Antimicrobials
Austin Vermont
The WHO Advisory Group on Integrated Surveillance of Antimicrobial Resistance (AGISAR) reviews and updates the WHO list of critically important antimicrobials for human medicine in every two years. The current revision took place at the fifth meeting of the AGISAR held in Bogota, Colombia in 2013.
AMR is a natural process that happens over time through genetic changes in pathogens. Its emergence and spread is accelerated by human activity, mainly the misuse and overuse of antimicrobials to treat, prevent or control infections in humans, animals and plants.
Antimicrobial stewardship is a systematic approach to educate and support health care professionals to follow evidence-based guidelines for prescribing and administering antimicrobials. The education of the health workforce is of crucial importance, as they form the front line in safeguarding the effectiveness of antimicrobial medicines. WHO guides countries to develop and implement Antimicrobial Stewardship Programmes as one of the most cost-effective interventions to optimize the use of antimicrobial medicines, improve patient outcomes and reduce AMR and health care-associated infections.
WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015 to fill knowledge gaps and inform strategies at all levels. GLASS progressively incorporates data from surveillance of AMR in humans, surveillance of the use and consumption of antimicrobials, and integrated AMR data in the One Health sectors including the food chain and in the environment.
To guide research and development into new antimicrobials, diagnostics and vaccines, and inform public health action, WHO developed the first WHO bacterial priority pathogens list in 2017 and updated this in 2023 (publication forthcoming), and published the WHO fungal priority pathogen list in 2022.
To help fill the major gaps in R&D for antimicrobials, vaccines and diagnostic tools, WHO works closely with organizations such as the Global Antibiotic Research & Development Partnership (GARDP), the AMR Action Fund, and the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X). Various governments are also piloting different models to incentivize research and development of newer antimicrobials to ultimately ensure access to treatment.
AMR is a natural process that happens over time through genetic changes in pathogens. Its emergence and spread is accelerated by human activity, mainly the misuse and overuse of antimicrobials to treat, prevent or control infections in humans, animals and plants.
Antimicrobial stewardship is a systematic approach to educate and support health care professionals to follow evidence-based guidelines for prescribing and administering antimicrobials. The education of the health workforce is of crucial importance, as they form the front line in safeguarding the effectiveness of antimicrobial medicines. WHO guides countries to develop and implement Antimicrobial Stewardship Programmes as one of the most cost-effective interventions to optimize the use of antimicrobial medicines, improve patient outcomes and reduce AMR and health care-associated infections.
To guide research and development into new antimicrobials, diagnostics and vaccines, and inform public health action, WHO developed the first WHO bacterial priority pathogens list in 2017 and updated this in 2023 (publication forthcoming), and published the WHO fungal priority pathogen list in 2022.
To help fill the major gaps in R&D for antimicrobials, vaccines and diagnostic tools, WHO works closely with organizations such as the Global Antibiotic Research & Development Partnership (GARDP), the AMR Action Fund, and the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X). Various governments are also piloting different models to incentivize research and development of newer antimicrobials to ultimately ensure access to treatment.
Sanitizers are the weakest public-health antimicrobials. They reduce bacteriaon surfaces.1 Some sanitizers may be used on food-contact surfaces such ascountertops, cutting boards, or children's high chairs. The label will indicatehow a sanitizer can be used. Some sanitizers can be used only for non-foodcontact surfaces like toilet bowls and carpets, or air.5,6
Judicious therapeutic use of antimicrobials is a core principle of the broader goal of antimicrobial stewardship. Antimicrobial Stewardship involves maintaining animal health and welfare by implementing a variety of preventive and management strategies to prevent common diseases; using an evidence-based approach in making decisions to use antimicrobial drugs; and then using antimicrobials judiciously, sparingly, and with continual evaluation of the outcomes of therapy, respecting the client's available resources. In addition, other management and intervention strategies may be considered prior to antimicrobial therapy for infectious diseases.
Antimicrobials are valuable therapeutics whose efficacy is seriously compromised by the emergence and spread of antimicrobial resistance. The provision of antibiotics to food animals encompasses a wide variety of nontherapeutic purposes that include growth promotion. The concern over resistance emergence and spread to people by nontherapeutic use of antimicrobials has led to conflicted practices and opinions. Considerable evidence supported the removal of nontherapeutic antimicrobials (NTAs) in Europe, based on the "precautionary principle." Still, concrete scientific evidence of the favorable versus unfavorable consequences of NTAs is not clear to all stakeholders. Substantial data show elevated antibiotic resistance in bacteria associated with animals fed NTAs and their food products. This resistance spreads to other animals and humans-directly by contact and indirectly via the food chain, water, air, and manured and sludge-fertilized soils. Modern genetic techniques are making advances in deciphering the ecological impact of NTAs, but modeling efforts are thwarted by deficits in key knowledge of microbial and antibiotic loads at each stage of the transmission chain. Still, the substantial and expanding volume of evidence reporting animal-to-human spread of resistant bacteria, including that arising from use of NTAs, supports eliminating NTA use in order to reduce the growing environmental load of resistance genes.
Peptidoglycan (PG) is the major structural component of the bacterial cell wall. Bacteria have autolytic PG hydrolases that allow the cell to grow and divide. A well-studied group of PG hydrolase enzymes are the bacteriophage endolysins. Endolysins are PG-degrading proteins that allow the phage to escape from the bacterial cell during the phage lytic cycle. The endolysins, when purified and exposed to PG externally, can cause "lysis from without." Numerous publications have described how this phenomenon can be used therapeutically as an effective antimicrobial against certain pathogens. Endolysins have a characteristic modular structure, often with multiple lytic and/or cell wall-binding domains (CBDs). They degrade the PG with glycosidase, amidase, endopeptidase, or lytic transglycosylase activities and have been shown to be synergistic with fellow PG hydrolases or a range of other antimicrobials. Due to the coevolution of phage and host, it is thought they are much less likely to invoke resistance. Endolysin engineering has opened a range of new applications for these proteins from food safety to environmental decontamination to more effective antimicrobials that are believed refractory to resistance development. To put phage endolysin work in a broader context, this chapter includes relevant studies of other well-characterized PG hydrolase antimicrobials.
FDA recognizes that fluctuations in sales volume may occur over time in response to various factors, including changing animal health needs or changes in animal populations. Given the substantial change that occurred with transitioning a large number of products containing medically important antimicrobials from over-the-counter use to a marketing status requiring veterinary oversight at the beginning of 2017, some rebound in the reported sales volume in subsequent years was not unexpected as affected stakeholders adjusted to the new requirements.
While sales data on antimicrobial drug products intended for food-producing animals do not necessarily reflect the actual use of antimicrobial drugs, sales volume observed over time can be a valuable indicator of market trends related to these products. However, when evaluating the progress of ongoing efforts to support judicious use of antimicrobials, it is important to take into account additional information sources including actual use data, animal demographics, animal health data, and data on antimicrobial resistance.
npj Antimicrobials and Resistance is an online Open Access journal dedicated to publishing basic, applied, and clinical research that advances our understanding of all aspects of antimicrobials and antimicrobial resistance.
The following antimicrobials have been selected for restriction by the CAUSE Advisory Board, a group of physicians, pharmacists, and microbiologists representing many medical disciplines throughout the medical center.
Scientists, veterinarians and other animal healthcare professionals, risk assessors and policy makers in Member States use the results of the annual report as a reference for antimicrobial policies and for guidance on the responsible use of antimicrobials.
Overall, most participating countries have been successful in reducing the use of antimicrobials in food-producing animals. The latest results show the potential in other countries as well.
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