Transcript Treatment of MDR-TB TRC Experience (1985

Treatment of MDR-TB
TRC Experience (1980-2005)
Tuberculosis Research Centre (ICMR)
Chennai
TRC
Tuberculosis Research Centre
Chennai
ICMR
 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
TRC
ICMR
Principles of management of
MDR TB at TRC
 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
TRC
ICMR
Drugs for MDRTB
Drug
Dose (mgm)
 Kanamycin
1000
 Ofloxacin
400 – 600
 Ethionamide
500
 Cycloserine
500
 Amikacin
500
 Ethambutol
600 – 1200
 PAS
10 gms
 Thioacetazone
150
 Isoniazid
600
TRC
ICMR
Contents
TRC experience in managing MDR TB
 Pre-quinolone era
 Quinolone era
 Field experience
TRC
ICMR
Pre-quinolone era
TRC
ICMR
Response of H/SH resistant pts. to
re-treatment regimens
Regimens
No. of
patients
Favourable
response
K+R+E
70
90%
Cyclo + Eth + Z
51
73%
Cyclo + Eth +E
25
64%
TRC
ICMR
Response of pts. to re-treatment
regimens according to resistance pattern
Res. to
Regimens
No. of pts.
Fav. resp. %
H
6SREZ2 / 6REZ2
47
75
HS
6KREZ2 /6EZ2
47
73
HR
3S3 Eth EZ7 /
35
38
52
42
9Eth EZ7
HRS
3K3 Eth EZ7 /
9Eth EZ7
TRC
ICMR
Response of MDR-TB pts. to
re-treatment/ Salvage regimens
Regimen
Tot. Fav.resp. Failure Default
pts.
%
%
%
Re-treatment
(E+Eth+Z+S/K)
Salvage
O + H 600 + 2-4
105
31
49
19
30
47
40
13
105
45
40
13
drugs
(Am/K/S/Eth/T/Z/PAS)
Overall response
TRC
ICMR
Quinolone era
TRC
ICMR
MDR management TRC
experience 1980 – 2002 (RCTs)
Total pts.
218
Age
15 – 64 yrs ( Median 34 )
Sex - males
159 ( 73 % )
Weight range
24 – 69.5 kg (Mean 41.6)
TRC
ICMR
Drug susceptibility profile among MDR pts
(n=218)
Resistant to
HR
HRS
HRE
HRSE
HRSO
HRKSE
TOTAL
Initial res.to HR
Acquired res.to HR
Initial res. to H
Initial res. to R
No.of
patients
72
114
3
25
1
3
218
121
97
65
4
TRC
ICMR
Details of radiological
findings (n=218)
Bilateral
176
Cavity
74
Infiltrates
203
Extensive
35
Upper zone alone
38
TRC
ICMR
Details of previous
anti-tuberculosis therapy
Previous antituberculous Drugs
No.of
patients
(n=218 )
With H & R
Without H & R
99
50
No previous therapy 69
149
Duration of
Treatment
(months)
No.of
patients
(n=149)
< 1
11
1–6
64
6 – 12
26
> 12
48
TRC
ICMR
Drug regimens Used
Group 1: First line regimens
Emb, H, Z, Sm
Group 2: Ofloxacin containing regimen
O, Eth, Y, Emb, Z, Sm / K
Group 3: Non-ofloxacin regimen
Emb, Eth, Z, Sm / K
Group 4: Any drug combination from the above
groups with other second line drugs
PAS, Amikacin,Thioacetazone
TRC
ICMR
Treatment outcome with SCC regimens
Regimen
No. pts
Cure
Death
Default
Initial SCC
218
17
2
3
SCC Re-treatment
12
5
2
5
All
218
22
4
8
( 10 %)
( 2 %)
(4%)
Failure
(requiring
further Rx )
184
TRC
ICMR
Response to first Rx regimen
for MDR TB
Regimen
No. pts
Cure
Oflo regimen
13
5 (38)
Non-oflo regimen
171
37(22)
Total pts
184
42(23)
TRC
ICMR
Treatment outcome based on initial
& further change of regimens
Regimen
No. pts
Cure
Death
Default
Failure
Initial SCC
218
17
2
3
196
SCC Re-treatment
12
5
2
5
0
Ist MDR regimen
184
42
16
37
89
2nd MDR regimen
89
16
10
15
48
3rd/4th MDR regimen
48
13
17
14
4
All
218
93
44
74
7
( 43 %)
( 22 %)
(34%)
(3%)
TRC
ICMR
Month of smear conversion
among cured patients
Month of conversion
1
2
3
4
5
6
8
No. of pts. (93)
27
34
14
12
3
2
1
(%)
29
37
15
13
3
2
1
TRC
ICMR
MDRTB at TRC: Outcome of Treatment
1980-2002 (n=184)
33%
22%
3%
42%
Cured
Dead
Defaulted
Failure
TRC
ICMR
Adverse reactions in TRC studies
Type of Adverse
No. of pts.
Drugs terminated
reactions
184
184
Any adv. reaction
73 (40%)
15 (8%)
Gastro-intestinal
50
6
Psychiatric
7
2
Cutaneous
7
3
Visual
3
3
Auditory
1
1
Others( Arthralgia,
9
Nil
renal,hepatic, CNS)
TRC
ICMR
Field experience
TRC
ICMR
When to evaluate for MDR TB ?
Patients not showing any reduction in
bacillary population after 3-months of
regular treatment with Cat II regimen
Sputum
positive
patients
who
contacts of a known MDR TB patient
are
TRC
ICMR
How to evaluate MDR TB ?
MDR TB is only a laboratory proved HR
resistance
Clinical suspicion should be followed by
lab. Confirmation
Laboratories should be quality controlled
TRC
ICMR
Drug Resistance in TB
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
TRC
ICMR
Drug susceptibility profile at
the time of failure (Cat I: N=74)
HR Res.
14%
16
H Res.
23%
Sp. Not
collected
19%
Cul Neg.
1822%
Sen.
22%
10
TRC
ICMR
Susceptibility profile at the
time of relapse (Cat I) : N 43
Sp. Not
collected
7%
HR Res.
7%
Sen.
57%
H Res.
29%
TRC
ICMR
Management of MDR TB in the field
 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
TRC
ICMR
Results
 Patients admitted from May 2000 – Dec’2003
 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)
TRC
ICMR
Pattern of drug resistance (N=51)
Resistant to
No
%
2 drugs
HR
11
22
3 drugs
HR +S/O/E/Eth
23
45
4 drugs
SHRE
5
SHREthE
4
HREthE
2
S,E,Eth, O, H, R
6
>4 drugs
22
12
TRC
ICMR
Drug regimens used
Duration of Rx 18-24 months
Resistance
No of
pts.
HR
11
S3 (Oflo, Eth, E, PZA)7
HRS
26
K3 (Oflo, Eth, E, PZA)7
14
Individually tailored
including
Others
Regimen
PAS & Cycloserine
TRC
ICMR
Smear & culture conversion at 6-m
Resistance
n
Negative
HR
11
5 (45%)
HRS/HRE/SHRE
26
10 (38%)
others
14
5 (36%)
Total
51
20 (39%)
TRC
ICMR
Status at 6-m according to
resistance pattern
Resistant
HR
SHR/HER/
No. Smear
Cul.at 6-m
of
neg. at 6 Pos Neg
pts mths
Death Default
NA
11
5
2
5
1
2
1
26
10
6
10
7
2
1
14
5
4
5
4
1
-
51
20
12
20
12
5
2
SHRE
HR+ other
drugs
Total
TRC
ICMR
Measures to improve Rx outcome
for MDR-TB
 Standardised / Individualised treatment
 Supervision
 Hospitalisation
TRC
ICMR
Individualised Regimen for MDR-TB
Study
site
Turkey
Korea
Denver
No. of
MDRTB pts.
158
1011
134
Supervision
Yes
No
Yes
Hosp.
Regimen
Outcome
Yes
(Am/S/K),
77%Favour
Ofl,PTH,Cys.PA 11% Default
S,Emb,PZA
4% Death
No
(S/K/EVM),
Oflo,PTH,Cys,
PAS
48%Cured
39% Default
1% Death
(Am/K/S/Cap),
Clo,Cys,PAS,
Pza, Emb, Eth
65%
Responded
Yes
TRC
ICMR
Standardised Regimen for MDR-TB
Study site MDR-TB Supervision Hosp.
Regimen
Outcome
3KCOPHZE /
69% cured
12OPHZE / 6
12% Default
EP
14% Death
3KCipEthZE
46% Cured
/15CipEthZE
11% Default
(N)
B’desh
Peru
58
298
Yes
Yes
Yes
No
11% Death
South
Korea
142
(Retro )
No
No
3S/KZOPthY/3
44% Cured
ZOPthY/
28% Default
OYPth
3% Death
TRC
ICMR
To conclude
 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
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 36 mths of period is recommended for better
outcome