scholarly journals Spray-Dried Powder Formulation of Capreomycin Designed for Inhaled Tuberculosis Therapy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2044
Author(s):  
Zitong Shao ◽  
Waiting Tai ◽  
Yingshan Qiu ◽  
Rico C. H. Man ◽  
Qiuying Liao ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Public Health Problem ◽  
Inlet Temperature ◽  
Second Line ◽  
Intratracheal Administration ◽  
Powder Formulation ◽  
First Choice ◽  
Mdr Tb ◽  
Multiple Drugs ◽  
Spray Dried

Multi-drug-resistant tuberculosis (MDR-TB) is a huge public health problem. The treatment regimen of MDR-TB requires prolonged chemotherapy with multiple drugs including second-line anti-TB agents associated with severe adverse effects. Capreomycin, a polypeptide antibiotic, is the first choice of second-line anti-TB drugs in MDR-TB therapy. It requires repeated intramuscular or intravenous administration five times per week. Pulmonary drug delivery is non-invasive with the advantages of local targeting and reduced risk of systemic toxicity. In this study, inhaled dry powder formulation of capreomycin targeting the lung was developed using spray drying technique. Among the 16 formulations designed, the one containing 25% capreomycin (w/w) and spray-dried at an inlet temperature of 90 °C showed the best overall performance with the mass median aerodynamic diameter (MMAD) of 3.38 μm and a fine particle fraction (FPF) of around 65%. In the pharmacokinetic study in mice, drug concentration in the lungs was approximately 8-fold higher than the minimum inhibitory concentration (MIC) (1.25 to 2.5 µg/mL) for at least 24 h following intratracheal administration (20 mg/kg). Compared to intravenous injection, inhaled capreomycin showed significantly higher area under the curve, slower clearance and longer mean residence time in both the lungs and plasma.

scholarly journals The epidemiologic impact and cost-effectiveness of new tuberculosis vaccines on multidrug-resistant tuberculosis in India and China

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chathika K Weerasuriya ◽  
Rebecca C Harris ◽  
C Finn McQuaid ◽  
Fiammetta Bozzani ◽  
Yunzhou Ruan ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Cost Effective ◽  
Multidrug Resistant ◽  
Second Line ◽  
Second Line Therapy ◽  
China And India ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Line Therapy ◽  
Mdr Tb

Abstract Background Despite recent advances through the development pipeline, how novel tuberculosis (TB) vaccines might affect rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is unknown. We investigated the epidemiologic impact, cost-effectiveness, and budget impact of hypothetical novel prophylactic prevention of disease TB vaccines on RR/MDR-TB in China and India. Methods We constructed a deterministic, compartmental, age-, drug-resistance- and treatment history-stratified dynamic transmission model of tuberculosis. We introduced novel vaccines from 2027, with post- (PSI) or both pre- and post-infection (P&PI) efficacy, conferring 10 years of protection, with 50% efficacy. We measured vaccine cost-effectiveness over 2027–2050 as USD/DALY averted-against 1-times GDP/capita, and two healthcare opportunity cost-based (HCOC), thresholds. We carried out scenario analyses. Results By 2050, the P&PI vaccine reduced RR/MDR-TB incidence rate by 71% (UI: 69–72) and 72% (UI: 70–74), and the PSI vaccine by 31% (UI: 30–32) and 44% (UI: 42–47) in China and India, respectively. In India, we found both USD 10 P&PI and PSI vaccines cost-effective at the 1-times GDP and upper HCOC thresholds and P&PI vaccines cost-effective at the lower HCOC threshold. In China, both vaccines were cost-effective at the 1-times GDP threshold. P&PI vaccine remained cost-effective at the lower HCOC threshold with 49% probability and PSI vaccines at the upper HCOC threshold with 21% probability. The P&PI vaccine was predicted to avert 0.9 million (UI: 0.8–1.1) and 1.1 million (UI: 0.9–1.4) second-line therapy regimens in China and India between 2027 and 2050, respectively. Conclusions Novel TB vaccination is likely to substantially reduce the future burden of RR/MDR-TB, while averting the need for second-line therapy. Vaccination may be cost-effective depending on vaccine characteristics and setting.

scholarly journals Maillard reaction products formation and antioxidative power of spray dried camel milk powders increases with the inlet temperature of drying

LWT ◽  
2021 ◽  
Vol 143 ◽  
pp. 111091 ◽  
Author(s):  
Marija Perusko ◽  
Sami Ghnimi ◽  
Ana Simovic ◽  
Nikola Stevanovic ◽  
Mirjana Radomirovic ◽  
...  
Keyword(s):  
Maillard Reaction ◽  
Camel Milk ◽  
Inlet Temperature ◽  
Maillard Reaction Products ◽  
Reaction Products ◽  
Spray Dried

scholarly journals Valorization of Flaxseed Oil Cake Residual from Cold-Press Oil Production as a Material for Preparation of Spray-Dried Functional Powders for Food Applications as Emulsion Stabilizers

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 153 ◽  
Author(s):  
Emilia Drozłowska ◽  
Łukasz Łopusiewicz ◽  
Monika Mężyńska ◽  
Artur Bartkowiak
Keyword(s):  
Antioxidant Activity ◽  
Binding Capacity ◽  
Flaxseed Oil ◽  
Inlet Temperature ◽  
Emulsifying Activity ◽  
Cold Press ◽  
Food Applications ◽  
Water Holding ◽  
Spray Dried ◽  
Oil Binding

Flaxseed oil cake extract (residual from cold-press oil production and rich in proteins and polysaccharides) was evaluated as a potential substrate for the preparation of spray-dried powders with emulsifying activity. Three variants of powders were obtained using different spray-drying process inlet temperatures: 160 °C, 180 °C, and 200 °C. The influence of temperature on physicochemical features (water holding capacity, oil binding capacity, water activity, solubility, color, chemical composition, antioxidant activity, and surface morphology) of the powders was estimated. Additionally, the emulsifying activity of the powders and the stability of oil-in-water emulsions prepared with their various content (0.5%, 1%, and 3%) were determined. Results showed that inlet temperature had significant influence on all physicochemical and functional properties of the powders. Increased inlet temperature decreased solubility and antioxidant activity but increased water-holding capacity, oil-binding capacity, and emulsifying activity. The emulsions prepared with the powder obtained at 200 °C showed the highest stability. SEM images showed the production of relatively spherical particles which were folded or wrinkled with a lot of dentures. This study could open a promising pathway for producing natural and plant-based spray-dried powders for food applications as emulsion stabilizers.

scholarly journals Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral and Second Line Anti-TB Treatment in Mumbai, India

PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e40781 ◽  
Author(s):  
Petros Isaakidis ◽  
Bhanumati Varghese ◽  
Homa Mansoor ◽  
Helen S. Cox ◽  
Joanna Ladomirska ◽  
...  
Keyword(s):  
Adverse Events ◽  
Second Line ◽  
Tb Treatment ◽  
Mdr Tb

scholarly journals Increasing prevalence of resistance to second-line drugs among multidrug-resistant Mycobacterium tuberculosis isolates in Kuwait

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Noura M. Al-Mutairi ◽  
Suhail Ahmad ◽  
Eiman Mokaddas
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Mutation Detection ◽  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Genetic Mutations ◽  
Second Line ◽  
Injectable Drugs ◽  
Mdr Tb ◽  
Phenotypic Susceptibility

AbstractMolecular methods detect genetic mutations associated with drug resistance. This study detected resistance-conferring mutations in gyrA/gyrB for fluoroquinolones and rrs/eis genes for second-line injectable drugs (SLIDs) among multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates in Kuwait. Fifty pansusceptible M. tuberculosis and 102 MDR-TB strains were tested. Phenotypic susceptibility testing was performed by MGIT 960 system using SIRE drug kit. GenoType MTBDRsl version 1 (gMTBDRslv1) and GenoType MTBDRsl version 2 (gMTBDRslv2) tests were used for mutation detection. Results were validated by PCR-sequencing of respective genes. Fingerprinting was performed by spoligotyping. No mutations were detected in pansusceptible isolates. gMTBDRslv1 detected gyrA mutations in 12 and rrs mutations in 8 MDR-TB isolates. gMTBDRsl2 additionally detected gyrB mutations in 2 and eis mutation in 1 isolate. Mutations in both gyrA/gyrB and rrs/eis were not detected. gMTBDRslv1 also detected ethambutol resistance-conferring embB mutations in 59 isolates. Although XDR-TB was not detected, frequency of resistance-conferring mutations for fluoroquinolones or SLIDs was significantly higher among isolates collected during 2013–2019 versus 2006–2012. Application of both tests is warranted for proper management of MDR-TB patients in Kuwait as gMTBDRslv2 detected resistance to fluoroquinolones and/or SLIDs in 3 additional isolates while gMTBDRslv1 additionally detected resistance to ethambutol in 58% of MDR-TB isolates.

scholarly journals Understanding the social determinants of TB and HIV in South Asia

2014 ◽  
Author(s):  
Bishwajit Ghose ◽  
Cheng Zhaohui ◽  
He Zhifei
Keyword(s):  
South Asia ◽  
Healthcare System ◽  
Social Determinants ◽  
Social Life ◽  
Public Health Problem ◽  
Asian Population ◽  
Major Public Health Problem ◽  
South Asian Population ◽  
Wide Range ◽  
Mdr Tb

South Asian population suffer a particularly wide range of infectious diseases among which TB and HIV appear to produce most profound influence across various dimensions of social life, healthcare and the economy. Although the countries in this region have a relatively lower prevalence of HIV/AIDS compared to other developing regions until now, the future looks rather bleak in terms of preparedness for emerging healthcare realities. Tuberculosis on the other hand, has always been a major public health problem plaguing the healthcare system and the economy for decades. Moreover, the emergence of the drug resistant (MDR-TB & XDR-TB) strains are making the existing intervention and prevention strategies less effective and posing ever-growing threats to the underdeveloped healthcare infrastructure. Understanding the underlying social-determinants of these diseases can prove crucial to design more comprehensive intervention approaches. This article aims to clarify why the healthcare system in South Asia needs to adopt a social-determinants-of-health (SDOH) approach as a long-term strategy for more efficient prevention and control of TB and HIV infection.

scholarly journals Second line therapy in type 2 diabetes: legacy effect activation

2017 ◽  
Vol 20 (5) ◽  
pp. 356-362
Author(s):  
Ekaterina A. Shestakova
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Patients ◽  
Second Line ◽  
Type 2 Diabetic Patients ◽  
Antidiabetic Therapy ◽  
First Line Therapy ◽  
Legacy Effect ◽  
Line Therapy ◽  
Multiple Drugs

Type 2 diabetes causes hundred thousand deaths worldwide every year. Though new antidiabetic drugs appear annually and new classes of drugs are invented approximately every ten years still a lot of type 2 diabetic patients remain to be out of the target glycemic levels. According to most of the guidelines for type 2 diabetes,treatment metformin is the first line therapy for this disease. The choice of second-line antidiabetic drug usually depends on doctors preference. That is why defining the correct drug for exact patient is still an urgent question. This review provides data on antidiabetic drugspotential for preventing the progression of micro- and macrovascular complications.The question of the potential of early antidiabetic therapy intensification to activate legacy effect is debated. Early and lasting compensation of diabetes with the use of multiple drugs can become a basis for primary prevention of cardiovascular disease in such patients.

scholarly journals A prospective observational pharmacovigilance study of adverse drug reaction monitoring in patients of MDR-TB at tertiary care hospital

2018 ◽  
Vol 7 (7) ◽  
pp. 1291
Author(s):  
Mirza Shiraz Baig ◽  
Monali Raghunath Kale ◽  
Avinash Lamb
Keyword(s):  
Adverse Drug Reactions ◽  
Health Care Professionals ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Public Health Problem ◽  
Treatment Withdrawal ◽  
Care Hospital ◽  
Drug Reactions ◽  
Medical College ◽  
Mdr Tb

Background: The emergence of drug resistant mycobacteria has become a significant public health problem world over creating an obstacle to effective TB control. ADRs are common in patients of MDR-TB on DOTs-Plus drug regimen. Present study was carried out in tertiary care hospital. Identification of types and frequency of adverse drug reactions in Intensive and continuation phase of MDR-TB Patients.Methods: It was a prospective observational study conducted in Department of TB- Chest and Medicine, Govt. Medical College, Aurangabad, Maharashtra, India. All the MDR-TB patients admitted at the directly observed treatment, short course plus (DOTS plus) Center at Medical College Hospital were enrolled and were monitored for ADRs. The causality and severity of the reactions were determined using Naranjo algorithm and Hartwig questionnaire, respectively.Results: A total of 121 tuberculosis patients of MDR-TB on DOTS therapy were enrolled for the study. Out of 121 patients, 13 were dropouts, 6 died, 7 defaulted so 108 patients assessed for ADRs, 48 patients developed 61 (56.48%) adverse drug reactions. The higher numbers of ADRs were observed in age group 31-40yrs followed by 21-30yrs which were more common in men. Majority of adverse drug reactions were Gastrointestinal (GI) problems 32 (52.45%), followed by Ototoxicity 7 (11.48%) and Psychiatric Manifestations 6 (9.84%) and skin problems 3 (4.92%). On evaluation of the causality of ADRs, majority were found to be Possible (59.02%). The severity assessment showed that most of the patients ADRs were of moderate level (50.82%).Some patients required treatment withdrawal and replacement with other drug and most of the patients were managed with supportive medication without removing anti-tubercular drug from their treatment regimen.Conclusions: ADRs are major factor limiting completion of drug therapy under RNTCP and occurrence of drug resistance which requires attention of all health care professionals.

scholarly journals Prevalence and Molecular Characterization of Second-Line Drugs Resistance among Multidrug-ResistantMycobacterium tuberculosisIsolates in Southwest of China

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Y. Hu ◽  
L. Xu ◽  
Y. L. He ◽  
Y. Pang ◽  
N. Lu ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Multidrug Resistant ◽  
Rapid Screening ◽  
Second Line ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Improper Use ◽  
Mdr Tb

This study aimed to investigate the prevalence of multidrug-resistant tuberculosis (MDR-TB) isolates resistant to the second-line antituberculosis drugs (SLDs) and its association with resistant-related gene mutations inMycobacterium tuberculosis(M.tb) isolates from Southwest of China. There were 81 isolates resistant to at least one of the SLDs among 156 MDR-TB isolates (81/156, 51.9%). The rates of general resistance to each of the drugs were as follows: OFX (66/156, 42.3%), KAN (26/156, 16.7%), CAP (13/156, 8.3%), PTO (11/156, 7.1%), PAS (22/156, 14.1%), and AMK (20/156, 12.8%). Therefore, the most predominant pattern was resistant to OFX compared with other SLDs (P<0.001). The results of sequencing showed that 80.2% OFX-resistant MDR-TB isolates containedgyrAmutation and 88.5% KAN-resistant isolates hadrrsmutations with the most frequent mutation being A1401G. These results suggest that improper use of SLDs especially OFX is a real threat to effective MDR-TB treatment not only in China but also in the whole world. Furthermore the tuberculosis control agencies should carry out SLDs susceptibility testing and rapid screening in a broader population of TB patients immediately and the SLDs should be strictly regulated by the administration in order to maintain their efficacy to treat MDR-TB.

scholarly journals Pharmacokinetics of Second-Line Antituberculosis Drugs in Children with Multidrug-Resistant Tuberculosis in India

2018 ◽  
Vol 62 (5) ◽  
Author(s):  
Agibothu Kupparam Hemanth Kumar ◽  
Alok Kumar ◽  
Thiruvengadam Kannan ◽  
Rakesh Bhatia ◽  
Dipti Agarwal ◽  
...  
Keyword(s):  
High Performance ◽  
Linear Regression Analysis ◽  
Multidrug Resistant ◽  
Control Programme ◽  
Second Line ◽  
Time Curve ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
The Government

ABSTRACTWe studied the pharmacokinetics of levofloxacin (LFX), pyrazinamide (PZA), ethionamide (ETH), and cycloserine (CS) in children with multidrug-resistant tuberculosis (MDR-TB) who were being treated according to the Revised National TB Control Programme (RNTCP) guidelines in India. This observational, pharmacokinetic study was conducted in 25 children with MDR-TB at the Sarojini Naidu Medical College, Agra, India, who were being treated with a 24-month daily regimen. Serial blood samples were collected after directly observed administration of drugs. Estimations of plasma LFX, PZA, ETH, and CS were undertaken according to validated methods by high-performance liquid chromatography. Adverse events were noted at 6 months of treatment. The peak concentration (Cmax) of LFX was significantly higher in female than male children (11.5 μg/ml versus 7.3 μg/ml;P= 0.017). Children below 12 years of age had significantly higher ETH exposure (area under the concentration-time curve from 0 to 8 h [AUC0–8]) than those above 12 years of age (17.5 μg/ml · h versus 9.4 μg/ml;P= 0.030). Multiple linear regression analysis showed significant influence of gender onCmaxof ETH and age onCmaxand AUC0–8of CS. This is the first and only study from India reporting on the pharmacokinetics of LFX, ETH, PZA, and CS in children with MDR-TB treated in the Government of India program. More studies on the safety and pharmacokinetics of second-line anti-TB drugs in children with MDR-TB from different settings are required.

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