Nosocomial infections and antimicrobial resistance in critical care medicine

Objective: To review the human and companion animal veterinary literature on nosocomial infections and antimicrobial drug resistance as they pertain to the critically ill patient. Data sources: Data from human and veterinary sources were reviewed using PubMed and CAB. Human data synthesis: There is a large amount of published data on nosocomially‐acquired bloodstream infections, pneumonia, urinary tract infections and surgical site infections, and strategies to minimize the frequency of these infections, in human medicine. Nosocomial infections caused by multi‐drug‐resistant (MDR) pathogens are a leading cause of increased patient morbidity and mortality, medical treatment costs, and prolonged hospital stay. Epidemiology and risk factor analyses have shown that the major risk factor for the development of antimicrobial resistance in critically ill human patients is heavy antibiotic usage. Veterinary data synthesis: There is a paucity of information on the development of antimicrobial drug resistance and nosocomially‐acquired infections in critically ill small animal veterinary patients. Mechanisms of antimicrobial drug resistance are universal, although the selection effects created by antibiotic usage may be less significant in veterinary patients. Future studies on the development of antimicrobial drug resistance in critically ill animals may benefit from research that has been conducted in humans. Conclusions: Antimicrobial use in critically ill patients selects for antimicrobial drug resistance and MDR nosocomial pathogens. The choice of antimicrobials should be prudent and based on regular surveillance studies and accurate microbiological diagnostics. Antimicrobial drug resistance is becoming an increasing problem in veterinary medicine, particularly in the critical care setting, and institution‐specific strategies should be developed to prevent the emergence of MDR infections. The collation of data from tertiary‐care veterinary hospitals may identify trends in antimicrobial drug resistance patterns in nosocomial pathogens and aid in formulating guidelines for antimicrobial use.     

我国动物源细菌耐药状况、存在问题和对策

动物源细菌耐药性问题不仅关系到动物的用药安全,也与公共卫生安全密切相关,日益引起各国的关注。中国兽医药品监察所从事动物源细菌耐药性检测工作10余年,对我国动物源细菌的耐药性状况进行了系统的调查。本文从动物源细菌耐药性监测工作的重要性、我国动物源细菌的耐药性状况、存在的问题以及应对策略四个方面进行了综述,以期对我国的动物源细菌耐药性监测工作起一定的参考作用。     

Stakeholder position paper: companion animal veterinarian

The total quantity of use in companion animals is generally believed to be relatively small in comparison with antimicrobial use in food animals. Use in companion animals is principally for treatment, whereas the greater proportion of use in food animals is for prophylaxis, metaphylaxis and growth promotion. Therefore, it is important to collect data on end use in companion animals so that overall estimates of use in companion animals can be generated and separated from estimates for food animals. However, data from antimicrobial use in companion animals are extremely limited and no serious attempts to collect such data have ever been made in the United States. The lack of usage data in is concomitant with the dearth of information on antimicrobial resistance in companion animals. Companion animals have been involved in the transmission to humans of, or become infected with, foodborne zoonotic bacteria such as Salmonella and Campylobacter. Companion animals are an integral part of the ecology of antimicrobial resistance through their contact with food animals and exposure to antimicrobials for disease treatment and through contact with humans and the environment. In the practice of companion animal medicine, antimicrobial use data are important for understanding the potential impact on companion animal heath posed by antimicrobial resistance transferred from food animals, humans and the environment, and the threat to humans and other companion animals posed by antimicrobial use in companion animals. Basic information on the patterns and quantities of antimicrobial use in combination with resistance surveillance data, could help companion animal veterinarians understand the potential for development, or evidence of, an antimicrobial resistance problem in their practices, the role of companion animals in the overall epidemiology of antimicrobial resistance, and for comparison with local, regional, or national data. The combination of data from either a sentinel site system of clinics or a use survey with national data from the pharmaceutical industry should provide sufficient data to credibly estimate the total volume and patterns of antimicrobial use in companion animal medicine. The time and effort for use monitoring or to complete a survey would likely become burdensome. Practice management software now utilized at most companion animal clinics could be used to generate antimicrobial use data as well as patient population data as surrogate for the true population at risk for patient encounters in a companion animal practice.     

Monitoring of antimicrobial resistance in healthy dogs: first report of canine ampicillin-resistant Enterococcus faecium clonal complex 17

National surveillance programs on antimicrobial usage and antimicrobial resistance in animals have been established in various countries but few of them include bacteria from pets. The objectives of this study were to assess the prevalence of antimicrobial resistance in healthy dogs and to search for resistance phenotypes of clinical relevance. Escherichia coli and Enterococcus spp. were isolated from faecal swabs obtained from 127 dogs. Disk diffusion was used to measure antimicrobial susceptibility in 117 Escherichia coli, 10 Enterococcus faecium and 51 Enterococcus faecalis of canine origin. Resistance was relatively low compared with food animal species in Denmark. All Escherichia coli isolates were susceptible to broad-spectrum aminopenicillins, third generation cephalosporins and fluoroquinolones. Despite the low prevalence of resistance, statistical analysis of questionnaire data revealed a significant association (p=0.02) between recent antimicrobial treatment and resistance in Escherichia coli. Interestingly, two dogs were found to shed Enterococcus faecium resistant to ampicillin. Multilocus sequence typing of these isolates indicated that the two isolates belonged to sequence types associated with human nosocomial infections, and one (ST-192) was genetically related to human epidemic clonal complex 17. The detection of ampicillin-resistant Enterococcus faecium warrants further studies on the prevalence of these bacteria in dogs and on the possible implications to both animal and human health. The results suggest that distinct methods for detection and assessment of antimicrobial resistance in animals should be considered depending on the target animal species and the purposes of the study.     

Antimicrobial resistance in bacteria from horses: Epidemiology of antimicrobial resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections. While the epidemiology of antimicrobial resistance in bacteria from man has been studied extensively, less work has been undertaken in companion animals, particularly horses. Methicillin‐resistant Staphylococcus aureus has been identified as a cause of infections, with a low prevalence of nasal carriage by horses in the community but higher for hospitalised horses. Molecular characterisation has shown methicillin‐resistant Staphylococcus aureus strains either to be predominantly of types associated with horses or of sequence type ST398. Antimicrobial‐resistant Escherichia coli (including multidrug‐resistant and extended spectrum β‐lactamase‐producing isolates) have caused infections and been documented in faecal carriage by horses, with many significant resistance mechanisms identified. More sporadic reports and molecular characterisation exist for resistance in other bacteria such as enterococci, Salmonella, Acinetobacter and Pseudomonas species. Limited work has been undertaken evaluating risk factors and much of the epidemiology of antimicrobial resistance in bacteria from horses remains to be determined.     

ACVIM Consensus Statement on Therapeutic Antimicrobial Use in Animals and Antimicrobial Resistance

The epidemic of antimicrobial resistant infections continues to challenge, compromising animal care, complicating food animal production and posing zoonotic disease risks. While the overall role of therapeutic antimicrobial use in animals in the development AMR in animal and human pathogens is poorly defined, veterinarians must consider the impacts of antimicrobial use in animal and take steps to optimize antimicrobial use, so as to maximize the health benefits to animals while minimizing the likelihood of antimicrobial resistance and other adverse effects. This consensus statement aims to provide guidance on the therapeutic use of antimicrobials in animals, balancing the need for effective therapy with minimizing development of antimicrobial resistance in bacteria from animals and humans.     

The management of risk arising from the use of antimicrobial agents in veterinary medicine in EU/EEA countries – a review

Antimicrobials are essential medicines for the treatment of many microbial infections in humans and animals. Only a small number of antimicrobial agents with new mechanisms of action have been authorized in recent years for use in either humans or animals. Antimicrobial resistance (AMR) arising from the use of antimicrobial agents in veterinary medicine is a concern for public health due to the detection of increasing levels of resistance in foodborne zoonotic bacteria, particularly gram‐negative bacteria, and due to the detection of determinants of resistance such as Extended‐spectrum beta‐lactamases (ESBL) in bacteria from animals and in foodstuffs of animal origin. The importance and the extent of the emergence and spread of AMR from animals to humans has yet to be quantified. Likewise, the relative contribution that the use of antimicrobial agents in animals makes to the overall risk to human from AMR is currently a subject of debate that can only be resolved through further research. Nevertheless, risk managers have agreed that the impact on public health of the use of antimicrobials in animals should be minimized as far as possible and a variety of measures have been introduced by different authorities in the EU to achieve this objective. This article reviews a range of measures that have been implemented within European countries to reduce the occurrence and the risk of transmission of AMR to humans following the use of antimicrobial agents in animals and briefly describes some of the alternatives to the use of antimicrobial agents that are being developed.     

Stakeholder position paper: epidemiological perspectives on antibiotic use in animals

Epidemiologists studying antimicrobial resistance are often interested in analyzing the association between antimicrobial resistance and antimicrobial use in animals, and on the impact of antimicrobial use in animals on the occurrence of resistance in bacteria affecting human populations. Given the various potential antimicrobial use data sources, it seems likely there will be some variability in the utility of the data for interpreting trends in antimicrobial resistance and investigating the relationship between antimicrobial use in animals and antimicrobial resistance in bacteria affecting human health. From an epidemiologic perspective, the major issues related to incorporation of antimicrobial use data into antimicrobial resistance monitoring programs are the further development of epidemiologic methods for collecting, quantifying, analyzing and interpreting use data; an open and realistic consideration of the limitations of the data; developing an understanding of scaling, temporal and spatial heterogeneity issues; and the interpretative problems of ecologic and atomistic fallacy. Given the many potential biases in antimicrobial use data, attempts to relate levels of antimicrobial use to levels of antimicrobial resistance should be done with caution until the data are better understood and the aforementioned issues have been addressed.     

Animal health pharmaceutical industry

The animal health pharmaceutical industry has proactively reported on the volumes of member company antimicrobial active ingredients sold in the U.S. At the individual company level, reporting of finished product distribution data to the FDA is a regulatory requirement, with applications to surveillance and pharmacovigilance. An accounting of product manufactured is done for purposes of good business practices, as well as marketing analyses. Additional applications of antimicrobial usage data might include use in risk assessments, such as for the FDA's Center for Veterinary Medicine Guidance for Industry #152 for the evaluation of the microbiological safety of antimicrobials intended for use in food animals. Compilation of national usage data will be a complex undertaking, hindered by issues such as confidentiality, auditing, field use practice variations, population dynamics (e.g. disease incidence, market conditions for poultry and livestock production), and generic usage. The amounts or volumes in pounds should be considered relative to the large number of animals under husbandry in the United States. Large volumes might seem impressive unless put into proper context. Until such time as a clearly defined application of national usage data is agreed, it is recommended that local usage programs will provide more useful information to perpetuate prudent antimicrobial use in animals.     

Antimicrobial drug use in veterinary medicine

Recognizing the importance of antimicrobial resistance and the need for veterinarians to aid in efforts for maintaining the usefulness of antimicrobial drugs in animals and humans, the Board of Regents of the American College of Veterinary Internal Medicine charged a special committee with responsibility for drafting this position statement regarding antimicrobial drug use in veterinary medicine. The Committee believes that veterinarians are obligated to balance the well-being of animals under their care with the protection of other animals and public health. Therefore, if an animal's medical condition can be reasonably expected to improve as a result of treatment with antimicrobial drugs, and the animal is under a veterinarian's care with an appropriate veterinarian-client-patient relationship, veterinarians have an obligation to offer antimicrobial treatment as a therapeutic option. Veterinarians also have an obligation to actively promote disease prevention efforts, to treat as conservatively as possible, and to explain the potential consequences associated with antimicrobial treatment to animal owners and managers, including the possibility of promoting selection of resistant bacteria. However, the consequences of losing usefulness of an antimicrobial drug that is used as a last resort in humans or animals with resistant bacterial infections might be unacceptable from a public or population health perspective. Veterinarians could therefore face the difficult choice of treating animals with a drug that is less likely to be successful, possibly resulting in prolonged or exacerbated morbidity, to protect the good of society. The Committee recommends that voluntary actions be taken by the veterinary profession to promote conservative use of antimicrobial drugs to minimize the potential adverse effects on animal or human health. The veterinary profession must work to educate all veterinarians about issues related to conservative antimicrobial drug use and antimicrobial resistance so that each individual is better able to balance ethical obligations regarding the perceived benefit to their patients versus the perceived risk to public health. Specific means by which the veterinary profession can promote stewardship of this valuable resource are presented and discussed in this document.     

Fluoroquinolones in animal health

The fluoroquinolones are a series of synthetic antibacterial agents that are undergoing extensive investigation for both human and veterinary use in the treatment of a variety of bacterial infections. These agents work through the inhibition of DNA gyrase, interfering with the supercoiling of bacterial chromosomal material. As a result, these agents are rapidly bactericidal primarily against gram-negative bacteria, mycoplasma, and some grampositive bacteria, with most having little to no activity against group D streptococci and obligate anaerobic bacteria. Resistance develops slowly and is almost always chromosomal and not plasmid-mediated. However, development of resistance to the fluoroquinolones and transfer of that resistance among animal and human pathogens have become a hotly debated issue among microbiologists. The fluoroquinolones are a current antimicrobial class whose use in veterinary medicine is being scrutinized. From a pharmacokinetic perspective, these agents are variably but well absorbed from the gastrointestinal tract and almost completely absorbed from parenteral injection sites, and they are well distributed to various tissues in the body. The fluoroquinolones are metabolized and renally excreted, with many of them having approximately equal excretion by the hepatic and the renal excretory systems. The primary toxicity observed at therapeutic doses involves the gastrointestinal system and phototoxicity, although at higher doses central nervous system toxicity and ocular cataracts are observed. Administration to immature animals may result in erosive arthropathies at weight-bearing joints, and administration of high doses to pregnant animals results in maternotoxicity and occasionally embryonic death. The fluoroquinolones are approved for indications such as urinary tract infections and soft tissue infections in dogs and cats and colibacillosis in poultry. Approval for bovine respiratory disease in the United States is being sought. Other indications for which the fluoroquinolones have been used in animal health include deep-seated infections, prostatitis, and other bacterial infections resistant to standard antimicrobial therapy.     

The human health implication of the use of antimicrobial agents in animal feeds

Antimicrobials given in subtherapeutic levels in feed are credited with having contributed to lower cost of meat, milk and eggs. The practice often is associated with the acquisition of resistant enteric flora by the involved animals, and this may in turn contribute to the human reservoir of antimicrobial resistant coliforms and salmonellae. Associated farm workers may transiently acquire resistant flora and on rare occasions develop salmonellosis. Although irrefutable evidence of growth promotant properties of antibiotics in animal feed was provided 30 to 40 years ago, additional studies on mechanisms of the effect are presently needed. It may be possible to identify factors effective in promoting growth without deleterious effects on flora. A national surveillance programme of antimicrobial utilisation (both subtherapeutic and therapeutic) among food producing animals should be established. Molecular epidemiologic research efforts will need to be undertaken to establish whether genetic information of animal origin importantly contributes to the human environmental pool of antimicrobial resistance. In the meantime, it does not appear that the use of drugs as feed additives, while allowing their unrestricted use for therapy in both animals and persons, would favorably influence the problems of antimicrobial resistance of salmonellosis in human populations.     

Extended-spectrum beta-lactamases-producing gram-negative bacteria in companion animals: action is clearly warranted!

Extended-spectrum beta-lactamases (ESBL)-producing Gram-negative bacteria pose a serious threat to Public Health in human medicine as well as increasingly in the veterinary context worldwide. Several studies reported the transmission of zoonotic multidrug resistant bacteria between food-producing animals and humans, whilst the contribution of companion animals to this scenario is rather unknown. Within the last decades a change in the social role of companion animals has taken place, resulting in a very close contact between owners and their pets. As a consequence, humans may obtain antimicrobial resistant bacteria or the corresponding resistance genes not only from food-producing animals but also via close contact to their pets.This may give rise to bacterial infections with limited therapeutic options and an increased risk of treatment failure. As beta-lactams constitute one of the most important groups of antimicrobial agents in veterinary medicine, retaliatory actions in small animal and equine practices are urgently needed. This review addresses the increasing burden of extended-spectrum beta-lactam resistance among Enterobacteriaceae isolated from companion animals. It should emphasize the urgent need for the implementation of antibiotic stewardship as well as surveillance and monitoring programs of multi resistant bacteria in particular in view of new putative infection cycles between humans and their pets.     

Antimicrobial drug use and resistance in dogs

Fifteen years (1984-1998) of records from a Veterinary Teaching Hospital were analyzed to determine whether antimicrobial drug resistance in coagulase-positive Staphylococcus spp. (S. aureus, S. intermedius) isolated from clinical infections in dogs has increased, and whether there has been a change in the species of bacteria isolated from urinary tract infections in dogs. In coagulase-positive Staphylococcus spp., a complex pattern showing both increases and decreases of resistance to different classes of antimicrobial drugs was observed, reflecting the changing use of different antimicrobial drug classes in the hospital over a similar period (1990-1999). In canine urinary tract infections identified from 1984 to 1998, an increase in the incidence of multiresistant Enterococcus spp. was apparent, with marginal increases also in incidence in Enterobacter spp. and in Pseudomonas aeruginosa, both of which, like Enterococcus spp., are innately antimicrobial-resistant bacteria. A survey of directors of veterinary teaching hospitals in Canada and the United States identified only 3 hospitals that had any policy on use of "last resort" antimicrobial drugs (amikacin, imipenem, vancomycin). Evidence is briefly reviewed that owners may be at risk when dogs are treated with antimicrobial drugs, as well as evidence that some resistant bacteria may be acquired by dogs as a result of antimicrobial drug use in agriculture. Based in part on gaps in our knowledge, recommendations are made on prudent use of antimicrobial drugs in companion animals, as well as on the need to develop science-based infection control programs in veterinary hospitals.     

Monitoring of antimicrobial resistance among food animals: principles and limitations

Large amounts of antimicrobial agents are in the production of food animals used for therapy and prophylactics of bacterial infections and in feed to promote growth. The use of antimicrobial agents causes problems in the therapy of infections through the selection for resistance among bacteria pathogenic for animals or humans. Current knowledge regarding the occurrence of antimicrobial resistance in food animals, the quantitative impact of the use of different antimicrobial agents on selection for resistance and the most appropriate treatment regimes to limit the development of resistance is incomplete. Programmes monitoring the occurrence and development of resistance are essential to determine the most important areas for intervention and to monitor the effects of interventions. When designing a monitoring programme it is important to decide on the purpose of the programme. Thus, there are major differences between programmes designed to detect changes in a national population, individual herds or groups of animals. In addition, programmes have to be designed differently according to whether the aim is to determine changes in resistance for all antimicrobial agents or only the antimicrobial agents considered most important in relation to treatment of humans. In 1995 a continuous surveillance for antimicrobial resistance among bacteria isolated from food animals was established in Denmark. Three categories of bacteria, indicator bacteria, zoonotic bacteria and animal pathogens are continuously isolated from broilers, cattle and pigs and tested for susceptibility to antimicrobial agents used for therapy and growth promotion by disc diffusion or minimal inhibitory concentration determinations. This programme will only detect changes on a national level. However, isolating the bacteria and testing for several antimicrobial agents will enable us to determine the effect of linkage of resistance. Since 1995 major differences in the consumption pattern of different antimicrobial agents have occurred in Denmark. The Danish monitoring programme has enabled us to determine the effect of these changes on the occurrence of resistance. The Danish monitoring is, however, not suited to determine changes on a herd level or to detect emergence of new types of resistance only occurring at a low level.     

Overview of issues pertaining to the manufacture, distribution, and use of antimicrobials in animals and other information relevant to animal antimicrobial use data collection in the United States

This paper provides condensed literature review and contextual information concerning antimicrobial use in animals and antimicrobial use data collection techniques. Information is summarized into the following topics: (I) antimicrobial use for animal growth promotion; (II) regulatory framework for approval of veterinary antimicrobials and feed additives in the United States; (III) animal health product manufacturing and distribution networks; (IV) existing estimates of animal antimicrobial use in the United States; (V) additional sources for animal use data in the United States; (VI) recommendations from international expert groups; (VII) animal antimicrobial use surveillance systems in other nations and (VIII) human use data collection systems in the United States.     

Stakeholder position paper: economist's perspectives on antibiotic use in animals

Economics seeks to understand and explain the allocation of resources within society and to suggest appropriate policy to achieve goals such as optimal efficiency. Relating antimicrobial use and antibiotic resistance is a complex task and requires very clear and careful analyses of many relationships. To address these relationships, antibiotic use data must be linked with other basic data. Ideally, a complex relational database needs to be developed. These must include data on: antimicrobial usage, farm-level animal productivity, basic disease, basic farm management, consumer response, and antimicrobial resistance at multiple levels (farm, during process, on a variety of both animal, vegetable and grain-derived food products, from humans, from other animal species, and from the environment) among other data. Such a complex relational database can help with the attribution and risk assessment process. Also these linked data are needed in order to develop the economic production models and other economic models, as well as control for confounding so that there is both adequate and appropriate statistical control. Antimicrobial usage data may become economically important for reasons unrelated to animal productivity and animal health. With expanding global trade of animals and animal products, there have been changes in restrictions and regulations associated with the movement of products. Future trade opportunities may be linked to antimicrobial usage. The European Union banned the use of antimicrobials for growth-promoting purposes based on perceived risk and on public opinion. Monitoring antimicrobial use, disease occurrence, and resistance patterns following changes in usage that are a result of either policy changes or response to new information will help in the understanding of the complex relationships in microbial and disease ecology. There is a lot of evidence substantiating the productivity and profitability gains to producers from the use of antimicrobials. There is also evidence for the potential gains to consumers, both from an economic perspective as well as from a health perspective. Economists can help identify the implications of these relationships both at a micro- and macro-economic level; both relative to producer and to consumer welfare. We are at a pivotal time in history with sufficient analytical expertise and tools to address this complex issue from a scientific perspective. Linking various agencies so there can be coordination of data collection and data sharing is needed to successfully address this topic.     

The human health implication of the use of antimicrobial agents in animal feeds

Summary

Antimicrobials given in subtherapeutic levels in feed are credited with having contributed to lower cost of meat, milk and eggs. The practice often is associated with the acquisition of resistant enteric flora by the involved animals, and this may in turn contribute to the human reservoir of antimicrobial resistant coliforms and salmonellae. Associated farm workers may transiently acquire resistant flora and on rare occasions develop salmonellosis. Although irrefutable evidence of growth promotant properties of antibiotics in animal feed was provided 30 to 40 years ago, additional studies on mechanisms of the effect are presently needed. It may be possible to identify factors effective in promoting growth without deleterious effects on flora. A national surveillance programme of antimicrobial utilisation (both subtherapeutic and therapeutic) among food producing animals should be established. Molecular epidemiologic research efforts will need to be undertaken to establish whether genetic information of animal origin importantly contributes to the human environmental pool of antimicrobial resistance. In the meantime, it does not appear that the use of drugs as feed additives, while allowing their unrestricted use for therapy in both animals and persons, wouldfavorably influence the problems of antimicrobial resistance of salmonellosis in human populations.     

Antimicrobial resistance in bacteria from Swiss veal calves at slaughter

Bacteria with antimicrobial resistance can be transferred from animals to humans and may compromise antimicrobial treatment in case of infection. To determine the antimicrobial resistance situation in bacteria from Swiss veal calves, faecal samples from 500 randomly selected calves originating from 129 farms were collected at four big slaughterhouses. Samples were cultured for Escherichia coli, Enterococcus sp. and Campylobacter sp. and isolated strains were tested for antimicrobial susceptibility to selected antimicrobial agents by the minimal inhibitory concentration technique using the broth microdilution method. From 100 farms, data on farm management, animal husbandry and antimicrobial treatments of the calves were collected by questionnaire. Risk factors associated with antimicrobial resistance were identified by logistic regression. In total, 467 E. coli, 413 Enterococcus sp. and 202 Campylobacter sp. were isolated. Of those, 68.7%, 98.7% and 67.8%, respectively, were resistant to at least one of the tested antimicrobial agents. Resistance was mainly observed to antimicrobials frequently used in farm animals. Prevalence of resistance to antimicrobials important for human treatment was generally low. However, a rather high number of quinupristin/dalfopristin-resistant Enterococcus faecium and ciprofloxacin-resistant Campylobacter sp. were detected. External calf purchase, large finishing groups, feeding of milk by-products and administration of antimicrobials through feed upon arrival of the animals on the farm significantly increased the risk of antimicrobial resistance at farm level. Participation in a quality assurance programme and injection of a macrolide upon arrival of the animals on the farm had a protective effect. The present study showed that veal calves may serve as a reservoir for resistant bacteria. To ensure food safety, veal calves should be included in the national monitoring programme for antimicrobial resistance in farm animals. By improving farm management and calf husbandry the prevalence of resistance may be reduced.     

Developing new regulatory approaches to antimicrobial safety

Resistance to antimicrobial agents is of concern to public health officials worldwide. In industrialized countries, a significant source of antimicrobial-resistant food-borne infections in humans is the acquisition of resistant bacteria originating from animals. The US Food and Drug Administration (FDA) is committed to resolving the public health impact arising from the use of antimicrobial drugs in food-producing animals. The FDAs goal is to ensure that significant human antimicrobial therapies are not compromised or lost while providing for the safe use of antimicrobials in food animals. Recently the FDA published a guidance document titled 'Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to their Microbiological Effects on Bacteria of Human Health Concern' (US Food and Drug Administration, Center for Veterinary Medicine, 2003). This document outlines a pathway drug sponsors can use to address concerns about antimicrobial resistance prior to approval of their drug. The process uses a qualitative risk assessment approach to assess the potential of the intended use of a product to develop resistance in bacteria that may harm humans. The level of risk determines the level of risk management that is required for the drug to be used. The Food and Drug Administration (FDA) always has the option of not approving a drug if the risk of a public health consequence is too high.