0 Recommendations

Shorter MDR TB regimen

By Khurshid Zaman | 25 Jul, 2019

Dear Collegues
I have 2 questions,please answer with evidence

1) In the light of Consolidated guidelines on Drug resistant TB 2019, in
an eligible candidate ,what are the drugs to be used in Intensive and
continuation phase.

2) In the light of same ,is there any role of High dose INH in management
of MDR TB.

                                                                       Dr

Replies

 

Khurshid Zaman Replied at 3:20 AM, 25 Jul 2019

Sorry to mention ,my question is regarding Shorter Regimens

Abdul ghafoor Replied at 3:30 AM, 25 Jul 2019

Dear Dr. Khursheed,
Consolidated WHO Guidelines on DR TB Treatment mentions STR treatment as
1. Total Duration ; 9-11 months
2. Regimen;
Intensive phase
Inj Am 4 months (extendable to six months). Mfx, Cfz, Eto, High dose INH, Ethambutol, Z ,
Continuation phase; 5 months
Regimen
Mfx, Cfz,Ethambutol, Z,
There can be a Modified STR under Operation Research Conditions replacing Amikacin with Bdq.

Joven Jebio Ongole Replied at 1:50 PM, 25 Jul 2019

Dear Dr
The evidence is in the guidelines and country programs. The main document
is WHO DRTB guidelines and has been adopted with modification by different
countries. WHO recommends four core drugs (bedaquiline, linezolid,
clofazemione and levofloxaccin) and one none core (pyrazinamide) for 4-6
months of intensive phase and clofazemine, levofloxaccin and pyrazinamide
for 5 months continuation phase. Linezolid is 2 months and bedaquiline 6
months.

I practice in South Africa and adopted WHO five drugs and added High dose
isoniazid (600- 900mg for 4-6 month in intensive phase) and ethambutol
1.2gm for 9-11 month (used in both intensive and continuation phase).
Conyinuation phase is fixed 5 months with ethambutol and pyrazinamide that
are none core and clofazimine and levoflaxaccin that are core.

Abdul ghafoor Replied at 9:47 PM, 25 Jul 2019

Thank you.Kindly quote the reference to this combination of STR .WHO in its
recent guidelines has not changed STR regimen at all.The core drugs
mentioned by your good self(Lfx ,bdq, Lzd , Cfz , z) are part of long
treatment regimen 18-20 months.
Is there any study that has assessed the used of afore mentioned drugs in
STR.
I respect your personal experience but is there a-structured study,
Thank you

Joven Jebio Ongole Replied at 1:35 AM, 26 Jul 2019

Long regimen use five drugs - Terizidone is the fifth core drug

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Khurshid Zaman Replied at 2:38 AM, 26 Jul 2019

;WHO recommends four core drugs (bedaquiline, linezolid,
clofazemione and levofloxaccin) and one none core (pyrazinamide) for 4-6
months of intensive phase and clofazemine, levofloxaccin and pyrazinamide
for 5 months continuation phase. Linezolid is 2 months and bedaquiline 6
months,
Dear Dr Joven
From consolidated guidelines,this is exactly what i understood,but now
there is lot confusion
Secondly if you can make regimens from Group A and B,why add medicines from
Droup C and that too injectables

Abdul ghafoor Replied at 2:59 AM, 26 Jul 2019

STR regimen is standardized. Intensive phase is 4-6 months with following
drugs:
Am, Mfx, Cfz, Eto, High dose INh, E, Z

And continuation phase is :

Mfx, Cfz, Z, E for 5 months.

Total duration is 9-11 months. Modified shorter regimen replaces Am with
BDQ for 6 months under operational research condition. This is WHO
recommendation, any thing not consistent with this may be some studies or
personal experiences but surely not recommended by WHO in its recent
guidelines under programmatic conditions.

Dr. Saswata Dutt Replied at 4:00 AM, 26 Jul 2019

Please see the latest statement from WHO on July 24, 2019.
*WHO Director-General with the WHO Civil Society Task Force on TB:*
*Transition to an all-oral regimen to treat people with drug-resistant TB
by World TB Day 2020: *
In 2018, WHO issued new consolidated guidelines for the treatment of people
with multidrug-resistant TB (MDR-TB)
<https://who.us8.list-manage.com/track/click?u=f093a7c38a3780cd9504f8d9d&id=e0...>
that
could lead to major improvements in treatment outcomes and quality-of-life
for patients. A fully oral regimen is strongly recommended as a preferred
option for MDR-TB treatment. WHO and the Civil Society Task Force strongly
recommend that all countries transition to an all-oral regimen for
drug-resistant TB by World TB Day 2020.
Thanks & regards.

Tom Yates Replied at 5:18 AM, 26 Jul 2019

I think Kelly Dooley is looking into the role of high dose INH in MDR
patients with both inhA and katG mutations.

Regards the short course regimens, it is worth noting the mortality signal
in people with HIV co-infection in STREAM 1 ...

[image: image.png]

Sadly, guidelines moving ahead of evidence means we may not get any more
randomised data, which is the only reliable way to know whether this is a
true mortality signal or a chance observation.

Dr. Saswata Dutt Replied at 6:04 AM, 26 Jul 2019

Attached three documents with interesting discussion on the role of INH in
inhA and/or katG resistance.

About the second statement, please correct me and enlighten me. Because of
the long, arduous and time consuming treatment with high morbidity and
mortality in developing countries, most if not all DR-TB (RR, MDR,pre-XDR,
XDR) regimens have been formulated after implementation trials.

Thanks & regards.

Tom Yates Replied at 8:43 AM, 26 Jul 2019

Dear Dr Dutt,

I liked the following articles on the need for RCTs in MDR TB and the
specific challenges in undertaking these important studies ...

https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002767
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(19)30215-4/fu...

Dr. Saswata Dutt Replied at 9:04 AM, 26 Jul 2019

Thank you so much Dr. Tom. Yes, I cannot agree more with you and the
articles. I have seen one of them before.
The challenge is - the 'disease TB' probably does not have the same luxury
footing as 'disease HIV' or 'disease HCV'!!
Without international donor support, most of the countries where TB is
prevalent (I am working for more than ten years in Africa) are struggling
to buy basic medicines for these diseases.
Regards.

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