|Ahead of print publication
Trend of antitubercular drug sensitivity test at a multispecialty hospital in Western India
Shishir Jain1, Ashish Bahal2, HS Sidhu3, Muqtadir Malik2, Siddharth Singh2
1 Col Med (Health), O/o DGAFMS, Army Hospital Research and Referral, New Delhi, India
2 Department of Microbiology, Army Hospital Research and Referral, New Delhi, India
3 Department of Pathology, Military Hospital CTC, Pune, Maharashtra, India
|Date of Submission||01-Oct-2019|
|Date of Decision||02-Oct-2019|
|Date of Acceptance||29-Jun-2020|
|Date of Web Publication||02-Sep-2020|
Department of Microbiology, Army Hospital Research and Referral, Dhaula Kuan, New Delhi - 110 010
Source of Support: None, Conflict of Interest: None
Context: Tuberculosis (TB) infection is still a major public health burden in India. India accounts for about 25% of the global TB burden. Worldwide India is the country with highest burden of both TB and multidrug-resistant (MDR) TB. Aim: The aim of this study was to evaluate the pattern of resistance of Mycobacterium tuberculosis to first and second line antitubercular drugs among specimens from a multispecialty hospital in Western Maharashtra. Settings and Design: This record-based study was conducted from January 2018. Records of sputum from 2013 to 2017 were obtained from patients with suspected TB. Subjects and Methods: Drug-sensitivity testing was performed by the mycobacterial growth indicator tube method. Sensitivity to first line and second line antitubercular drugs was tested. Statistical Analysis Used: Trend analysis and charts using MS Excel. Results: Among 734 patients, 701 (95.5%) were male and 33 (4.5%) were female. The analysis of our study result showed that 21.7% of patients were monodrug resistant. Out of 734 isolates, 56 (7.62%) showed multi- and 39 (5.6%) out of the 734 samples showed extensive drug-resistant TB. Conclusions: Our study confirms that drug resistance, including MDR, observed against all first-line TB drugs was a real threat in the management of TB infection. The resistance pattern in this study could assist the clinicians in providing appropriate treatment regimen to TB patients and improve their clinical outcome.
Keywords: Drug resistance, first line, pulmonary tuberculosis, second line
| Introduction|| |
India accounts for one fourth of the global tuberculosis (TB) burden. In 2018, an estimated 27 lakh cases occurred and 4.5 lakh people died due to TB. India has highest burden of both TB and multidrug-resistant (MDR) TB based on estimates reported in Global TB Report 2017. An estimated 1.3 lakh incident MDR TB patients emerge annually in India which includes 79,000 MDR-TB Patients estimates among notified pulmonary cases. India bears the second highest number of estimated HIV associated TB in the world. An estimated 1.1 lakh HIV-associated TB occurred in 2015 and 37,000 estimated number of patients died among them.
MDR-TB is an important emerging public health problem of great importance across the world. A rise in the number of cases of MDR TB has recently been recognized, which is a cause of higher mortality rates than drug-sensitive TB.
It is becoming increasingly important to detect the antibiotic resistance among Mycobacterium tuberculosis strains with the global recognition of drug-resistant strains and their adverse impact on clinical outcome. Globally, an estimated 10 million people suffered from TB; however, India harbors the highest number of TB cases and many of them are MDR-TB.
A number of studies have described the prevalence of MDR-TB in a number of different geographical locations across the country.,,,,,,, The emergence of mutated strains of M. tuberculosis that are resistant to the major anti-TB drugs poses a deadly threat worldwide including our country. TB is predominantly a disease of the poor with over 80% of cases occurring in Asia and Africa. Although the greatest numbers of patients live in highly populous countries of Asia the highest incidence of disease is found in African region.
Drug-resistance TB notably MDR-TB, was higher in patients with previously incomplete anti-TB treatment. A high level of drug resistance among the re-treatment TB patients poses a threat of transmission of resistant strains to susceptible persons in the community. In March 2017, the Government of India (GOI) announced that the new aim for TB in India was the elimination of TB by 2025.
However, as studies so far tried to emphasize the diagnosis, treatment, and care of MDR-TB, there is a lack of literature highlighting trends of resistance patterns over the years among selected populations.
The aim of this study was to document the patterns of drug resistance observed in TB patients receiving anti-TB treatment in a super-specialty hospital in India and to identify the trends and patterns in these patients over time.
| Subjects and Methods|| |
A record-based retrospective, observational study using routinely collected laboratory data of patients visiting the Department of Respiratory Medicine at a Tertiary Care Hospital in Western Maharashtra.
Study population and setting
Epidemiological data of TB patients and data on M. tuberculosis resistance to first and second line TB drugs were retrospectively collected from January 1, 2013, to December 31, 2017. Data were collected from Master Record Register at the Department of Microbiology at a Tertiary Care Hospital in Western Maharashtra. Patients giving inadequate/inappropriate samples in the laboratory were excluded from the study.
The institution followed standard international and national guidelines on diagnosis and treatment of TB throughout the study period.
Drug resistance profiles
Drug sensitivity test (DST) to first-line and second-line antitubercular drugs were carried out using the mycobacterial growth indicator tube (MGIT) (Ms Becton Dickinson, New Jersey) as per manufacturer's instructions. DST of second-line antitubercular drugs was performed using MGIT method only in cases where resistant to first-line drugs was present especially rifampicin (RIF).
A case of MDR-TB was defined as sputum/isolate in which the positive culture of M. tuberculosis was found to havein vitro resistance to isoniazid (INH) and RIF with or without resistance to other antitubercular drugs based on additional DST.
Extensively drug-resistant (XDR) TB case was defined as having an MDR-TB strain that is resistant to any fluoroquinolone (ofloxacin, levofloxacin, or moxifloxacin) and at least one second-line injectable anti-TB drug (kanamycin, amikacin, or capreomycin).
| Results|| |
A total of 9545 patients suspected of TB were registered in respiratory disease Centre of Western Maharashtra during the year 2013–2017. Proportion of female sputum smear positive cases was higher (8.3%) as compared to males (7.6%). Out of total sputum smear positive cases 95.5% were male and 4.5% were female [Table 1] and [Table 2].
Among total suspected cases, proportion of sputum positive cases showed upward trend of TB from year 2013 to 2015 but thereafter linear downward by 2017 [Figure 1].
Drug resistance patterns
Percentages of resistance to individual drugs are shown in [Figure 2]. The drug sensitivity profile of 13 drugs was evaluated. Of 734 isolates from sputum samples, 160 showed mono-resistance, i.e., resistance to one first-line drugs (INH, RIF, Streptomycin (SM), Pyrazinamide (PYZ), Ethambutol (EMB)]) and the remaining 574 were sensitive to all five first-line drugs.
Out of 734 isolates, 56 (7.62%) showed MDR (resistance to INH and RIF) whereas 39 (5.6%) out of the 734 samples showed XDR (resistance to INH and RIF, in addition to fluoroquinolones and to at least one injectable second-line drugs).
The trends in drug resistance [Figure 3] and [Figure 4] showed a spike in resistance to all first-line and second-line anti-TB drugs in 2016.
| Discussion|| |
The present record-based evaluation study conducted in Western Maharashtra since year 2013–2017 has been shown the upward trend of sputum positivity from year 2013 to 2015 but thereafter linear downward by 2017. The difference in incidence of TB although cannot be ascertained specifically but findings reported by GOI shows that the incidence of TB has reduced from 289 per lakh per year in 2000-217 per lakh per year in 2015 and the mortality due to TB has reduced from 56 per lac per year in 2000-36 per lac per year in 2015. The main contributors of increase in incidence being lack of adequate infrastructure, population explosion, and poverty. A similar study done in Maharashtra displays previous 5 years trend from year 2008 to 2012 and shows upward trend from 2008 to 2010 but linear downward trend from 2010 to 2012. A similar linear downward trend is noted from year 2015 to 2016 in study done in North India. The decrease in the sputum smear positive TB could be related to the success of TB control strategy.
Opposite trend was reported from a study done in Ghana showing increase in sputum smear positive pulmonary TB from 2013 to 2016. This could be due to ineffective strategies and TB control program. TB was declared as an emergency in Africa in 2005 when the annual incidence increased four time in African countries from the 1990 incidence and continues to rise, killing more than half a million every year. Gender is an important variable in infectious disease epidemiology. A 1998 review on gender differences in TB suggested that women in low-income countries were probably under notified. Proportion of female sputum smear positive cases was higher (8.3%) as compared to males (7.6%). Out of total sputum smear positive cases 95.5% were male and 4.5% were female and same trend was reported in earlier study in Maharashtra. Studies done in India shows similar gender distribution pattern having a wide sex gap with male patients outnumbering female patients.,
This retrospective study regarding drug resistance patterns among TB cases has generated valuable information in the context of the drug-resistant TB situation in India. The development of drug resistance TB, including MDR, is attributed to poor patient compliance, inappropriate TB drug regimen, inadequate laboratory facilities for drug-susceptibility testing, and acceleration of HIV epidemic.
Resistance to INH and INH plus RIF in India was 6.2% and 13.1%, respectively whereas Shah et al. studied 482 previously treated pulmonary TB patients and reported that resistance to INH and INH plus RIF was 12.86% and 15.77%, respectively. In our study, resistance to INH and INH plus RIF was 17.6% and 7.6%, respectively. Although INH resistance was higher than in the study by Shah et al. (2002), INH plus RIF resistance was lesser.
Kadam et al. reported that resistance to INH, either alone or in combination with another drug, was highest, at 27.4%. SM resistance India was 6.8% which was lower than the 16% observed in their study and corroborated with this meta-analysis. Resistance against RIF in India was found to be 5.1% whereas it was 14.28% in the present study but was lower than the RIF resistance (15.5%) reported in a previous study.
Noncompliance among patients is an important factor in this regard. Second, we found the highest of resistance (78.51%) against cycloserine among the second-line drugs. Although the reason for this resistance may be attributed to the cross-resistance among drugs, for example, cross-resistance of ethionamide with INH. This study shows a low resistance to fluoroquinolones among the strains tested in this study. This study underlines the necessity of direct observed therapy in Indian patients.
Globally, India has one of the highest burdens of MDR-TB, with an estimated 63,000 patients having MDR strains among pulmonary TB cases in 2013, which accounts for more than 20 percent of the estimated global burden of drug-resistant TB.
In India, the incidence of MDR TB is 3.4%. A high degree (7.62%) of MDR-TB was observed among patients in this study. However, 462 (63%) isolates were sensitive to all four first-line drugs (INH, RIF, SM, and EMB) that were tested. Although noncompliance is a major factor for poor outcome of therapy, this study underscores the presence of MDR-TB strains among these patients.
| Conclusions|| |
Data in this study show that TB is a great challenge and there is a need to intensify the awareness program about TB, involvement of public private partnership, early case detection and adherence with treatment to control the burden of TB. Efforts to increase the gender sensitivity of health services and to promote community awareness of TB are of utmost importance.
The study also confirms that drug resistance, including MDR, observed against all first-line TB drugs was a real threat in the management of TB infection. The resistance patterns observed in this study may give an insight to the clinician for early suspicion of MDR-TB at early stage and improve their clinical outcome in TB patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]