TB CPG Dr Jamalul Aziz

7/27/2019 TB CPG Dr Jamalul Aziz

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TREATMENT of TB

in ADULTS

1

Jamalul Azizi Bin Abdul Rahaman


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GET A COPY OF TB CPG

TB CPG launched on World TB Day 2013 Accessible

Hard copy & soft copy uploaded in MoH,

Academy of Medicine & MTS websites

Smartphones and tablets (Android)

Quick reference

For all healthcare providers

"KKM/BKP"


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INTRODUCTION

Tuberculosis (TB) remains an importantdisease both globally & in Malaysia

Number of TB cases in the countrycontinues to increase unabated

High rates of morbidity & mortality due to: Delayed presentation

Advanced HIV

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RATIONALE FOR CPG

TB issues in Malaysia

A common disease

Affects many organs in the body

Managed by doctors at all levels

Primary care

General medicine

Subspecialty

Lack of standardisation in TB management

Inaccurate diagnosis

Inappropriate empirical treatment

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There is a need to standardise TB management to minimise the

risk of multidrug-resistant (MDR) TB


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OBJECTIVES OF CPG

To assist clinicians & other healthcareproviders in making evidence-baseddecisions about appropriate managementof TB specifically on:

screening

diagnosis

treatment

follow-up

prevention

referral

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SCOPE OF CPG

Epidemiology & High Risk Groups

Investigations

Treatment of TB in Adults

LTBI in Adults

TB in Children

TB in Pregnancy, Lactation & Use of Oral Contraceptive Pills

Liver & Renal Impairment

HIV Infection

Follow-up & Adverse Drug Events

MDR-TB

Prevention

Referral Criteria

Implementing the Guidelines

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TARGET USERS

Healthcare professionals & relevantstakeholders in all healthcare settingsincluding

Doctors

Pharmacists

Allied health professionals

Medical students & trainees

Tuberculosis programme managers

Patients & carers/non-governmental

organisations8


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3rd Edition CPG vs 2nd Edition CPG

Evidence-based Systematic review approach Expansion of chapters e.g.:-

Lab. investigations

EPTB TB in Children

HIV

MDR-TB

Appendices (inc. Drug Table)

New chapters e.g.:- LTBI

Referral criteria Peer review (external reviewers) Quick Reference

Consensus-based

(2012) (2002)


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43RECOMMENDATIONS

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TB LABORATORYINVESTIGATIONS

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INTRODUCTION

Diagnosis of TB is based on thedetection of acid fast bacilli (AFB) onsmears & culture of Mycobacterium

tuberculosisfrom clinical specimens.

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MICROSCOPY

Microscopy

Presumptive diagnosis

Sputum

Ziehl-Neelsen staining for AFB

Conventional microscope

low sensitivity (20 - 60%)1

Light emitting diode-based

fluorescence microscopy (LED FM)2

10% more sensitive

shorter time spent

quicker turnaround time 1Steingart KR et al., Lancet Infect Dis, 2006

2Shenai S et al., Int J Tuberc Lung Dis, 2011

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Acid fast bacilli

CONVENTIONAL LIGHT MICROSCOPY


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IMMUNOFLUORESCENCE MICROSCOPY


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iMAGING IN TB


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INTRODUCTION

iMAGING may assist in:

identifying the lesion

characterising the lesion assessing the extent/severity

assisting in intervention

There are NO imaging features that are

pathognomonic for TB & the findings maymimic those of many other diseases.


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US can be used in intestinal TB (to assess ascites &lymphadenopathy), renal TB & also in soft tissueinvolvement.

CT is the preferred imaging modality in assessingabdominal TB & may also be used in musculoskeletalinvolvement of TB.

MRI is the preferred modality in cranial andmusculoskeletal TB.

CXR is indicated in all cases of EPTB

iMAGING MODALITIES IN EPTB


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iMAGING


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TREATMENT of TBin ADULTS


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INTRODUCTION

Important to provide a standardised TBregimen for all TB cases

This section will cover all aspects oftreatment:

Pulmonary TB (PTB)

New cases

Relapse cases

Extrapulmonary TB (EPTB)

Standard regimes & duration

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AIM OF TREATMENT

Cure & reduce transmission

Risk of developing TB is determined:

infectiousness of index case

smear positive PTB; PTB with cavities;

laryngeal TB

nature & duration of contact

immune status of contact

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EDUCATION

a. Nature of disease b. Necessity of strict adherence with

prolonged treatment

c. Risks of defaulting treatment d. Side effects of medication

e. Risks of transmission & need for

respiratory hygiene as well as cough/sneeze etiquette

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PULMONARY TUBERCULOSIS (PTB)

IN ADULTS


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NEW CASES

6-month regimen consisting of 2 monthsof EHRZ (2EHRZ) followed by 4 monthsof HR (4HR) is recommended for newly-diagnosed PTB.

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RECOMMENDED ANTITB DRUGS

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DRUG

RECOMMENDED DOSES

Daily 3X a week

Dose (range)in mg/kg body weight

Maximum inmg

Dose (range)in mg/kg body weight

Maximum inmg

Isoniazid (H) 5 (4 - 6) 300 10 (8 - 12) 900

Rifampicin (R) 10 (8 - 12) 600 10 (8 - 12) 600

Pyrazinamide

(Z)

25 (20 - 30) 2000 35 (30 40)* 3000*

Ethambutol(E)

15 (15 - 20) 1600 30 (25 35)* 2400*

Streptomycin

(S)

15 (12 - 18) 1000 15 (12 18)* 1500*


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NEW CASES (cont.)

Pyridoxine 10 - 50 mg daily needs to beadded if isoniazid is prescribed.

*Daily treatment is the preferred regimen. Adopted from WHO. Treatment of Tuberculosis Guidelines (4th Ed.), 2010

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IMPORTANT POINTS

Rifampicin

should be used for the whole duration of treatment.

NS difference in effectiveness & safety betweenrifampicin & other antibiotics in the rifamycin group.

whenever possible, rifampicin dosage should not belower than recommended dosage (10 - 12 mg/kg).

Pyrazinamide beyond 2 months during theintensive phase does not confer further

advantage if the organism is fully susceptible. Recurrence rate is low for both ethambutol-based

regimen & for streptomycin-based regimen.

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TREATMENT OF NEW CASES

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FLOW CHART FOR 6 MONTHS


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FLOW CHART FOR 6 MONTHSTREATMENT OF PTB

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FOLLOW-UP AFTER COMPLETIONOF ANTITB TREATMENT

Follow-up clinic visits should not beconducted routinely after treatmentcompletion.

Patients should be told to watch forsymptoms of relapse & how to contact the

TB service rapidly through primary care ora TB clinic.

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FOLLOW-UP

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PREVIOUSLY TREATED TB

New cases who have taken treatment formore than one month & are currentlysmear or culture positive again (i.e. failure,relapse or return after default)

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DEFINITION


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DEFINITION

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Previously treated Patient previously treated for TBincluding relapse, failure & default

Relapse A patient whose most recent treatmentoutcome was cured or treatment

completed, & who is subsequentlydiagnosed with bacteriologically positive TB

by sputum smear microscopy or culture.

Treatment failure A patient who has received Category Itreatment for TB & in whom treatment has

failed.

Treatment afterdefault A patient who returns to treatment,bacteriologically positive by sputum smear

microscopy or culture, following interruptionof treatment for 2 or more consecutive

months.


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PREVIOUSLY TREATED TB

Recommend: retreatment regimen containing first-line drugs 2HRZES/1HRZE/5HRE if country-specific data show low or medium levels of MDR-TB in these patients or if such data is not available.

Drug sensitivity test (DST) must be done forpatients. When results become available, drugregimen should be adjusted appropriately.

*This is WHO statement, no retrievable evidence

available.

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TO START OR NOT?

Interruption in intensive phase: If 14 days, to restart from beginning i.e. Day

1.

If


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TO START OR NOT?

Interruption in maintenance phase:

If interruption occurs after patient receives 80% oftotal planned doses, treatment may be stopped if

sputum AFB smear was negative at initial

presentation. If sputum AFB smear was positive,treatment should be continued to achieve total

number of doses.

If total doses


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OPTIMAL DURATION

Patients with sputum positive PTB should receiveantiTB drugs for a minimum duration of 6 months.

Regimens with shorter duration of rifampicin are

associated with higher risk of failure, relapse &acquired drug resistance.

Even in patients with non-cavitary disease &

confirmed sputum culture, conversion at 2months fares poorer with a 4-month regimencompared to 6-month regimen.

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OPTIMAL DURATION

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MAINTENANCE PHASE

In new patients with PTB, WHO recommendsdaily dosing throughout the course of antiTB

treatment.

However, a daily intensive phase followed bythrice weekly maintenance phase is an option

provided that each dose is directly observed &

patient has improved clinically.

A maintenance phase with twice weekly dosing

is not recommended.

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MAINTENANCE PHASE

There is no difference in treatment failure,relapse & acquired drug resistance rates

between daily & different intermittent dosing

regimens in the maintenance phase.1, 2, 31Menzies D et al., PLoS Med, 2009

2Mwandumba HC et al., Cochrane, 20013Chang KC et al., Thorax, 2011

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MAINTENANCE PHASE

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FDC IN MOH

4-Drug combination: isoniazid 75 mg,rifampicin 150 mg, pyrazinamide 400 mg &ethambutol 275 mg tablet

3-Drug combination: isoniazid 75 mg,rifampicin 150 mg & pyrazinamide 400 mgtablet

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RECOMMENDED DOSES

30 - 37 kg body weight: 2 tablets daily



More than 70 kg body weight: 5 tablets

daily

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EFFECTIVENESS

FDCs compared to separate-drugregimens significantly reduce risk of non-compliance by 17% & consequentlyimprove effectiveness of therapy.1

In term of bioavailability, FDCs are provento be bioequivalent to separate-drugsformulations at the same dose levels.2

1Bangalore S et al., Am J Med, 20072Agrawal S et al., Int J Pharm, 2002

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OTHER ADVANTAGES

Smaller number of tablets to be ingestedmay also encourage patient adherence.

Prescription errors are likely to be lessfrequent for FDCs due to easy adjustmentof dosage according to patient weight.

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FDC

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DIRECTLY OBSERVED THERAPY


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DIRECTLY OBSERVED THERAPY(DOT)

Direct observation of drug ingestion of theDOTS component should not be the soleemphasis in TB control programmes.

It should not be a blanket approach;instead it should be a process ofnegotiation & support, incorporatingpatients characteristics & choices.

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DIRECTLY OBSERVED THERAPY


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DIRECTLY OBSERVED THERAPY(DOT)

Enhanced DOTS involving intensivecontact tracing & treating the contacts withTB can reduce incidence of TB within acommunity (p=0.04).1

1Cavalcante SC et al., Int J Tuberc & Lung Dis. 2010

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DOT

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EXTRAPULMONARY

TUBERCULOSIS (EPTB) IN ADULTS

DURATION OF EPTB TREATMENT


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- NICE RECOMMENDATION1

Meningeal TB 2 months S/EHRZ+10HR*

Peripheral lymph node TB shouldnormally be stopped after 6 months

Bone & joint TB 6 months Pericardial TB 6 months

1National Collaborating Centre for Chronic Conditions and the Centre for Clinical Practice. Tuberculosis: clinicaldiagnosis and management of tuberculosis, and measures for its prevention and control. 2011

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DURATION OF EPTB TREATMENT- WHO RECOMMENDATION1

Regimen should contain 6 months ofrifampicin: 2HRZE/4HR*

Duration of treatment for TB meningitis is 9- 12 months &, bone & joint TB is 9 months

1World Health Organization. Treatment of tuberculosis Guidelines. Fourth ed. 2010

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MILIARY & DISSEMINATED TB


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MILIARY & DISSEMINATED TB

There is no retrievable evidence onoptimal duration of treatment fordisseminated TB & miliary TB.

There should be low threshold to suspectTB meningitis in these groups of patients &treatment duration should be prolongedbetween 9 to 12 months.

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OPTIMAL DURATION OFEPTB TREATMENT

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CORTICOSTEROIDS IN EPTB


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CORTICOSTEROIDS IN EPTB

Corticosteroid therapy may benefit patientswith some forms of EPTB. Howeverliterature on corticosteroids in various formof EPTB is scant.

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CORTICOSTEROIDS INEPTB TREATMENT

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TB MENINGITIS


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TB MENINGITIS

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Severity Regime

Grade Idisease Week 1: IV dexamethasone sodium phosphate0.3 mg/kg/day Week 2: 0.2 mg/kg/day Week 3: Oral dexamethasone 0.1 mg/kg/day Week 4: Oral dexamethasone a total of 3 mg/day,

decreasing by 1 mg each week

Grade II & IIIdisease

Week 1: IV dexamethasone sodium phosphate0.4 mg/kg/day Week 2: 0.3 mg/kg/day Week 3: 0.2 mg/kg/day Week 4: 0.1 mg/kg/day, then oral dexamethasone

for 4 weeks, decreasing by 1 mg each week

Prasad K et al., Cochrane, 2008


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TB PERICARDITIS

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SURGERY IN PTB


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SURGERY IN PTB

Diagnosis & obtaining tissue for culture &drug sensitivity

Management of TB complications

Treatment of the disease itself where drug

therapy alone may be deemed insufficientto achieve cure

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SURGERY IN PTB


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SURGERY IN PTB

While the advancement in surgicaltechniques including video-assistedthoracoscopy surgery/thoracotomy hasreduced the surgical mortality & morbidity,

surgery for PTB is still associated withsignificant complications due to thepresence of adhesions & scarring.

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WHEN TO REFER


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WHEN TO REFER

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MAIN CHANGES IN CPG TB 2012


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MAIN CHANGES IN CPG TB 2012

Evidence-based

Treatment after interruption explained in moredetail

Treatment regimes (maintenance) changed to

daily or 3X a week FDCs mentioned

DOTS covered in more detail & done to suitMalaysian context

Duration of treatment for EPTB more concise

Use of steroids recommended for TB meningitis &pericarditis

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TAKE HOME MESSAGES


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TAKE HOME MESSAGES

Adhere to standard regime

Use correct doses & adequate duration

Ensure compliance

Treatment needs to be individualised

Consult a doctor/physician with experiencein TB management when in doubt

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THANK YOU

[email protected]

TB CPG Dr Jamalul Aziz

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