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BACKGROUND: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on 'best practice´ for dosing and management of TB drugs. METHODS: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants. RESULTS: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified. CONCLUSION: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.

The World Health Organization (WHO) recommends countries introduce new anti-TB drugs in the treatment of multidrug-resistant tuberculosis. The aim of the study is to prospectively evaluate the effectiveness of bedaquiline (and/or delamanid)- containing regimens in a large cohort of consecutive TB patients treated globally. This observational, prospective study is based on data collected and provided by Global Tuberculosis Network (GTN) centres and analysed twice a year. All consecutive patients (including children/adolescents) treated with bedaquiline and/or delamanid were enrolled, and managed according to WHO and national guidelines. Overall, 52 centres from 29 countries/regions in all continents reported 883 patients as of January 31st 2021, 24/29 countries/regions providing data on 100% of their consecutive patients (10-80% in the remaining 5 countries). The drug-resistance pattern of the patients was severe (>30% with extensively drug-resistant -TB; median number of resistant drugs 5 (3-7) in the overall cohort and 6 (4-8) among patients with a final outcome). For the patients with a final outcome (477/883, 54.0%) the median (IQR) number of months of anti-TB treatment was 18 (13-23) (in days 553 (385-678)). The proportion of patients achieving sputum smear and culture conversion ranged from 93.4% and 92.8% respectively (whole cohort) to 89.3% and 88.8% respectively (patients with a final outcome), a median (IQR) time to sputum smear and culture conversion of 58 (30-90) days for the whole cohort and 60 (30-100) for patients with a final outcome and, respectively, of 55 (30-90) and 60 (30-90) days for culture conversion. Of 383 patients treated with bedaquiline but not delamanid, 284 (74.2%) achieved treatment success, while 25 (6.5%) died, 11 (2.9%) failed and 63 (16.5%) were lost to follow-up., (Copyright © 2021 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Multidrug-resistant tuberculosis (MDR-TB) is an increasing problem worldwide, and 24% occurs in India. Linezolid is associated with improved MDR-TB treatment outcomes but causes significant side-effects and drug susceptibility testing (DST) is rarely available. This study assessed whether clinical factors could predict linezolid resistance., Methods: An observational cohort of adults and adolescents with MDR-TB at a tertiary care hospital in Mumbai, India was analyzed for clinical, laboratory, and radiographic findings associated with linezolid resistance., Results: In total, 343 MDR-TB patients had linezolid DST performed, and 23 (6.7%) had linezolid-resistant MDR-TB. Univariable analysis associated linezolid resistance with underweight (odds ratio (OR)-1.07, 95% confidence interval (CI):1.01-1.12); number of previous providers (OR:1.03, 95% CI:1.00-1.05); previous treatment with linezolid (OR:1.12, 95% CI:1.06-1.05), bedaquiline (OR:1.55, 95% CI:1.22-1.98), or clofazimine (OR:1.08 95% CI:1.03-1.16); cavitary disease (OR:1.10, 95% CI:1.04-1.16) and percent lung involvement (OR:1.02, 95% CI:1.01-1.03) on radiograph. DST associated linezolid resistance with resistance to fluoroquinolones (OR:1.08, 95% CI:1.01-1.14), injectables (OR:1.09, 95% CI:1.03-1.15), ethionamide (OR:1.09, 95% CI:1.03-1.15), and PAS (OR:1.13, 95% CI:1.06-1.21). In multivariate analysis, only prior linezolid and percent lung involvement were associated with linezolid resistance., Conclusion: To maximize treatment benefits while minimizing toxicity, DST remains an important tool to identify linezolid resistance., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors.)

Tuberculosis is one of the top ten causes of death and the leading cause from a single infectious agent. Drug-resistant Tuberculosis continues to be a public health crisis. Urgent action is required to improve the coverage and quality of diagnosis, treatment and care for people with drug-resistant Tuberculosis. Patients with pulmonary Tuberculosis can spread the disease by coughing, sneezing, or simply talking. For that reason, it is important to diagnosis Tuberculosis in order to start treatment as soon as possible. In the present manuscript we present the case of a 25-year-old Indian HIV-negative female, no comorbidity, with a history of drug susceptible tuberculosis diagnosed in 2015 which advanced in extensively drug-resistant tuberculosis after two years of treatment. This case report highlights the risk of mismanagement of patient affected by Tuberculosis and the consequences related which could harm the patient's health., (Copyright © 2019 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Setting: Tertiary referral centre, private hospital, Mumbai, India., Objective: To analyse the incidence of fluoroquinolone (FQ) resistant Mycobacterium tuberculosis (TB) in our laboratory from 1995 to 2004., Design: Retrospective review and analysis of the drug susceptibility test records of all M. tuberculosis culture-positive samples from our Microbiology Department from 1995 to 2004., Results: FQ resistance has increased exponentially in our laboratory, from 3% in 1996 to 35% in 2004. The incidence of multidrug-resistant tuberculosis has also increased during the same period, from 33% in 1995 to 56% in 2004., Conclusion: The incidence of FQ-resistant M. tuberculosis is gradually increasing to alarming levels. This may be due to widespread use of this vital group of drugs in the treatment of community-acquired infections. We urge that these broad spectrum antibiotics be used judiciously, and ideally be reserved for treatment of resistant TB in TB-endemic areas.

A 13-year-old boy was diagnosed as a case of idiopathic pulmonary haemosiderosis on the basis of clinical presentation, radiological assessment and open lung biopsy. The patient had a complete clinical and radiological remissions with oral corticosteroids.

Hypereosinophilic syndrome (HES) is classically defined as prolonged, unexplained peripheral eosinophilia in a patient presenting with evidence of end-organ damage. The heart is involved in two forms; endomyocardial fibrosis (Davies disease) and eosinophilic endocarditis (Loffler's endocarditis). It was first reported in 1968 by Hard and Anderson. Chusid and co-workers formulated a definition with strict criteria for the diagnosis of HES as 1) peripheral blood eosinophilia more than 1500 cells/cu mm for at least six months duration 2)signs, symptoms of end-organ (heart, lungs, gastrointestinal tract, skin, bone-marrow, brain) involvement with eosinophil tissue infiltration/injury 3) exclusion of known secondary causes of eosinophilia. We report a case of hypereosinophilic syndrome with Loffler's endocarditis, in the absence of endomyocardial fibrosis. The patient presented with a eosinophilic vegetation over the posterior leaflet of the mitral valve. There was complete resolution of the vegetation after two months of corticosteroid therapy.

Objectives: Cryptogenic Organizing Pneumonia (COP) is a relatively rare disorder which is gratifying to treat due to its prompt steroid responsiveness. There have been only 2 case reports on COP from India but no large series entity reported from this country., Methods: The medical records of all patients with biopsy (histopathology) proven COP admitted in a tertiary care hospital in Mumbai (2000-2005) were retrospectively analyzed. We looked at clinical and radiographic profiles, initial diagnosis and treatment, lag period to starting definitive therapy and steroid responsiveness., Results: When compared to other series of patients with COP, our series showed several similarities and some differences. Distinctive features were the striking female preponderance and the utility of transbronchial biopsies in establishing the diagnosis. Long delays in diagnosis with patients mislabeled as tuberculosis or pneumonia, lead to delays in starting steroids resulting in 21% of our patients continuing to deteriorate., Conclusions: This comprehensive review of COP, the first of its kind from India, reveals its varied clinical and radiographic spectrum. A high index of suspicion will lead to prompt steroid therapy which will result in better patient outcome.

India harbors approximately one-third of the world's tuberculosis cases. The disease being multi-factorial; various political, social and economic factors play pivotal roles in causation and control. The country's policy-makers, via the Revised National Tuberculosis Programme (RNTCP), have embraced DOTS, i.e. Directly Observed Treatment; short course, as a means of combating the disease. Today, a decade after being launched, the DOTS programme in India is the largest in the world. The achievements of the programme have been significant in reaching out to the millions and having impressive cure rates, but the disease is far from eradicated. Social taboos, economic obstacles, and deficient infrastructure are impediments that hamper the success of the programme. With multidrug-resistant TB and HIV co-infection complicating the management of TB; the task has become more daunting. In a country as heterogeneous as India, novel holistic strategies that address individual needs will have to be developed to successfully curb the spread of the disease in the future.

A 52-year-old, asymptomatic patient presented with bilateral lung nodules on chest radiograph. She was diagnosed to have "pulmonary hyalinizing granuloma" on an open lung biopsy. We review the clinical features of this rare disease.

Objective: Pneumocystis carinii pneumonia (PCP) is believed to be rare in the developing world and no large prospective Indian series have been reported to date. The present study was conducted to study the clinical profile and outcome of PCP in patients with HIV infection., Methods: All HIV positive patients with PCP admitted over 4 years (2000-2003) to a tertiary referral centre in Mumbai were prospectively studied., Results: There were 38 patients with proven PCP from 300 HIV admissions. The patients with PCP were predominantly male (M: F = 5.4:1), with a mean age of 40.1 years. The median CD4 count of the PCP group was 96 cells/microL. Bronchoscopy was needed to make a definitive diagnosis in 17 of the 38 patients. PCP co-existed with tuberculosis in 4 of the 38 patients. The mortality of the group was high at 15.8% with all patients needing ventilatory support dying., Conclusions: PCP is not an uncommon infection in Indians with advanced HIV. Lack of recognition has probably been responsible for the absence of any large series from this country. In our series of hospitalised HIV positive patients, PCP was the second commonest pulmonary disease after tuberculosis accounting for 32% of pulmonary admissions and 13 % of all HIV positive admissions.

Aim: The aim of the study was to screen for the common deltaF508 mutation and the poly T polymorphism and to determine their frequency in the cystic fibrosis transmembrane conductance regulator (CFTR) gene among the suspected CF cases referred to our clinical care centre for sweat chloride tests., Methodology: Sweat and EDTA blood samples were obtained from 23 clinically suspected cystic fibrosis (CF) cases. Sweat was estimated by pilocarpine iontophoresis procedure. Poly T polymorphism was detected by the multiplex-PCR based on ARMSTM technique and deltaF508 mutation by PCR-mediated site-directed mutagenesis method., Results: Five cases, mainly with respiratory abnormalities and followed by steatorrhea had elevated sweat chloride levels (> 60 mmol/l), three of them, each with nutritional, respiratory and pancreatic abnormalities were borderline (40-60 mmol/l) and the remaining 15 clinically suspected CF cases had normal sweat chloride levels (< 40 mmol/l). The 9T variant was frequently observed (75%) in cases with elevated sweat chloride, including those exhibiting borderline values; with no 5T variant. The 7T was the most common variant (77%) observed in the cases with normal sweat chloride, with only one 5T variant (33%). Of the five cases with high sweat chloride, four cases were homozygous for deltaF508, whereas one was heterozygous with borderline sweat chloride, thus showing an overall frequency of 56.25% in the CF chromosome. DeltaF508 was found to be present with the 9T variant in all the instances., Conclusion: The presence of the 9T variant along with elevated sweat chloride levels can be used to predict a high risk of the individual harboring the severe deltaF508 mutation. It would be advisable to test for to the deltaF508 mutation along with the sweat chloride estimation in all the critically suspected CF cases diagnose CF with a higher degree certainty.

India has the highest number of tuberculosis cases of any country in the world, and many of these cases are MDR TB. A combination of contributing factors has led to the current public health crisis: a failing National Tuberculosis Programme, denial and lack of compliance on the part of patients, lack of regulation of doctors in private practice, governmental policy failure and corruption, social and economic problems, and a growing HIV epidemic. This situation must be combatted on several fronts, including promoting social change; increasing government funding; seeking global aid; implementing DOTS, non-DOTS, and NGO programs; integrating TB and HIV programs; funding research; enacting regulatory legislation; and establishing continuing medical education programs among private practitioners.