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 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 8  |  Issue : 2  |  Page : 53-63

Recent changes in guidelines on programmatic management of drug resistant tuberculosis in India 2019: a paradigm shift in tuberculosis control


Professor, Department of Respiratory Medicine, R.G. Kar Medical College, Kolkata, West Bengal, India

Date of Submission13-Jul-2020
Date of Acceptance14-Jul-2020
Date of Web Publication10-Sep-2020

Correspondence Address:
Prof. (Dr.) Arunabha Datta Chaudhuri
Designation - Professor, Department of Respiratory Medicine R.G. Kar Medical College, Kolkata, Residence - BF-130, Sector - I, Salt Lake City, Kolkata - 700064
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jacp.jacp_47_20

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  Abstract 


The new version of guidelines of programmatic management of drug resistant tuberculosis in India 2019 by Revised National Tuberculosis Control Programme, Central TB Division, Directorate General of Health Services, Ministry of Health & Family Welfare, Nirman Bhawan, New Delhi, integrates use of the shorter MDR TB regimen and all oral longer MDR TB regimen with new drugs under RNTCP with opportunity to modify the regimen based on DST results. There are mammoth and comprehensive changes in the guidelines on programmatic management of drug resistant tuberculosis in India 2019.

Keywords: DRTB, DRTB 19, PMDT 19, PMDT guideline 2019


How to cite this article:
Chaudhuri AD. Recent changes in guidelines on programmatic management of drug resistant tuberculosis in India 2019: a paradigm shift in tuberculosis control. J Assoc Chest Physicians 2020;8:53-63

How to cite this URL:
Chaudhuri AD. Recent changes in guidelines on programmatic management of drug resistant tuberculosis in India 2019: a paradigm shift in tuberculosis control. J Assoc Chest Physicians [serial online] 2020 [cited 2020 Oct 30];8:53-63. Available from: https://www.jacpjournal.org/text.asp?2020/8/2/53/294594




  Introduction Top


The first WHO endorsed programmatic management of Drug Resistant Tuberculosis (PMDT) services began in the year 2000 in all over the World. In 2002, the global fund to fight AIDS, TB and malaria started financing TB programme including drug resistant Tuberculosis, thus greatly reducing the economic barrier to countries for DRTB services. Thereafter PMDT services have expanded rapidly. Based on data and experience from these projects and practices, further scientific evidence continues to evolved with respect to services of DRTB. After successfully establishing RNTCP services across the countries in 2006, the PMDT services were introduced in 2007 and complete geographic coverage was achieved in 2013.

There are new drugs like Bedaquiline and Delamanid currently approved for conditional use by drug regularity authorities and for which WHO had provided interim guidance for their use under programmatic settings few years back. Similarly some of the earlier drugs like Clofazimine and Linezolid are being repurposed and recommended for use in the management of DRTB. Recently WHO has recommended an all oral longer regimen with new drugs for the treatment of MDR / RR TB patients. The new version of guidelines of PMDT in India 2019 integrates use of the shorter MDR TB regimen and all oral longer MDR TB regimen with new drugs under RNTCP with opportunity to modify the regimen based on DST results.


  Causes of drug resistance Top


  • Microbial: As a result of genetic mutation. Caused by random chromosomal mutations at predictable frequencies. (H resistant bacilli 1 in 106, R 1 in 108, HR 1 in 1014)
  • Essentially drug resistance is a man-made phenomenon
  • Providers/Programmes: Inadequate regimens, Unsupervised treatment, Absence of guidelines or inappropriate guidelines, non-compliance with guidelines, Inadequate training of health staff, No monitoring of treatment, Poorly organized or funded TB control programmes.
  • Drugs: Inadequate supply, non-availability of certain drugs (stock-outs or delivery disruptions), poor quality, poor storage conditions, wrong dosages or combination.
  • Patients: Inadequate drug intake, unobserved treatment (Poor DOT), poor adherence, lack of information, non-availability of free drugs, adverse drug reactions, social & economic barriers, malabsorption, substance abuse disorders.


Prevention of DRTB

  • Strong systems to detect early, successfully treat and ensure long-term disease-free status of TB patients.
  • Systems for early detection and treatment of drug-resistant forms of TB be integrated into existing TB services.
  • Health care facilities and congregate settings to focus on proper infection control measures
  • Measures to prevent incidence and transmission of TB are also effective in prevention of drug-resistance.


Universal drug susceptibility testing

  • Program is committed to providing Universal Drug Susceptibility testing (UDST) for all notified TB patients.
  • A range of rapid molecular tests are available for UDST: Cartridge Based Nucleic Acid Amplification Test (CBNAAT), Line Probe Assay (LPA), TruNAAT
  • ToG 2016–as per revised diagnostic algorithm, selected presumptive TB patients tested on CBNAAT for reliable and early microbiological confirmation of TB and R resistance status is available as a byproduct
  • Several additional DST technologies in the development pipeline, will be made available progressively as they are endorsed for use by WHO


Decentralized DR-TB management

  • Concept of decentralized DR-TB Centres at district level.
  • Previously, centralized PMDT treatment initiation in inpatient settings.
  • This version, guidance on both in-patient and out-patient based treatment initiation.
  • Decentralised drug supply chain management to the district level.


Customized treatment supervision and patient support

  • Move to patient centric approach focussing patient’s needs and preferences for better adherence.
  • Development of information communication technology (ICT) also gives an option of self-report drug consumption, monitored and supported by various levels simultaneously.
  • Most appropriate modality of adherence monitoring may be used as a collective decision for the patient, treatment supporter and the Medical Officer (MO).


Newer drugs and regimen

  • Scale up plan of all oral regimen and shorter MDR-TB regimen.
  • There are newer drugs like Bedaquiline (Bdq) and Delamanid (Dlm) currently approved to be used under the programme only.
  • Drugs are reclassified based on the evidences to manage the patient and recommended for use in the management of DR-TB.
  • few shorter MDR-TB regimens are being studied worldwide using combination therapy with newer drugs.


Structure and responsibilities for PMDT

  1. State-level structure − State PMDT Committee
  2. Nodal DR-TB Centre − Nodal DR-TBC Committee
  3. District DR-TB Centre − District DR-TBC Committee


Functions and responsibilities of nodal/district DR-TB centres

  1. Pre-treatment evaluation,
  2. Counselling to Patient and Family Members,
  3. Treatment initiation of DR-TB patients,
  4. Coordination with C-DST labs and districts,
  5. Nikshay entries and periodic reporting,
  6. Travel enablers
  7. Follow up monitoring, Management of adverse drug reactions,
  8. Providing clinical decision, referral, management support and training to districts,
  9. AIC measures, nutritional assessment, mental health and palliative care,
  10. Submit regularly reports to the State TB Cell and State PMDT committee [Figure 1].
    Figure 1 Overall PMDT Structures and Roles

    Click here to view


Methods for drug susceptibility testing

  1. Rapid molecular Drug Resistance Testing (DRT) − Genotype
    1. Nucleic Acid Amplification Test (NAAT)
      1. cartridge based Gene-Xpert platform,
      2. chip based TruNAAT platform
    2. Line Probe Assay (LPA)
      1. First line (H & R),
      2. Second line (Lfx, Mfx, Km, Cm, Am)
  2. Growth-based phenotypic drug susceptibility testing (DST)
    1. First-line drugs: R, H, E, Z
    2. Second-line drugs: S, Lfx, Mfx, Km, Cm, Am
    3. Other drugs: Lzd, Cfz, Bdq, Dlm PAS etc.,


Genotypic testing is much faster than phenotypic methods.

Choice of diagnostic technology

1st Choice − NAAT/LPA, 2nd Choice − Liquid culture isolation and LPA DST, 3rd Choice Liquid culture isolation and liquid DST

Turnaround time

Solid LJ media- of up to 84 days, Liquid Culture (MGIT) up to 42 days, LPA up to 72 hours, NAAT - 2 hours.

Good quality specimen

  • Volume of 2-5 ml.
  • Preferably mucopurulent and not heavily blood stained or contaminated.
  • Collect the specimen in a sterile container (50 ml conical tube) after thorough rinsing of the mouth with clean water.
  • Specimens should be transported to the NAAT or C-DST laboratory as soon as possible after collection.
  • If a delay is unavoidable the specimens should be refrigerated to inhibit the growth of unwanted micro-organisms.


The presumptive TB persons

PLHIV, EPTB, Smear −ve/NA with X-ray suggestive of TB including paediatric, vulnerable populations, contact of DR TB patient.
  • All notified TB patients and non-responder to treatment and presumptive TB patients Offer NAAT.
  • Based on the result, the patient would be classified as R resistant detected (RR TB) or R resistance not detected to guide decision of the appropriate treatment.
  • For patients with NAAT result as M.tb detected (irrespective of R status), the second specimen will be transported to the C-DST lab in cold chain.
  • In rare circumstances when the second specimen is used at NAAT lab itself to repeat the test, a fresh specimen is to be collected from the patient and transported in cold chain to the concerned C-DST lab. However, this may not be always possible for EP specimen.
  • Reconfirmation of RR among the new TB patients will be carried out at C-DST lab by FL LPA with the second specimen sent from NAAT site.
  • If Rifampicin Resistant detected then FL LPA, SL LPA (for FQ or SLI), DST to Mfx (1.0), Lzd, Cfz, Z, Bdq, Dlm (whenever available) will be set up on liquid culture using the decontaminated deposits only for RR TB patients (Base line SL DST).


If Rifampicin Resistant not detected then for all patients − FL LPA (for H mono resistance detection), subsequently if H mono / Poly resistant detected then do SL LPA and DST for Z,

Subsequently if H+FQ or Z resistant detected then do DST to Mfx (1.0) & Lzd.

At the C-DST laboratory, smear microscopy is done on the second specimen received from NAAT lab. LPA will be carried out for smear positive specimen and if sputum microscopy negative then perform liquid culture followed by LPA [Figure 2].
Figure 2 DR-TB diagnostic algorithm

Click here to view


Pre-treatment evaluation for DR-TB patients

Pretreatment evaluation for any TB patient including DR TB patients should include, a thorough clinical evaluation by a physician including
  1. history and physical examination,
  2. height/weight,
  3. random blood sugar (RBS),
  4. chest X-ray and
  5. HIV testing. No additional investigations are required for H mono/poly DR TB patients unless clinically indicated.


Pre-treatment evaluation for MDR/RR TB patients

  1. Complete Blood Count (Hb, TLC, DLC, Platelet count),
  2. Blood Urea & S. Creatinine,
  3. Audiometry (only if on injectable),
  4. Liver Function Tests,
  5. Thyroid Stimulating Hormone levels to assess the thyroid function (TSH levels alone are usually sufficient to assess the thyroid function of the patient),
  6. Urine examination − Routine and Microscopic,
  7. Psychiatric evaluation if required,
  8. Serum electrolytes (Na, K, Mg, Ca) only for new drugs,
  9. S. protein (Albumin, Globulin and total proteins) (only if on Dlm),
  10. ECG (if on Mfx, Bdq, Cfz or Dlm),
  11. urine pregnancy test (in women of reproductive age group),
  12. Ophthalmologist opinion − rule out chorioretinitis/uveitis (only if on Linezolid),
  13. Surgical evaluation should be done at appropriate time if required.


Points of consideration for pre-treatment evaluation

  • In majority of MDR/RR TB patients, pretreatment evaluation can be done on an outpatient basis.
  • The physician may decide for admission for initiation of treatment or get it done on an outpatient basis.
  • A specialist consultation along with reports of pre-treatment evaluation tests can be arranged, if required.
  • Must ensure that laboratory capacity and specialists for consultation are available, either in-house or through an outsourced mechanism
  • For infection control purposes, a separate space for specimen and blood collection should be identified



  CLASSES OF ANTI TB DRUGS RECOMMENDED FOR TREATMENT OF DR-TB Top


Group A: Include all three medicines :– 1.Levofloxacin OR Moxifloxacin (Lfx /Mfx),2. Bedaquiline (Bdq), 3.Linezolid (Lzd)

Group B: Add one or both medicines :-1. Clofazimine (Cfz). 2. Cycloserine OR Terizidone (Cs Trd)

Group C: Add to complete the regimen and when medicines from Group A and B cannot be used: −1. Ethambutol (E),2. Delamanid (Dlm), 3. Pyrazinamide (Z), 4. Imipenem-cilastatin OR Meropenem (Ipm-Cln /Mpm),

5. Amikacin (OR Streptomycin) (Am/(S), 6. Ethionamide OR Prothionamide (Eto /Pto), 7. p-aminosalicylic acid (PAS)

Principles of designing a WHO recommended all oral longer MDR TB regimen (WHO-2019)

  • In MDR/RR TB patients on longer regimens, all three Group A agents (Lfx/Mfx, Bdq &Lzd) and one Group B agent (Cfz &Cs) should be included to ensure that treatment starts with at least four TB agents likely to be effective, and that at least three agents are included for the rest of the treatment after Bdq is stopped.
  • If only one or two Group A agents are used, both Group B agents are to be included.
  • If the regimen cannot be composed with agents from Groups A and B alone, Group C agents are added to complete it.


All oral longer MDR TB regimen Guidelines for PMDT in India 2019

As the likelihood of stopping Lzd due to toxicity is greater, the all oral longer MDR TB regimen for India would include the fifth drug Cs upfront to prevent the need for replacing Lzd or Cfz, if dropped.

Standard DRTB Regimen [Table 1]
Table 1 Standard DRTB regimen

Click here to view


All oral H mono/poly DR TB regimen is of 6 months with no separate IP/CP. Shorter MDR TB regimen is of 9-11 months with 4-6 months of IP containing injectables and 5 months of CP. If the IP is prolonged, the injectable is only given three times a week in the extended intensive phase. All oral longer MDR TB regimen is of 18-20 months with no separate IP/CP. New drugs like Bdq and Dlm would be given for 6 months duration while the dose of Lzd will be tapered to 300 mg after the initial 6-8 months of treatment. This regimen will also be used for treatment of XDR TB patients with 20 months duration.

Inclusion criteria for new drugs (Bdq/Dlm)

  • Bdq/Dlm can be provided to the patient ≥ 18 yrs.
  • Dlm can be provided to age group 6 to 17 years.
  • Use of Bdq for 6 to 17 yrs and Dlm for 3 to 6 yrs may be considered only after approval of DCGI.
  • non-pregnant females or females not on hormonal birth control methods are eligible. They should be willing to continue practicing birth control methods throughout the treatment period or have been post-menopausal for past 2 years; and
  • patients with controlled stable arrhythmia can be considered after obtaining cardiac consultation.


Exclusion criteria for new drugs (Bdq/Dlm)

  • Pregnancy & lactating mother
  • currently having uncontrolled cardiac arrhythmia that requires medication;
  • QTcF interval characteristics at base line:
    1. QTcF ≥ 500 at baseline & normal electrolytes, ECG to be repeated after 6 hours and If both ECGs show QTcF>500 then the patient should not be challenged with cardiotoxic drugs.
  • history of additional risk factors for Torsade de Pointes, e.g. heart failure, hypokalaemia, family history of long QT syndrome;
  • If results of the serum chemistry panel, haematology or urinalysis are outside the normal reference range (including above listed parametres), the patient may still be considered if the physician judges that the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable.
  • Hypokalaemia, hypomagnesaemia and hypocalcaemia should be corrected prior to a patient receiving any QTc prolonging drugs.
  • Bdq/Dlm is not added to a failing regimen in any MDR/RR TB patient


Caution to be exercised in choosing other group A and B drugs

  • Lzd may cause anaemia, thrombocytopenia, peripheral neuritis and optic neuritis. Adequate precaution may be taken accordingly.
  • Cs should be used carefully in pre-existing seizure disorders not adequately control with medication. Neurologist consultation should be taken prior to initiation of Cs in such patients, also psychiatrist opinion should be taken in severe depression as Cs can cause depression and suicidal tendency.
  • Cfz causes dark brown discoloration of the skin. Accordingly, the patient should be counselled prior to initiation of treatment with Cfz


Patient Flow for H mono/poly resistance [Figure 3] [Table 2]
Figure 3 Integrated drug resistant algorithm

Click here to view
Table 2 Criteria for patients to receive standard DR TB regimen

Click here to view


  • If H is found to be resistant, the patient will be initiated on all oral H mono-poly DR TB regimen at the PHI level while awaiting the results of SL LPA
  • Modify the regimen appropriately at the N/DDR TBC if Lfx/Mfx(h) resistance is detected on SL LPA.


Patient Flow for MDR RR TB [Figure 3] [Table 2]

The patients with RR TB will be considered for shorter MDR TB regimen at N/DDR TBC after ruling out the exclusion criteria for shorter MDR TB regimen.

Decision to start shorter MDR TB regimen will be based on non-DST and DST based exclusion criteria.

If DST result is not available, exclude the patients who has the history of drug consumption Mfx(h), Km, Eto or Cfz for ≥ 1 month.

The patients excluded from shorter MDR TB regimen would be initiated on all oral longer MDR TB regimen at N/DDR TBC.

In case of additional resistance on LC DST, the all oral longer MDR TB regimen would be appropriately modified.

Treatment initiation on outpatient basis

  • All oral longer MDR TB regimen can be initiated on outpatient basis if the patient is satisfying all following risk assessment criteria:
    • QTcF < 450 ms in males and <470 ms in females at baseline.
    • Normal serum K, Mg, Ca at baseline.
    • No history of structural cardiac abnormalities (LVH or RVH secondary to hypertension can also cause ECG changes, however mere presence of LVH need not be an exclusion criteria) or ECG abnormalities.
  • Patients with QTcF between >450 to 500 ms in male and > 470 to 500 ms in female upto 500ms require daily monitoring of ECG for 3 days along with evaluation and correction of any electrolyte abnormalities. A cardiologist opinion may need to be taken.
  • The first dose is given under supervision at the treatment initiating facility for ambulatory patients.
  • Patient should be initiated from Monthly patient wise box
  • Entire one-month box needs to be handed over at the time of discharge.


Replacement drugs in sequence of preference [Table 3] and [Table 4]

  • Replacement of drugs required in following conditions: −1. adverse drug reaction, 2. poor tolerance, 3.contraindication, 4.resistance detected on baseline LC DST.
Table 3 Sequence of using replacement drugs to modify the regimen

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Table 4 Sequence of using replacement drugs to modify the all oral longer regimen

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Principles apply for replacement of drugs

  • The regimen should preferably be fully oral. However, in certain circumstances, an Injectable may have to be used for the need of efficacy and side-effect profile
  • Five drugs are to be used in IP and at least four drugs in the CP.
  • Newer drugs (Bdq or DLm) should be given for 24 weeks only.
  • Dlm and Am will not be used in CP.
  • Replacement sequence: Z*, Am* , Eto*, PAS, E, Imp/ clm or Mpm with Amx/ clv in that order of preference (*Z if resistance not detected, Am if SL LPA suggest and Eto if no inh A mutation detected)


Dosage of DR-TB drugs [Table 5]

Details of dosage of DRTB drugs according to weight band are described in [Table 5]
Table 5 Dosage of DR-TB drugs for adults

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Extension of treatment in H mono/poly DR TB regimens [[Table 6]

Total duration of H mono-poly DR TB regimen is 6 months.
Table 6 Duration of regimen

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Treatment may be extended to 9 months
  • In patients with extensive disease;
  • uncontrolled comorbidity;
  • extra-pulmonary TB and
  • if smear at the end of 4th month is found positive; based on smear microscopy and clinical monitoring;


In CNS, skeletal and milliary TB, treatment may be given up to a year.

In patients who remain sputum smear positive at the end of 5-month or later of treatment, the outcome will be declared as treatment failure.

Extension of treatment in Shorter MDR TB regimen [Table 6]

  • Total duration of shorter MDR TB regimen is for 9-11 months
  • IP should be given for at least four months. After fourth month of treatment, if the result of sputum microscopy is negative then CP should be initiated.
  • If sputum smear microscopy does not become negative by the fourth month of treatment, subject the patient to FL LPA and SL LPA and culture DST.
  • If no additional resistance is detected, the IP should be prolonged until sputum smear converts maximum till 6 months.
  • If the intensive phase is prolonged, the injectable agent is only given three times a week.
  • IP should be extended to 5th or 6th month based on smear results. This will be done for a maximum of 2 months
  • If the patient remains smear positive at the end of 6th month of treatment, the patient will be declared as “Treatment Failure”, re-evaluated as per integrated DR TB algorithm and initiated on an appropriate modified regimen based on the extended DST.


Extension of treatment in All oral longer MDR TB regimen [Table 6]

  • Total duration of all oral longer MDR TB regimen is 18-20 months.
  • At the end of 6th month, the dose of Lzd will be tapered to half if the 4th or 5th month culture result is negative.
  • If the 4th or 5th month culture result remains positive, the regimen with same Lzd dosage need to be extended for 1 more month. However, new drug (Bdq or Dlm) is given for 24 weeks only.
  • Decision for continuation of extended IP with Lzd (600/300 mg) beyond 7th month, is decided based on the culture results of 6th/5th month and the clinical/radiographic response.
  • Extension of IP beyond 8th month is not permitted and patient should be switched to CP. (i.e., total duration of treatment is not more than 20 months).
  • If the patient continues to remain culture positive or reverts back to culture positive after 8 months of treatment, the patient is declared as “Treatment failed”, re-evaluated as per integrated DR TB algorithm and initiated on an appropriate modified regimen based on the extended DST.
  • For XDR TB patients, all oral longer MDR TB regimen would be given for 20 months.


Management of DR-TB patients with Treatment Interruptions and Loss to Follow up

All the missed doses during IP must be completed prior to switching the patient to CP.

Similarly all missed doses during CP must be administered prior to ending treatment.

Patients who interrupt treatment for less than one month during IP

Resume IP treatment, however the duration of treatment will be extended to complete IP. The follow up cultures will be done as per the revised schedule.

Patients who interrupt treatment for less than one month during CP

Resume CP treatment, however the duration of treatment will be extended to complete the CP. The follow up cultures will be done as per the revised schedule.

Missing Bedaquiline doses and return after interruption

Initial 2 weeks of BDQ course and returns to resume the treatment:

If interruption is up to 7 days:

BDQ containing regimen will be continued to complete the doses and the duration of treatment will be extended to complete IP..

If interruption is more than 7 consecutive days

BDQ course will be re-loaded (started afresh) if returns within 1 month and a sputum sample will be collected for culture.

3-24 weeks of BDQ course and returns to resume the treatment:

If interruption is up to 1 month:

BDQ containing regimen will be continued to complete the doses and duration of treatment will be extended to complete full course of BDQ

If interruption is more than 1 months:

BDQ will be permanently discontinued. Such patients will be given an outcome of “Lost to follow up” (LTFU) register afresh and initiate All oral MDR TB regimen with modification

Clinical monitoring

  • After initiation of Rx from the DR-TB Centre, MO D/NDR TB center,
    • at monthly intervals during the IP, and
    • at 3-monthly intervals during the CP until the end of treatment
  • Assess clinical, microbiologic, and radiologic response to treatment
  • Measure weight
  • Assess possible adverse drug reactions (ADR)
  • Encourage the patient to continue treatment
  • Verify treatment card


Follow-up sputum examination

  • Smear examination would be used on a monthly basis from 3rd month onwards to guide the decision on moving from IP to CP in shorter MDR TB regimen and extension of treatment from 6 months to 9 months and treatment outcome for all oral H mono/poly regimen.
  • For H mono/poly regimen,
    • positive smear result at 4th month, treatment will be extended to 9 months.
    • Follow up positive at end of 5th month, declare as treatment failed.
    • Follow up culture would be done at 3rd, 6th and 9th month (if applicable). If found culture positive, DST will be done.
  • For shorter MDR TB regimen,
    • If smear/culture remains positive at the end of IP and/or extended IP, a fresh specimen/culture isolate of that time will be subjected to FL/SL-LPA to check for amplification of resistance to FQ/ SLI or InhA mutation.
    • If the patient is found to be susceptible to both FQ and SLI at end of IP, the intensive phase will be extended on monthly basis up to a maximum of six months.
    • At end of extended IP or later, if any resistance is detected by SL-LPA OR InhA mutation detected on FL-LPA OR if found to be culture positive, the patient will be declared as treatment failure.
    • The patient is then re-evaluated for all oral longer MDR TB regimen with appropriate modification if required.


  • Follow-up culture should be done using liquid culture.
  • final treatment outcome of all MDR-TB patients will be declared on the basis of follow-up culture results only
  • For all oral longer MDR TB regimen
    • In case of extension of IP, the follow-up culture months will shift by every month of extension of IP till maximum limit of IP for all regimen classes.
    • Extension of treatment is based on the follow up culture result of 5th month or 4th month culture result is negative at the end of 6 months of treatment, reduce the dose of Lzd for subsequent period of treatment. If 5th month culture result is not available, decision should be based on the 4th month culture result.
    • If the follow up culture result (5th or 4th month) is positive, continue the regimen for one more month and extend the total duration of treatment for one more month.
    • Extend the treatment maximum for 2 more months based on the follow up culture results of 6th or 7th month, beyond this, reduce the dose of Lzd to half for subsequent period in all the weight bands.
    • Patient should have received minimum 8 months of treatment before declaring the patient as treatment failed if the patient is not converted.


Interim outcomes

  • Culture conversion: Patient is considered to have culture converted when two consecutive cultures, taken at least 1 month apart, are found to be negative. In such a case, the specimen collection date of the first negative culture is used as the date of conversion.
  • Culture reversion: Patient is considered to have culture reverted when, after an initial culture conversion, two consecutive cultures, taken at least 1 month apart, are found to be positive. For the purpose of defining Treatment failed, reversion is considered only when it occurs in the continuation phase.
  • Smear conversion: Patient is considered to have smear converted when two consecutive smears, taken at least 1 month apart, are found to be negative. In such a case, the specimen collection date of the first negative smear is used as the date of conversion.
  • Smear reversion: Patient is considered to have smear reverted when, after an initial smear conversion, two consecutive smears, taken at least 1 month apart, are found to be positive. For the purpose of defining Treatment failed, reversion is considered only when it occurs in the continuation phase.


Outcomes for all oral H mono/ poly DR TB patients

  • Cured: A microbiologically confirmed patient at the beginning of treatment who was smear negative at the end of the complete treatment and on at least one previous occasion.
  • Treatment completed: A patient who has completed treatment according to guidelines but does not meet the definition for cure or treatment failure due to lack of microbiological results.
  • Treatment failed: A patient whose biological specimen is positive by smear at 5 months or later
  • Died: A patient who has died due to any reason during the course of anti-TB treatment
  • Lost to follow up: A patient whose treatment was interrupted for continuous 1 month or more.
  • Not Evaluated: A patient for whom no treatment outcome is assigned. This includes former “transfer-out” & “still on treatment”
  • Regimen Changed: A need for permanent discontinuation of existing regimen and initiation of new regimen with change of at least one or more anti-TB drugs prior to being declared as failed.


Outcomes for shorter MDR TB regimen

  • Cured: A microbiologically confirmed MDR/RR TB patient who has completed treatment without evidence of failure and was culture negative at end of treatment and on at least one previous occasion.
  • Treatment completed: A patient who has completed treatment according to guidelines but does not meet the definition for cure or treatment failure due to lack of microbiological results.
  • Treatment failed: Treatment terminated or need for permanent regimen change of any anti-TB drugs in CP because of
    • lack of microbiological conversion by the end of extended IP or
    • microbiological reversion in CP after conversion to negative or
    • evidence of additional acquired resistance for drugs in regimen or
    • adverse drug reactions (ADR).
  • Died: A patient who dies for any reason during the course of anti TB treatment.
  • Lost to follow-up: A patient whose treatment was interrupted for continuous one month or more.
  • Not evaluated: A patient for whom no treatment outcome is assigned, this includes former “transfer-out” & “still on treatment”.
  • Regimen changed: A need for permanent discontinuation of existing regimen and initiation of new regimen with change of at least one or more anti-TB drugs prior to being declared as failed.


Outcomes for all oral longer regimen for MDR/RR TB

  • Cured: A microbiologically confirmed MDR/RR TB patient who has completed treatment without evidence of failure and three or more consecutive cultures taken at least 1 month apart from 8 months onwards are negative including culture at the end of treatment.
  • Treatment completed: A patient who has completed treatment according to guidelines but does not meet the definition for cure or treatment failure due to lack of microbiological results.
    • Treatment failed: Treatment terminated or need for permanent regimen change of at least two or more anti-TB drugs from 8th months onwards because of lack of microbiological conversion by the end of the 8th month of treatment or
    • microbiological reversion in the 8th month or later after conversion to negative or
    • evidence of additional acquired resistance for drugs in regimen or
  • Died: A patient who dies for any reason during the course of anti TB treatment.
  • Lost to follow-up: A patient whose treatment was interrupted for one month or more for any reasons prior to being declared as failed.
  • Not evaluated: A patient for whom no treatment outcome is assigned, this includes former ‘transfer- out’ & “still on treatment”.


Therefore, there are mammoth and comprehensive changes in the guidelines on programmatic management of drug resistant tuberculosis in India 2019.

Major salient changes are being described here and remaining parts of the guidelines (DRTB in children, management in special situation, adverse events during management, monitoring and evaluation, infection control measures, non tubercular mycobacterium etc.) to be discussed in due course.

Source: Guidelines on programmatic management of drug resistant tuberculosis in India 2019. Revised National Tuberculosis Control Programme, Central TB Division, Directorate General of Health Services, Ministry of Health & Family Welfare, Nirman Bhawan, New Delhi.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.




    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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Abstract
Introduction
Causes of drug r...
CLASSES OF ANTI ...
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