Treatment of Tuberculosis and Latent TB Infection

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