journal club discussion on clinical profile and treatment outcome of drug resistant tuberculosis patients of western Maharashtra

1. Clinical Profile and Treatment Outcome
of Drug Resistant Tuberculosis Patients
of Western Maharashtra, India
DR. AHMED KHAN
DR. ARPAN SINGH CHOUHAN
GUIDE: DR. JAISHREE GHANEKAR
Sachin S Dole1, VN Waghmare2, AM Shaikh3
Journal of The Association of Physicians of
India ■ Vol. 65 ■ October 2017
O R I G I N A L A R T I C L E

2. Introduction
▪ Multidrug resistant tuberculosis (MDR-TB) is tuberculosis
resistant to isoniazid and rifampicin.
▪ In India MDR-TB in new cases has been reported to be nearly
3% and in treated patients has been reported to be 12%.
▪ Use of second line anti -tubercular drugs which are expensive
and associated with adverse drug reactions given for longer
duration often results in decreased compliance and success
rates.
▪ So, study was conducted at tertiary care centre of Western
Maharashtra, India to evaluate clinical profile and treatment
outcome of drug resistant tuberculosis patients who were
treated with standardized MDR-TB regimen.

3. Materials and Methods
• Total 2127 suspected DR-TB cases from Solapur district,
attending outpatient department of pulmonary medicine of
Dr. Vaishampayan Memorial Government Medical College,
Solapur from September 2012 to December 2014 were
screened of which 203 cases were confirmed as having
MDR-TB.
• All confirmed DR-TB cases which were diagnosed at RNTCP
certified Intermediate Reference Laboratory(IRL), Aundh,
Pune, India with either Line Probe Assay (LPA) or Xpert
MTB/RIF assay (Cephaleid, Sunnyvale USA) technology also
called as genexpert which are WHO recommended standard,
rapid diagnostic tests for diagnosis of DR-TB cases were
screened.

4. • Those confirmed DR-TB cases who were
1) Not willing for standardised MDR-TB regimen;
2) Died before stating the regimen and
3) Not fit for initiation of treatment were excluded from the study.
• Total 146 confirmed DR-TB cases registered for starting
standardized MDR-TB regimen were enrolled in this study.
• All MDR-TB cases were treated with standardized regimen which
consists of 6-9 months of intensive phase with kanamycin,
levoflox acin , ethionamide , pyrazinamide, ethambutol and
cycloserine and continuation phase of 18 months with ethambutol,
levofloxacin, ethionamide and cycloserine on daily basis. All data
of MDR-TB cases were collected from pretreatment evaluation
records.

5. ➢Definition of treatment outcome of MDR-TB
patients according to WHO 2013 guidelines are-
1. Cured: patient who has completed MDR-TB
treatment, is culture-negative in the last month
of treatment and has been culture-negative
during the preceding 11 months of treatment.
2. Treatment completed: patient who completed
MDR-TB treatment but did not meet the
definition for cure or failure due to lack of
bacteriologic results.

6. 3. Treatment failure: defined as more than one
positive culture in the last 12 months of treatment,
with a minimum of five cultures performed during
the last 12 months, or if patient is persistently
culture-positive and a clinical decision has been
made to terminate treatment early.
4. Death: defined as patient who dies for any reason
during the course of MDR-TB treatment.
5. Treatment default: defined as patient whose MDR-
TB treatment was interrupted for two or more
consecutive months.

7. ➢Chest radiographs was obtained for every patient
and classified according to the National
Tuberculosis Association of USA (1961).
1. Minimal: Non-cavitatory lesions involving one or
both lungs but the volume of involvement
regardless of distribution less than or equal to one
zone.
2. Moderately advanced: More advanced lesions than
minimal but the total involvement not more than
the volume of one lung. Cavities, if present, not to
exceed a total diameter (of all cavities) of 4 cm.

8. 3. Far advanced(Extensive) (III): Any lesion
more advanced than moderate
• Culture conversion was defined as three
negative consecutive cultures taken at least
one month apart after treatment initiation.

9. Results
• Out of total 146 bacteriologically proven cases of DR-TB, 95
were males and 51 females. 41% of patients were residents
of Solapur city and the rest from different parts of Solapur
district. Out of the 146 patients, 130 (89%) patients
achieved sputum culture conversion within three months.
• Treatment outcome of these patients was as follows
treatment success in 84 (58%), 20(14%) died, 28(19%)
defaulted and failure in 14(9%) patients. Three predictors
were identified for successful treatment outcome of DR-TB
that include urban residence, patients with chest x-ray
findings of moderately advanced disease and patients
whose DR-TB status diagnosed by genexpert technology.

12. Discussion
• The emergence of MDR-TB is a global
problem, which is threatening to destabilize
the best efforts of TB control.
• To manage MDR-TB in poor economically
settings, WHO launched the DOTS Plus
initiative to develop a global policy to provide
technical assistance to DOTS programmes
and to enable access to second-line drugs
under rational use.

13. ▪ Higher treatment success rate was observed in patients
of urban area, this may be due to better facility of
transportation and more awareness of disease.
Similarly better treatment success rate was observed in
patients with moderately advanced disease.
▪ In the study among tests used for diagnosing DR-TB,
patients who were diagnosed with genexpert test has
shown fairly high treatment success as result of above
test is available within 90 minutes compared to LPA,
where diagnosis takes 72 hours. Earlier the results are
obtained, patients can be started on treatment earlier,
thus increasing the success rate.

14. Conclusions
• From this study, it appears feasible to treat MDRTB
patients effectively in India on the predominantly
ambulatory RNTCP standardized regimen. This
study has shown that standardized treatment of
MDR- TB can provide satisfactory results.
• The standardized treatment strategy may be a
justifiable alternative to the individually tailored
regimens. Use of rapid diagnostic tests for MDR-TB
like genexpert should be increasingly use to
achieve higher treatment success in these
patients.

15. • Total 1799 suspected TB cases from
MGM HOSPITAL attending OPD/ IPD
patient department of pulmonary
medicine from may- 2015 to oct 2017
were screened; of which 77 cases were
confirmed as having MDR-TB.
• 77 patients enrolled, 4 were cured, 9
died, 5 defaulted and 7 failed treatment.

16. Countries in the three TB high-burden country lists that will
be used by WHO during the period 2016–2020, and their
areas of overlap

17. India is initiating the DOTS-Plus
strategy at the national level
To highlight the results, constraints and
issues of a pilot DOTS-Plus experience in an
urban setting in India.
• Records of 126 patients with multidrug-
resistant tuberculosis (MDR-TB) enrolled from
January 2002 to December 2006, who
received a daily fully supervised standardised
treatment regimen under a pilot DOTS-Plus
study in India, were analysed retrospectively.

18. 126 patients enrolled, 61% were cured, 19% died, 18%
defaulted and 3% failed treatment. There was an average
delay of 5 months in the diagnosis of MDR-TB and a
subsequent delay of approximately 3.3 months in initiating
treatment. Of the 24 patients who died, 29% did so within a
month of starting treatment. Migration was the most common
reason for default. Cycloserine (CYC) had to be stopped in 15
patients and kanamycin (KM) in five due to major adverse
effects.
• The DOTS-Plus programme in resource-poor settings may
provide reasonable results; however, it may confront
significant operational difficulties in the timely diagnosis and
early initiation of treatment. Early diagnosis and start of
treatment may prevent some deaths. Default is commonly
due to migration. CYC proved to be the most toxic drug,
followed by KM.

19. References
1. Iseman MD. Treatment of multi-drug-resistant tuberculosis. N
Engl J Med 1993; 329:784-791.
2. Espinal M A, Laszlo A, Simonsen L, et al. Global trends in
resistance to antituberculosis drugs. N Engl J Med 2001;
344:1294–1303.
3. Central TB Division. Directorate General of Health Services,
Ministry of Health and Family Welfare, Government of India; New
Delhi. Summary and recommendations of the expert group
meeting on drug resistance surveillance 1997. New Delhi:
Directorate General of Health Services, Ministry of Health and
Family Welfare, Government of India; 1997: pp. 1-5.
4. WHO guidelines for the programmatic management of drug-
resistant tuberculosis 2013
5. Definitions and reporting framework for tuberculosis – 2013
revision. Geneva: World Health Organization; 2013
6. Singla R, Sarin R, Khalid UK, et al. Seven-year DOTS- Plus pilot
experience in India: Results, constraints and issues. Int J
Tuberc Lung Dis 2009; 13:976-81.

20. THANK YOU