Global Research And Development Priority Setting For Amr
In 2017, to guide research and development into new antimicrobials, diagnostics and vaccines, WHO developed the WHO priority pathogens list. It will be updated in 2022. On an annual basis, WHO reviews the pre-clinical and clinical antibacterial pipelines to see how the pipeline is progressing with respect to the WHO priority pathogens list. A critical gap remains in research and development, in particular for antibacterial targeting of the gram-negative carbapenem resistant bacteria.
Antibiotic Resistance And Virulence
Bacteria reside on human skin, mucous membrane, and inside the human body as well. Among these, bacteria include harmless organisms, many of them are useful commensals, and few are even essential. However, some are known pathogens which cause infection these are competent enough to colonize, invade, and harm the host tissue.50 Pathogenicity is the ability of a bacterium to cause disease, and a pathogen carries a number of factors that facilitate the bacterium to increase their degree of pathogenicity known as virulence. The most important properties which help a pathogen to cause a disease include toxicity and invasiveness. The ultimate sense of balance of a bacterial disease course may be influenced by virulence and the host immune status. Both host and bacteria have coevolved with time, which may be as long as millions of years. Pathogens have amended virulence to get used to the immune system of the host during this time period.51 This is contrary to the evolution of antibiotic resistance which is a relatively recent occurrence mostly in the past five decades after the discovery of antibiotics. It is therefore believed that resistance and virulence have evolved during different eras.52
Various mechanisms of antibiotic resistance, including drug efflux with the help of efflux pump, enzymatic modifications of the antibiotic, enzymatic breakdown of the antibiotics, and modification in the target sites.
The Global Antimicrobial Resistance And Use Surveillance System
WHO launched the Global Antimicrobial Resistance and Use Surveillance System in 2015 to continue filling knowledge gaps and to inform strategies at all levels. GLASS has been conceived to progressively incorporate data from surveillance of AMR in humans, surveillance of the use of antimicrobial medicines, AMR in the food chain and in the environment. GLASS provides a standardized approach to the collection, analysis, interpretation and sharing of data by countries, territories and areas, and monitors the status of existing and new national surveillance systems, with emphasis on representativeness and quality of data collection. Some WHO regions have established surveillance networks that provide technical support to countries and facilitate enrollment into GLASS.
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The Global Threat Of Antimicrobial Resistance
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Nearly 90 years ago, the antibiotics era began when a chance discovery by Alexander Fleming, a professor of bacteriology at St. Marys Hospital in London, spawned a series of laboratory experiments that culminated in the isolation of penicillin from mold juice. So began a nearly 20-year global effort to manufacture pure penicillin on a commercial level, culminating in this lifesaving wonder drugs first wide use by Allied forces during the final year of World War II.
In the years after the war, the challenge was how to increase supply and how to manufacture the medicine on a large scale while initiating demand: helping the drug enter routine use in hospitals around the world so that its remarkable benefits could be realized by all.
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Drug Resistance In Malaria Parasites
The emergence of drug-resistant parasites poses one of the greatest threats to malaria control and results in increased malaria morbidity and mortality. Artemisinin-based combination therapies are the recommended first-line treatment for uncomplicated P. falciparum malaria and are used by most malaria endemic countries. ACTs are a combination of an artemisinin component and a partner drug. In the WHO Western Pacific Region and in the WHO South-East Asia Region, partial resistance to artemisinin and resistance to a number of the ACT partner drugs has been confirmed in Cambodia, Lao Peoples Democratic Republic, Myanmar, Thailand, and Viet Nam through studies conducted between 2001 and 2019. This makes selecting the right treatment more challenging and requires close monitoring.
In the WHO Eastern Mediterranean Region, P. falciparum resistance to sulfadoxine-pyrimethamine led to artesunate-sulfadoxine-pyrimethamine failures in some countries, necessitating a change to another ACT.
In Africa, evidence has recently been published showing emergence of mutations linked to partial artemisinin resistance in Rwanda. So far, ACTs that have been tested remain highly efficacious. However, further spread of resistance to artemisinin and ACT partner drugs could pose a major public health challenge and jeopardize important gains in malaria control.
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Naturezas Patented Formulations Introduce A Transformative New Class Of Antibiotic Agents That Overcome Bacterial Resistance And Removes The Time Barrier Of Investment Return
Naturezas research offers a true paradigm shift, one that would remove the imbalance in development cost by eliminating the ability of bacteria to become resistant. With the promise of new drugs being able to be marketed for years providing not only the time to recover investment, but a profit as well, a new investment environment would emerge that would encourage the development of new, much needed antibiotics.
This work is protected by several US and foreign patents and patent applications.
Drug Resistance In Mycobacterium Tuberculosis
Antibiotic resistant Mycobacterium tuberculosis strains are threatening progress in containing the global tuberculosis epidemic. WHO estimates that, in 2018, there were about half a million new cases of rifampicin-resistant TB identified globally, of which the vast majority have multi-drug resistant TB , a form of tuberculosis that is resistant to the two most powerful anti-TB drugs. Only one-third of the approximately half a million people who developed MDR/RR-TB in 2018 were detected and reported. MDR-TB requires treatment courses that are longer, less effective and far more expensive than those for non-resistant TB. Less than 60% of those treated for MDR/RR-TB are successfully cured.
In 2018, an estimated 3.4% of new TB cases and 18% of previously treated cases had MDR-TB/ RR-TB and the emergence of resistance to new last resort TB drugs to treat drug resistant TB poses a major threat.
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World Antimicrobial Awareness Week
Held annually since 2015, WAAW is a global campaign that aims to increase awareness of antimicrobial resistance worldwide and to encourage best practices among the general public, health workers and policy makers to avoid the further emergence and spread of drug-resistant infections. Antimicrobials are critical tools in helping to fight diseases in humans, animals and plants. They include antibiotics, antivirals, antifungals and antiprotozoa. WAAW takes place every year from 18 to 24 November. The slogan has previously been, Antibiotics: Handle with Care but changed to Antimicrobials: Handle with Care in 2020 to reflect the broadening scope of drug resistant infections.
Why Is Antimicrobial Resistance A Global Concern
The emergence and spread of drug-resistant pathogens that have acquired new resistance mechanisms, leading to antimicrobial resistance, continues to threaten our ability to treat common infections. Especially alarming is the rapid global spread of multi- and pan-resistant bacteria that cause infections that are not treatable with existing antimicrobial medicines such as antibiotics.
The clinical pipeline of new antimicrobials is dry. In 2019 WHO identified 32 antibiotics in clinical development that address the WHO list of priority pathogens, of which only six were classified as innovative. Furthermore, a lack of access to quality antimicrobials remains a major issue. Antibiotic shortages are affecting countries of all levels of development and especially in health- care systems.
Antibiotics are becoming increasingly ineffective as drug-resistance spreads globally leading to more difficult to treat infections and death. New antibacterials are urgently needed for example, to treat carbapenem-resistant gram-negative bacterial infections as identified in the WHO priority pathogen list. However, if people do not change the way antibiotics are used now, these new antibiotics will suffer the same fate as the current ones and become ineffective.
The cost of AMR to national economies and their health systems is significant as it affects productivity of patients or their caretakers through prolonged hospital stays and the need for more expensive and intensive care.
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Global Action Plan To Control The Menace Of Antibiotic Resistance
The global burden of AMR has no signs of receding, rather it piles up the pressure on human and veterinary medicine. Akin to global warming, AMR is an ecological calamity of indefinite magnitude and has no apparent way out. Until the first decade of the current century, scientists and clinicians were not up-to-the-minute about AMR, whereas resistant bacteria had been identified before the discovery of penicillin.98 Consequently, WHO made a landmark by declaring and promoting AMR as a global health concern. The agenda for such global health concerns is at the developmental stages for example, a book named The evolving threat of antimicrobial resistance options for action is a valuable addition to the archive.99
Use of alternative therapies for the treatment and control of infectious diseases could also be a different and a prolific option to fend off AMR. These therapies include anti-virulence strategies , biological therapies , and vaccines .111,112 Moreover, herbal medicines have elusive properties there is a strong viewpoint that it could be a practicable alternate option.
Need For Coordinated Action
AMR is a complex problem that requires a united multisectoral approach. The One Health approach brings together multiple sectors and stakeholders engaged in human, terrestrial and aquatic animal and plant health, food and feed production and the environment to communicate and work together in the design and implementation of programmes, policies, legislation and research to attain better public health outcomes.
Greater innovation and investment is required in operational research, and in research and development of new antimicrobial medicines, vaccines, and diagnostic tools especially those targeting the critical gram-negative bacteria such as carbapenem-resistant Enterobacteriaceae and Acinetobacter baumannii. The launch of the Antimicrobial Resistance Multi Partner Trust Fund , the Global Antibiotic Research & Development Partnership , AMR Action Fund and other funds and initiatives could fill a major funding gap. Various governments are piloting reimbursement models including Sweden, Germany, the USA and the United Kingdom. More initiatives are needed to find lasting solutions.
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Opinion: We Need More Than New Antibiotics To Fight Resistance
Metabolic disrupters, phages, and other approaches are going to be needed to treat the broadest possible range of patients infected by bacterial pathogens resistant to multiple drugs. In 1924 President Coolidge’s youngest son developed a blister on a toe playing tennis. The blister became infected with staph, and he died a week later at just 16 years old. Two decades later, penicillin could have saved him, but this drug is now useless against staph because of drug resistance, which has now become a broader crisis in medicine.
Preventing And Managing Antimicrobial Resistance In The African Region: A Scoping Review Protocol
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* E-mail:
Affiliation Faculty of Medicine and Health Sciences, Department of Nursing and Midwifery, Stellenbosch University, Cape Town, South Africa
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Affiliation Cochrane South Africa, South African Medical Research Council, Cape Town, South Africa
- Ishmael Festus Jaja,
Roles Writing review & editing
Affiliations Faculty of Science and Agriculture, Department of Livestock and Pasture Sciences, University of Fort Hare, Alice, South Africa, Department of Agriculture and Animal Health, University of South Africa, Roodepoort Johannesburg, South Africa
- Portia Jordan,
Roles Supervision, Writing review & editing
Affiliation Faculty of Medicine and Health Sciences, Department of Nursing and Midwifery, Stellenbosch University, Cape Town, South Africa
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Affiliation Cochrane South Africa, South African Medical Research Council, Cape Town, South Africa
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The Truly Staggering Cost Of Inventing New Drugs
During the Super Bowl, a representative of the pharmaceutical company Eli Lilly posted the on the companys corporate blog that the average cost of bringing a new drug to market is $1.3 billion, a price that would buy 371 Super Bowl ads, 16 million official NFL footballs, two pro football stadiums, pay of almost all NFL football players, and every seat in every NFL stadium for six weeks in a row. This is, of course, ludicrous. The average drug developed by a major pharmaceutical company costs between $4-$11 billion.
Drug Resistance In Viruses
Antiviral drug resistance is an increasing concern in immunocompromised patient populations, where ongoing viral replication and prolonged drug exposure lead to the selection of resistant strains. Resistance has developed to most antivirals including antiretroviral drugs.
All antiretroviral drugs, including newer classes, are at risk of becoming partly or fully inactive because of the emergence of drug-resistant HIV . People receiving antiretroviral therapy can acquire HIVDR, and people can also be infected with HIV that is already drug resistant. Levels of pretreatment HIVDR to non-nucleoside reverse-transcriptase inhibitors among adults initiating first-line therapy exceeded 10% in the majority of the monitored countries in Africa, Asia and Latin America. The prevalence of PDR among infants is alarmingly high. In sub-Saharan Africa, over 50% of the infants newly diagnosed with HIV carry a virus that is resistant to NNRTI. Informed by these findings, latest WHO ARV guidelines now recommend the adoption of a new drug, dolutegravir, as the preferred first-line treatment for adults and children. The use of this drug is particularly urgent in averting the negative effects of resistance to NNRTIs.
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Lack Of Availability Of Diagnostic Tests
At a general level, the health system is lacking in identifying pathogens . Antibiotics are often prescribed in medical care centers without a positive result of bacterial infection, contributing to the indiscriminate use of antibiotics and, therefore, the appearance of multidrug-resistant bacteria . Antibiotics are also prescribed without knowing the pathogen causing the infection and the resistance profile, leading to the administration of ineffective treatments. Requesting diagnostic tests could resolve these issues. However, the most accepted diagnostic tests for microorganisms are based on microscopy, culture, and sensitivity. They need 2448 h to show the result, which can discourage healthcare professionals from ordering laboratory tests . Therefore, doctors often do not order antimicrobial tests before prescribing antibiotics, contributing to the indiscriminate use of antibiotics.
In this context, the implementation of molecular biological-based tests for the detection of bacteria during the COVID-19 pandemic could considerably help the easy and rapid identification of co-infections or secondary infections, leading to the administration of antibiotics only when necessary. The primary test for the diagnosis of COVID-19 is PCR . PCR is a susceptible and efficient molecular biology-based test that detects SARS-CoV-2 or even Nanopore sequencing .
Antibiotic Resistance: A Global Threat
Originally Posted as a CDC Feature on: September 2018
Antibiotic resistance requires a collaborative approach across countries to detect, prevent, and respond to these threats. Global leaders are joining CDCs AMR Challenge
Antibiotic resistance, when germs develop the ability to defeat the drugs designed to kill them, is a top threat to the publics health and a priority across the globe. In the U.S. alone, it causes more than 2 million infections and 23,000 deaths per year. Worldwide, antibiotic resistance threatens our progress in healthcare, food production, and ultimately life expectancy.
Antibiotic resistance has been found in all regions of the world. Modern travel of people, animals, and goods means antibiotic resistance can easily spread across borders and continents. Collaborative, coordinated efforts will help slow the development and spread of antibiotic resistance and protect people.
In Vietnam, CDC, partners like the Ministry of Health, and local experts are working to establish a national surveillance system, which provides structure to track antibiotic resistance, guide prevention strategies, and report results at the local and global level. The system is currently implemented in 16 laboratories across Vietnam and allows the country to detect resistant bacteria where they start, before they spread. Vietnam has made fighting antibiotic resistance a national priority.
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Review On Antimicrobial Resistance
The Review on Antimicrobial Resistance , was commissioned in July 2014 by the UK Prime Minister, who asked economist Jim ONeill to analyse the global problem of rising drug resistance and propose concrete actions to tackle it internationally. The Review on AMR was jointly supported by the UK Government and Wellcome Trust, although operated with full independence from both. The final report and recommendations were published in the summer of 2016.
Antibiotic Discovery And Supremacy
In various parts of the world, from Greece to China, control of microbial infection has been well documented in the past. In 1928, the discovery of penicillin opened the door to the modern era of medicine. Ever since these magic bullets have transformed medicine and saved countless lives. In the 1940s, the very first prescription of antibiotics was made. During World War II, penicillin was considered as the drug of choice and used to control bacterial infections among the armed forces.24,25 Unfortunately, soon after that resistance against penicillin turned out to be a significant clinical concern. So, most of the advancements made in the 1940s were threatened during the 1950s. However, to maintain the use of antibiotic treatment strategies, scientists soon discovered and developed novel -lactam antibiotics. Howbeit, the first case of methicillin-resistant Staphylococcus aureus was reported in the UK and the US in 1962 and 1968, respectively, the same decade when new antibiotics were applied.24,26
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What Is Antimicrobial Resistance
Antimicrobial Resistance occurs when bacteria, viruses, fungi and parasites change over time and no longer respond to medicines making infections harder to treat and increasing the risk of disease spread, severe illness and death.
As a result of drug resistance, antibiotics and other antimicrobial medicines become ineffective and infections become increasingly difficult or impossible to treat.
