New Delhi Metallo – beta lactamase – 1 containing Enterobacteriaceae: Origin, Diagnosis, Treatment and Public health concern

One of the biggest problems associated with the antibiotic therapy is resistance. Recently published studies have revealed that enterobacteriaceae, like E. coli and Klebsiella, isolated from several Indian centers are resistant to many antibiotics including some highly potent antibiotics like carbapenems. It has been proposed that this resistance is because of a carbapenemase enzyme called NDM- 1 (New Delhi Metallo-betalactamase-1). This carbapenemase is class B carbapenemase also called metallolactamases as they require zinc at their active site. This enzyme is coded by a gene called bla - NDM -1 or gene NDM -1. NDM -1 containing enterobacteriaceae can be screened in laboratory by few techniques. Metallolactamase production can be detected by disk approximation test or Modified Hodge test and NDM -1 gene can be detected by polymerase chain reaction by the use of specific primer targeting the gene. Infections caused by such bacteria are associated with high morbidity and mortality. Two classes of antibiotics i.e., polymyxins (colistin) and glycylcyclines (tigecyclines), have shown in vitro activity against NDM -1 harboring enterobacteriaceae. The safety profile of both of these antibiotics is questionable. There is a need for active screening of microorganisms for NDM -1 and research should be directed towards the development of safe antibiotics for the treatment of these kinds of infections

Rapid review of suspected adverse drug events due to remdesivir in the WHO database; findings and implications

Objectives: Remdesivir has shown promise in the management of patients with COVID-19 although recent studies have shown concerns with its effectiveness in practice. Despite this there is a need to document potential adverse drug events (ADEs) to guide future decisions as limited ADE data available before the COVID-19 pandemic. Methods: Interrogation of WHO VigiBase® from 2015 to 2020 coupled with published studies of ADEs in COVID-19 patients. The main outcome measures are the extent of ADEs broken down by factors including age, seriousness, region and organ. Results: A total 1086 ADEs were reported from the 439 individual case reports up to July 19, 2020, in the VigiBase®, reduced to 1004 once duplicates were excluded. Almost all ADEs concerned COVID-19 patients (92.5%), with an appreciable number from the Americas (67.7%). The majority of ADEs were from males > 45 years and were serious (82.5%). An increase in hepatic enzymes (32.1%), renal injury (14.4%), rise in creatinine levels (11.2%), and respiratory failure (6.4%) were the most frequently reported ADEs. Conclusions: Deterioration of liver and kidney function are frequently observed ADEs with remdesivir; consequently, patients should be monitored for these ADEs. The findings are in line with ADEs included in regulatory authority documents

Utilisation, availability and price changes of medicines and protection equipment for COVID-19 among selected regions in India : findings and implications

Background: COVID-19 has already claimed a considerable number of lives worldwide. However, there are concerns with treatment recommendations given the extent of conflicting results with suggested treatments and misinformation, some of which has resulted in increased prices and shortages alongside increasing use and prices of personal protective equipment (PPE). This is a concern in countries such as India where there have been high patient co-payments and an appreciable number of families going into poverty when members become ill. However, balanced against pricing controls. Community pharmacists play a significant role in disease management in India, and this will remain. Consequently, there is a need to review prices and availability of pertinent medicines during the early stages of the COVID-19 pandemic in India to provide future direction. Objective: Assess current utilisation and price changes as well as shortages of pertinent medicines and equipment during the early stages of the pandemic. Our Approach: Multiple approach involving a review of treatments and ongoing activities across India to reduce the spread of the virus alongside questioning pharmacies in selected cities from early March to end May 2020. Our Activities: 111 pharmacies took part, giving a response rate of 80%. Encouragingly, no change in utilisation of antimalarial medicines in 45% of pharmacies despite endorsements and for antibiotics in 57.7% of pharmacies, helped by increasing need for a prescription for dispensing. In addition, increased purchasing of PPE (over 98%). No price increases were seen for antimalarials and antibiotics in 83.8 and 91.9% of pharmacies respectively although shortages were seen for antimalarials in 70.3% of pharmacies, lower for antibiotics (9.9% of pharmacies). However, price increases were typically seen for PPE (over 90% of stores) as well as for analgesics (over 50% of pharmacies). Shortages were also seen for PPE (88.3%). Conclusion: The pandemic has impacted on utilisation and prices of pertinent medicines and PPE in India but moderated by increased scrutiny. Key stakeholder groups can play a role with enhancing evidenced-based approaches and reducing inappropriate purchasing in the future

Rapid assessment of possible price instability and shortages of medicines and equipment during the COVID-19 pandemic across Asia and the public health implications

Background: Countries have introduced a variety of measures to prevent and treat COVID-19 with some countries adopting preventative strategies earlier than others. There has been considerable controversy surrounding some treatments especially hydroxychloroquine with the initial hype and misinformation leading to shortages, price rises, and suicides. Such activities can have catastrophic effects on patients where there are high co-payment levels and issues of affordability. Consequently, a need to investigate this further. Objective: Assess changes in utilisation, prices, and availability of relevant medicines and PPE during the pandemic among Asian countries. Method: Interviews among community pharmacists from beginning of March until end of May 2020. In addition, suggestions on ways to reduce misinformation. Results: 308 pharmacists took part from 5 Asian countries. There was an appreciable increase in the utilisation of antimicrobials in Pakistan (in over 88% of pharmacies), with lower increases or no change in Bangladesh, India, Malaysia and Vietnam. Encouragingly, increased use of Vitamins/ immune boosters and PPE across the countries and limited price rises for antimicrobials in India, Malaysia and Vietnam. Appreciable price increases seen for PPE across some countries. Conclusion: Encouraging to see increases in utilisation of vitamins/ immune boosters and PPE. However, increases in the utilisation and prices of antimicrobials is a concern that needs addressing alongside misinformation and any unintended consequences from lockdown measures. Community pharmacists can play key role in providing evidence-based advice, helping moderate price increases, reducing self-purchasing of antimicrobials, and addressing some of the unintended consequences of the pandemic

Ameliorations in dyslipidemia and atherosclerotic plaque by the inhibition of HMG-CoA reductase and antioxidant potential of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd in rabbits

The assigned work was aimed to examine the capability of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd to inhibit HMG-CoA reductase and regression of the atherosclerotic plaque. The chemical fingerprinting of the test extract was assessed by LC-MS/MS. Consequently, the analyses of in-vitro, in-vivo, and in-silico were executed by using the standard protocols. The in-vitro assessment of the test extract revealed 74.1% inhibition of HMG-CoA reductase. In-vivo assessments of the test extract indicated that treated hypercholesterolemic rabbits exhibited a significant (P≤0.001) amelioration in the biomarker indices of the dyslipidaemia i.e., atherogenic index, Castelli risk index(I&II), atherogenic coefficient along with lipid profile. Subsequently, significant reductions were observed in the atherosclerotic plaque and antioxidant levels. The in-silico study of molecular docking shown interactions capabilities of the leading phytoconstituents of the test extract i.e., eicosanoic acid, linoleic acid, and flavan-3-ol with target protein of HMG-CoA reductase. The values of RSMF and potential energy of top docked complexes were show significant interactions. Accordingly, the free energy of solvation, interaction angle, radius of gyration and SASA were shown significant stabilities of top docked complex. The cumulative data of results indicate phytoconstituents of an aqueous seed extract of Acacia senegal have capabilities to inhibit the HMG-CoA reductase and improve the levels of antioxidants

The current situation regarding long-acting insulin analogues including biosimilars among selected African, Asian, European and South American countries : findings and implications for the future

Background: Diabetes mellitus rates continue to rise, which coupled with increasing costs of associated complications has appreciably increased global expenditure in recent years. The risk of complications are enhanced by poor glycaemic control including hypoglycaemia. Long-acting insulin analogues were developed to reduce hypoglycaemia and improve adherence. Their considerably higher costs though have impacted their funding and use. Biosimilars can help reduce medicine costs. However, their introduction has been affected by a number of factors. These include the originator company dropping its price as well as promoting patented higher strength 300 IU/ml insulin glargine. There can also be concerns with different devices between the manufacturers. Objective: To assess current utilisation rates for insulins, especially long-acting insulin analogues, and the rationale for patterns seen, across multiple countries to inform strategies to enhance future utilisation of long-acting insulin analogue biosimilars to benefit all key stakeholders. Our approach: Multiple approaches including assessing the utilisation, expenditure and prices of insulins, including biosimilar insulin glargine, across multiple continents and countries. Results: There was considerable variation in the use of long-acting insulin analogues as a percentage of all insulins prescribed and dispensed across countries and continents. This ranged from limited use of long-acting insulin analogues among African countries compared to routine funding and use across Europe in view of their perceived benefits. Increasing use was also seen among Asian countries including Bangladesh and India for similar reasons. However, concerns with costs and value limited their use across Africa, Brazil and Pakistan. There was though limited use of biosimilar insulin glargine 100 IU/ml compared with other recent biosimilars especially among European countries and Korea. This was principally driven by small price differences in reality between the originator and biosimilars coupled with increasing use of the patented 300 IU/ml formulation. A number of activities were identified to enhance future biosimilar use. These included only reimbursing biosimilar long-acting insulin analogues, introducing prescribing targets and increasing competition among manufacturers including stimulating local production. Conclusions: There are concerns with the availability and use of insulin glargine biosimilars despite lower costs. This can be addressed by multiple activities

Demand of COVID-19 medicines without prescription among community pharmacies in Jodhpur, India : findings and implications

Background: COVID-19 pandemic led to increased self-medication of antimicrobials, vitamins, and immune boosters among the common people and consuming without prescription can lead to adverse consequences including antimicrobial resistance. Methods: A cross-sectional study was conducted on community pharmacies in Jodhpur, India. They were inquired regarding the prescription and increased sales (75% increase in vitamin C sales. Conclusion: There was an increase in the demand for COVID-19 medications without prescription. This study was unable to detect a significant increase in sales of antimicrobials, which is encouraging

Tocilizumab in COVID-19: a study of adverse drug events reported in the WHO database

leading to pneumonitis with a poor prognosis. Tocilizumab, a type of humanized monoclonal antibody antagonizing interleukin-6 receptors, is currently utilized to treat COVID-19. The present study reviews tocilizumab adverse drug events (ADEs) reported in the World Health Organization (WHO) pharmacovigilance database. Research design and methods: All suspected ADEs associated with tocilizumab between April to August 2020 were analyzed based on COVID-19 patients’ demographic and clinical variables, and severity of involvement of organ system. Results: A total of 1005 ADEs were reported among 513 recipients. The majority of the ADEs (46.26%) were reported from 18–64 years, were males and reported spontaneously. Around 80%, 20%, and 64% were serious, fatal, and administered intravenously, respectively. ‘Injury, Poisoning, and Procedural Complications’ remain as highest (35%) among categorized ADEs. Neutropenia, hypofibrinogenemia were common hematological ADEs. The above 64 years was found to have significantly lower odds than of below 45 years. In comparison, those in the European Region have substantially higher odds compared to the Region of Americas. Conclusion: Neutropenia, superinfections, reactivation of latent infections, hepatitis, and cardiac abnormalities were common ADEs observed that necessitate proper monitoring and reporting

Tocilizumab in COVID-19: a study of adverse drug events reported in the WHO database

leading to pneumonitis with a poor prognosis. Tocilizumab, a type of humanized monoclonal antibody antagonizing interleukin-6 receptors, is currently utilized to treat COVID-19. The present study reviews tocilizumab adverse drug events (ADEs) reported in the World Health Organization (WHO) pharmacovigilance database. Research design and methods: All suspected ADEs associated with tocilizumab between April to August 2020 were analyzed based on COVID-19 patients’ demographic and clinical variables, and severity of involvement of organ system. Results: A total of 1005 ADEs were reported among 513 recipients. The majority of the ADEs (46.26%) were reported from 18–64 years, were males and reported spontaneously. Around 80%, 20%, and 64% were serious, fatal, and administered intravenously, respectively. ‘Injury, Poisoning, and Procedural Complications’ remain as highest (35%) among categorized ADEs. Neutropenia, hypofibrinogenemia were common hematological ADEs. The above 64 years was found to have significantly lower odds than of below 45 years. In comparison, those in the European Region have substantially higher odds compared to the Region of Americas. Conclusion: Neutropenia, superinfections, reactivation of latent infections, hepatitis, and cardiac abnormalities were common ADEs observed that necessitate proper monitoring and reporting

Rapid assessment of price instability and paucity of medicines and protection for COVID-19 across Asia : findings and public health implications for the future

Background: Countries have introduced a variety of measures to prevent and treat COVID-19 with medicines and personal protective equipment (PPE), with some countries adopting preventative strategies earlier than others. However, there has been considerable controversy surrounding some treatments. This includes hydroxychloroquine where the initial hype and misinformation lead to shortages, price rises and suicides. Price rises and shortages have also been seen for PPE. Such activities can have catastrophic effects on patients where there are high co-payment levels and issues of affordability. Consequently, there is a need to investigate this further. Objective: Assess changes in the availability, utilization and prices of relevant medicines and PPE during the pandemic among a range of Asian countries. Our approach: Narrative literature review combined with interviews among community pharmacists to assess changes in consumption, prices and shortages of medicines and PPE from the beginning of March 2020 until end of May 2020. In addition, suggestions on ways to reduce misinformation. Results: 308 pharmacists took part from five Asian countries. There was an appreciable increase in the utilization of antimicrobials in Pakistan (in over 88% of pharmacies), with lower increases or no change in Bangladesh, India, Malaysia and Vietnam. Encouragingly, there was increased use of vitamins/immune boosters and PPE across the countries, as well as limited price rises for antimicrobials in India, Malaysia and Vietnam, although greater price rises seen for analgesics and vitamin C/immune boosters. Appreciable price increases were also seen for PPE across some countries. Conclusion: Encouraging to see increases in utilization of vitamins/immune boosters and PPE. However, increases in the utilization and prices of antimicrobials is a concern that needs addressing alongside misinformation and any unintended consequences from the pandemic. Community pharmacists can play a key role in providing evidence-based advice, helping to moderate prices, as well as helping address some of the unintended consequences of the pandemic