tb cpg dr jamalul aziz
TRANSCRIPT
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TREATMENT of TB
in ADULTS
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Jamalul Azizi Bin Abdul Rahaman
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Like us on
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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 ðambutol 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
38 - 54 kg body weight: 3 tablets daily
55 - 70 kg body weight: 4 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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DURATION OF EPTB TREATMENT
- 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
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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