Treatment of Tuberculosis and Latent TB Infection

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Treatment of Tuberculosis and Latent TB Infection

• Division of TB Control
• Virginia Department of Health

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TB Diagnosis

• The first rule of TB diagnosis is to think
  TB.
• Include TB in your differential diagnosis when
  history, symptoms are consistent with TB
  diagnosis
• Order the appropriate diagnostic tests

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TB Diagnosis

• Symptoms persistent cough, fever, night sweats,
  weight loss
• Risk factors for exposure to TB close contact of
  case, residence/travel in high prevalence
  country, congregate living with other high risk
  individuals
• Risk factors for development of active disease 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-ray
• Standard PA and lateral films apical lordotic
  views may be helpful
• Infiltrates, nodular densities, cavities, /-
  hilar adenopathy
• Abnormalities may be subtle in immunocompromised
  patients
• Previous x-rays for comparison may be useful
• CT scans
• Often obtained
• Nice to have but rarely critical to diagnosis
• Expensive

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Diagnosis of Pulmonary TB

• TST
• Positive supports but does not make diagnosis
• Negative does not exclude TB as possible
  diagnosis
• Quantiferon
• Screening test only, not diagnostic

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Diagnosis of Pulmonary TB

• Mycobacteriology laboratory tests
• AFB smear
• Culture
• ID of isolate confirm M.tb
• Antimicrobial susceptibility testing
• Rapid, direct tests

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Diagnosis of Pulmonary TB

• Coughed sputum
• Best specimen when available
• Early AM best, supervise collection
• AFB smear best available tool for assessing
  infectiousness
• Most likely to yield positive culture
• Multiple specimens recommended to maximize
  chances for AFB/culture

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Diagnosis of Pulmonary TB

• Induced sputum
• Useful if no/non-productive cough
• Unpleasant but safe, well tolerated, efficient
  way to quickly collect specimens
• Specimen may be scant, difficult to interpret
  smears to assess infectiousness
• Multiple specimens recommended to maximize
  chances for AFB/culture

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Yield of smear and culture from repeated sputum
induction for the diagnosis of pulmonary
tuberculosis
Induced sputum ( yield)
Int J Tuberc Lung Dis. 2001 Sep5(90855-60. Al
Zahrani K, et al.
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Diagnosis of Pulmonary TB

• Bronchoscopy (/- transbronchial biopsy)
• Specimen dilute (saline lavage)
• Cannot compare AFB or to sputum
• Only one specimen available
• May result in increased cough
• Collect coughed or induced sputum x3 after
  bronchoscopy use AFB smear results to assess
  infectiousness
• Must collect sputum (coughed or induced) x3 to
  assess infectiousness after bronch culture result
  reported
• Lung biopsy
• Must culture as well as send for pathology
• Still 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
  read
• Not diagnostic for M.tb All AFB look alike
• Assess infectiousness
• Need for isolation, contact investigation
• Monitor response to treatment
• Decrease in AFB on smear correlates with
  effectiveness of treatment

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Laboratory Tests for M.tb

• Culture and Identification of Isolate
• Gold standard for TB diagnosis
• Usually complete in 2-4 weeks
• Not signed out as negative until 8 weeks
• Traditional identification based on growth
  characteristics, biochemical tests
• ID by probe now standard
• Requires isolate (2-4 weeks)
• Tests DNA can ID M.tb complex, M.avium, /-
  others
• More rapid than chemicals, just as accurate
• Cannot distinguish among M.tb complex species
  (M.tb vs. M.bovis)

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Laboratory Tests for M.tb

• Antimicrobial susceptibility testing
• Requires isolate
• 2-4 weeks after isolate available
• IREZ /- S testing standard
• Second line drug testing only on request
• Discuss w/ DTC
• 3-10 of VA TB isolates resistant to gt 1 first
  line TB drug
• Continue IREZ until susceptibility results
  available

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Other Laboratory Tests for M.tb

• Direct/rapid tests for M.tb in sputum
• Nucleic acid amplification
• Results in 3-5 days
• Limited experience, generally reliable
• May help with decisions on isolation, contact
  investigations
• Not useful for follow-up
• Genotyping
• New technique limited field experience
• May be useful epi tool
• No role in patient management

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Diagnosis/Follow-up of Pulmonary vs.
Extra-Pulmonary TB

• Pulmonary
• Sputum for AFB smear and culture
• Chest x-ray helpful
• Follow-up sputum smears and cultures useful to
  monitor treatment

• Extra-pulmonary
• More variability in presentation may be more
  difficult to diagnose
• AFB smear and culture done on tissue or fluid
• Follow-up smears/cultures may not be possible
• Must evaluate for pulmonary disease
• Chest x-ray may be normal x-rays/scans may be
  helpful

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Diagnosis and Treatment of Pulmonary vs.
Extra-Pulmonary TB

• AFB smears, culture and antimicrobial sensitivity
  tests critical
• Antimicrobial drug resistance rates similar
• Same drugs, same doses, duration of treatment may
  vary
• Prospects for survival, cure similar permanent
  damage depends on location of infection
• Rapidly progressive and/or disseminated TB more
  likely in very 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 not infectious

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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 Use in the US

• First-line Drugs
• Isoniazid
• Rifampin
• Rifapentine
• Rifabutin
• Ethambutol
• Pyrazinamide

• Second-line Drugs
• Cycloserine
• Ethionamide
• Levofloxacin
• Moxifloxacin
• Gatifloxacin
• P-Aminosalicylic acid
• Streptomycin
• Amikacin/kanamycin
• Capreomycin
• Linezolid

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Treatment of TB Disease

• Standard regimen
• IREZ x 8 weeks, then IR x 18 weeks
• 5 days/week x 8 weeks, then 2x/week for remainder
  of treatment
• Treatment extended if necessary to achieve
  required number of doses
• Doses based on patients weight
• Standard regimen ok for 75 of patients
• 90 of eligible patients complete standard
  course of treatment within 12 months

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Treatment of TB Disease

• Patients who require non-standard regimens
• Drug resistant TB
• Drug side effects/toxicity
• Other medical conditions
• HIV
• Renal failure
• Liver disease
• Conditions causing malabsorption
• Children (sometimes)
• Elderly (sometimes)
• Pregnant women

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Drug resistant TB

• Choice of drugs depends on resistance pattern
• May require second line drug(s)
• Requires DOT
• Requires gt26 weeks of treatment
• Usually requires daily therapy
• Monitoring for culture conversion, clinical
  improvement, side effects/toxicity critical

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Resistance to First Line Antimicrobial
AgentsTreatment of Cases and Contacts
(Standard treatment IREZ x8wk IR x18wk)
I INH R Rifampin E Ethambutol Z
Pyrazinamide S Streptomycin
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Drug Side Effects/Toxicity

• Some side effects (e.g., nausea) almost
  universal do not require modifications in
  treatment
• Some adverse events uncommon but serious,
  reversible if identified early require
  monitoring
• Hepatitis
• Hearing loss
• Visual acuity, color vision
• Selection of drugs and dosage based on weight,
  liver function and renal function can prevent
  toxicity
• Limit use of hepatotoxic drugs in patients with
  liver disease
• Change dosing frequency in patients with renal
  disease
• Some adverse effects cannot be accurately
  predicted
• Hepatitis in patients without known liver disease
• Bone 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 conditions
• HIV
• Interactions with anti-retroviral agents
• TB may be disseminated and/or slow to respond
  require longer treatment
• Renal failure
• Liver disease (alcohol, hepatitis B, hepatitis C)
• Conditions causing malabsorption
• HIV, severe debility, malnutrition

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TB Treatment in Patients with Other Medical
Conditions

• Careful monitoring critical
• Sputum for smears, cultures
• Monitor for signs of drug toxicity
• Clinical improvement (weight gain, feeling
  better)
• LFTs, renal function tests
• Consider drug levels

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TB treatment in special populations

• Children
• Same as adults
• Dosage based on weight
• Fewer problems with toxicity
• Harder to administer
• Harder to monitor
• Pills (crushed) vs. liquid preparations
• Some clinicians reluctant to use ethambutol

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TB treatment in special populations

• Elderly
• Same as younger adults
• Dosage based on weight
• Can be difficult to monitor for side effects
• May not tolerate 2 or 3 x per week dosing
• Pregnant women
• Avoid aminoglycosides, PZA

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Treatment of Latent TB Infection

• Recommended regimen
• Isoniazid for 9 months is optimal, 6 months
  acceptable
• Four month course of rifamycin acceptable
• Recommendation for PZA/rifamycin has been
  withdrawn
• Problems with liver toxicity
• Extremely close monitoring required if used
• Remember its still efficacious !

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Treatment of Latent TB Infection

• Monthly clinical monitoring required
• Monthly Clinical Assessment form
• AST or ALT and serum bilirubin in selected cases
• Baseline
• HIV infection
• History of liver disease
• Alcoholism
• Pregnancy
• Repeat
• Baseline results abnormal
• Pregnancy, immediate postpartum (first 3 months),
  or at high risk for adverse reactions
• Symptoms of adverse reactions

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References

• Radiographic Manifestations of Tuberculosis A
  Primer for Clinicians Frances J. Curry National
  Tuberculosis Center, 2003
• 2003 ATS TB Treatment Statement
• Pediatric Redbook 2003 Edition
• Drug-Resistant Tuberculosis A Survival Guide
  for Clinicians (Frances J. Curry National
  Tuberculosis Center, 2004
• PDR or package insert
• Laboratory Diagnosis call DTC for references
• Drug Side Effects, Toxicity call DTC for
  references
• Targeted Tuberculin Testing and Treatment of
  Latent Tuberculosis Infection MMWR 200049 (No.
  RR-6)

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VDH/DTC

• Phone [phone]
• Fax [phone]

www.vdh.virginia.gov
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Thank youQuestions?