given a name of “The White Plague” in the 1800s 1882 – Koch’s bacillus named after the person discovering it Robert Koch 1885-1900s – Sanatorium (Quarantine centers) 1895 – Roentgenograph (CXR) 1900s – Plombage (Surgical tx) 1940s/50s – 1st effective drugs Epidemiolog y • • • • “Disease of poverty” 1 in 3 humans infected (1 in 10 active) 2 million deaths annually worldwide 7,860 reported cases in US in 2021 • 8,904 cases in US in 2019 (40% US-born) • 25% of TB deaths worldwide, HIV (+) • 10% of TB (+) in US also HIV (+) Epidemiolog y US Source: CDC.gov Tuberculos is Worldwide Source: Cdc.gov Risk Factors • • • • • • • Immune suppressed (HIV; Cancer; steroids) Occupational (Health Care Worker; prison guard) Substance abuse (EtOH) Diabetes Malnutrition Poor medical care Location, location, location Factor Risk Factors Relative Risk/Odds Recent infection (<1 year) 12.9 Fibrotic lesions (spontaneously healed) Comorbidity HIV infection 2–20 100 - 300 Silicosis 30 Chronic renal failure/hemodialysis 10–25 Diabetes Intravenous drug use Immunosuppressive treatment Gastrectomy Jejunoileal bypass Posttransplantation period (renal, cardiac) Malnutrition and severe underweight 2–4 10–30 10 2–5 30–60 20–70 2 Source: Harrison’s Principles of Internal Medicine Table 158.1  Rod-shaped, aerobic Koch’s Bacillus (1882). It is a slowgrowing organism. Has Multiorgan effects. Tuberculosis  Mycobacterium tuberculosis infection is acquired by inhaling organisms within aerosol droplets expelled during coughing by and individual with active disease  Most exposed people mount an immune response sufficient to prevent progression from initial infection to clinical illness  T cells and macrophages surround the organism in forming a granuloma  10% of persons infected with TB will develop the disease, primary TB “TB” is caused by Mycobacterium tuberculosis – it is a thin rod with lipid – laden cell walls = high lipid content makes them acid-fast on staining (AFB = acid-fast bacilli…or rod) Pathophysiolo gy exposure: usually by inhalation of aerosolized droplet nuclei into the lungs ↓ they land in the areas of the lung with the highest air flow: middle and lower regions ↓ inhaled bacteria cause a local infiltration of neutrophils and macrophages (although the organisms are not destroyed) ↓ multiplication of the AFB occurs – live in the macrophages ↓ bacteria cruise through the lymph system and blood and set-up camp at distant sites…usually short-lived b/c the body develops its major defense against the critters…cell-mediated immunity Transmissio n • Aerosolized droplet transmission (cough, sneezing, speaking, singing) • Particles <1-5 micrometers diameter • Particles remain airborne and disperse • A cough…3000 droplets • <10 droplets can initiate infection • Likelihood of transmission • number of organisms expelled • concentration of organisms • length of time of exposure breathing in contaminated air • immune status of the exposed individual  Progressive Primary TB= Approximately 5% exposed people fail to contain the primary infection and progress to active TB Tuberculosis  Latent TB (LTBI)= Approx. 95% of infected persons will contain the bacterium without being symptomatic  These patients are not considered to be infectious nor can they spread the disease. They are asymptomatic but have inactive TB in their body, most commonly in the apices of the lungs.  Reactivation TB illness develops from LTBI in the setting of immune compromise. Next is: Presentati on Diagnosis Prevention Treatment  Clinical Features Signs and Symptoms  Dry cough that progresses to a productive cough, with or without hemoptysis, typically over 3 weeks or longer  Fever, Chills, drenching night sweats  Anorexia, weight loss,  Pleuritic chest pain  Dyspnea,  Post-tussive rales  Hemoptysis  Usually appears chronically ill/ Malnourished  ****HISTORY, HISTORY, HISTORY **** Physical Exam • On PE patient mostly appears chronically ill and malnourished. • + / - Cachexia • + / - Fever • + / - lymphadenopathy • + / - hepatosplenomegaly • + / - tachycardia, friction rub • + / - hypoxia, rales, decreased breath sounds, dullness to percussion, egophony, decreased tactile fremitus • Tb • Asthma • Influenza / H1N1 • EtOH / drug abuse • Asbestosis • Aspergillosis • Bronchitis Cough DDx • Histoplasmosis • Pneumothorax • Non-TB mycobacterium • Silicosis • Pneumonia • ARDS • Lung Neoplasms • HIV / AIDS* • α-1 anti-trypsin • Lung abscess • Pleural effusion • Bronchiolitis  CXR/ Chest CT may show bilateral patchy infiltrates  Tuberculin Skin test—Mantoux Diagnostic studies  Interferon-gamma release blood test also known as Quanti-FERON Gold.  Blood test --FDA approved 2005  Serial sputum smears and cultures  Bronchoscopy  Biopsy  Diagnosis  Demonstration of acid-fast bacilli on sputum gram stain supports for preliminary detection Definitive Diagnosis  Definitive diagnosis requires the identification of M.tuberculosis from sputum cultures or by DNA (PCR) or RNA amplification techniques.  Biopsy revealing caseating granulomas (necrotizing granulomas) is the histologic hallmark Tuberculin Skin Test • • • • Purified protein derivative (PPD) / Mantoux method Used for > 100 years T-cell mediated / Delayed-type hypersensitivity reaction Positive 8-10 weeks s/p exposure http://www.stanford.edu/group/parasites/ParaSites2006/TB_Diagnosis/Current%20Diagnostic%20Techniques.html Induration Size Tuberculin Skin Test The size of a positive test result depends on the exposure history and health status of the individual and a measure of the actual induration rather than the erythema produced. Disadvantages of TST •Requires follow-up •False-positives • • BCG-vaccinated individuals Other mycobacterial infections •False-negatives • • Anergic Immune suppressed individuals  CXR  Primary TB: Homogenous infiltrates, hilar/paratracheal lymph node enlargement, segmental atelectasis, cavitations with progressive disease Radiologic Findings  Lower likelihood of having apical cavitary disease on chest x-ray if patient is living w/HIV  Reactivation TB: fibro cavitary apical disease, nodules, infiltrates, posterior and apical segments of the right upper lobe, apical-posterior segments of the left upper lobe, superior segments of the lower lobes  Ghon complexes(calcified primary focus) and Ranke complexes (calcified primary focus and calcified hilar lymph node) represent healed primary infection Source: https://radiopaedia.org/articles/primarypulmonary-tuberculosis Radiologic Findings • • • • • • • • • • Airspace consolidation Infiltrates Cavitations Volume loss Pleural effusions (ipsilateral to TB) Linear Opacities Nodules Hilar adenopathy Ghon / Ranke complexes *Often absent in immune suppressed pts Hilar adenopathy RUL cavitation RUL opacities Ghon complex  Treatment Tuberculosis  Isolation untill a minimum of 2 weeks of treatment is completed  Confirmed or suspected cases should be reported to local public health agencies within 5 working days • Isolation precautions during initial 2-4 weeks of treatment • Pharm regimen includes: Active TB treatment • Isoniazid 300 mg PO daily • Rifampin 600 mg PO daily • Pyrazinamide 1500 mg PO daily • Ethambutol 1200 mg PO daily • Use all of the above 4 drugs for 2 months • After 2 months based on culture and sensitivities continue multi drug treatment is continued for 4 more months • Most commonly --STOP pyrazinamide and ethambutol and CONTINUE isoniazid and rifampin for 4 more months • Total therapy 6-9 months Latent TB infection • • • • • • Positive TST Negative CXR Asymptomatic Non-contagious Progression risk greatest in first 2 years s/p infection Treatment • Treat only after active TB is ruled out • Isoniazid Daily for 9 months • or • Rifampin daily for 4 months • or • Isoniazid + Rifampin for 3 months • or • Rifampin and Pyrazinamide daily for 2 months (If resistant to Isoniazid) • Isoniazid for 1 year in HIV+ patients  Further management considerations Tuberculosis  Patients infected with HIV require therapy for atleast 1 year  INH for 6-12 months is indicated for prophylaxis in patients who have tested negative in the past but are now positive with known or unknown exposure  Patients exposed to active TB should be screened with TST. Indurations greater than 5mms should be treated aggressively.  An individual vaccinated with the Calmette-Guerin (BCG) vaccine will have a positive PPD. Use a quantiferon gold TB test to avoid false positives  Children, adolescents and immunocompromised people who have been in close contact with a person with active TB should be offered treatment until a TST is negative 12 weeks after exposure.  Defined as resistant to Rifampin and Izoniazid Multi drug resistant TB • 4% of all active TB cases (440,000 cases worldwide in 2008) • Lung resection combined with anti-TB chemotherapy for MDR-TB has shown success rates of 89-96% • Drug regimen is based on which drug patient is resistant too. • Primary • Reduce risk factors • BCG vaccination • Secondary Prevention • Identification and isolation of active cases* • Treatment: Infectivity greatly reduce after 2 weeks of appropriate treatment • 3 consecutive (-) AFB sputum smears • Evaluate risk to household contacts • *left untreated, 10-15 infections/case Pharmacolo gy • • • • • INH = isoniazid RIF = rifampin Eth = ethambutol PZA = pyrazinamide STM = streptomycin INH = isoniazid Available in IV and PO Adverse effects neurotoxicity 1. peripheral neuropathy uncommon with the recommended doses of isoniazid; can be prevented by administration of pyridoxine 10-50mg q day to high risk patients Pharmacolo gy hepatotoxicity 1) overt hepatitis  occurs in 1% of patients receiving isoniazid  occurs in 4% of patients receiving rifampin and isoniazid  Synergistic effect  usually develops within the first 1-2 months of therapy  the risk increases with concomitant alcohol use and age > 35 years 2) asymptomatic increases in serum transaminases (LFTs)  occurs in 10-20% of patients  usually occurs within the first 4-6 months of therapy  transaminase levels usually return to pretreatment levels even if isoniazid is continued RIF = rifampin Available in IV and PO Adverse Effects a. discoloration of body fluids (red/orange) urine b. gastrointestinal 1) most common adverse effect of rifampin 2) rarely requires drug discontinuation Pharmacolo gy c. “flushing reaction” 1) up to 5% of patients experience the “flushing reaction” 2) usually occurs 2-3 hours after drug ingestion; usually self-limited d. hepatotoxicity 1) up to 1% of patients develop rifampin-induced hepatitis 2) 4% of patients receiving both rifampin and INH develop hepatitis e. immune mediated reactions • influenza syndrome, hemolytic anemia, thrombocytopenia, acute renal failure • uncommon at currently recommended rifampin doses Eth = ethambutol Available in PO only Adverse Effects NO HEPATOTOXICITY generally, well tolerated Pharmacolo gy optic neuritis • uncommon with a dose of 25mg/kg/day for 60 days, then decreased to 15mg/kg/day for the remainder of therapy • uncommon with intermittent therapy • usually reversible if ethambutol is discontinued with the onset of initial symptoms Arthralgias • majority of patients develop mild hyperuricemia while receiving ethambutol • acute gouty arthritis is rare  c. arthralgias • majority of patients develop mild hyperuricemia while receiving ethambutol • acute gouty arthritis is rare PZA = pyrazinamide Pharmacolo gy Available in PO only Adverse Effects Generally, well tolerated b. arthralgia 1) 40% of patients receiving pyrazinamide experience nongouty, polyarthralgia's 2) acute gouty arthritis is rare c. “flushing reaction”—very common  similar presentation as rifampin  Rifampin has the worst and most commonly seen (FLUSHING REACTION) d. hepatotoxicity STM = streptomycin ONLY AND ONLY MED THAT IS PARENTERAL (IV and IM) Pharmacolo gy Adverse Effects a. nephrotoxicity • the mechanism of toxicity is acute tubular necrosis • risk factors include: high serum concentrations, increasing age, prolonged use, concurrent use of other nephrotoxic drugs, pre-existing renal impairment b. ototoxicity • vestibular more common than cochlear toxicity • risk factors include: high serum concentrations, total dose (>120gm), concomitant ototoxins, prior aminoglycoside use increasing age, pre-existing hearing loss Basic Principles of Antitubercular Therapy Pharmacolo gy  multiple drugs are utilized to prevent the emergence of resistance • first line drugs are the most potent: isoniazid, rifampin, pyrazinamide, ethambutol and streptomycin • second line drugs are less potent and are associated with a greater number of ADEs: capreomycin, kanamycin, ethionamide, para-aminosalicylic acid, cycloserine, levofloxacin, moxifloxacin, gatifloxacin, amikacin • NEVER add a single agent to a failing regimen • duration of therapy is much longer than for most bacterial infections • adherence to therapy is CRUCIAL for a successful outcome THE END