TB: Management in an era of multiple drug resistance. Bob Belknap M.D. Denver Public Health November 2012

Transcription

1 TB: Management in an era of multiple drug resistance Bob Belknap M.D. Denver Public Health November 2012

2 Objectives: 1. Explain the steps for diagnosing latent and active TB role of interferon-gamma release assays (IGRAs) sensitivity of sputum smears and nucleic acid amplification tests (NAATs) 2. List the first-line drugs used for latent and active TB treatment 3. Describe the resistance patterns that define MDR and XDR TB.

3 Case 1: 52 y/o male Born in the Pacific Islands; some travel in the U.S. military Known (+) TST (h/o BCG) 1 month of cough, fever, weight loss Refused admission

4 Case 1: 52 y/o male Hospitalized 2 weeks later QuantiFERON negative Lung bx shows granulomas, AFB smear (-) Presumed to have hypersensitivity pneumonitis or sarcoidosis

5 Case 1: 52 y/o male Clinically worse after 1 month on steroids Died shortly after readmission What went wrong?

6 Missed Opportunity for Prevention (2) Known (+) TST but never treated for LTBI h/o BCG - protects children from dying of TB but does not protect from infection The TST is considered reliable for diagnosing LTBI if the BCG was given > 1 year prior Reactions due to BCG wane over time so the CDC recommends interpreting (+) tests the same as persons without BCG

7 Interferon-gamma Release Assays (IGRAs) 1.Blood tests for detecting TB infection 2.Requires 1 visit 3.Results retrievable electronically 4.Better in BCG-vaccinated

8 Objective 1 Diagnosing LTBI (1) Think about TB risks Risk for Infection : Born or travelled to TB endemic countries, known close contact to TB Risk for Progression : HIV, DM, ESRD, TNF-α blocker, silicosis, fibrotic disease on x-ray

9 Objective 1 Diagnosing LTBI (2) TST or IGRA Rule out active TB Symptom review CXR on everyone sputum collection if the CXR is abnormal or the person is symptomatic Determine prior history of treatment for LTBI or TB disease Assess risks of toxicity

10 Case 2-25 yr old female Radiology reading: Fibrotic opacity in the right upper lobe with pleural thickening consistent with scarring from old TB

11 Case 2-25 yr old female 3 sputa grew MTB If you collect sputa, wait to start LTBI Rx

12 Online TB Risk Calculator

13 Objective 2 LTBI treatment options Isoniazid (INH) daily x 9 months Longest history / most data More completion rates INH/Rifapentine once weekly by DOT x 12 weeks Safe and effective but cost limited due to DOT Rifampin daily x 4 months Remember to look for drug-drug interactions

14 Case 1: 52 y/o male Hospitalized 2 weeks later QuantiFERON negative Lung bx shows granulomas, AFB smear (-) Presumed to have hypersensitivity pneumonitis or sarcoidosis

15 Objective 1 Diagnosing Active TB Risk for Infection : Born or travelled to TB endemic countries, known close contact to TB Risk for Progression : HIV, DM, ESRD, TNF-α blocker, silicosis, fibrotic disease on x-ray Concerning Symptoms

16 Objective 1: Diagnosing Active TB 1. History (including travel) 2. Physical examination (non-specific) 3. Chest x-ray 4. TB Skin Test (aka TST, PPD) or Interferon-γ Release Assay (IGRA) 5. Bacteriologic or histologic examination * Avoid empiric fluoroquinolones

17 Concerning Symptoms General: fever, night-sweats, weight loss, fatigue Pulmonary: Cough > 3wks, hemoptysis, shortness of breath, chest pain Extrapulmonary - lymphadenopathy, headache, stiff neck, altered mental status, hematuria, chest or abdominal pain

18 TB Symptoms and HIV Symptom/sign HIV positive (%) HIV negative (%) Dyspnea Fever Sweats Weight loss Diarrhea Hepatomegaly Splenomegaly Lymphadenopathy Chest 1994;106:1471-6

19 TST and IGRA: Sensitivity for Active TB Meta-analysis Data presented for TST and the commercially available assays (QFT-GIT and T-SPOT) Results: % (95% CI) TST 70( 67-72) QFT-GIT 84 (81-87) T-SPOT 88 (85-90) Diel, Chest April (4):

20 Case 1: 52 y/o male AFB smear (-) on lung biopsy Smear Sensitivity 50% from sputa Less from tissue Worse in HIV (+)

21 All BAL (+) patients were diagnosed by induced sputa BAL missed 2 patients No difference in yield between sputa collected over 3 days vs. 1 day

22 Empirical TB treatment without a positive smear or culture Clinical reasons at risk for life-threatening TB, including ones often never confirmed (e.g. < 50% of TB meningitis is culture positive) Public health reasons return to work/school while cultures are pending, children at home, staying in a congregate setting (nursing home or homeless shelter)

23 Objective 2: First-line TB Therapy Medication Rifampin (Rif) Isoniazid (INH) Pyrazinamide (PZA) Ethambutol (EMB) Side Effects P450 inducer,hepatitis, rash, flu-like symptoms, hypersensitivity Fatigue, peripheral neuropathy, hepatitis GI upset, rash, hepatitis, uric acid elevation (rare gout attack) Rare optic neuritis

24 Standard Treatment of Tuberculosis 1. Intensive Phase INH, Rifampin, Pyrazinamide and Ethambutol x 2 months First 2 to 3 weeks are spent in home isolation can t work, go to school or be out in public places 2. Continuation Phase INH and Rifampin x 4 months

25 Case 3-18y/o male Born in Somalia, moved from Chicago Empty bottle of rifampin 600 mg, #30 filled at Chicago health dept 2 months earlier Says his chest X-ray was abnormal & sputum cultures negative Denies any symptoms or signs of TB

26 Case 3-18y/o male Smears: Neg/Neg/1+ Fax report from Chicago: 3 negative smears & cultures Is this active TB? Is it drug resistant?

27 Culture and Susceptibility Testing Method Time to Detection Time to Susceptibility Comments Solid 3-4 weeks 3-4 weeks Gold standard Media Broth d 5-10 days Molecular 1 day 1 day Newer technologies are making this more feasible

28 Case 3-18y/o male Confirmed TB resistant to INH and Rif in 72 hours Cx (+) MTB resistant to INH, Rifampin, PZA, EMB and streptomycin Is this XDR-TB?

29 Objective 3: Drug Resistant Tuberculosis Multi-drug Resistant (MDR) Resistant to at least INH and Rifampin Extensively Drug Resistant (XDR) Resistant to INH and Rifampin plus Fluoroquinolones Second-line injectable agent (amikacin, kanamycin, or capreomycin)

30 Treatment of Suspected Drug-resistant TB Consider when a patient has a prior history of TB treatment and appears to have relapsed Consult an expert in TB treatment Never add a single drug to a failing regimen (eg. fluoroquinolones)

31 A previously healthy student died of a preventable & treatable illness News Alerts POSTED: 1:16 pm June 11, 2007 Colorado Springs Student From Nepal Dies From TB COLORADO SPRINGS, Colo. -- Tuberculosis was confirmed as the cause of death of a patient who died shortly after arriving at the emergency room on Friday.

32 Why do people still die of TB in the U.S.? Clinician Factors Failure to diagnose and treat latent infection Delays considering TB in the differential Delays working up symptomatic patients Misperception about the accuracy of our diagnostic tests Empiric use of fluoroquinolones Failure to report suspect cases to the health department and to start empiric TB treatment Failure to monitor appropriately while on treatment

33 Contact Information Denver Metro TB Clinic Randall Reves MD (clinic director) Bob Belknap MD (ID physician) CDC Division of TB Elimination - guidelines

34 Resources CDC Francis J Curry Center Stop TB Partnership WHO