TB: Siriraj Internal Medicine Board Review 2018 · WHO Guideline 2016 Group of Drugs for...

เช่ียวชาญศาสตร์สรรพ์ ยดึม่ันคุณธรรม ชีน้ าสังคม

Nitipatana Chierakul

Division of Respiratory Disease and Tuberculosis,

Department of Medicine,

Siriraj medical School,

Bangkok, THAILAND

TB: Siriraj Internal Medicine Board Review

2018


TB-HIV 8 %


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

Achievement for End-TB Strategy in 2025


Conventional Diagnosis


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


Consideration in AFB+

Tuberculosis (viable vs non-viable), especially in those considering treatment failure before starting empiric drug-resistant regimen by reviewing clinical, microbiological, and radiological responses

Non-tuberculous mycobacteria infection (colonization vsdisease)

Other organisms: Rhodococcus, Nocardia, Gordonia, Tsukamurella, Dietzia


Mycobacterial Culture

Conventional culture and drug susceptibility testing (DST) has turnaround time (TAT) of 9-12 weeks for first-line drugs (FLD) and 12-16 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)

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Indication for Initial Culture & DST

Previous TB treatment for more than 1 month, especially treatment failure, regardless of smear status

HIV co-infection, especially CD4 < 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


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


WHO Policy Statement 2011

IGRAs

Interferon-gamma Release Assays


Category II regimen (2SHRZE/1HRZE/5HRE) should no longer be used

and rapid DST should be conducted to inform the choice of regimen


First-line Anti-TB Drugs

Dose Adverse reactions Remarks

H 300 mg/d

5/mg/kg/d

(BW < 30 kg)

Rash, hepatitis, neuritis Pyridoxine 50-100

mg/d in those at

risk, acne

R 10 mg/kg/d

Maximum 600

Rash, hepatitis, immune

dysregulation, drug

interaction

Potent enzyme

inducer, body fluid

discoloration, acne

Z 25 mg/kg/d

Maximum 2,000

Rash, hepatitis,

hyperuricemia

Dose adjustment

for low GFR

E 15 mg/kg/d Rash, retrobulbar neuritis,

hyperuricemia

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


WHO Guideline 2016

Group of Drugs for rifampicin-resistant-TB and MDR-TB Treatment

Empiric MDR-TB regimen

1A, 1B, 2C, 1D1

6-8 Km Lfx Eto Cs Z (E or PAS)

+

12-14 Lfx Eto Cs ± Z (E or PAS)

Shorter MDR-TB regimen

4-6 Km Mfx Pto Cfz Z Hhigh E +

5 Mfx Cfz Z E


Cutaneous Reaction to Anti-TB Drugs

Severity Skin lesion Systemic

symptomsManagement

MildMaculopapular,

transient-

Reassure,

antihistamine

Moderate Persistent +Stop, steroid,

rechallenge

SevereExtensive, mucosal

involvement+

Admit, stop,

steroid,

desensitize


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


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


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


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


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 (drug-

susceptible pulmonary TB), a 6-month standard

treatment regimen is recommended over an

extended treatment for 8 months or more


Paradoxical Response (Non-HIV)PTB (AFB+) with Mediastinal TB Lymphadenopathy

Fever with right pleuritic chest pain 2 weeks after anti-TB


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


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


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


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


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


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


Action for Those with Unfavorable Responses Smear +

Persistent + after M2: check for compliance and control of of co-morbidities

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


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


Thailand Renown

for Tuberculosis


Suggested Readings

นิธิพฒัน์ เจียรกลุ. วณัโรค. ใน : ต ำรำอำยรุศำสตรท์ัว่ไป. นิธิพฒัน์ เจียรกลุ(บรรณำธิกำร). กรงุเทพมหำนคร, ภำพพิมพ ์2556; 286-295

World Health Organization

Treatment of tuberculosis: guidelines, 4th ed.

WHO/HTM/TB/2009.420

Companion handbook to the WHO guidelines for the

programmatic management of drug-resistant tuberculosis

WHO/HTM/TB/2014.11

The End TB Strategy

WHO/HTM/TB/2015.30

Global Tuberculosis Report 2017

WHO/HTM/TB/2017.23

TB: Siriraj Internal Medicine Board Review 2018 · WHO Guideline 2016 Group of Drugs for...

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