Clinical standards for the dosing and management of TB drugs.

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.

Clinical standards for drug-susceptible pulmonary TB.

BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice´ for diagnosis, treatment and management of drug-susceptible pulmonary TB (PTB).METHODS: A panel of 54 global experts in the field of TB care, public health, microbiology, and pharmacology were identified; 46 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 46 participants.RESULTS: Seven clinical standards were defined: Standard 1, all patients (adult or child) who have symptoms and signs compatible with PTB should undergo investigations to reach a diagnosis; Standard 2, adequate bacteriological tests should be conducted to exclude drug-resistant TB; Standard 3, an appropriate regimen recommended by WHO and national guidelines for the treatment of PTB should be identified; Standard 4, health education and counselling should be provided for each patient starting treatment; Standard 5, treatment monitoring should be conducted to assess adherence, follow patient progress, identify and manage adverse events, and detect development of resistance; Standard 6, a recommended series of patient examinations should be performed at the end of treatment; Standard 7, necessary public health actions should be conducted for each patient. We also identified priorities for future research into PTB.CONCLUSION: These consensus-based clinical standards will help to improve patient care by guiding clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment for PTB.

Outcome of treatment of MDR-TB or drug-resistant patients treated with bedaquiline and delamanid: Results from a large global cohort.

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.

Clinical features associated with linezolid resistance among multidrug resistant tuberculosis patients at a tertiary care hospital in Mumbai, India.

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.

From pulmonary susceptible tuberculosis to extensively drug resistant tuberculosis: An interesting case report of a young Indian girl.

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.

Mobility patterns of persons at risk for drug-resistant tuberculosis in Mumbai, India.

SETTING: Tuberculosis (TB) hospital in Mumbai, India. OBJECTIVE: To describe the mobility patterns of persons with suspected drug-resistant tuberculosis (DR-TB) and to assess whether there were significant differences in demographic or risk characteristics based on mobility. DESIGN: Observational cohort study of TB clinic patients at risk for DR-TB. RESULTS: Among 602 participants, 37% had ever moved from their place of birth; 14% were local movers (within state), and 23% were distant movers, between states or countries. Univariate multinomial logistic regression models showed that distant movers were more likely than non-movers to have lower income, less education, a greater number of previous TB episodes, and to have ever smoked. Compared to non-movers, local movers were more likely to have lower income and were more likely to have seen a doctor in the past 2 years. Clinical outcomes, including DR-TB, diabetes, and human immunodeficiency virus (HIV), did not differ between the three mobility groups. CONCLUSION: Mobility was common among patients at risk for DR-TB in Mumbai. TB programs should consider the implications of mobility on the protracted treatment for DR-TB in India.

Initial experience of bedaquiline use in a series of drug-resistant tuberculosis patients from India.

Drug-resistant tuberculosis (DR-TB) is a major problem both in India and worldwide. Newer drugs such as TMC-207 (bedaquiline) may have an important role to play in making up an effective drug regimen in such cases. There have been a few reports of bedaquiline use in a non-trial setting from Europe. Our series of five patients is the first series of DR-TB patients from India to receive bedaquiline. All five patients showed striking improvement, with microbiological conversion and an absence of notable adverse effects (e.g., prolonged QTcF), indicating the potential impact of this drug in such a population.

Thoracoscopic and endovascular management of retained haemothoarx associated with an intercostal artery pseudoaneurysm.

Intercostal artery pseudoaneurysm (IAP) is a rare entity and may complicate a percutaneous intervention through an intercostal space or follow thoracic trauma. Its rupture into the pleural space can give rise to haemothorax, which if untreated may lead to a retained haemothorax (RH). Traditionally both the IAP and the RH are managed by a thoracotomy. We report a patient who developed an IAP with haemothorax following a trauma. The diagnosis was established by computed tomography. The patient was treated by endovascular embolisation of the IAP followed by thoracoscopic decortications of the RH.

Increasing incidence of fluoroquinolone-resistant Mycobacterium tuberculosis in Mumbai, India.

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.

Cryptogenic organizing pneumonia: clinical profile in a series of 34 admitted patients in a hospital in India.

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.

Idiopathic pulmonary haemosiderosis: complete remission with steroids.

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 with isolated Loeffler's endocarditis: complete resolution with 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.

Review series: the politics of TB: the politics, economics and impact of directly observed treatment (DOT) in India.

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.

Pulmonary hyalinizing granuloma with ureteric fibrosis: A case report and review of relevant literature.

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.

Pneumocystis carinii pneumonia in HIV infected patients from Mumbai.

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.