Public health and policy

Antimicrobial agent usage data are essential for focusing efforts to reduce misuse and overuse of antimicrobial agents in food producing animals because these practices may select for resistance in bacteria of animals. Transfer of resistant bacteria from animals to humans can lead to human infection caused by resistant pathogens. Resistant infections can lead to treatment failures, resulting in prolonged or more severe illness. Multiple World Health Organization (WHO) reports have concluded that both antimicrobial resistance and antimicrobial usage should be monitored on the national level. The system for collecting antimicrobial usage data should be clear and transparent to facilitate trend analysis and comparison within and among countries. Therapeutic, prophylactic and growth promotion use should be recorded, along with route of administration and animal species and/or production class treated. The usage data should be compared to resistance data, and the comparison should be made available in a timely manner. In the United States, surveillance of antimicrobial resistance in foodborne bacteria is performed by the National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria, however, the United States still lacks a mechanism for collecting antimicrobial usage data. Combined with antimicrobial resistance information from NARMS, antimicrobial usage data will help to direct education efforts and policy decisions, minimizing the risk that people will develop antimicrobial resistant infections as a result of eating food of animal origin. Ultimately mitigation strategies guided by usage data will be more effective in maintaining antimicrobial drugs for appropriate veterinary use and in protecting human health.     

Infections caused by multidrug-resistant bacteria in an equine hospital (2012–2015)

Multidrug-resistant (MDR) bacteria are an emerging threat in human and veterinary medicine. There are few reports about infections caused by MDR isolates in horses. The aim of this study was to provide an overview of infections caused by MDR bacteria at the Equine Hospital Zurich between 2012 and 2015. Medical records were searched for horses with confirmed MDR bacterial infection. Multidrug resistance was defined according to human guidelines specific for each pathogen. MDR isolates were most commonly isolated from post-procedural infections (53/110, 48%), followed by musculoskeletal (16/110, 15%) and soft tissue infections (16/110, 15%). Escherichia coli (32/158, 20%) and Staphylococcus aureus (25/158, 16%) were the most common isolates. High resistance rates precluded therapy with commonly used antimicrobial drugs. The overall mortality rate was 20% (22/108) but depended on the localisation of the infection. Antimicrobial treatment prior to development of infection was reported for 89% (91/102) of horses. This study showed that MDR pathogens, mainly MDR E. coli and MRSA, cause a considerable number of infections in horses. A wide range of infections was seen, however, nosocomial infections predominated. These cases are typically hospitalised, pretreated with antibiotics, and suffering from comorbidities putting them at high-risk for acquiring infections caused by MDR isolates. The mortality of such infections was generally low but depended on site of infection.     

Antibiotic prophylaxis in veterinary cancer chemotherapy: A review and recommendations

Bacterial infection following cancer chemotherapy‐induced neutropenia is a serious cause of morbidity and mortality in human and veterinary patients. Antimicrobial prophylaxis is controversial in the human oncology field, as any decreased incidence in bacterial infections is countered by patient adverse effects and increased antimicrobial resistance. Comprehensive guidelines exist to aid human oncologists in prescribing antimicrobial prophylaxis but similar recommendations are not available in veterinary literature. As the veterinarian's role in antimicrobial stewardship is increasingly emphasized, it is vital that veterinary oncologists implement appropriate antimicrobial use. By considering the available human and veterinary literature we present an overview of current clinical practices and are able to suggest recommendations for prophylactic antimicrobial use in veterinary cancer chemotherapy patients.     

Responsible antimicrobial use in critically ill adult horses

Due to increasing antimicrobial resistance, pressure on veterinarians is mounting to adhere to responsible use of antimicrobial drugs. Antimicrobials are frequently included in the treatment of systemically ill horses due to the strong likelihood of an infection and the innate difficulties in differentiating systemic inflammation secondary to noninfectious from infectious causes. In light of increasing antimicrobial drug resistance and the potential negative impact of antimicrobials on equine patients, every attempt should be made to identify noninfectious disease, choose first-line antimicrobials and discontinue treatment as soon as possible. In most cases, a short duration of antimicrobial therapy ranging from a single dose (e.g. preoperatively) to 24–72 h might be sufficient with long-term treatment being rarely required. This article aims to provide practical guidelines for antimicrobial drug usage in critically ill adult horses by describing ancillary diagnostic aids that can help establishing whether or not an infection is present, discussing commonly encountered pathogens and their typical antimicrobial drug sensitivity patterns, and providing some guidance how to safely shorten the duration of antimicrobial therapy.     

Antimicrobial labelling in Australia: a threat to antimicrobial stewardship?

Antimicrobial resistance is a public health emergency, placing veterinary antimicrobial use under growing scrutiny. Antimicrobial stewardship, through appropriate use of antimicrobials, is a response to this threat. The need for antimicrobial stewardship in Australian veterinary practices has had limited investigation. A 2016 survey undertaken to investigate antimicrobial usage patterns by Australian veterinarians found that antimicrobial dose rates were varied and often inappropriate. Doses of procaine penicillin in horses and cattle were often low, with 68% and 90% of respondents, respectively, reporting doses that were unlikely to result in plasma concentrations above minimum inhibitory concentrations for common equine and bovine pathogens. Frequency of penicillin administration was also often inappropriate. Gentamicin doses in horses were largely appropriate (89% of dose rates appropriate), but 9% of respondents reported twice daily dosing. Amoxycillin and amoxycillin‐clavulanate were administered at the appropriate doses, or above, to dogs and cats by 54% and 70% of respondents, respectively. Here, we explore the potential reasons for inappropriate antimicrobial dose regimens and report that antimicrobial labels often recommend incorrect dose rates and thus may be contributing to poor prescribing practices. Changes to legislation are needed to ensure that antimicrobial drug labels are regularly updated to reflect the dose needed to effectively and safely treat common veterinary pathogens. This will be especially true if changes in legislation restrict antimicrobial use by veterinarians to the uses and doses specified on the label, thus hampering the current momentum towards improved antimicrobial stewardship.     

Hypocalcemia in a critically ill patient

Objective: To present a case of clinical hypocalcemia in a critically ill septic dog. Case summary: A 12‐year old, female spayed English sheepdog presented in septic shock 5 days following hemilaminectomy surgery. Streptococcus canis was cultured from the incision site. Seven days after surgery, muscle tremors were noted and a subsequent low serum ionized calcium level was measured and treated. Intensive monitoring, fluid therapy, and antibiotic treatment were continued because of the sepsis and hypocalcemia, but the dog was euthanized 2 weeks after surgery. New or unique information provided: Low serum ionized calcium levels are a common finding in critically ill human patients, especially in cases of sepsis, pancreatitis, and rhabdomyolysis. In veterinary patients, sepsis or streptococcal infections are not commonly thought of as a contributing factor for hypocalcemia. Potential mechanisms of low serum ionized calcium levels in critically ill patients include intracellular accumulation of calcium ions, altered sensitivity and function of the parathyroid gland, alterations in Vitamin D levels or activity, renal loss of calcium, and severe hypomagnesemia. Pro‐inflammatory cytokines and calcitonin have also been proposed to contribute to low ionized calcium in the critically ill. Many veterinarians rely on total calcium levels instead of serum ionized calcium levels to assess critical patients and may be missing the development of hypocalcemia. Serum ionized calcium levels are recommended over total calcium levels to evaluate critically ill veterinary patients.     

2019年我国兽用抗菌药物使用情况分析研究

对2019年国内兽用抗菌药物销量数据进行了统计分析,按照兽用抗菌药销售量等同于使用量的评价指标,结果发现,国内兽药使用总量为37159.12吨;其中,使用量最大的是四环素类,占比36.56%;促生长用抗菌药的用量为14871.05吨,占比48.12%;每吨动物产品兽用抗菌药使用量为160 g。与2018年相比,兽用抗菌药物使用量略有上升,每吨动物产品使用的抗菌药物量也同比增加,这提示我国兽用抗菌药物使用管理不能放松,减抗政策需继续实施,久久为功。     

Antimicrobial use in food and companion animals

The vast literature on antimicrobial drug use in animals has expanded considerably recently as the antimicrobial resistance (AMR) crisis in human medicine leads to questions about all usage of antimicrobial drugs, including long-term usage in intensively managed food animals for growth promotion and disease prevention. Attention is also increasingly focusing on antimicrobial use and on bacterial resistance in companion animals, which are in intimate contact with the human population. They may share resistant bacteria with their owners, amplify resistant bacteria acquired from their owners, and act as a reservoir for human infection. Considerable effort is being made to describe the basis of AMR in bacterial pathogens of animals. Documentation of many aspects of use of antimicrobials in animals is, however, generally less developed and only a few countries can describe quantities of drugs used in animals to kg levels annually. In recent years, many national veterinary associations have produced 'prudent use guidelines' to try to improve antimicrobial drug use and decrease resistance, but the impact of guidelines is unknown. Within the evolving global movement for 'antimicrobial stewardship', there is considerable scope to improve many aspects of antimicrobial use in animals, including infection control and reduction of use, with a view to reducing resistance and its spread, and to preserving antimicrobial drugs for the future.     

Relative adrenal insufficiency in critical illness

Objective: To review the effects of critical illness on hypothalamic–pituitary–adrenal (HPA) function in human and veterinary medicine. Data sources: Data from human and veterinary literature was reviewed. Human data synthesis: Relative adrenal insufficiency (RAI) appears to be common in critically ill human patients with sepsis or septic shock. Hypotension that is refractory to fluid therapy and requires vasopressors is the most common presentation of RAI in the human intensive care unit (ICU). Many investigators now advocate the use of a low‐dose adrenocorticotropin hormone stimulation test to diagnose RAI. It is important to evaluate for the presence of adrenal dysfunction, because current data suggest that treatment with ‘stress’ or low doses of glucocorticoids (200–300 mg hydrocortisone daily) may improve patient outcome in humans. Veterinary data synthesis: There is a paucity of controlled studies in the veterinary literature regarding the effects of critical illness on HPA function. The results of these studies are varied. However, research models of sepsis and hemorrhagic shock suggest the existence of RAI in animals. Prospective clinical studies are needed to further examine pituitary–adrenal response to severe illness in veterinary patients, and to determine if there are therapeutic options, including glucocorticoid administration, which will improve patient outcome in animals. Conclusions: RAI is well documented in critically ill human patients, yet little is known about adrenal dysfunction in veterinary critically ill patients. A small number of studies suggest that RAI may exist in certain subpopulations of veterinary patients. The syndrome of RAI could be considered as a differential diagnosis in seriously ill veterinary patients that fail to respond to appropriate therapy, especially when hypotension refractory to fluid and vasopressor therapy is encountered. This disorder may represent a previously unidentified syndrome in critically ill veterinary patients with important therapeutic implications.     

Antimicrobial resistance in livestock

Antimicrobial resistance may become a major problem in veterinary medicine as a consequence of the intensive use and misuse of antimicrobial drugs. Related problems are now arising in human medicine, such as the appearance of multi-resistant food-borne pathogens. Product characteristics, dose, treatment interval and duration of treatment influence the selection pressure for antimicrobial drug resistance. There are theoretical, experimental and clinical indications that the emergence of de novo resistance in a pathogenic population can be prevented by minimizing the time that suboptimal drug levels are present in the infected tissue compartment. Until recently, attention has been focused on target pathogens. However, it should be kept in mind that when antimicrobial drugs are used in an individual, resistance selection mainly affects the normal body flora. In the long term, this is at least equally important as resistance selection in the target pathogens, as the horizontal transfer of resistance genes converts almost all pathogenic bacteria into potential recipients for antimicrobial resistance. Other factors contributing to the epidemiology of antimicrobial resistance are the localization and size of the microbial population, and the age, immunity and contact intensity of the host. In livestock, dynamic herd-related resistance patterns have been observed in different animal species.     

Nosocomial infections.

Nosocomial infections and antimicrobial resistance are topics that have been intensely studied in human medicine because of their significant impact on human health. In recent years, concerns have been raised that the use of antibiotics in veterinary medicine, animal husbandry, and agriculture may be contributing to the development of resistance in common bacterial species affecting human beings. Although there is inadequate proof at this time that the resistance is transmitted from animals to people, if antibiotics continue to be used indiscriminately in veterinary medicine, veterinarians may find themselves facing regulations restricting the use of some antibiotics. Nosocomial infections have been reported in veterinary medicine and are likely to increase in prevalence with the increase in intensive care practices in many hospitals. Prolonged hospitalization and the use of invasive devices and procedures increase the risk of nosocomial disease. As in human medicine, organisms isolated in the nosocomial infections reported in veterinary patients have an increasingly broad spectrum of antimicrobial resistance. Despite these findings, the use of empiric and prophylactic antibiotic therapy is still widespread in veterinary medicine. Nosocomial infections and antimicrobial resistance may have a serious impact on the future of [table: see text] veterinary medicine, because the cost and ability to treat our patients may be affected by the loss of access to or effectiveness of antimicrobial drugs. Despite the millions of dollars spent on research to reduce the incidence of nosocomial infections in human patients, the strategies that have consistently proven successful are simple and inexpensive to implement. The most important factor in preventing nosocomial infections is improving the hygiene practices of health care providers. Hand-washing or the use of disposable gloves can dramatically reduce the transmission of bacteria between patients. Aseptic technique should be used in the placement and management of all invasive devices. All staff members should be educated on the risks and symptoms associated with nosocomial infections so that cases can be detected early and treated appropriately. We in the veterinary profession have the opportunity to learn from the experiences of the human medical profession and can take steps to prevent the escalation of nosocomial infections and their impact on our profession.     

Current controversies in equine antimicrobial therapy

Controversies exist regarding the use, misuse and potential overuse of antimicrobial treatments in foals and adults. When antimicrobials are required for treatment of infectious diseases, veterinarians should follow a logical approach and not simply reach for the newest drug. Targeted, single drug therapy is probably best, and culture and sensitivity testing should be undertaken. The most likely infectious agent, potential drug toxicities, and age‐appropriate dose and route should be considered. The development of an increasing number of different multiple drug resistant pathogens requires that veterinarians use antimicrobial drugs responsibly to protect veterinary patients and the public at large.     

The distribution of pathogens and their antimicrobial susceptibility patterns among canine surgical wound infections in Sweden in relation to different risk factors

Background

Surgical site infection (SSI) is a common nosocomial infection in dogs and a growing concern in veterinary hospitals as an increase in multidrug-resistant pathogens is reported. Despite the need for rational and prudent antimicrobial use, few peer-reviewed and published veterinary studies have investigated the pathogenic growth including susceptibility patterns of the isolated pathogens in canine SSIs.The first objective of the present study was to estimate the distribution of bacterial pathogens in dogs with SSI and to investigate whether this was influenced by type of surgical procedure (clean, clean-contaminated, contaminated or dirty), duration of hospitalization, wound classification and depth of the infection, or antimicrobial treatment. The second objective was to assess susceptibility patterns to clinically relevant antimicrobials.During three years, four animal referral hospitals and three small animal clinics submitted bacterial swabs from canine SSIs for culture and susceptibility, together with a questionnaire completed by the attending clinician.

Results

Approximately two thirds of the in total 194 isolates were staphylococci. Staphylococcus pseudintermedius was the most prevalent finding (46%) followed by beta haemolytic Streptococcus spp. (24%). No associations between distribution of the isolated pathogens and classification of the surgical procedure, duration of hospitalization or depth of the SSI were shown, with the exception of Escherichia coli isolates being significantly more often found in deep wound infections than in superficial skin infections.Overall the possibilities of finding first generations antimicrobials to treat the SSIs included in the study were favorable, as the isolated pathogens were mostly without acquired antimicrobial resistance and multidrug resistance was uncommon. There were only three cases of methicillin-resistant S. pseudintermedius-infections (one percent of all isolates), one case of extended-spectrum beta-lactamase producing E. coli-infection, and no methicillin-resistant Staphylococcus aureus infections.

Conclusions

None of the investigated factors were shown to influence the distribution of bacterial pathogens. The majority of SSIs were caused by staphylococci, and S. pseudintermedius was the most prevalent pathogen. Based on the study results, use of first-line antimicrobials prior to receiving culture and susceptibility results is a rational empirical antimicrobial therapy for the studied dog population.     

Multidrug-resistant E. coli and enterobacter extraintestinal infection in 37 dogs

BACKGROUND: Extraintestinal infections caused by multidrug-resistant (MDR) Escherichia coli and Enterobacter are becoming more common in veterinary medicine. OBJECTIVE: To generate hypotheses for risk factors for dogs acquiring extraintestinal infection caused by MDR E. coli and Enterobacter, describe antimicrobial resistance profiles and analyze treatment and clinical outcomes. ANIMALS: Thirty-seven dogs diagnosed with extraintestinal infection caused by MDR E. coli and Enterobacter spp. between October 1999 and June 2006. METHODS: Retrospective case series assembled from hospital records data, including clinical history before 1st MDR isolation and treatment outcome. Identity and antimicrobial susceptibility profiles were confirmed by standard microbiological techniques for 57 isolates. RESULTS: Most dogs had an underlying disease condition (97%), received prior antimicrobial treatment (87%), were hospitalized for >or =3 days (82%), and had a surgical intervention (57%). The urinary tract was the most common infection site (62%), and urinary catheterization, bladder stasis, or both were common among dogs (24%). Some dogs were treated with high doses of co-amoxyclavulanate (n = 14) and subsequently recovered even though the isolates showed in vitro resistance to this antimicrobial. Other dogs were successfully treated with chloramphenicol (n = 11) and imipenem (n = 2). CONCLUSION AND CLINICAL IMPORTANCE: Predisposing disease condition, any prior antimicrobial use rather than a specific class of antimicrobial, duration of hospitalization, and type of surgical procedure might be risk factors for acquiring MDR extraintestinal infections. Whereas culture and sensitivity results can indicate use of last-resort antimicrobials such as imipenem for MDR infections, some affected dogs can recover after administration of high doses of co-amoxyclavulanate.     

Enrofloxacin use in a long-distance transport model of equine respiratory disease

Successful clinical management of bacterial pneumonia in horses depends on the administration of an appropriate antimicrobial agent at an adequate dosage and frequency, given by the correct route of administration for an adequate duration. Empiric antimicrobial therapy should be based on the clinician's experience and current veterinary literature. Based on the frequency of Gram-positive bacterial pathogens isolated from horses with bacterial pneumonia, every effort should be made to provide antimicrobial coverage for this class of pathogens. Gram-negative pathogens may co-exist; therefore, broad spectrum antimicrobial coverage may be necessary. Antimicrobial agents posing potential drug related risks (e.g. nephrotoxicity in dehydrated patients, peracute colitis in racehorses) may not be appropriate for empiric use and enrofloxacin offers an enhanced spectrum of antimicrobial activity with reduced risk of complication. Our findings indicate that in cases of exclusive Gram-positive respiratory disease, solo therapy with enrofloxacin is not indicated.     

Blood thiamine levels in clinically normal goats and goats with suspected polioencephalomalacia

Abstract

AIMS: To identify and describe culture and antimicrobial resistance (AMR) patterns in bacteria isolated from canine urinary samples submitted to a New Zealand veterinary diagnostic laboratory.

METHODS: Records from a veterinary diagnostic laboratory were examined for bacterial isolates cultured from canine urine samples between January 2005 and December 2012. Culture and susceptibility results were compiled with information on the age, sex and breed of dog. Repeat submissions were removed. Susceptibility was assessed using results of the Kirby-Bauer disk diffusion method, for a standard panel including amoxicillin-clavulanic acid (AMC), cefovecin (from 2010–2012), cephalothin, clindamycin, enrofloxacin and trimethoprim-sulphonamide (TMS).

RESULTS: A total of 5,786 urine samples were submitted for analysis, and 3,135 bacterial isolates were cultured from 2,184 samples. Of these 3,135 isolates, 1,104 (35.2%) were Escherichia coli, 442 (14.1%) were Staphylococcus spp., 357 (11.4%) Proteus mirabilis and 276 (8.8%) were Enterococcus spp. The frequency of culture-positive samples increased with increasing age in both female and male dogs (p<0.001). The percentage of E. coli isolates resistant to AMC and cephalothin increased between 2005 and 2012 (p<0.001), as did resistance to enrofloxacin (p=0.022), but there was no change in resistance to TMS (p=0.696). Enrofloxacin was the antimicrobial with the least resistance shown by the four most common bacteria isolated during the course of the study.

CONCLUSIONS AND CLINICAL RELEVANCE: The results of this study provide important regional information regarding the prevalence of bacterial uropathogens and their susceptibility patterns. There was an increase in resistance to some commonly used antimicrobials in the treatment of urinary tract infections. Having access to regional antimicrobial susceptibility results is crucial when forming guidelines for the use of antimicrobials for the treatment of urinary tract infections. Given changes in practising habits and antimicrobial usage over time, ongoing monitoring and surveillance of resistance in pathogens is needed.     

Research Progress on Main Pathogen Resistance of Dairy Cows and Control Technology

At present, the usual and effective method of treating the cow disease caused by pathogens is still antimicrobials. The irrational use of antimicrobials makes bacteria produce resistance, and has become a global problem. The main pathogens of dairy cows include Staphylococcus aureus, Streptococcus, Escherichia coli and so on, which show a trend of multiple drug resistance. It not only brings great challenges for the clinical treatment of dairy cow, but also gives a threat to human health. Antimicrobial resistance is far more than the speed of people developing antimicrobials. Therefore, it is necessary to maintain the efficacy of existing antimicrobials for treating infections. On the one hand, we should master the bacterial resistance mechanism, such as bacterial molecular resistance mechanism, antibiotic efflux mechanism or reducing the intake mechanism, biofilm, so as to help us find the adequate therapeutics; On the other hand, taking different measures to reduce the emergence bacterial resistance, such as plasmid elimination, antibiotic substitutes, the development of efficient and safe antimicrobials, clinical rational drug (combined treatment) and so on. This article reviews dairy cow's main pathogen resistance, drug resistance mechanism, drug resistance control technology and make a prospect for this. It would provide reference for reducing the drug resistance, regulating the use of antimicrobials and improving the therapeutic effect.     

奶牛主要病原菌耐药性及控制技术研究进展

抗菌药仍是治疗病原菌引起的奶牛疾病的常用方法。抗菌药的不合理使用使得细菌产生耐药性已成为全球性的问题,应引起人们的足够重视。奶牛的主要病原菌金黄色葡萄球菌、链球菌、大肠杆菌等也显现出多重耐药的趋势,给奶牛疾病的临床治疗带来困难,同时也威胁人类健康。细菌产生耐药性的速度远超过人们研发抗菌药的速度,因此,保持现有抗菌药的疗效很有必要。一方面应该掌握细菌的耐药机制,如细菌分子耐药机制、抗菌药物外排机制或降低摄入机制、生物膜等,以便找到合适的治疗方法;另一方面采用不同措施减少耐药细菌的出现,如质粒消除、抗菌药替代品、开发高效安全的抗菌药物、临床合理用药（联合治疗）等。作者对奶牛主要病原菌的耐药情况、耐药机制、耐药控制技术进行综述,以期为减少耐药性、规范抗菌药的使用和提高治疗效果提供参考。     

国内外食品源及动物源弯曲菌流行性及耐药性调查研究进展

弯曲菌是重要的食品源性致病微生物,在很多动物中属于正常携带细菌,能通过食物链传递给人类,可引起人类肠炎的暴发流行和食物中毒。在畜牧养殖业大量抗菌药物的使用,造成动物源弯曲菌耐药性日益增加,给人类带来健康风险。发达国家很早就开展了动物源性弯曲菌流行性和耐药性监测工作,很多发展中国家也对弯曲菌流行性和耐药性监测越来越重视,文章将就近年来国内外动物源性弯曲菌的流行及耐药情况调查工作做简单的总结,为中国动物源性弯曲菌流行性和耐药性工作的开展提供比较及理论分析数据。     

Prevalence of Salmonella associated with chick mortality at hatching and their susceptibility to antimicrobial agents

The prevalence of Salmonella associated mortality at hatching was investigated in three hatcheries in Jos, central Nigeria. Their susceptibility to antimicrobial agents was also evaluated. S. Kentucky and S. Hadar were isolated. While half of the isolates were from internal organs, 26.7% came from meconial swabs of dead-in-shell embryos, 17.8% from intestinal samples and 4.4% from egg shells. S. Hadar is known to colonise only the gut and is classified as non-invasive, but in this study 82% were obtained from internal organs which suggests that infections with this serotype may also cause invasive disease. Antimicrobial susceptibility tests showed a high prevalence of antimicrobial resistance in the study area with complete resistance to gentamycin, enrofloxacin, nalidixic acid, tetracycline and streptomycin and substantial resistance to triple sulphur and ciprofloxacin. Six multiple resistance profiles were recorded with a high level of multiple resistance to quinolones. Quinolone resistance has implications for veterinary and human therapy as their misuse in poultry could lead to the emergence of resistant animal and zoonotic pathogens.