Tb And Ltbi Treatment

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  • Preventive therapy may be given to persons who have a negative skin test reaction High-risk contacts Children younger than 6 months of age who have been exposed to TB Persons receiving preventive therapy are those who have a positive skin test, and those who are: more likely to be exposed to or infected with M. tuberculosis more likely to develop TB disease once infected All persons receiving preventive therapy should receive a medical evaluation to: Exclude the possibility of TB disease Determine whether they have ever been treated for TB infection or disease Identify any medical problems that may complicate therapy or require more careful monitoring
  • Tb And Ltbi Treatment

    1. 1. Treatment of Tuberculosis and Latent TB Infection Division of TB Control Virginia Department of Health
    2. 2. TB Diagnosis <ul><li>“ The first rule of TB diagnosis: is to think TB….” </li></ul><ul><ul><li>Include TB in your differential diagnosis when history, symptoms are consistent with TB diagnosis </li></ul></ul><ul><ul><li>Order the appropriate diagnostic tests </li></ul></ul>
    3. 3. TB Diagnosis <ul><li>Symptoms: persistent cough, fever, night sweats, weight loss </li></ul><ul><li>Risk factors for exposure to TB: close contact of case, residence/travel in high prevalence country, congregate living with other high risk individuals </li></ul><ul><li>Risk factors for development of active disease if infected: recent infection, HIV/AIDS, other underlying medical condition </li></ul>
    4. 4. Diagnosis of Pulmonary TB (80-85% of TB Cases) <ul><li>Chest x-ray </li></ul><ul><ul><li>Standard PA and lateral films; apical lordotic views may be helpful </li></ul></ul><ul><ul><li>Infiltrates, nodular densities, cavities, +/- hilar adenopathy </li></ul></ul><ul><ul><li>Abnormalities may be subtle in immunocompromised patients </li></ul></ul><ul><ul><li>Previous x-rays for comparison may be useful </li></ul></ul><ul><li>CT scans </li></ul><ul><ul><li>Often obtained </li></ul></ul><ul><ul><li>Nice to have but rarely critical to diagnosis </li></ul></ul><ul><ul><li>Expensive </li></ul></ul>
    5. 5. Diagnosis of Pulmonary TB <ul><li>TST </li></ul><ul><ul><li>Positive supports but does not make diagnosis </li></ul></ul><ul><ul><li>Negative does not exclude TB as possible diagnosis </li></ul></ul><ul><li>Quantiferon </li></ul><ul><ul><li>Screening test only, not diagnostic </li></ul></ul>
    6. 6. Diagnosis of Pulmonary TB <ul><li>Mycobacteriology laboratory tests </li></ul><ul><ul><li>AFB smear </li></ul></ul><ul><ul><li>Culture </li></ul></ul><ul><ul><li>ID of isolate – confirm M.tb </li></ul></ul><ul><ul><li>Antimicrobial susceptibility testing </li></ul></ul><ul><ul><li>Rapid, direct tests </li></ul></ul>
    7. 7. Diagnosis of Pulmonary TB <ul><li>Coughed sputum </li></ul><ul><ul><li>Best specimen when available </li></ul></ul><ul><ul><li>Early AM best, supervise collection </li></ul></ul><ul><ul><li>AFB smear best available tool for assessing infectiousness </li></ul></ul><ul><ul><li>Most likely to yield positive culture </li></ul></ul><ul><ul><li>Multiple specimens recommended to maximize chances for +AFB/culture </li></ul></ul>
    8. 8. Diagnosis of Pulmonary TB <ul><li>Induced sputum </li></ul><ul><ul><li>Useful if no/non-productive cough </li></ul></ul><ul><ul><li>Unpleasant but safe, well tolerated, efficient way to quickly collect specimens </li></ul></ul><ul><ul><li>Specimen may be scant, difficult to interpret smears to assess infectiousness </li></ul></ul><ul><ul><li>Multiple specimens recommended to maximize chances for +AFB/culture </li></ul></ul>
    9. 9. Yield of smear and culture from repeated sputum induction for the diagnosis of pulmonary tuberculosis Int J Tuberc Lung Dis. 2001 Sep;5(90:855-60. Al Zahrani K, et al. Induced sputum (% yield) 100 99 91 70 AFB culture 98 91 81 64 AFB smear four three two one specimen
    10. 10. Diagnosis of Pulmonary TB <ul><li>Bronchoscopy (+/- transbronchial biopsy) </li></ul><ul><ul><li>Specimen dilute (saline lavage) </li></ul></ul><ul><ul><li>Cannot compare AFB + or – to sputum </li></ul></ul><ul><ul><li>Only one specimen available </li></ul></ul><ul><ul><li>May result in increased cough </li></ul></ul><ul><ul><ul><li>Collect coughed or induced sputum x3 after bronchoscopy; use AFB smear results to assess infectiousness </li></ul></ul></ul><ul><ul><li>Must collect sputum (coughed or induced) x3 to assess infectiousness after bronch culture result reported </li></ul></ul><ul><li>Lung biopsy </li></ul><ul><ul><li>Must culture as well as send for pathology </li></ul></ul><ul><ul><li>Still need sputum for smear, culture </li></ul></ul>
    11. 11. Laboratory Tests for M.tb <ul><li>AFB smear </li></ul><ul><ul><li>Available in 24-48 hours </li></ul></ul><ul><ul><li>Simple test; requires skilled technologist to read </li></ul></ul><ul><ul><li>Not diagnostic for M.tb : All AFB look alike </li></ul></ul><ul><ul><li>Assess infectiousness </li></ul></ul><ul><ul><ul><li>Need for isolation, contact investigation </li></ul></ul></ul><ul><ul><li>Monitor response to treatment </li></ul></ul><ul><ul><ul><li>Decrease in AFB on smear correlates with effectiveness of treatment </li></ul></ul></ul>
    12. 12. Laboratory Tests for M.tb <ul><li>Culture and Identification of Isolate </li></ul><ul><ul><li>“ Gold standard” for TB diagnosis </li></ul></ul><ul><ul><li>Usually complete in 2-4 weeks </li></ul></ul><ul><ul><li>Not signed out as negative until 8 weeks </li></ul></ul><ul><ul><li>Traditional identification based on growth characteristics, biochemical tests </li></ul></ul><ul><ul><li>ID by “probe” now standard </li></ul></ul><ul><ul><ul><li>Requires isolate (2-4 weeks) </li></ul></ul></ul><ul><ul><ul><li>Tests DNA – can ID M.tb complex , M.avium , +/- others </li></ul></ul></ul><ul><ul><ul><li>More rapid than chemicals, just as accurate </li></ul></ul></ul><ul><ul><ul><li>Cannot distinguish among M.tb complex species ( M.tb vs. M.bovis) </li></ul></ul></ul>
    13. 13. Laboratory Tests for M.tb <ul><li>Antimicrobial susceptibility testing </li></ul><ul><ul><li>Requires isolate </li></ul></ul><ul><ul><li>2-4 weeks after isolate available </li></ul></ul><ul><ul><li>IREZ +/- S testing standard </li></ul></ul><ul><ul><li>Second line drug testing only on request </li></ul></ul><ul><ul><ul><li>Discuss w/ DTC </li></ul></ul></ul><ul><ul><li>3-10% of VA TB isolates resistant to > 1 first line TB drug </li></ul></ul><ul><ul><ul><li>Continue IREZ until susceptibility results available </li></ul></ul></ul>
    14. 14. Other Laboratory Tests for M.tb <ul><ul><li>Direct/rapid tests for M.tb in sputum </li></ul></ul><ul><ul><ul><li>Nucleic acid amplification </li></ul></ul></ul><ul><ul><ul><li>Results in 3-5 days </li></ul></ul></ul><ul><ul><ul><li>Limited experience, generally reliable </li></ul></ul></ul><ul><ul><ul><li>May help with decisions on isolation, contact investigations </li></ul></ul></ul><ul><ul><ul><li>Not useful for follow-up </li></ul></ul></ul><ul><ul><li>Genotyping </li></ul></ul><ul><ul><ul><li>New technique; limited field experience </li></ul></ul></ul><ul><ul><ul><li>May be useful epi tool </li></ul></ul></ul><ul><ul><ul><li>No role in patient management </li></ul></ul></ul>
    15. 15. Diagnosis/Follow-up of Pulmonary vs. Extra-Pulmonary TB <ul><li>Pulmonary </li></ul><ul><ul><li>Sputum for AFB smear and culture </li></ul></ul><ul><ul><li>Chest x-ray helpful </li></ul></ul><ul><ul><li>Follow-up sputum smears and cultures useful to monitor treatment </li></ul></ul><ul><li>Extra-pulmonary </li></ul><ul><ul><li>More variability in presentation; may be more difficult to diagnose </li></ul></ul><ul><ul><li>AFB smear and culture done on tissue or fluid </li></ul></ul><ul><ul><li>Follow-up smears/cultures may not be possible </li></ul></ul><ul><ul><li>Must evaluate for pulmonary disease </li></ul></ul><ul><ul><li>Chest x-ray may be normal; x-rays/scans may be helpful </li></ul></ul>
    16. 16. Diagnosis and Treatment of Pulmonary vs. Extra-Pulmonary TB <ul><li>AFB smears, culture and antimicrobial sensitivity tests critical </li></ul><ul><li>Antimicrobial drug resistance rates similar </li></ul><ul><li>Same drugs, same doses, duration of treatment may vary </li></ul><ul><li>Prospects for survival, cure similar; permanent damage depends on location of infection </li></ul><ul><li>Rapidly progressive and/or disseminated TB more likely in very young, immunocompromised patients </li></ul><ul><li>Guidelines for monitoring (drug side effects/toxicity) similar </li></ul><ul><li>Guidelines for supervision of treatment (DOT) similar – less strict for extra-pulmonary because usually not infectious </li></ul>
    17. 17. Treatment of TB Disease <ul><li>The first rules of TB treatment are: </li></ul><ul><ul><li>Enough drugs (4 to start) </li></ul></ul><ul><ul><li>The right drugs (antimicrobial sensitivities) </li></ul></ul><ul><ul><li>Enough milligrams of each drug (patient weight) </li></ul></ul><ul><ul><li>Enough doses (count doses) </li></ul></ul><ul><ul><li>Enough attention to detail (monitoring of laboratory studies and clinical course) </li></ul></ul>
    18. 18. Antituberculosis Drugs Currently in Use in the US <ul><li>First-line Drugs </li></ul><ul><ul><li>Isoniazid </li></ul></ul><ul><ul><li>Rifampin </li></ul></ul><ul><ul><li>Rifapentine </li></ul></ul><ul><ul><li>Rifabutin </li></ul></ul><ul><ul><li>Ethambutol </li></ul></ul><ul><ul><li>Pyrazinamide </li></ul></ul><ul><li>Second-line Drugs </li></ul><ul><ul><li>Cycloserine </li></ul></ul><ul><ul><li>Ethionamide </li></ul></ul><ul><ul><li>Levofloxacin </li></ul></ul><ul><ul><li>Moxifloxacin </li></ul></ul><ul><ul><li>Gatifloxacin </li></ul></ul><ul><ul><li>P -Aminosalicylic acid </li></ul></ul><ul><ul><li>Streptomycin </li></ul></ul><ul><ul><li>Amikacin/kanamycin </li></ul></ul><ul><ul><li>Capreomycin </li></ul></ul><ul><ul><li>Linezolid </li></ul></ul>
    19. 19. Treatment of TB Disease <ul><li>Standard regimen </li></ul><ul><ul><li>IREZ x 8 weeks, then IR x 18+ weeks </li></ul></ul><ul><ul><li>5 days/week x 8 weeks, then 2x/week for remainder of treatment </li></ul></ul><ul><ul><li>Treatment extended if necessary to achieve required number of doses </li></ul></ul><ul><ul><li>Doses based on patient’s weight </li></ul></ul><ul><li>Standard regimen ok for ~75% of patients </li></ul><ul><li>90+% of eligible patients complete standard course of treatment within 12 months </li></ul>
    20. 20. Treatment of TB Disease <ul><li>Patients who require non-standard regimens </li></ul><ul><ul><li>Drug resistant TB </li></ul></ul><ul><ul><li>Drug side effects/toxicity </li></ul></ul><ul><ul><li>Other medical conditions </li></ul></ul><ul><ul><ul><li>HIV </li></ul></ul></ul><ul><ul><ul><li>Renal failure </li></ul></ul></ul><ul><ul><ul><li>Liver disease </li></ul></ul></ul><ul><ul><ul><li>Conditions causing malabsorption </li></ul></ul></ul><ul><ul><li>Children (sometimes) </li></ul></ul><ul><ul><li>Elderly (sometimes) </li></ul></ul><ul><ul><li>Pregnant women </li></ul></ul>
    21. 21. Drug resistant TB <ul><li>Choice of drugs depends on resistance pattern </li></ul><ul><li>May require second line drug(s) </li></ul><ul><li>Requires DOT </li></ul><ul><li>Requires >26 weeks of treatment </li></ul><ul><li>Usually requires daily therapy </li></ul><ul><li>Monitoring for culture conversion, clinical improvement, side effects/toxicity critical </li></ul>
    22. 22. Resistance to First Line Antimicrobial Agents Treatment of Cases and Contacts I = INH; R = Rifampin; E = Ethambutol; Z = Pyrazinamide; S = Streptomycin (Standard treatment = IREZ x8wk + IR x18wk) 174 (6%) S IE + second line med; Extend treatment to 12-18mo 0 RZ IZ + second line med: Extend treatment to 12-18mo 0 RE 8 (<1%) IZ 10 (<1%) IE Second line meds: Treat > 24 mo 13 (<1%) IREZ E + second line meds: Treat 24 mo 20 (<1%) IRZ Z + second line meds: Treat 24 mo 14 (<1%) IRE EZ + second line meds; Treat 18-24 mo 29 (1%) IR Extend treatment to 9mo 13 (<1%) Z 13 (<1%) E Extend treatment to 12-18mo 11 (<1%) R R for contacts 169 (6%) I Treatment Modifications # Resistant Isolates Drug(s)
    23. 23. Drug Side Effects/Toxicity <ul><li>Some side effects (e.g., nausea) almost universal; do not require modifications in treatment </li></ul><ul><li>Some adverse events uncommon but serious, reversible if identified early; require monitoring </li></ul><ul><ul><li>Hepatitis </li></ul></ul><ul><ul><li>Hearing loss </li></ul></ul><ul><ul><li>Visual acuity, color vision </li></ul></ul><ul><li>Selection of drugs and dosage based on weight, liver function and renal function can prevent toxicity </li></ul><ul><ul><li>Limit use of hepatotoxic drugs in patients with liver disease </li></ul></ul><ul><ul><li>Change dosing frequency in patients with renal disease </li></ul></ul><ul><li>Some adverse effects cannot be accurately predicted </li></ul><ul><ul><li>Hepatitis in patients without known liver disease </li></ul></ul><ul><ul><li>Bone marrow suppression or destruction of red blood cells, white blood cells, platelets </li></ul></ul>
    24. 24. TB Treatment in Patients with Other Medical Conditions <ul><ul><li>Common co-existing conditions </li></ul></ul><ul><ul><ul><li>HIV </li></ul></ul></ul><ul><ul><ul><ul><li>Interactions with anti-retroviral agents </li></ul></ul></ul></ul><ul><ul><ul><ul><li>TB may be disseminated and/or slow to respond; require longer treatment </li></ul></ul></ul></ul><ul><ul><ul><li>Renal failure </li></ul></ul></ul><ul><ul><ul><li>Liver disease (alcohol, hepatitis B, hepatitis C) </li></ul></ul></ul><ul><ul><ul><li>Conditions causing malabsorption </li></ul></ul></ul><ul><ul><ul><ul><li>HIV, severe debility, malnutrition </li></ul></ul></ul></ul>
    25. 25. TB Treatment in Patients with Other Medical Conditions <ul><ul><li>Careful monitoring critical </li></ul></ul><ul><ul><ul><li>Sputum for smears, cultures </li></ul></ul></ul><ul><ul><ul><li>Monitor for signs of drug toxicity </li></ul></ul></ul><ul><ul><ul><li>Clinical improvement (weight gain, feeling better) </li></ul></ul></ul><ul><ul><ul><li>LFTs, renal function tests </li></ul></ul></ul><ul><ul><ul><li>Consider drug levels </li></ul></ul></ul>
    26. 26. TB treatment in special populations <ul><ul><li>Children </li></ul></ul><ul><ul><ul><li>Same as adults </li></ul></ul></ul><ul><ul><ul><li>Dosage based on weight </li></ul></ul></ul><ul><ul><ul><li>Fewer problems with toxicity </li></ul></ul></ul><ul><ul><ul><li>Harder to administer </li></ul></ul></ul><ul><ul><ul><li>Harder to monitor </li></ul></ul></ul><ul><ul><ul><li>Pills (crushed) vs. liquid preparations </li></ul></ul></ul><ul><ul><ul><li>Some clinicians reluctant to use ethambutol </li></ul></ul></ul>
    27. 27. TB treatment in special populations <ul><ul><li>Elderly </li></ul></ul><ul><ul><ul><li>Same as younger adults </li></ul></ul></ul><ul><ul><ul><li>Dosage based on weight </li></ul></ul></ul><ul><ul><ul><li>Can be difficult to monitor for side effects </li></ul></ul></ul><ul><ul><ul><li>May not tolerate 2 or 3 x per week dosing </li></ul></ul></ul><ul><ul><li>Pregnant women </li></ul></ul><ul><ul><ul><li>Avoid aminoglycosides, PZA </li></ul></ul></ul>
    28. 28. Treatment of Latent TB Infection <ul><li>Recommended regimen </li></ul><ul><ul><li>Isoniazid for 9 months is optimal, 6 months acceptable </li></ul></ul><ul><ul><li>Four month course of rifamycin acceptable </li></ul></ul><ul><li>Recommendation for PZA/rifamycin has been withdrawn </li></ul><ul><ul><li>Problems with liver toxicity </li></ul></ul><ul><ul><li>Extremely close monitoring required if used </li></ul></ul><ul><ul><li>Remember its still efficacious ! </li></ul></ul>
    29. 29. Treatment of Latent TB Infection <ul><li>Monthly clinical monitoring required </li></ul><ul><ul><li>Monthly Clinical Assessment form </li></ul></ul><ul><li>AST or ALT and serum bilirubin in selected cases </li></ul><ul><ul><li>Baseline </li></ul></ul><ul><ul><ul><li>HIV infection </li></ul></ul></ul><ul><ul><ul><li>History of liver disease </li></ul></ul></ul><ul><ul><ul><li>Alcoholism </li></ul></ul></ul><ul><ul><ul><li>Pregnancy </li></ul></ul></ul><ul><ul><li>Repeat </li></ul></ul><ul><ul><ul><li>Baseline results abnormal </li></ul></ul></ul><ul><ul><ul><li>Pregnancy, immediate postpartum (first 3 months), or at high risk for adverse reactions </li></ul></ul></ul><ul><ul><ul><li>Symptoms of adverse reactions </li></ul></ul></ul>
    30. 30. References <ul><li>Radiographic Manifestations of Tuberculosis: A Primer for Clinicians – Frances J. Curry National Tuberculosis Center, 2003 </li></ul><ul><li>2003 ATS TB Treatment Statement </li></ul><ul><li>Pediatric Redbook – 2003 Edition </li></ul><ul><li>Drug-Resistant Tuberculosis – A Survival Guide for Clinicians (Frances J. Curry National Tuberculosis Center, 2004 </li></ul><ul><li>PDR or package insert </li></ul><ul><li>Laboratory Diagnosis – call DTC for references </li></ul><ul><li>Drug Side Effects, Toxicity – call DTC for references </li></ul><ul><li>Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection – MMWR 2000;49 (No. RR-6) </li></ul>
    31. 31. VDH/DTC Phone: 804 864 7906 Fax: 804 371 0248 www.vdh.virginia.gov
    32. 32. Thank you Questions?

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