Preventing Risks of Infections and Medication Errors in IV therapy (PRIME): a patient safety initiative.

BACKGROUND: Two major avoidable reasons for adverse events in hospital are medication errors and intravenous therapy-induced infections or complications. Training for clinical staff and compliance to patient safety principles could address these. METHODS: Joint Commission International (JCI) consultants created a standardised, 6-month training programme for clinical staff in hospitals. Twenty-one tertiary care hospitals from across south-east Asia took part. JCI trained the clinical consultants, who trained hospital safety champions, who trained nursing staff. Compliance and knowledge were assessed, and monthly audits were conducted. RESULTS: There was an overall increase of 29% in compliance with parameters around medication preparation and vascular access device management. CONCLUSION: The programme improved safe practice around preparing medications management and managing vascular access devices. The approach could be employed as a continuous quality improvement initiative for the prevention of medication errors and infusion-associated complications.

Influence of N-acetyltransferase 2 (NAT2) genotype/single nucleotide polymorphisms on clearance of isoniazid in tuberculosis patients: a systematic review of population pharmacokinetic models.

PURPOSE: Significant pharmacokinetic variabilities have been reported for isoniazid across various populations. We aimed to summarize population pharmacokinetic studies of isoniazid in tuberculosis (TB) patients with a specific focus on the influence of N-acetyltransferase 2 (NAT2) genotype/single-nucleotide polymorphism (SNP) on clearance of isoniazid. METHODS: A systematic search was conducted in PubMed and Embase for articles published in the English language from inception till February 2022 to identify population pharmacokinetic (PopPK) studies of isoniazid. Studies were included if patient population had TB and received isoniazid therapy, non-linear mixed effects modelling, and parametric approach was used for building isoniazid PopPK model and NAT2 genotype/SNP was tested as a covariate for model development. RESULTS: A total of 12 articles were identified from PubMed, Embase, and hand searching of articles. Isoniazid disposition was described using a two-compartment model with first-order absorption and linear elimination in most of the studies. Significant covariates influencing the pharmacokinetics of isoniazid were NAT2 genotype, body weight, lean body weight, body mass index, fat-free mass, efavirenz, formulation, CD4 cell count, and gender. Majority of studies conducted in adult TB population have reported a twofold or threefold increase in isoniazid clearance for NAT2 rapid acetylators compared to slow acetylators. CONCLUSION: The variability in disposition of isoniazid can be majorly attributed to NAT2 genotype. This results in a trimodal clearance pattern with a multi-fold increase in clearance of NAT2 rapid acetylators compared to slow acetylators. Further studies exploring the generalizability/adaptability of developed PopPK models in different clinical settings are required.

Evaluation of clinical, diagnostic features and therapeutic outcome of neurobrucellosis: a case series and review of literature.

AIM: In this study, we aimed to discuss the clinical features, laboratory findings, treatment and outcome of seven cases of neurobrucellosis from a tertiary care center and review the available global literature. MATERIALS AND METHODS: The diagnosis of neurobrucellosis was established using the following criteria in our setting: (1) signs and symptoms of neurological infection with examination of cerebrospinal fluid (CSF) revealing signs of meningitis, (2) isolation of Brucella spp. from blood and/or CSF and/or antibody titer ≥1:160 in serum using standard agglutination test (SAT) and/or the presence of anti-Brucella antibodies in CSF and/or detection of Brucella spp.-specific DNA from CSF using PCR. A literature search was performed to review previous cases of neurobrucellosis published worldwide during the last 30 years. RESULTS: The proportion of neurobrucellosis was 2.8% in our setting. Fever with headache and altered sensorium were the major presenting complaints. Brucella melitensis was isolated from blood culture in 6 patients. From the literature search, a total of 221 cases of neurobrucellosis were reviewed and analyzed. Meningitis (32.6%), loss of hearing (25.8%) and encephalitis (14.9%) were the most common clinical features. Involvement of cranial nerves, polyradiculopathy and paraplegia were the major complications found in patients with neurobrucellosis. CONCLUSIONS: Neurobrucellosis should always be considered in the differential diagnosis of befitting neurological, rheumatological, and neuropsychiatric presentations in endemic regions for brucellosis. To prevent morbidity and mortality associated with neurobrucellosis, a multimodal diagnostic approach is essential for early and accurate diagnosis and effective treatment.

COVID-19 Palliative and End-of-Life Care Plan: Development and Audit of Outcomes.

Objectives: Palliative care (PC) referral in serious and critical COVID-19 improves decision-making, health resource utilisation, end-of-life symptom management and family support. In this study, we explored developing a systematic decision-making matrix for PC referral in COVID-19 and audited its outcomes. Materials and Methods: A team of interdisciplinary experts developed a hospital COVID-19 PC plan. PC referral and outcomes of PC referral in hospitalised COVID-19 patients were audited. Results: Out of 1575 inpatients, 1066 (67.7%) had mild and 509 (32.3%) had serious and critical COVID-19 illness. Among 50 (3.1%) referred to PC, 5 (0.4%) had mild and 45 (8.8%) had serious and critical COVID-19 illness. Out of 45 serious and critical COVID-19 patients referred to PC, 38 (84%) received end-of-life care (EOLC), 4 (9%) self-discharged against medical advice and 3 (7%) recovered. Forty-seven (94%) were referred for goals-of-care discussion. About 78% received opioids, 70% benzodiazepines and 42% haloperidol for symptom management. Among 45 serious and critical COVID-19 patients referred to PC, foregoing life-sustaining treatment was documented in 43 (96%) but implemented only in 23 (53%). Out of 38 who received EOLC, ICU was the place of death in 31 (82%) and ward in 7 (18%). Conclusion: Despite interdisciplinary experts developing a hospital COVID-19 PC, low referral of serious and critical COVID-19 patients to PC was observed. PC referral enabled access to management of end-of-life symptoms and facilitated limitation of life-sustaining treatment in some COVID-19 patients with serious illness. Educating critical care physicians about the scope of PC in the COVID-19 setting might improve PC referral.

Current Understanding of the Pathogenesis of Dengue Virus Infection.

The pathogenesis of dengue virus infection is attributed to complex interplay between virus, host genes and host immune response. Host factors such as antibody-dependent enhancement (ADE), memory cross-reactive T cells, anti-DENV NS1 antibodies, autoimmunity as well as genetic factors are major determinants of disease susceptibility. NS1 protein and anti-DENV NS1 antibodies were believed to be responsible for pathogenesis of severe dengue. The cytokine response of cross-reactive CD4+ T cells might be altered by the sequential infection with different DENV serotypes, leading to further elevation of pro-inflammatory cytokines contributing a detrimental immune response. Fcγ receptor-mediated antibody-dependent enhancement (ADE) results in release of cytokines from immune cells leading to vascular endothelial cell dysfunction and increased vascular permeability. Genomic variation of dengue virus and subgenomic flavivirus RNA (sfRNA) suppressing host immune response are viral determinants of disease severity. Dengue infection can lead to the generation of autoantibodies against DENV NS1antigen, DENV prM, and E proteins, which can cross-react with several self-antigens such as plasminogen, integrin, and platelet cells. Apart from viral factors, several host genetic factors and gene polymorphisms also have a role to play in pathogenesis of DENV infection. This review article highlights the various factors responsible for the pathogenesis of dengue and also highlights the recent advances in the field related to biomarkers which can be used in future for predicting severe disease outcome.

Transmission of SARS-CoV-2 Infection by Children: A Study of Contacts of Index Paediatric Cases in India.

The susceptibility of children to coronavirus disease-19 (COVID-19) and transmission of COVID-19 from children to others is a relatively unexplored area. The aim of this study was to understand the transmission dynamics of Severe Acute Respiratory Syndrome Coronavirus 2 in children. This was a retrospective observational study where a total of 19 paediatric index cases (including a set of twins) with COVID-19 and 42 primary contacts (adults-36, paediatric-6) from the immediate family members were included. All the index cases and four of the five positive contacts were asymptomatic. Despite adults staying with positive children in the same vehicle, same room in the quarantine centre and the same ward, only four of the parents became positive.

Plasma angiogenesis and oxidative stress markers in patients with diabetic retinopathy.

Background: Neovascularization in the retina and hyperglycaemia-induced oxidative stress are implicated in the pathogenesis of diabetic retinopathy (DR). In this study, we hypothesized that the plasma angiogenic and oxidative stress markers associated with these derangements could aid in the screening of diabetic patients who are at an increased risk of developing retinopathy.Methods: This study included normal (n = 148), type2 diabetes without retinopathy (DNR; n = 148), proliferative DR (PDR; n = 74) and non-PDR (NPDR; n = 148) subjects. Plasma concentrations of vascular endothelial growth factor-A (VEGF-A), hypoxia-inducible factor-1α (HIF-1α), matrix metalloproteinase-9 (MMP-9), pigment epithelium-derived factor (PEDF), nitric oxide (NO), soluble receptors for advanced glycation end products (sRAGE), malondialdehyde (MDA) and protein thiols were estimated.Results: A statistically significant increase was observed in the plasma concentrations of pro-angiogenic factors and markers of oxidative stress in both retinopathy groups. By contrast, the concentrations of anti-angiogenic factors and antioxidants were decreased significantly in these groups. Receiver operating characteristic analysis indicated that the plasma thresholds of HIF-1α and PEDF can be suitable markers in case of NPDR. However, in PDR, HIF-1α, NO, MMP-9 and PEDF showed high sensitivity and specificity.Conclusions: The factors associated with hypoxia, matrix degradation and angiogenic inhibition play a crucial role in predicting DR.

Assessment of Pyrexia and Associated Sickness Behavior in Patients with Chronic Periodontitis.

BACKGROUND AND OBJECTIVES: The purpose of this study was to assess pyrexia and sickness behavior such as anxiety, depression, lethargy, and weight loss in subjects with chronic periodontitis, and evaluate inflammatory mediators such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in the patients with fever. METHODS: This was a cross-sectional study that consisted of 150 chronic periodontitis and 150 healthy subjects. Sublingual and subgingival temperatures were assessed using a digital temperature probe. Associated sickness behavior was assessed for all the subjects. Pathological tests, i.e., ESR and CRP were done for subjects with fever. RESULTS: Evaluating the presence of fever with the severity of periodontal disease, 66.7% of the subjects with fever were in the group diagnosed with severe periodontitis, 20.4% had with moderate periodontitis, and 5.3% were in the healthy group. Subjects diagnosed with periodontitis comprised 66.2% of the subjects with higher (i.e., > 36.3°C) subgingival temperatures and healthy subjects made up the remaining 33.8% (p < 0.001). A correlation between the sublingual and subgingival temperature with the Pearson ρ correlation coefficient of 0.227 (p < 0.001) was observed. A statistically significant mean value of 37.05 ± 11.24 of ESR and 1.59 ± 1.11 mg/L of CRP was reported amongst the subjects with fever (p < 0.001). The association of sickness behavior with the severity of periodontitis was found to be significant: depression 40.006, anxiety 50.857, reported weight loss 76.463, and lethargy 141.581 (p < 0.001). DISCUSSION AND CONCLUSION: The study demonstrated that there is a significant increase in the sublingual temperature amongst patients with severe chronic periodontitis. The subgingival temperature has a positive correlation with the sublingual temperature. There was a linear trend of an association of sickness behavior with the severity of chronic periodontitis. A significant increase in the circulating inflammatory mediators, CRP and ESR, were noticed in subjects with elevated body temperature.

Invasive nontyphoidal Salmonella disease in southern India: a 5-year experience from a tertiary care hospital

Background/aim: The current study was carried out to describe the clinical presentation, antimicrobial susceptibility pattern, and outcome of invasive nontyphoidal Salmonella disease (iNTS) in a tertiary care center. Materials and methods: A 5-year hospital-based retrospective study was carried out on blood culture-confirmed cases of iNTS. Medical records of patients were reviewed to obtain information on demography, clinical manifestations, comorbidities, complications, immune status, treatment, and clinical outcome. Results: A total of 40 blood culture-confirmed cases of iNTS were diagnosed during the study period. Among these 40 isolates, 9 (22.5%) were identified as Salmonella Typhimurium. Fever (67.5%) with gastrointestinal disturbance (40%) was the most common clinical presentation. The majority of the patients were immunosuppressed (75%). All isolates were susceptible to all the antimicrobials tested. Ceftriaxone (92.5%) was the most common antimicrobial used in our setting. A total of 15% patients died during the hospital stay. Conclusion: We conclude that iNTS disease is a severe infection prevailing in India with a high mortality rate. Anemia and diabetes were the two most common comorbidities. Though all NTS organisms isolated were sensitive to all the antimicrobials tested, we suggest that continued surveillance is necessary to monitor the presence of multidrug-resistant strains.

Antibiotic prophylaxis in organophosphorus poisoning: A study of health and economic outcomes.

Objective: Organophosphorus poisoning (OPP) is a major concern for developing countries. There are no guidelines for the prophylactic use of antibiotics in the management of OPP which in such critical cases might add to the economic burden of the patients as well as antibiotic resistance. We compared the health and economic outcomes in patients prescribed with prophylactic antibiotics with respect to the patients not prescribed with any antibiotics. Methods: A retrospective observational study was carried out for two years for patients admitted to ICU with OPP. Patients were graded for severity of OPP, and divided into two groups based on prophylactic prescription and no prescription of antibiotics. The length of stay (LOS), hospitalization cost and outcomes were measured and compared between the two groups using statistical tests. Results: Out of the 254 patients observed, 108 were prescribed with prophylactic antibiotics and 94 were not prescribed with any antibiotic. There was a significant difference between LOS, cost of treatment and outcomes in the two groups (p < 0.001). When antibiotics were not prescribed, the odds of improvement was 1.854 times higher compared to those who received prophylactic antibiotics although after adjusting for severity of poisoning, significance was lost. On an average, 2-3 antibiotics were prescribed to every patient in the first group. Conclusion: OPP is an important health concern where issues of antibiotic misuse and overuse are practiced. Our study suggested that systemic antibiotic prophylaxis did not offer any advantage over non-use of any antibiotics in patients with OPP.

Association of hyponatremia with in-hospital outcomes in infective endocarditis: A 5-year review from an Indian Intensive Care Unit.

Hyponatremia is commonly noted with cardiovascular disorders, but its role in infective endocarditis (IE) is limited to being a marker of increased morbidity in IE patients with intravenous drug use. This was a 5-year retrospective review from an Indian Intensive Care Unit (ICU). Patients >18 years with IE and available serum sodium levels were included in the study. Pediatric and pregnant patients were excluded from the study. Hyponatremia was defined as admission sodium <135 mmol/L. Detailed data were abstracted from the medical records. Primary outcomes were need for invasive mechanical ventilation, ICU length of stay, and in-hospital mortality. Secondary outcomes included development of acute kidney injury, acute decompensated heart failure (ADHF), acute respiratory distress syndrome, stroke, and severe sepsis in the ICU. Two-tailed P < 0.05 was considered statistically significant. Between January 2010 and December 2014, 96 patients with IE were admitted to the ICU with 85 (88.5%) (median age 46 [34.5-55] years, 51 [60.0%] males) meeting our inclusion criteria. The comorbidities, echocardiographic, and microbiological characteristics were comparable between patients with hyponatremia (56; 65.9%) and eunatremia (29; 34.1%). Median sodium in the hyponatremic cohort was 131 mmol/L (127.25-133) compared to the eunatremic cohort 137 mmol/L (135-139) (P < 0.001). The primary outcomes were not different between the two groups. Hyponatremia was associated more commonly with ADHF (12 [21.4%] vs. 0; P = 0.007) during the ICU stay. Hyponatremia is commonly seen in IE patients and is not associated with worse hospital outcomes. ADHF was seen more commonly in the hyponatremic patients in comparison to those with eunatremia.

Diagnostic validation of selected serological tests for detecting scrub typhus.

Clinical diagnosis of scrub typhus is often difficult because the symptoms are very similar to those of other febrile illness such as dengue, leptospirosis, malaria and other viral hemorrhagic fevers. Though better diagnostic tests are available for rickettsial diseases and scrub typhus elsewhere, the Weil-Felix test is still commonly used in India, mainly because microimmunofluorescence assays (M-IFA) were not available in India till recently and relevant staff had insufficient training. The present study was performed to investigate the performance of M-IFA, IgM ELISA, and Weil-Felix test on 546 non-repeated serum samples from subjects suspected of having scrub typhus. One hundred and forty-three of these 546 samples were positive by M-IFA; these cases were also confirmed clinically to have scrub typhus based on their dramatic responses to doxycycline therapy. IgM ELISA was positive in 122 of the 143 M-IFA positive cases and the Weil-Felix test in 96. Though the Weil-Felix test is a heterophile agglutination test, it was found in this study to have good specificity but far too little sensitivity to use as a routine diagnostic test. IgM ELISA can be a good substitute for M-IFA. Incorporation of multiple prototype antigens on M-IFA slides is likely one of the reasons for its superior performance. As newer and better diagnostic assays become available for scrub typhus diagnosis in developed countries, it will be imperative to also use such tests in other endemic countries to prevent over- or under-diagnosis of scrub typhus.

Demographics, clinical characteristics and management of herbicide poisoning in tertiary care hospital.

Herbicide poisoning is most common method of suicide in India and it is associated with high morbidity and mortality. Among different herbicidal poisonings the most predominantly found poisonings are paraquat and glyphosate. These compounds are highly toxic and their poisonings require proper management techniques. High fatality is seen in these cases which are mainly due to its inherent toxicity and lack of effective treatment. Common symptoms of these poisonings includes gastrointestinal corrosive effects with mouth and throat, epigastric pain and dysphagia, acid-base imbalance, pulmonary edema, shock and arrhythmia. Long term health effects include pulmonary fibrosis, renal failure, hepatic failure, heart failure, multi-organ failure or death. No proven antidote exists for these poisonings. So the treatment is mainly supportive. Initially gastric lavage or whole-gut irrigation using adsorbents such as Fuller's earth, bentonite or activated charcoal is recommended. In case of renal failure hemodialysis or hemoperfusion may be considered. However novel approaches like treatment with N-acetylcysteine, vitamin C, vitamin E, cyclophosphamide may also be helpful.

Diagnostic insights into disseminated histoplasmosis: a case report highlighting bone marrow analysis.

We present a case of a 43-year-old immunocompromised female patient diagnosed with disseminated histoplasmosis on bone marrow examination, at clinical laboratory of Kasturba Hospital, Manipal, Karnataka, India. The patient, presenting with symptoms like weight loss, appetite loss, and pancytopenia, underwent bone marrow aspiration and biopsy. The bone marrow studies revealed HIV-associated changes and the yeast form of Histoplasma capsulatum, confirming disseminated histoplasmosis. Bone marrow examination is highlighted as a diagnostic tool with significant sensitivity in such cases. The report stresses on the importance of awareness and early diagnosis of histoplasmosis in immunocompromised patients, given its potential lethality and the need for timely therapeutic intervention for better prognosis.

Influence of N-acetyltransferase 2 polymorphisms and clinical variables on liver function profile of tuberculosis patients.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in the N-acetyltransferase 2 (NAT2) gene as well as several other clinical factors can contribute to the elevation of liver function test values in tuberculosis (TB) patients receiving antitubercular therapy (ATT). RESEARCH DESIGN AND METHODS: A prospective study involving dynamic monitoring of the liver function tests among 130 TB patients from baseline to 98 days post ATT initiation was undertaken to assess the influence of pharmacogenomic and clinical variables on the elevation of liver function test values. Genomic DNA was extracted from serum samples for the assessment of NAT2 SNPs. Further, within this study population, we conducted a case control study to identify the odds of developing ATT-induced drug-induced liver injury (DILI) based on NAT2 SNPs, genotype and phenotype, and clinical variables. RESULTS: NAT2 slow acetylators had higher mean [90%CI] liver function test values for 8-28 days post ATT and higher odds of developing DILI (OR: 2.73, 90%CI: 1.05-7.09) than intermediate acetylators/rapid acetylators. CONCLUSION: The current study findings provide evidence for closer monitoring among TB patients with specific NAT2 SNPs, genotype and phenotype, and clinical variables, particularly between the period of more than a week to one-month post ATT initiation for better treatment outcomes.

Temporal cytokine storm dynamics in dengue infection predicts severity.

The immunopathogenesis of dengue severity is convoluted. The primary objective of the research was to examine the dynamics of cytokine storm and its correlation with disease development in individuals affected by DENV infection. Additionally, the study aimed to discover potential biomarkers that could indicate severe dengue infection and determine the most suitable timeframe for predicting the severity of these biomarkers during the acute stage of dengue infections. We conducted a temporal analysis of the daily viral load and cytokine levels in 60 hospitalized dengue patients until discharge. Our findings reveal a distinct cytokine profile (elevated IL-8, IL-10, IL-6, GM-CSF, MCP-1, IL-13, and IL-4 and decreased IL-12, MIP-1ß) on the third day after symptom onset is predictive of severe dengue in secondary dengue infection. The imbalanced cytokine signature may inform clinical decision-making in treating severe dengue infections.

Predictors and patterns of empirical antibiotic therapy and associated outcomes in COVID-19 patients: a retrospective study in a tertiary care facility in South India.

BACKGROUND: The coronavirus disease (COVID-19) led to a global health crisis. Inappropriate use of antibiotics in COVID-19 patients has been a concern, leading to antimicrobial resistance. This study evaluated the patterns and predictors of empirical antibiotic therapy in COVID-19 patients and associated outcomes. METHODS: A hospital-based retrospective study was conducted with 525 patients admitted to Kasturba Hospital, Manipal, India, with moderate and severe COVID-19 from 1 March to 1 August 2021. They were divided based on empirical therapy, and predictors of antibiotic usage were assessed by logistic regression. RESULTS: Four hundred and eighty (91.4%) COVID-19 patients received at least one course of antibiotics, with 440 (83.8%) initiating empirical therapy. Patients with severe COVID-19 manifestations were more likely to be prescribed empirical antibiotics. Multivariable analysis showed that patients initiated on empirical antibiotics had significantly elevated levels of procalcitonin [OR: 3.91 (95% CI: 1.66-9.16) (p = 0.001)], invasive ventilation [OR: 3.93 (95% CI: 1.70-9.09) (p = 0.001)], shortness of breath [OR: 2.25 (95% CI: 1.30-3.89) (p = 0.003)] and higher CRP levels [OR: 1.01 (95% CI: 1.00-1.01) (p = 0.005)]. Most antibiotics (65.9%) were prescribed from the 'Watch' group, the highest being ceftriaxone. Only 23.8% of the patients had microbiologically confirmed infections. CONCLUSION: The study identified predictors for initiating empirical antibacterial therapy in our setting.

Clostridium difficile infection at a tertiary care hospital in south India.

OBJECTIVE: The objective of this study was to detect C. difficile in patients presenting with Antibiotic Associated Diarrhoea. METHODS: Stool samples from twenty-five patients collected over a period of four months were processed for C. difficile by culture and the isolates were identified following standard methods. C. difficile toxins A and B and C. perfringens enterotoxin were detected by ELISA performed directly on stool specimens. RESULTS: Four patients (16%) were found positive for C. difficile infection. All patients with C. difficile infection received prior treatment with third-generation cephalosporins or beta-lactam/beta-lactamase inhibitor antibiotics. C. perfringens enterotoxin was found in two (8%) patients. Severe colitis was seen in one (25%) of the four patients who had co-infection with C. difficile and C. perfringens. CONCLUSION: This study demonstrated a significant occurrence of C. difficile infection in this hospital population. There is a need to further evaluate the role of C. perfringens in causing antibiotic associated diarrhoea. Good clinical and laboratory studies to generate local epidemiological data are essential to increase awareness among the treating clinicians about C. difficile infection. Also limited and rational use of broad spectrum antibiotics is recommended.

Atypical mycobacterium infection following anterior cruciate ligament reconstruction.

A man in his 20s presented with instability of the right knee following an incident of fall from a height. He was clinicoradiologically diagnosed to have an anterior cruciate ligament (ACL) tear for which he underwent ACL reconstruction. Postoperatively, he was started on an accelerated ACL rehabilitation protocol. Six weeks postoperatively, he developed features of subclinical septic arthritis for which he underwent arthroscopic debridement. Intraoperative samples cultured Mycobacterium abscessus complex on MGIT 960 system. The patient subsequently had to undergo another debridement after 1 month as there were clinical signs of persisting infection. The graft was intact even on the second debridement and after removing the implants. This case reports a rare complication of ACL reconstruction with infection by atypical mycobacterium and the clinical outcome. It also emphasises that prompt surgical intervention can save the graft.

Lineage classification and antitubercular drug resistance surveillance of Mycobacterium tuberculosis by whole-genome sequencing in Southern India.

Whole-genome sequencing has created a revolution in tuberculosis management by providing a comprehensive picture of the various genetic polymorphisms with unprecedented accuracy. Studies mapping genomic heterogeneity in clinical isolates of Mycobacterium tuberculosis using a whole-genome sequencing approach from high tuberculosis burden countries are underrepresented. We report whole-genome sequencing results of 242 clinical isolates of culture-confirmed M. tuberculosis isolates from tuberculosis patients referred to a tertiary care hospital in Southern India. Phylogenetic analysis revealed that the isolates in our study belonged to five different lineages, with Indo-Oceanic (lineage 1, n = 122) and East-African Indian (lineage 3, n = 80) being the most prevalent. We report several mutations in genes conferring resistance to first and second line antitubercular drugs including the genes rpoB, katG, ahpC, inhA, fabG1, embB, pncA, rpsL, rrs, and gyrA. The majority of these mutations were identified in relatively high proportions in lineage 1. Our study highlights the utility of whole-genome sequencing as a potential supplemental tool to the existing genotypic and phenotypic methods, in providing expedited comprehensive surveillance of mutations that may be associated with antitubercular drug resistance as well as lineage characterization of M. tuberculosis isolates. Further larger-scale whole-genome datasets with linked minimum inhibition concentration testing are imperative for resolving the discrepancies between whole-genome sequencing and phenotypic drug sensitivity testing results and quantifying the level of the resistance associated with the mutations for optimization of antitubercular drug and precise dose selection in clinics. IMPORTANCE Studies mapping genetic heterogeneity of clinical isolates of M. tuberculosis for determining their strain lineage and drug resistance by whole-genome sequencing are limited in high tuberculosis burden settings. We carried out whole-genome sequencing of 242 M. tuberculosis isolates from drug-sensitive and drug-resistant tuberculosis patients, identified and collected as part of the TB Portals Program, to have a comprehensive insight into the genetic diversity of M. tuberculosis in Southern India. We report several genetic variations in M. tuberculosis that may confer resistance to antitubercular drugs. Further wide-scale efforts are required to fully characterize M. tuberculosis genetic diversity at a population level in high tuberculosis burden settings for providing precise tuberculosis treatment.