Bedaquiline, a mycobacterial ATP synthase inhibitor 1, is the first new tuberculosis (TB) drug in almost 50 years. So far, over 800 patients have received the drug globally through compassionate use ...(CU) programmes. Drug-resistant TB has emerged as global public health priority 2 and TB strains are being reported with increasing levels of resistance, such as those that are multidrug resistant (MDR), extensively drug resistant (XDR) and beyond 2–4. India bears the burden of the largest number of MDR cases in the world 2 and alarming patterns of resistance are frequently encountered in urban hot-spots like Mumbai, including the first Indian cases resistant to all first-line drugs and second-line drugs (SLDs) 5. Several studies around the world have shown increased treatment efficacy after addition of bedaquiline to optimised background regimens (OBRs) 6–8. In such settings, newer drugs like bedaquiline are urgently needed; however, accessing them has proven to be challenging in India. Of the 76 applications received from India, no more than 52 Indian patients throughout the country have received bedaquiline under the CU programme (personal communication: Janssen Pharmaceuticals, India, August 2, 2016). At the P.D. Hinduja hospital, a large private hospital in Mumbai, we have been treating patients with MDR-TB for the last two decades 9. Between January 2013 and September 2015, 27 patients with drug-resistant TB strains were considered for bedaquiline. Applications for all 27 patients were made to the Janssen pharmaceuticals CU programme and, of these, 20 were approved and bedaquiline was administered. The resulting cohort is the largest in India to have received bedaquiline (20 patients from a countrywide total of 52). Bedaquiline was considered for patients based on the clinical judgement of the treating physician and there was no consultation with any panel of experts or TB consilium at this stage.
In 2018 cycloserine was elevated to World Health Organization (WHO) group B status for multidrug-resistant tuberculosis (MDR-TB), and is recommended in longer MDR-TB treatment regimens 1. Inclusion ...of cycloserine is associated with improved MDR-TB treatment success and reduced mortality, but is limited by treatment-associated depression, psychosis and neuropathy, forcing 9% of patients to stop therapy 1–3. Cycloserine also demonstrates wide interindividual pharmacokinetic variation, with significant food and drug interactions, leaving nearly half of patients with inappropriate drug levels 4, 5. Optimal dosing is unknown 6, but modelling studies suggest doses from 250 mg to 750 mg twice daily, with 500 mg twice daily for paucibacillary disease and 750 mg twice daily for cavitary pulmonary disease 7. Therefore, clinicians must balance the known benefits of cycloserine with the dearth of susceptibility- and drug-monitoring capacity and the spectre of treatment-limiting side-effects. To evaluate the impact of cycloserine prescription and dose on incident depression during MDR-TB treatment, we analysed longitudinal cohort data from India.
In a longitudinal cohort of MDR-TB patients receiving individualised, DST-based treatment, neither the inclusion of cycloserine in a multidrug regimen nor the dose used (up to 750 mg daily) significantly increased incidence of depression during treatment
https://bit.ly/3GtQmOH
Denying access to bedaqualine in India costs lives Udwadia, Zarir F; Ganatra, Shashank Rajen; Mullerpattan, Jai B
Lancet. Infectious diseases/The Lancet. Infectious diseases,
August 2017, 2017-08-00, 20170801, Letnik:
17, Številka:
8
Journal Article
Recenzirano
Odprti dostop
India's National Tuberculosis Program's (RNTCP) insistence on reserving bedaqualine for patients who have at least three susceptible drugs in the background regimen,2 denies this drug to the very ...patients who would most benefit from it, especially since it doubles the chance of a cure.3 It worries us that such patients,...
Nintedanib is a tyrosine kinase inhibitor which has shown to reduce the progression of idiopathic pulmonary fibrosis (IPF). ...a follow-up PFT was available in only 12/20 patients. ...significant ...numbers (6/25) of patients prescribed nintedanib could not commence or continue it due to high costs.
Pirfenidone is an anti-fibrotic drug which has been approved for the management of patients with Idiopathic Pulmonary Fibrosis (IPF). However, its role in interstitial lung disease (ILD) due to other ...causes such as systemic sclerosis (SSc) is not clear. We present a case of a patient with SSc associated ILD who showed a subjective as well as objective improvement in lung function with pirfenidone.
Healthcare workers (HCWs) are at high risk of Mycobacterium tuberculosis (Mtb) infection and tuberculosis disease, but also play a crucial role in implementing healthcare. Preexposure tuberculosis ...vaccination, including revaccination with BCG, might benefit Mtb-uninfected HCWs, but most HCWs in tuberculosis-endemic countries are already sensitized to mycobacteria. A new postexposure tuberculosis vaccine offers greatest potential for protection, in the setting of repeated occupational Mtb exposure. Novel strategies for induction of mycobacteria-specific resident memory T cells in the lung by aerosol administration, or induction of T cells with inherent propensity for residing in mucosal sites, such as CD1-restricted T cells and mucosa-associated innate T cells, should be explored. The need for improved protection of HCWs against tuberculosis disease is clear. However, health systems in tuberculosisendemic countries would need significantly improved occupational health structures to implement a screening and vaccination strategy for HCWs.
Tropical pulmonary eosinophilia--a review Mullerpattan, Jai B; Udwadia, Zarir F; Udwadia, Farokh E
Indian journal of medical research (New Delhi, India : 1994),
09/2013, Letnik:
138, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Tropical pulmonary eosinophilia (TPE) is a syndrome of wheezing, fever and eosiniphilia seen predominantly in the Indian subcontinent and other tropical areas. Its etiological link with Wuchereria ...bancrofti and Brugia malayi has been well established. The pathogenesis is due to an exaggerated immune response to the filarial antigens which includes type I, type III and type IV reactions with eosinophils playing a pivotal role. Peripheral blood eosinophilia is usually striking with levels over 3000/μl being common. High serum levels of IgE and filarial-specific IgE and IgG are also found. The pathology may vary from an acute eosinophilic alveolitis to histiocytic infiltration depending on the stage of the disease. While earlier studies had suggested that the disease runs a benign course, more recent work has shown that untreated TPE could result in a fair degree of respiratory morbidity. Pulmonary function tests may show a mixed restrictive and obstructive abnormality with a reduction in diffusion capacity. The bronchoalveolar lavage (BAL) eosinophil count has a negative correlation with the diffusion capacity. Treatment consists of diethylcarbamazine (DEC) for at least three weeks. Despite treatment with DEC, about 20 per cent of patients may relapse. Steroids have shown to have a beneficial effect but the exact dose and duration is yet to be confirmed by randomized controlled trials. A specific and easily available marker is required for TPE in order to distinguish it from other parasitic and non-parasitic causes of pulmonary eosinophilia.
Abstract
Background
Mycobacterium tuberculosis (Mtb) strains resistant to isoniazid and rifampin (multidrug-resistant tuberculosis MDR-TB) are increasingly reported worldwide, requiring renewed focus ...on the nuances of drug resistance. Patients with low-level moxifloxacin resistance may benefit from higher doses, but limited clinical data on this strategy are available.
Methods
We conducted a 5-year observational cohort study of MDR-TB patients at a tertiary care center in India. Participants with Mtb isolates resistant to isoniazid, rifampin, and moxifloxacin (at the 0.5 µg/mL threshold) were analyzed according to receipt of high-dose moxifloxacin (600 mg daily) as part of a susceptibility-guided treatment regimen. Univariable and multivariable Cox proportional hazard models assessed the relationship between high-dose moxifloxacin and unfavorable treatment outcomes.
Results
Of 354 participants with MDR-TB resistant to moxifloxacin, 291 (82.2%) received high-dose moxifloxacin. The majority experienced good treatment outcomes (200 56.5%), which was similar between groups (56.7% vs 54.0%, P = .74). Unfavorable outcomes were associated with greater extent of radiographic disease, lower initial body mass index, and concurrent treatment with fewer drugs with confirmed phenotypic susceptibility. Treatment with high-dose moxifloxacin was not associated with improved outcomes in either unadjusted (hazard ratio HR, 1.2 95% confidence interval {CI}, .6–2.4) or adjusted (HR, 0.8 95% CI, .5–1.4) models but was associated with joint pain (HR, 3.2 95% CI, 1.2–8.8).
Conclusions
In a large observational cohort, adding high-dose (600 mg) moxifloxacin to a drug susceptibility test–based treatment regimen for MDR-TB was associated with increased treatment-associated side effects without improving overall outcomes and should be avoided for empiric treatment of moxifloxacin-resistant MDR-TB.
In a large observational cohort, adding high-dose moxifloxacin at 600 mg daily to a susceptibility testing–based regimen for multidrug-resistant tuberculosis (MDR-TB) with low-level moxifloxacin resistance did not improve overall outcomes and should be avoided for treatment of moxifloxacin-resistant MDR-TB.
Private healthcare is choice of point of care for 70% of Indians. Multidrug resistant tuberculosis (MDR-TB) treatment is costly and involves duration as long as 2 years.
To estimate costs to patients ...undergoing treatment for MDR-TB.
A health-economics questionnaire was administered to 50 consecutive patients who successfully completed ambulatory private treatment for MDR-TB. Direct costs included drug costs, investigations, consultation fees, travel costs, hospitalisation and invasive procedures and cost prior to presentation to us. Indirect costs included loss of income.
Of our cohort of 50 patients, 36 had pulmonary TB while 14 had extra-pulmonary TB (EPTB). 40 had MDR-TB and 10 had XDR-TB. There were 15 males and 35 females. Mean age was 30 years (range 16-61 years). Treatment cost for pulmonary MDR-TB averaged $5723 while it averaged $8401 for pulmonary XDR-TB and $5609 for EPTB. The major expense was due to drug costs (37%) while consultation fees were only 5%. Annual individual income for the cohort ranged from $0 to $63,000 (mean $11,430). On average, the cost of treatment ranged from 2.56% to 180.34% of the annual family income. 34/50 (68%) had total costs greater than 20% of annual family income and 39/50 (78%) had total costs greater than 10% of annual family income. The number of patients with total costs >40% of total family income was 22.
MDR-TB in the private sector results in "catastrophic health costs". Financial and social support is essential for patients undergoing treatment for MDR-TB.
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