TB: Siriraj Internal Medicine Board Review 2018

Transcription

1 TB: Siriraj Internal Medicine Board Review 2018 Nitipatana Chierakul Division of Respiratory Disease and Tuberculosis, Department of Medicine, Siriraj medical School, Bangkok, THAILAND

2 TB-HIV 8 %

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5 Achievement for End-TB Strategy in 2025 Indicator Target (%) Treatment coverage 90 Treatment success rate 90 Catastrophic costs due to TB in households 0 Initial WHO-recommended rapid diagnostic test 90 Latent TB infection treatment coverage 90 Contact investigation coverage 90 Drug-susceptibility testing (DST) coverage 100 Treatment coverage, new TB drugs 90 Documented HIV status among TB patients 100 Case fatality ratio (CFR) 5

6 Conventional Diagnosis

7 Options for Smear-negative PTB Start anti-tb drugs if CXR reveal new cavity, adenopathy, or miliary pattern Bronchoscopy CT scan if no suggestive CXR pattern and harbour risk of lung cancer Otherwise, follow-up clinical symptoms and radiological findings every 3 months for 2 years Also take risk for transmission and side effect of anti-tb drugs into consideration

8 Consideration in AFB+ Tuberculosis (viable vs nonviable), especially in those considering treatment failure before starting empiric drugresistant regimen by reviewing clinical, microbiological, and radiological responses Non-tuberculous mycobacteria infection (colonization vs disease) Other organisms: Rhodococcus, Nocardia, Gordonia, Tsukamurella, Dietzia

9 Mycobacterial Culture Conventional culture and drug susceptibility testing (DST) has turnaround time (TAT) of 9-12 weeks for firstline drugs (FLD) and weeks for second-line drugs (SLD) Novel liquid culture can shorten TAT to 3-5 weeks for multidrug-resistant TB (MDR- TB) and 4-9 weeks for extensively drug-resistant TB (XDR-TB) jjmicrobiol.com

10 Indication for Initial Culture & DST Previous TB treatment for more than 1 month, especially treatment failure, regardless of smear status HIV co-infection, especially CD 4 < 200 cells/µl Recent closely contact with MDR-TB case Every new case in place where initial incidence of MDR-TB > 3% Optional Smear-negative pulmonary or extrapulmonary TB where definite diagnosis is vital Deep-seated specimens: bronchoalveolar lavage fluid, CSF, joint fluid, pericardial effusion, percutaneous tissue aspiration or biopsy

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12 Tuberculin Skin test (TST) Indirect evidence of infection, not an active disease, interpretation should be based on clinical probability Quality of tuberculin and technique are vital Essential tool for childhood TB Confounded by BCG vaccination, immune status, non-tuberculous mycobacteria (NTM) infection The more positive, the more likelihood of TB infection, however, in THAILAND 30% of adult with other pulmonary diseases had TST > 15 mm 10% of adult with active pulmonary TB had TST < 10 mm

13 WHO Policy Statement 2011 IGRAs Interferon-gamma Release Assays

14 Category II regimen (2SHRZE/1HRZE/5HRE) should no longer be used and rapid DST should be conducted to inform the choice of regimen

15 H R Z First-line Anti-TB Drugs Dose Adverse reactions Remarks 300 mg/d 5/mg/kg/d (BW < 30 kg) 10 mg/kg/d Maximum mg/kg/d Maximum 2,000 Rash, hepatitis, neuritis Pyridoxine mg/d in those at risk, acne Rash, hepatitis, immune dysregulation, drug interaction Rash, hepatitis, hyperuricemia E 15 mg/kg/d Rash, retrobulbar neuritis, hyperuricemia Potent enzyme inducer, body fluid discoloration, acne Dose adjustment for low GFR Dose adjustment for low GFR S 15 mg/kg/d Ototoxicity, nephrotoxicity At least 5 times a week Ofx 400 mg/d CNS toxicity, tendinitis Avoid in children

16 Group of Drugs for rifampicin-resistant-tb and MDR-TB Treatment Shorter MDR-TB regimen 4-6 Km Mfx Pto Cfz Z Hhigh E + 5 Mfx Cfz Z E Empiric MDR-TB regimen 1A, 1B, 2C, 1D1 6-8 Km Lfx Eto Cs Z (E or PAS) Lfx Eto Cs ± Z (E or PAS) WHO Guideline 2016

17 Cutaneous Reaction to Anti-TB Drugs Severity Skin lesion Systemic symptoms Management Mild Maculopapular, transient - Reassure, antihistamine Moderate Persistent + Stop, steroid, rechallenge Severe Extensive, mucosal involvement + Admit, stop, steroid, desensitize

18 Anti-TB Drug-induced Liver Injury (DILI) Risk Factors Advanced age Alcoholism Previous significant liver abnormalities HBV, HCV, and HIV infection Malnutrition Concomitant potential hepatotoxic drugs: antiepileptics, methotrexate

19 Antituberculosis-DILI Inform the patients before prescription Avoid alcohol and hepatotoxic agents Baseline LFTs for those harbour risks Normal or near normal: repeat if symptomatic or every 2-4 weeks during the first 8 weeks Abnormal: close observe, repeat if symptomatic or 1-2/week during the first 2 weeks and then every 2 weeks during the intensive phase Always aware for confounding viral hepatitis

20 Antituberculosis-DILI Elevation of ALT > 3 times with symptoms or 5 times without, ¾ occurs in first 2 months Weigh between disease severity and degree of liver impairment, consider discontinue or replace less hepatotoxic agents (ethambutol, quinolones, aminoglycosides) Drug challenging with low-dose or full-dose (R H Z) every 3 days after ALT < 2 times, rechecking if symptoms recur, the last drug added should be stopped Up to ¾ of those with no pre-existing liver abnormality can resume HRZE Rechallenge with Z may be hazardous in those with prolonged or severe hepatotoxicity Alternative regimens: 6RZE, 2SHRE/6HR, 2HRE/7HR, 2 HZE/10HE, 2SHE/10HE, 2SOfxE/16OfxE Close follow-up in case suspected of TB hepatitis

21 Treatment Adjustment in CKD Patients Isoniazid and rifampicin can be used safely regardless of GFR Aminoglycosides should not be used Quinolones require dose adjustment in advanced case Adjust ethambutol to 10 mg/kg/d in stage 2 and 7.5 mg/kg/d in stage 3 with close monitoring for visual impairment, avoid in those stage 4 Pyrazinamide should be use at dose 10 mg/kg/d in those stage 3-4 In those on regular hemodialysis, prescribe ethambutol and pyrazinamide in usual dose, thrice weekly administered after dialysis

22 TB-HIV Treatment ART should be started in all TB patients living with HIV regardless of their CD4 count TB treatment should be initiated first, followed by ART as soon as possible within the first 8 weeks of TB treatment Those withcd4 count < 50 cells/µl should receive ART within the first 2 weeks of initiating TB treatment In patients receiving TB-HIV co-treatment (drugsusceptible pulmonary TB), a 6-month standard treatment regimen is recommended over an extended treatment for 8 months or more

23 Paradoxical Response (Non-HIV) PTB (AFB+) with Mediastinal TB Lymphadenopathy Fever with right pleuritic chest pain 2 weeks after anti-tb

24 TB-associated Immune Restoration Inflammatory Syndrome (IRIS) Definite TB diagnosis was made before starting ARV Initial response to TB treatment of more than 2 weeks before ARV initiation Alternative explanations must be excluded Drug resistance TB Poor adherence to treatment Another opportunistic infection or neoplasm, particularly in those with smear-negative PTB or EPTB Drug toxicity or reaction

25 Treatment after Interruption Non-compliance or temporary regimens for severe ADR Re-numbering after successful re-introduction At least 80% of prescribed dose can lead to no significant change in outcome (98% cure rate with 2%relapse rate for 2 HRZE / 4 HR) Continue 2 weeks allowance during intensive phase 4 weeks allowance during maintenance phase Otherwise re-number, except if 4 months has passed with symptoms and CXR are markedly improved and become negative smear

26 Adjunctive Corticosteroids In patients with tuberculous meningitis, an initial adjuvant corticosteroid therapy with dexamethasone or prednisolone tapered over 6-8 weeks should be used regardless of the severity of meningitis In patients with tuberculous pericarditis, an initial adjuvant corticosteroid therapy may be used for preventing constrictive pericarditis

27 Treatment Adherence Ensure health education and counseling on the disease and treatment adherence Community-based or home-based directly observed treatment (DOT) is recommended over health facility-based DOT or unsupervised treatment, DOT administered by trained lay providers or health-care worker may be considered Video observed treatment (VOT) can replace DOT when the video communication technology is available and can be appropriately organized and operated by health-care providers and patients

28 Resuming Social Function Abolishment or nearly absence of cough Smear conversion or significantly decreased Well ventilated space, no highly susceptible person (small children, older age, immunosuppressed) Less infectivity after treatment for at least 2 weeks Long travel and elective surgery should be postponed until sputum smears are negative

29 Disease Monitoring Cough, fever, appetite, weight, organ symptoms Sputum smears every 2 weeks in intensive phase, and every 4 weeks in maintenance phase CXR at the end of intensive phase in those initial smear-negative, and at the end of treatment regardless of smear status Organ examination, imaging, and inflammatory biomarker such as C-reactive protein (CRP) for extrapulmonary TB

30 Action for Those with Unfavorable Responses Smear + Persistent + after M2: check for compliance and control of of comorbidities If clinical not improved and stable or worsening CXR Available initial DST: adjust accordingly NA initial DST, step down with close clinical FU if Persistent + after M3, send DST Persistent + after M4, Xpert TB/RIF, empiric MDR-TB regimen if test+ Smear If smears convert to positive after M2 carefully consider for action as persistent+ after M4

31 Hemoptysis after Treatment Cause Relapse TB Infected bronchiectasis Mycetoma (aspergilloma) Scar tumor Rasmussen s aneurysm Repeat consecutive sputum smears, treat infected bronchiectasis, avoid quinolones Alert for lung cancer in those harbored risk Aspergillus precipitin or sputum fungal cultures for mycetoma

32 Thailand Renown for Tuberculosis

33 Suggested Readings น ธ พ ฒน เจ ยรก ล. ว ณโรค. ใน : ตำรำอำย รศำสตร ท วไป. น ธ พ ฒน เจ ยรก ล(บรรณำธ กำร). กร งเทพมหำนคร, ภำพพ มพ 2556; World Health Organization Treatment of tuberculosis: guidelines, 4th ed. WHO/HTM/TB/ Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis WHO/HTM/TB/ The End TB Strategy WHO/HTM/TB/ Global Tuberculosis Report 2017 WHO/HTM/TB/