Treatment of MDRTB TRC Experience 19802005

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Treatment of MDR-TB TRC Experience (1980-2005)

• Tuberculosis Research Centre (ICMR)
• Chennai

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TRC

ICMR
Tuberculosis Research CentreChennai

• Established in 1956
• Randomised clinical trials in pulmonary EPTB
• Rifampicin containing regimens used since 1974
• Supranational reference lab. for mycobacteriology
• Culture sensitivity available for all patients
• Monitoring DOTS programme in a rural area since
  1999

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Principles of management of MDR TB at TRC
TRC

ICMR

• When patients were failing/relapsing, regimen was
  chosen based on the last susceptibility results
  available
• Rx was changed according to patient response
  susceptibility results
• Choice of the regimen was based on the available
  drugs for managing MDR TB at the time
• Rx was supervised for the first 6-month of
  injection phase thrice weekly
• Subsequently, drugs were supplied once-a-
  week/fortnight and intake monitored by home
  visits
• Patients were seen every month with clinical and
  bacteriological monitoring and X-ray once in
  6-months

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Drugs for MDRTB
TRC

ICMR

• Drug Dose (mgm)
• Kanamycin 1000
• Ofloxacin 400 600
• Ethionamide 500
• Cycloserine 500
• Amikacin 500
• Ethambutol 600 1200
• PAS 10 gms
• Thioacetazone 150
• Isoniazid 600

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Contents
TRC

ICMR

• TRC experience in managing MDR TB
• Pre-quinolone era
• Quinolone era
• Field experience

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Pre-quinolone era
TRC

ICMR
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MDR-TB (TRC Experience)
TRC

ICMR

• Period 1985-94
• Pts. with culture positive PT 3025
• Pts. with resistance to Rif INH 158 (5)
• Initially Rif INH resistant 93 (3)
• Initially INH res. acq. Rif. res. 46
• Initially Rif. res. acq. INH res. 2
• Acquired Rif and INH resistant 17

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Response of H/SH resistant pts. to re-treatment
regimens
TRC

ICMR
9
Response of pts. to re-treatment regimens
according to resistance pattern
TRC

ICMR
10
Response of MDR-TB pts. to re-treatment/ Salvage
regimens
TRC

ICMR
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Quinolone era
TRC

ICMR
12
MDR management TRC experience 1980 2002 (RCTs)
TRC

ICMR
13
Drug susceptibility profile among MDR pts (n218)
TRC

ICMR
Initial res.to HR 121
Acquired res.to HR 97 Initial res.
to H 65 Initial res. to R
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Details of radiological findings (n218)
TRC

ICMR
15
Details of previous anti-tuberculosis therapy
TRC

ICMR
149
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Drug regimens Used
TRC

ICMR
17
Treatment outcome with SCC regimens
TRC

ICMR
18
Response to first Rx regimen for MDR TB
TRC

ICMR
19
Treatment outcome based on initial further
change of regimens
TRC

ICMR
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Month of smear conversion among cured patients
TRC

ICMR
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MDRTB at TRC Outcome of Treatment1980-2002
(n184)
TRC

ICMR
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Adverse reactions in TRC studies
TRC

ICMR
23
Field experience
TRC

ICMR
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When to evaluate for MDR TB ?
TRC

ICMR

• Patients not showing any reduction in bacillary
  population after 3-months of regular treatment
  with Cat II regimen
• Sputum positive patients who are contacts of a
  known MDR TB patient

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How to evaluate MDR TB ?
TRC

ICMR

• MDR TB is only a laboratory proved HR resistance
• Clinical suspicion should be followed by lab.
  Confirmation
• Laboratories should be quality controlled

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Drug Resistance in TB
TRC

ICMR

• When to suspect drug resistance?
• Persistent sputum positivity
• Fall and rise phenomenon of sputum AFB
• Clinical or radiological deterioration in the
  presence of positive sputum
• Provided patient has been regular in drug intake

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Drug susceptibility profile at the time of
failure (Cat I N74)
TRC

ICMR
16
18
10
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Susceptibility profile at the time of relapse
(Cat I) N 43
TRC

ICMR
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Management of MDR TB in the field
TRC

ICMR

• Basically 3 new drugs, S/K Eth O Z E
• Initial hospitalisation at least for one month
• Monthly supply of drugs given to respective PHI
• DOT provider identified
• TRC staff visits once a month
• Pt attends TRC once a month for review
• Clinical bacteriological evaluation monthly

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Results
TRC

ICMR

• Patients admitted from May 2000 Dec2003
• No. of MDR-TB patients 51
• Males 33 (65)
• Mean age in yrs 38 (14-75)
• Mean wt. In Kg 41.7 (
  23.2-60.5)

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Pattern of drug resistance (N51)
TRC

ICMR
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Drug regimens used Duration of Rx 18-24 months
TRC

ICMR
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Smear culture conversion at 6-m
TRC

ICMR
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Status at 6-m according to resistance pattern
TRC

ICMR
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TRC

ICMR
Measures to improve Rx outcome for MDR-TB

• Standardised / Individualised treatment
• Supervision
• Hospitalisation

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Individualised Regimen for MDR-TB
TRC

ICMR
37
Standardised Regimen for MDR-TB
TRC

ICMR
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To conclude
TRC

ICMR

• Availability of 2nd line drugs, including
  quinolone, alone was not adequate for managing
  MDR TB
• Early detection, individually tailored regimen
  did not help to improve the Rx outcome
• Directly observed treatment has given better
  results
• Hospitalisation for the entire period of
  treatment has given better outcome

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TRC

ICMR
Recommendations

• MDR TB should be always laboratory proved
  Clinical suspicion should be followed by lab.
  Confirmation
• Labs should be established in all states
• Hospitalisation supervision of Rx for the
  initial 3-6 mths of period is recommended for
  better outcome