MULTIDRUG RESISTANT TUBERCULOSIS

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MULTIDRUG RESISTANT TUBERCULOSIS EXPERIENCES
OF CENTRAL CHEST HOSPITAL
Dr. Charoen Chuchottaworn
Chief , Division of Academic
Affairs Consultant, Division of
Microbiology Central Chest Hospital, MOPH
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PROBLEMS OF DRUG RESISTANT TUBERCULOSIS

• Use clinical criteria for failure , no
  sputum examination
• Adding few drugs on an uncertain efficacy
  regimen
• Multiple courses of antituberculous drugs
  before transfer
• No susceptibility of failure regimen
• Use Category II regimen in Category I
  failure patients
• Over use of ofloxacin by general
  practitioner

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TREATMENT OF DRUG RESISTANT TUBERCULOSIS

• Complicated case (history of multiple
  courses of treatment),
• susceptibility is needed
• Uncomplicated case, treatment was started with
  expected
• susceptible drugs
• Past history of treatment was review for
  seeking
• the resistant drugs
• Compliance to treatment was reassure
• Admission in hospital for 2-4 weeks was
  recommended
• Susceptibility was done before starting
  treatment

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TREATMENT OF DRUG RESISTANT TUBERCULOSIS

• For drug resistant case who was not
  suspected
• to be MDR started with Category II
• (irregular, relapsed)
• Failure of Category I, II, III was treated
  as MDR-TB
• For MDR-TB, use three or more
  susceptibility drugs
• Avoid drugs which have ever been exposed
• Use ethionamide in case of suspected
  ethambutol resistant

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REGIMEN USE FOR MDR-TB

• Kanamycin 0.75 - 1 gm for 2 - 6 months or
• Streptomycin 0.75 - 1 gm I.M.
• Ofloxacin 400-600 mg once daily
• Levofloxacin 400 - 600 mg once daily
• PAS 8-12 gm two times a day
• Pyrazinamide 1.0 - 1.05 gm at bed time
• Ethambutol 0.8 - 1.2 gm. At bed time
• Ethionamide 0.5 - 0.75 gm. two time a day
• Cycloserine 0.5 - 0.75 gm. two time a day

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EVALUATION OF TREATMENT

• Clinical signs and symptoms
• Sputum smear and culture every month
• Liver function test every month for 3
  months
• and then every 3 months
• Renal function every month until
• aminoglycoside was stopped
• Chest X-ray was done every 6 months

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DURATION OF TREATMENT

• At least 18 months
• In late conversion case, continue treatment
  to
• 12 months after conversion
• Failure is defined by smear positive
  after
• treatment for 12 months or Fall and Rise
  
• is observed
• Monotherapy with INH is considered in
  hopeless case

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ETHIONAMIDE

• Derivative of thiosonicotinamide inhibit
  cell wall synthesis
• MIC of M.tuberculosis 0.6-2.5 ug/ml
• C max 20 ug/ml after 1 gm of Ethionamide
• T max 3 hours, T half 2 hours
• Well absorption and distribution in body
• GI intolerance, mental depression,
  convulsion, neuropathy,
• skin lesion
• Dosage 10-20 mg/day , 2 tablets in morning
  and 1 tablet
• in the afternoon

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CYCLOSERINE

• Broad spectrum antibiotics, inhibit cell
  wall synthesis
• MIC of M.tuberculosis 5 - 20 ug/ml
• C max 20 - 35 ug/ml after
• T max 3 - 4 hours
• Well absorption and distribution, 65
  excrete through renal
• No blood - brain barrier
• CNS adverse reaction convulsion, psychosis,
  surgical attempt,
• headache, somnolence
• Dosage 15 - 20 mg/kg/day, 2 - 3 tablets / day

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NEW TREATMENT OPTIONS FOR HIGHLY RESISTANT
MDR-TB

• Surgical plus - reserved drugs
• Oxazolidinones - Linezolid
• Ketolides - Telithromycin
• Immunotherapy - M.vaceae
• Cytokine therapy - IL-2, IL-12, gamma-IFN,
  GM-CSF
• Non - antibiotic - Chlorpromazine,
  Thioridazine

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A Thai female, 64 yr old

• She was transferred from one private
  hospital
• 2 year ago, she was treated with PZA,
  Levofloxacin,
• PAS, KM because resistant to INH, RMP, SM,
  EMB.
• No details of previous treatment
• PZA was stopped because of nausea,
  vomiting and
• KM discontinued after 6 months
• Levofloxacin and PAS was continued for 2
  years and
• symptoms were deteriorated
• All the treatment was done by an
  internist

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A Thai female, 42 yr old, health case worker

• 6 months ago, she was diagnosed as
  Pulm.TB, with sputum
• AFB ve
• She received treatment with 2 HRZE / 4 HR
• After 6 months, sputum smear was AFB ve
  with
• good compliance
• She was transferred to CCH and started
  treatment with
• Category II ( 2 HRZES)
• Sputum culture and sensitivity showed
  resistant to
• INH, RMP, EMB, OFX
• Treatment was changed to KM, ETA, CS, PAS

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THANK YOU FOR YOUR ATTENTION