TB and LTBI Treatment
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Treatment of Tuberculosis andLatent TB Infection
Division of TB ControlVirginia Department of Health
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TB Diagnosis
The first rule of TB diagnosis: is tothink TB.
Include TB in your differential diagnosis whenhistory, symptoms are consistent with TBdiagnosis
Order the appropriate diagnostic tests
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TB Diagnosis
Symptoms: persistent cough, fever, nightsweats, weight loss
Risk factors for exposure to TB: close contactof case, residence/travel in high prevalencecountry, congregate living with other high riskindividualsRisk factors for development of activedisease if infected: recent infection,HIV/AIDS, other underlying medical condition
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Diagnosis of Pulmonary TB(80-85% of TB Cases)
Chest x-rayStandard PA and lateral films; apical lordotic views may behelpful
Infiltrates, nodular densities, cavities, +/- hilar adenopathy Abnormalities may be subtle in immunocompromisedpatientsPrevious x-rays for comparison may be useful
CT scansOften obtainedNice to have but rarely critical to diagnosisExpensive
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Diagnosis of Pulmonary TB
TSTPositive supports but does not make diagnosis
Negative does not exclude TB as possiblediagnosis
QuantiferonScreening test only, not diagnostic
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Diagnosis of Pulmonary TB
Mycobacteriology laboratory tests AFB smear
CultureID of isolate confirm M.tb
Antimicrobial susceptibility testing
Rapid, direct tests
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Diagnosis of Pulmonary TB
Coughed sputumBest specimen when available
Early AM best, supervise collection AFB smear best available tool for assessinginfectiousnessMost likely to yield positive culture
Multiple specimens recommended to maximizechances for +AFB/culture
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Diagnosis of Pulmonary TB
Induced sputumUseful if no/non-productive cough
Unpleasant but safe, well tolerated, efficient wayto quickly collect specimensSpecimen may be scant, difficult to interpretsmears to assess infectiousness
Multiple specimens recommended to maximizechances for +AFB/culture
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Y ield of smear and culture from repeated sputuminduction for the diagnosis of pulmonary
tuberculosis
specimen one two three four
AFB smear 64 81 91 98
AFB culture 70 91 99 100
Int J Tuberc Lung Dis. 2001 Sep;5(90:855-60. Al Zahrani K, et al.
Induced sputum (% yield)
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Diagnosis of Pulmonary TB
Bronchoscopy (+/- transbronchial biopsy)Specimen dilute (saline lavage)Cannot compare AFB + or to sputum
Only one specimen availableMay result in increased cough
Collect coughed or induced sputum x3 after bronchoscopy; use AFB smear results to assessinfectiousness
Must collect sputum (coughed or induced) x3 to assessinfectiousness after bronch culture result reported
Lung biopsyMust culture as well as send for pathologyStill need sputum for smear, culture
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Laboratory Tests for M.tb
AFB smear Available in 24-48 hours
Simple test; requires skilled technologist to readNot diagnostic for M.tb : All AFB look alike
Assess infectiousnessNeed for isolation, contact investigation
Monitor response to treatmentDecrease in AFB on smear correlates witheffectiveness of treatment
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Laboratory Tests for M.tbCulture and Identification of Isolate
Gold standard for TB diagnosisUsually complete in 2-4 weeks
Not signed out as negative until 8 weeksTraditional identification based on growthcharacteristics, biochemical testsID by probe now standard
Requires isolate (2-4 weeks)
Tests DNA can ID M.tb complex , M.avium , +/-othersMore rapid than chemicals, just as accurateCannot distinguish among M.tb complex species(M.tb vs. M.bovis)
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Laboratory Tests for M.tb
Antimicrobial susceptibility testingRequires isolate
2-4 weeks after isolate availableIREZ +/- S testing standardSecond line drug testing only on request
Discuss w/ DTC
3-10% of VA TB isolates resistant to > 1 first lineTB drug
Continue IREZ until susceptibility results available
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Other Laboratory Tests for M.tb
Direct/rapid tests for M.tb in sputumNucleic acid amplificationResults in 3-5 days
Limited experience, generally reliableMay help with decisions on isolation, contactinvestigationsNot useful for follow-up
Genotyping
New technique; limited field experienceMay be useful epi toolNo role in patient management
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Diagnosis/Follow-up of Pulmonary vs.Extra-Pulmonary TB
PulmonarySputum for AFB smear and culture
Chest x-ray helpfulFollow-up sputum smearsand cultures useful tomonitor treatment
Extra-pulmonaryMore variability inpresentation; may be
more difficult to diagnose AFB smear and culturedone on tissue or fluidFollow-upsmears/cultures may notbe possible
Must evaluate for pulmonary diseaseChest x-ray may benormal; x-rays/scans maybe helpful
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Diagnosis and Treatment of Pulmonary vs.Extra-Pulmonary TB
AFB smears, culture and antimicrobial sensitivity testscritical
Antimicrobial drug resistance rates similar
Same drugs, same doses, duration of treatment may varyProspects for survival, cure similar; permanent damagedepends on location of infectionRapidly progressive and/or disseminated TB more likely invery young, immunocompromised patients
Guidelines for monitoring (drug side effects/toxicity) similar Guidelines for supervision of treatment (DOT) similar less strict for extra-pulmonary because usually notinfectious
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Treatment of TB Disease
The first rules of TB treatment are:Enough drugs (4 to start)
The right drugs (antimicrobial sensitivities)Enough milligrams of each drug (patient weight)Enough doses (count doses)
Enough attention to detail (monitoring of laboratory studies and clinical course)
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Antituberculosis Drugs Currently in Usein the US
First-line DrugsIsoniazidRifampin
RifapentineRifabutinEthambutolPyrazinamide
Second-line DrugsCycloserineEthionamide
LevofloxacinMoxifloxacinGatifloxacinP -Aminosalicylic acidStreptomycin
Amikacin/kanamycinCapreomycinLinezolid
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Treatment of TB Disease
Standard regimenIREZ x 8 weeks, then IR x 18+ weeks5 days/week x 8 weeks, then 2x/week for remainder of treatmentTreatment extended if necessary to achieve requirednumber of dosesDoses based on patients weight
Standard regimen ok for ~75% of patients90+% of eligible patients complete standardcourse of treatment within 12 months
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Treatment of TB Disease
Patients who require non-standard regimensDrug resistant TBDrug side effects/toxicity
Other medical conditionsHIVRenal failureLiver diseaseConditions causing malabsorption
Children (sometimes)Elderly (sometimes)Pregnant women
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Drug resistant TBChoice of drugs depends on resistancepattern
May require second line drug(s)Requires DOTRequires >26 weeks of treatment
Usually requires daily therapyMonitoring for culture conversion, clinicalimprovement, side effects/toxicity critical
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Resistance to First Line Antimicrobial AgentsTreatment of Cases and Contacts
Drug(s) # Resistant Isolates Treatment Modifications
I 169 (6%) R for contacts
R 11 (
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Drug Side Effects/ToxicitySome side effects (e.g., nausea) almost universal; do notrequire modifications in treatmentSome adverse events uncommon but serious, reversible if identified early; require monitoring
HepatitisHearing lossVisual acuity, color vision
Selection of drugs and dosage based on weight, liver functionand renal function can prevent toxicity
Limit use of hepatotoxic drugs in patients with liver diseaseChange dosing frequency in patients with renal disease
Some adverse effects cannot be accurately predictedHepatitis in patients without known liver diseaseBone marrow suppression or destruction of red blood cells,white blood cells, platelets
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TB Treatment in Patients with Other Medical Conditions
Common co-existing conditionsHIV
Interactions with anti-retroviral agentsTB may be disseminated and/or slow to respond;require longer treatment
Renal failureLiver disease (alcohol, hepatitis B, hepatitis C)
Conditions causing malabsorptionHIV, severe debility, malnutrition
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TB Treatment in Patients with Other Medical Conditions
Careful monitoring criticalSputum for smears, cultures
Monitor for signs of drug toxicityClinical improvement (weight gain, feeling better)LFTs, renal function testsConsider drug levels
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TB treatment in special populations
ChildrenSame as adults
Dosage based on weightFewer problems with toxicityHarder to administer Harder to monitor
Pills (crushed) vs. liquid preparationsSome clinicians reluctant to use ethambutol
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TB treatment in special populations
ElderlySame as younger adultsDosage based on weight
Can be difficult to monitor for side effectsMay not tolerate 2 or 3 x per week dosing
Pregnant women Avoid aminoglycosides, PZA
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Treatment of Latent TB Infection
Recommended regimenIsoniazid for 9 months is optimal, 6 months
acceptableFour month course of rifamycin acceptable
Recommendation for PZA/rifamycin has beenwithdrawn
Problems with liver toxicityExtremely close monitoring required if usedRemember its still efficacious !
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Treatment of Latent TB Infection
Monthly clinical monitoring requiredMonthly Clinical Assessment form
AST or ALT and serum bilirubin in selected casesBaseline
HIV infectionHistory of liver disease
AlcoholismPregnancy
RepeatBaseline results abnormalPregnancy, immediate postpartum (first 3 months), or athigh risk for adverse reactionsSymptoms of adverse reactions
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References
Radiographic Manifestations of Tuberculosis: A Primer for Clinicians Frances J. Curry National Tuberculosis Center,20032003 ATS TB Treatment StatementPediatric Redbook 2003 EditionDrug-Resistant Tuberculosis A Survival Guide for Clinicians(Frances J. Curry National Tuberculosis Center, 2004PDR or package insertLaboratory Diagnosis call DTC for referencesDrug Side Effects, Toxicity call DTC for referencesTargeted Tuberculin Testing and Treatment of LatentTuberculosis Infection MMWR 2000;49 (No. RR-6)
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VDH/DTC
Phone: 804 864 7906Fax: 804 371 0248
www.vdh.virginia.gov
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Thank youQuestions?