Antimicrobials are drugs that are used to prevent and treat infectious diseases in humans, animals, and plants. They include antibiotics, antivirals, antifungals, and antiparasitics.

When bacteria, viruses, fungi, and parasites stop responding to antimicrobial medications, it's known as antimicrobial resistance (AMR). Drug resistance makes antimicrobial medications, including antibiotics, ineffective and makes treating infections challenging or impossible. This raises the risk of infection spread, serious illness, disability, and death.

AMR is a natural process brought about by pathogen genetic alterations over time. Human activity, particularly the overuse and misuse of antibiotics for the treatment, prevention, or control of infections in people, animals, and plants, has accelerated its emergence and spread. Antimicrobial medicines are fundamental to contemporary healthcare, but the rise and dissemination of drug-resistant pathogens jeopardize our capacity to treat common infections and conduct critical procedures like cancer chemotherapy, cesarean sections, hip replacements, organ transplants, and other surgeries. Moreover, drug-resistant infections adversely affect the health of animals and plants, diminish farm productivity, and threaten food security.

The financial burden of antimicrobial resistance (AMR) is substantial for healthcare systems and national economies. It necessitates more costly and intensive care, prolongs hospital stays, reduces the productivity of patients and their caregivers, and hampers agricultural output.

AMR is a global issue, affecting countries across all income levels without regard to borders. Factors contributing to its spread include inadequate access to clean water, sanitation, and hygiene (WASH) for both humans and animals; insufficient infection and disease prevention and control in homes, healthcare facilities, and farms; poor availability of quality and affordable vaccines, diagnostics, and medicines; lack of awareness and knowledge; and weak enforcement of pertinent legislation. Those living in low-resource settings and vulnerable populations are particularly affected by both the causes and impacts of AMR.

What is the state of affairs right now?

Bacteria with drug resistance

Antibiotic resistance is a serious global health concern that reduces the effectiveness of common antibiotics against common bacterial infections. The Global Antimicrobial Resistance and Use Surveillance System (GLASS) report for 2022 shows that common bacterial pathogens have alarming resistance rates. It is extremely concerning that the median reported rates in 76 countries are 42% for third-generation cephalosporin-resistant E. Coli and 35% for methicillin-resistant Staphylococcus aureus. 2020 saw a 1 in 5 reduction in the susceptibility of E. Coli urinary tract infections to common antibiotics such as ampicillin, co-trimoxazole, and fluoroquinolones. As a result, treating common infections effectively is becoming more difficult.

Common intestinal bacteria Klebsiella pneumoniae also displayed high levels of resistance to important antibiotics. Rising resistance may also result in more people using antibiotics as last resorts, such as carbapenems, which is causing resistance in other areas as well. The likelihood of infections that are incurable rises as the efficacy of these last-resort medications is weakened. The Organisation for Economic Cooperation and Development (OECD) has projected that by 2035, resistance to antibiotics used as a last resort will have doubled from 2005 levels. This highlights the critical need for strong antimicrobial stewardship protocols and increased global surveillance coverage.

With the escalation of drug-resistant fungal infections, the World Health Organization (WHO) is closely monitoring their scale and public health implications. Treating fungal infections can be challenging, especially considering potential drug interactions, particularly for patients with concurrent infections like HIV. Of particular concern is the emergence and dissemination of multi-drug resistant Candida auris, an invasive fungal infection. The formulation of WHO's Fungal Priority Pathogens List, as outlined below, involved a thorough examination of fungal infections and drug-resistant fungi on a global scale.

Drug resistance poses significant challenges in the context of HIV, tuberculosis (TB), and malaria, undermining global efforts to combat these diseases.

• HIV drug resistance (HIVDR) arises due to genetic changes in the HIV virus, compromising the effectiveness of antiretroviral (ARV) drugs in suppressing viral replication. This resistance can be transmitted during infection or acquired due to inadequate adherence to treatment or drug interactions. The consequences of HIVDR include increased HIV transmission rates and associated morbidity and mortality. WHO recommends regular HIVDR surveys to guide the selection of appropriate ARV drug regimens for prevention and treatment.
• Tuberculosis (TB) is a leading cause of antimicrobial resistance, with multidrug-resistant tuberculosis (MDR-TB) posing a significant threat. MDR-TB does not respond to isoniazid and rifampicin, the primary TB drugs. While treatable with second-line drugs, MDR-TB treatment is expensive, toxic, and can lead to further drug resistance. Limited treatment options for extensively drug-resistant TB highlight the urgency of addressing this public health crisis. Access to treatment for drug-resistant TB remains inadequate, with only a fraction of affected individuals receiving care.

In malaria control, the emergence of drug-resistant parasites, particularly against artemisinin-based combination therapies (ACTs), presents a major challenge. ACTs are the frontline treatment for Plasmodium falciparum malaria, but partial resistance compromises their efficacy. Resistance to artemisinin and partner drugs has been confirmed in various regions, including the Greater Mekong Subregion and the WHO Eastern Mediterranean Region. While currently available ACTs remain effective, enhanced surveillance and monitoring are essential to prevent the further spread of resistance and maintain malaria control efforts.

Overall, addressing drug resistance in HIV, TB, and malaria requires concerted global efforts, including improved surveillance, access to quality treatment, and development of new therapeutic strategies to safeguard public health and combat these diseases effectively.

Antimicrobial resistance (AMR) represents a pressing global public health and developmental challenge. In 2019, bacterial AMR directly contributed to an estimated 1.27 million deaths worldwide and played a role in 4.95 million deaths. Misuse and overuse of antimicrobials in humans, animals, and plants are primary drivers of drug-resistant pathogens. AMR affects countries across all income levels and regions, with poverty and inequality exacerbating its drivers and consequences, particularly impacting low- and middle-income nations. The ramifications of AMR extend beyond health, endangering gains made in modern medicine by rendering infections harder to treat and making medical procedures like surgery, chemotherapy, and transplants riskier. Furthermore, AMR incurs significant economic costs, with the World Bank estimating potential healthcare costs of up to US$1 trillion by 2050 and annual gross domestic product (GDP) losses of US$1 trillion to US$3.4 trillion by 2030. The world is facing an antibiotics pipeline and access crisis, with insufficient research and development efforts amidst rising resistance levels and an urgent need for equitable access to new and existing vaccines, diagnostics, and medicines. Priorities in addressing AMR in human health include preventing infections, ensuring universal access to quality diagnosis and treatment, and fostering strategic information and innovation such as surveillance and research and development for novel solutions.

The present situation underscores the gravity of drug resistance across various pathogens. In bacteria, the global rise in antibiotic resistance poses a significant threat, with alarming resistance rates among prevalent bacterial pathogens such as E. coli and Staphylococcus aureus. The emergence of multi-drug resistant Klebsiella pneumoniae raises concerns about the utilization of last-resort antibiotics, with projections suggesting a twofold surge in resistance levels by 2035. In fungi, the spread of drug-resistant infections, including the multi-drug resistant Candida auris, necessitates vigilant monitoring to assess its magnitude and impact on public health. In HIV, tuberculosis (TB), and malaria, drug resistance complicates treatment regimens and jeopardizes control efforts. HIV drug resistance can lead to increased morbidity and mortality, while drug-resistant TB and malaria strains challenge existing treatment options and control strategies. The emergence of drug resistance in neglected tropical diseases (NTDs) further complicates efforts to control and eliminate these diseases, particularly affecting vulnerable populations. Monitoring drug resistance, implementing strategies to delay or curb resistance, and strengthening the pipeline of second-line medicines are crucial steps in addressing this multifaceted challenge across various pathogens and diseases.

• Coordinated global action is essential to effectively address antimicrobial resistance (AMR), a multifaceted challenge impacting human health, food production, animal welfare, and the environment. The One Health approach, which integrates efforts across these sectors, acknowledges the interconnectedness of human, animal, and environmental health, aiming for optimal and sustainable outcomes. Recognizing this, countries adopted the Global Action Plan (GAP) on AMR in 2015, committing to multisectoral national action plans aligned with a One Health approach. To drive this global response, the Quadripartite Joint Secretariat on Antimicrobial Resistance, comprising the World Health Organization (WHO), Food and Agriculture Organization of the United Nations (FAO), UN Environment Programme (UNEP), and World Organisation for Animal Health (WOAH), collaborates to coordinate efforts. The establishment of the Global Leaders Group on AMR and the Multi-Stakeholder Partnership Platform underscores these collaborative endeavors. High-level meetings and conferences, such as the upcoming High-level Meeting on AMR in 2024, provide crucial platforms for countries to make ambitious commitments and set targets, with support from the Quadripartite organizations.
• World AMR Awareness Week (WAAW) serves as a global campaign to raise awareness and promote best practices, engaging stakeholders across sectors and policymakers. At the national level, 178 countries have developed AMR national action plans, aligned with the GAP, emphasizing the importance of a functioning multisectoral governance mechanism, resource mobilization, and effective implementation. WHO's People-centred approach and core package of interventions prioritize preventing infections, ensuring universal access to quality diagnosis and treatment, and integrating antimicrobial stewardship initiatives. The AWaRe classification of antibiotics guides appropriate antibiotic use, complemented by Antimicrobial Stewardship Programmes aimed at optimizing antimicrobial use and reducing resistance. Strategic information, facilitated by the Global Antimicrobial Resistance and Use Surveillance System (GLASS), informs policy and action, with a focus on supporting low- and middle-income countries to improve data collection and usage.
• Prioritizing research and development (R&D) is crucial to addressing gaps in antimicrobial innovation and access. WHO's bacterial and fungal priority pathogen lists guide R&D efforts, supported by collaborations with organizations like GARDP, the AMR Action Fund, and CARB-X. Investment in epidemiological and operational research, including a One Health research agenda, is essential for informed decision-making and sustainable solutions. Coordinated global action, underpinned by a One Health approach, is imperative to combatting AMR and safeguarding human, animal, and environmental health for future generations.

Here's a summarized list of key points about antimicrobial resistance (AMR):

• AMR is a global public health threat, leading to millions of deaths annually.
• Misuse and overuse of antimicrobials in humans, animals, and plants are major drivers of AMR.
• AMR affects countries at all income levels and regions, exacerbated by poverty and inequality.
• It undermines the effectiveness of modern medicine, making infections harder to treat and medical procedures riskier.
• AMR incurs significant economic costs, potentially leading to trillion-dollar losses in healthcare costs and GDP.
• A coordinated, multisectoral approach is needed to address AMR, emphasizing the One Health approach.
• The Global Action Plan on AMR and AMR national action plans guide global and national efforts.
• The Quadripartite Joint Secretariat and High-level Meetings on AMR facilitate global coordination and commitments.
• World AMR Awareness Week raises awareness and promotes best practices.
• AMR national action plans prioritize prevention, universal access to treatment, and antimicrobial stewardship.
• The AWaRe classification and Antimicrobial Stewardship Programmes guide appropriate antimicrobial use.
• GLASS provides strategic information to inform policy and action, focusing on supporting low- and middle-income countries.
• Research and development efforts are essential to address gaps in antimicrobial innovation and access.

In conclusion, combating AMR requires concerted global efforts, including multisectoral collaboration, policy implementation, awareness-raising, surveillance, and research and development. By adopting a One Health approach and prioritizing prevention, access to treatment, and antimicrobial stewardship, we can mitigate the impact of AMR and safeguard human, animal, and environmental health for generations to come.

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