Antibiotic Resistance: Humanity's Next Health Challenge || pharmacyteach.com

 Antibiotic Resistance: Humanity's Next Health Challenge

 

One of the biggest dangers to global development and public health is antimicrobial resistance (AMR). Bacterial AMR is projected to have contributed to 4.95 million fatalities worldwide in 2019 and directly caused 1.27 million deaths.

Drug-resistant pathogens (AMR) are primarily caused by the overuse and misuse of antibiotics in humans, animals, and plants. AMR impacts nations across all regions and income levels, with low—and middle-income nations being the most affected. Poverty and inequality also exacerbate its causes and effects.

An insufficient research and development pipeline in the face of increasing antibiotic resistance and the pressing need for further steps to guarantee fair access to new and current vaccinations, diagnostics, and medications are the two main issues facing the globe today. AMR puts many of the advances in modern medicine at risk, including making infections more difficult to treat and increasing the danger of various medical operations and treatments including cancer chemotherapy, surgery, and cesarean deliveries.

 

Overview

Antimicrobial Resistance (AMR) is a natural process that occurs over time through genetic changes in pathogens. Human activity, primarily the misuse and overuse of antimicrobials to treat, prevent, or control infections in humans, animals, and plants, accelerate the emergence and spread of AMR. “Antimicrobial resistance (AMR) is the state in which bacteria, viruses, fungi, and parasites no longer respond to antimicrobial medicines, making antibiotics and other antimicrobial medicines ineffective and making infections difficult or impossible to treat.”

 

A global concern

The foundation of current medicine is antimicrobial medication. Our capacity to treat common illnesses and carry out life-saving operations like organtransplants, hip replacements, chemotherapy for cancer, and cesarean sections is under threat due to the rise and spread of drug-resistant microorganisms.

Drug-resistant diseases also affect plant and animal health, lower agricultural output, and jeopardize food security.

The costs of AMR to national economies and health systems are tremendous. For instance, it hinders agricultural output, necessitates more costly and extensive treatment, and impacts patient or caregiver productivity through extended hospital stays. 

Every nation, whatever of financial level, faces the challenge of AMR. Its dissemination transcends national boundaries. Lack of access to clean water, sanitation, and hygiene (WASH) for people and animals; inadequate infection and disease prevention and control in homes, hospitals, and farms; limited availability of high-quality and reasonably priced vaccines, diagnostics, and medications; ignorance and ignorance; and non-enforcement of pertinent laws are all contributing factors. The causes and effects of AM particularly affect vulnerable groups and those residing in low-resource environments.

 

What is the present situation?

Drug-resistance in bacteria

The effectiveness of ordinary antibiotics against common bacterial diseases is being weakened by the global growth of antibiotic resistance, which is a serious issue. Alarming resistance rates among common bacterial infections are highlighted in the 2022 Global Antimicrobial Resistance and Use Surveillance System (GLASS) report.  A significant worry is the median reported rates of 35% for methicillin-resistant Staphylococcus aureus and 42% for third-generation cephalosporin-resistant E.coli in 76 countries. In 2020, 1 in 5 E. coli urinary tract infection cases showed decreased sensitivity to common antibiotics such as ampicillin, co-trimoxazole, and fluoroquinolones. Common infections are becoming more difficult to cure as a result.

The common gut bacteria Klebsiella pneumoniae also exhibited high levels of resistance to important drugs. Elevated resistance levels may result in increased use of last-resort medications such as carbapenems, for which resistance is also being seen in various geographical areas. The danger of incurable infections raises as the efficacy of these last-resort medications declines. According to the Organization for Economic Cooperation and Development (OECD), by 2035, last-resort antibiotic resistance is expected to have doubled from 2005 levels. This highlights the critical need for strong antimicrobial stewardship protocols and increased surveillance coverage globally.

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Drug resistance in fungi 

WHO is keeping an eye on the prevalence of drug-resistant fungal diseases and their effects on public health. Treating fungal infections can be challenging, especially for individuals who also have other illnesses (such as HIV) because of medication interactions. It is especially concerning when multi-drug resistant Candida auris, an invasive fungal infection, appears and spreads. A thorough assessment of fungal diseases and drug-resistant fungi worldwide was part of the creation of who is Fungal Priority Pathogens List.

Drug resistance in HIV, tuberculosis and malaria

Changes in the HIV genome that impair antiretroviral (ARV) medications' capacity to prevent the virus from replicating are the root cause of HIV drug resistance (HIVDR). HIVDR can be acquired as a result of poor treatment compliance or drug-drug interactions, or it can be spread during infection. Increased HIV infections as well as HIV-related morbidity and death might result from HIVDR. In order to choose the best ARV medication regimens for HIV prevention and treatment, WHO advises that nations regularly conduct HIV-DR surveys.

 

One of the main causes of antibiotic resistance is tuberculosis (TB). The two most effective first-line TB medications, isoniazid and rifampicin, do not work against germs that produce multidrug-resistant tuberculosis (MDR-TB). Second-line medications can be used to treat and cure MDR-TB, but they are costly, hazardous, and can sometimes lead to the development of more widespread drug resistance. Patients may have very few alternatives for therapy if their TB is caused by germs that are resistant to the best second-line TB medications. Thus, MDR-TB poses a threat to health security and is a public health emergency. In 2022, only over two out of five patients with drug-resistant TB sought treatment.

One of the biggest threats to controlling malaria is the growth of drug-resistant parasites. The majority of malaria-endemic nations employ artemisinin-based combination treatments (ACTs), which are the suggested first-line therapy for uncomplicated Plasmodium falciparum malaria. When ACTs develop partial resistance to artemisinin and/or partner medications, choosing the best course of treatment becomes more difficult and necessitates careful observation. Since 2001, a number of countries in the Greater Mekong Subregion have proven partial resistance to artemisinin or a companion medication. Some countries in the WHO Eastern Mediterranean Region experienced treatment failure due to sulfadoxine-pyrimethamine resistance, necessitating a switch to an alternative ACT. Mutations associated with partial resistance to artemisinin have been found in a number of African nations. Tested ACTs are still effective, but increased resistance might pose a serious public health threat, therefore better surveillance is essential.

Drug resistance in neglected tropical diseases (NTDs)

Programs to manage, eradicate, and eradicate neglected tropical diseases (NTDs), which disproportionately impact poor and disadvantaged communities, are seriously threatened by the rise of drug resistance against medications for these diseases. Drugs used to treat leishmaniasis (pentavalent antimonials, miltefosine), human African trypanosomiasis (melarsoprol), leprosy (dapsone, rifampicine, and clofazimine)—and anti-helminthics (although resistance has so far only been observed in use in animals, which is a serious concern for the veterinary sector—have also been found to be resistant in a number of countries.  It is crucial to keep an eye on therapeutic efficacy and resistance, implement plans to postpone or stop resistance, and fortify the supply of second-line medications for NTDs. For instance, WHO offers guidelines for the global leprosy elimination program's surveillance of resistance, as well as assistance in managing distribution and keeping an eye on the standardized use, safety, and effectiveness of medications—including donated medications—in NTD programs.

Coordinated global action to address AMR

One Health approach

AMR is a complicated issue that needs both sector-specific responses in the fields of human health, agriculture, animal husbandry, and the environment, as well as a coordinated strategy among these sectors. An integrated, unifying strategy known as "One Health" seeks to provide humans, animals, and ecosystems with the best possible health results over the long term. It acknowledges the tight connections and interdependencies between the health of people, domestic and wild animals, plants, and the larger ecosystem. By bringing together stakeholders from many sectors, the One Health approach to AMR prevention and control facilitates communication and collaboration in the development, implementation, and oversight of policies, research, programs, and laws aimed at reducing AMR and improving health and economic outcomes.

Global Action Plan (GAP) on Antimicrobial Resistance

Countries committed to developing and implementing multisectoral national action plans using a One Health approach to combat AMR after adopting the Global Action Plan (GAP) on AMR during the 2015 World Health Assembly. The Governing Bodies of the United Nations Environment Program, the Food and Agriculture Organization (FAO), and the World Organization for Animal Health (WOAH, previously OIE) later approved the GAP.

Quadripartite Joint Secretariat on Antimicrobial Resistance

WHO collaborates closely with the World Organization for Animal Health (WOAH), the UN Environment Programme (UNEP), and the Food and Agriculture Organization of the United Nations (FAO) to coordinate the One Health global response to AMR. The Quadripartite refers to the four organizations: WOAH, UNEP, WHO, and FAO. WHO hosts a quadripartite joint secretariat to promote multi-stakeholder involvement in AMR. This has aided in the formation of many technical working groups, the Multi-Stakeholder Partnership Platform, which was introduced in November 2022, and the Global Leaders Group on AMR, which started operations in November 2020.

High-level meetings on AMR

A second High-level Meeting on AMR was formed in March 2022 by the United Nations General Assembly resolution A/RES/76/257, with the assistance of the Global Leaders Group and in cooperation with the Quadripartite Organizations, to take place in 2024. The Permanent Representatives of Malta and Barbados were chosen by the General Assembly President to co-facilitate the high-level gathering in October 2023. The Quadripartite Joint Secretariat is collaborating closely with the co-facilitators and Global Leaders Group to guarantee the best possible participation and inputs from the human, animal, agri-food, and environmental sectors. The high-level meeting is a significant chance for nations to agree on goals and make bold commitments.

Additionally, the Global Action Plan, the AMR Multi-Partner Trust Fund, and innovative multisectoral AMR objectives were the results of three Global High-level Ministerial Conferences on AMR, held in the Netherlands in 2014 and 2019 and Oman in 2022. In 2024, the Kingdom of Saudi Arabia will hold a fourth high-level ministerial meeting.

World AMR Awareness Week (WAAW)

A global initiative, World AMR Awareness Week (WAAW) aims to increase public knowledge, comprehension, and best practices among One Health stakeholders and other officials. World Health Organization's official health campaign since 2015, WAAW is observed annually from November 18 to 24.

A programmatic response to AMR in countries

AMR national action plans

As of November 2023, 178 countries had created AMR national action plans that were in line with the GAP. Prioritizing activities, creating a costed operational plan, mobilizing domestic and external resources, and successfully implementing the plan are all necessary for sustained progress. Monitoring mechanisms are required to track progress, identify obstacles, and provide periodic reports. To track the progress in implementing AMR national action plans globally, countries have committed to completing the multisectoral annual Tracking AMR Country Self-Assessment Survey (TrACSS), which was launched in 2016 and whose results are available at https://www.amrcountryprogress.org/.

The people-centred approach and WHO core package of interventions

WHO has developed the People-centered approach to addressing antimicrobial resistance in human health and WHO core package of interventions to support national action plans in order to address AMR in a programmatic way that places people, their needs, and equitable access to health services at the center of the AMR response in the community, in primary care, secondary, and tertiary care, as well as at the national and/or subnational level. Infection prevention and widespread access to healthcare services for accurate diagnosis and suitable treatment are the main goals of this. Countries can incorporate the core package of AMR interventions into their national plans and strategies for universal health coverage and health emergency planning and response as a critical component of their AMR response.

Antimicrobial stewardship and AWaRe

A methodical strategy to teaching and assisting medical personnel in adhering to evidence-based recommendations for the prescription and administration of antibiotics is known as antimicrobial stewardship. Since the health staff is the first line of defense for ensuring the efficacy of antimicrobial medications, their education is vital. As one of the most economical ways to maximize the use of antimicrobial medications, enhance patient outcomes, and lower AMR and infections linked to healthcare, WHO advises nations to create and execute Antimicrobial Stewardship Programs.

WHO created the AWaRe (Access, Watch, Reserve) categorization of antibiotics in order to decrease the improper use of antibiotics and increase access to appropriate therapy. For over 30 of the most prevalent clinical infections in children and adults, the WHO AWaRe antibiotic book offers succinct, evidence-based recommendations on the selection of antibiotic, dosage, mode of administration, and length of treatment in both primary care and hospital settings.

Strategic information to inform the AMR response

In order to close knowledge gaps and guide initiatives at all levels, WHO introduced the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015. Data from human AMR surveillance, antimicrobial use and consumption surveillance, and integrated AMR data across One Health domains, such as the environment and food chain, are gradually included into GLASS.

A standardized method for gathering, analyzing, interpreting, and disseminating data by nations, territories, and regions is offered by GLASS. With a focus on representativeness and data collecting quality, it also keeps an eye on the state of both new and current national surveillance systems. Some WHO regions have set up surveillance networks that help nations participate in GLASS and offer technical assistance. 

Through GLASS and nationally representative AMR prevalence surveys, WHO is particularly dedicated to helping low- and middle-income nations enhance data collection and use for policymaking.

Priority-setting for AMR research and product development

There is an antibiotic pipeline and access problem, and the clinical pipeline for novel antimicrobials is nearly empty. Only six of the 27 antibiotics under clinical development that target WHO bacterial priority diseases were deemed novel in the most recent yearly evaluation of the pre-clinical and clinical antibacterial pipelines by WHO. Furthermore, nations of all economic and development levels are impacted by shortages of generic off-patent antibiotics and limited access to high-quality antimicrobials.

WHO created the first WHO bacterial priority pathogens list in 2017 and updated it in 2023 (publication pending), and released the WHO fungal priority pathogen list in 2022 to direct research and development into new antimicrobials, diagnostics, and vaccines and to inform public health action.

WHO collaborates closely with groups like the Global Antibiotic Research & Development Partnership (GARDP), the AMR Action Fund, and the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) to help close the significant gaps in R&D for antimicrobials, vaccines, and diagnostic tools. To eventually guarantee access to therapy, some governments are also testing various strategies to encourage the study and creation of novel antimicrobials.

Additionally, more investment and innovation are needed in operational and epidemiological research. Together with the quadripartite organizations, WHO has developed a One Health priority research agenda for AMR, which includes 40 priority research themes for AMR in human health.