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.     

Antimicrobial regional limb perfusion: Does it really fight infection?

Over the last decades the use of antimicrobial regional limb perfusion (A-RLP) has increased and A-RLP is nowadays commonly used to treat orthopaedic infections by many equine practitioners. There have been a large number of studies published on the use of A-RLP, many of which describe regional drug pharmacokinetics and clinical safety of the administration of different antimicrobials by A-RLP. A limited number of studies describe the clinical use of A-RLP as prophylactic or therapeutic treatment. However, despite being in use for 30 years there is still limited evidence about the efficacy of A-RLP as a means to prevent and treat orthopaedic infections in horses.     

Stakeholder position paper: dairy producer

Bacterial antimicrobial resistance is a problem common to both animal and public health. An important public policy issue is to develop and implement prudent use practices where antimicrobials are used. As policy develops, there are questions regarding the use of antimicrobials in animal agriculture and whether these uses constitute prudent use. A series of papers assessing the risk to the public health from agricultural use of antimicrobials have consistently concluded that risk estimation is hampered by the lack of data that describe the amount, types, and uses of antimicrobials in animal agriculture. The absence of information has spurred efforts to develop a framework to collect these data. However, the reasons and benefit of collecting these data should be carefully defined. The dairy industry, contrasted to other major animal commodities, is not focused on meat production but on milk production. Milk production is constrained by disease and antimicrobial treatment is a common management tool, but unlike many other animal agricultural systems where the value and safety of the product is measured in the future; the value of milk is zero when an antimicrobial is used in a lactating cow and milk must be discarded because of residues. While there are exceptions, e.g. non-lactating cow therapy, this difference results in antimicrobials being used sporadically and directed at therapy rather than prophylactic uses. In the dairy industry, antimicrobial use data and its consequences may exist in sufficient detail or could be estimated from existing datasets without the expense of additional surveys. Finally, the main food product milk is mainly pasteurized and all shipments of milk from the farm to the processing plant are tested for the presence of antimicrobials. This makes the likelihood of farm-origin antimicrobials or bacteria appearing in finished product very low. This suggests that the use and quantity of antimicrobials in the dairy system has little impact on public health. This does not imply that the dairy industry does not have a significant role in developing guidelines for appropriate and careful application of antimicrobials, but the effort and cost to collect additional data should be used to fund efforts that improve our diagnostic and managerial skills. These data would change the use of antimicrobials by decreasing the rates of disease and ultimately decreasing prophylactic, metaphylactic and therapeutic use of antimicrobial. These studies and outcome are as important to the dairy industry as to public health.     

Overview of the use of antimicrobials for the treatment of bacterial infections in horses

Use of antimicrobial drugs is central to the treatment of primary and secondary bacterial infection in horses. When selecting an antimicrobial to treat confirmed or suspected bacterial infection multiple factors should be considered, including: the likely infectious agent; distribution and dosage of selected drugs; mechanisms of action; and potential side effects. Many of these issues will be covered in subsequent articles in this series. The aim of this paper is to aid the clinician in the rational selection of antimicrobials by reviewing the mode of action, spectrum of activity, pharmacokinetics, pharmacodynamics, indications and potential side effects of the main classes of antimicrobial drugs. Extralabel use of drugs is common in veterinary medicine due to a lack of licensed products. This increases the importance of a thorough understanding of antimicrobials and their possible adverse effects.     

Bacterial pneumonia

Bacterial pneumonia in the horse often occurs secondary to viral respiratory infection; however, primary infections can occur. A diagnosis of bacterial pneumonia is made on the basis of history, physical examination, and laboratory and radiographic findings. Treatment consists of appropriate antimicrobial therapy for at least 7 to 10 days; further therapy may be needed in more severe cases. Prevention of bacterial pneumonia includes attempting to prevent viral respiratory infections and appropriate management to prevent stress to the respiratory tract.     

EXTENSION EDUCATION SYMPOSIUM: The future of biosecurity and antimicrobial use in livestock production in the United States and the role of extension1

As the global population continues to grow, food needs will increase as well. The amount of land and other resources devoted to agriculture production is not expected to grow significantly, leading most to agree that the substantial increases in food production to meet food security needs will come through the development of technologies that improve production efficiency. Diseases are constant threats to efficiency in all segments of agriculture. In livestock production, many of the bacterial pathogens that infect food animals are controlled through the use of antimicrobials. Antimicrobials are currently used in the United States not only to treat specific diseases, but also as feed additives to prevent bacterial disease in general or to improve growth performance. In recent years, there have been several proposals in the United States, both at state and federal levels, aimed at curtailing or dramatically reducing the use antimicrobials as feed additives, creating a policy similar to that of the European Union. Here we review the current policies on antimicrobial use in the European Union and their impact on food animal production. In addition, we discuss the future of antimicrobial use in food animal production in the United States and the increasing role of biosecurity programs. Finally, we discuss the role of Cooperative Extension Service in creating improved biosecurity programs and extension programs that provide policy makers and voters information on modern food animal production practices and technologies so that policies and regulations are effective and appropriate.     

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.     

Modes of local drug delivery to the musculoskeletal system.

A number of methods for the local delivery of drugs to musculoskeletal tissues in the horse are now available. Further research is required to document the disposition of drugs delivered by such methods and to correlate this information with efficacy. Perhaps the greatest potential area for the methods discussed is the treatment of synovial and bone infections. To be able to provide high and sustained therapeutic concentrations of antimicrobials to the site of infection should increase the chances of success in such cases. These methods of drug delivery need to be used in conjunction with other management procedures, however, including bacterial culture and sensitivity procedures, systemic antimicrobials, surgical drainage, removal of dead bone or surgical implants, establishment of fracture stability, use of autogenous bone grafts, systemic NSAIDs, and rest.     

Prophylactic use of antibiotics in surgery

"Sound and careful surgery is the sine qua non of wound management; antimicrobials are adjunctive." The key to successful use of prophylactic antibiotics in surgery is careful selection of cases and medication. There are no final rule or formulas that will always give optimal results. Listed below are some guidelines that may assis the clinician in determining the need and form of antimicrobial use. 1. The operation must carry a significant risk of bacterial contamination. Refined-clean and clean procedures should not be given prophylactic antibiotics. 2. Bacterial cultures should be taken when possible, and the medication used for prophylaxis should be effective against the organisms expected to be encountered. 3. Narrow spectrum antibiotics should be used to conserve the body's normal flora. Broad spectrum antibiotics needed to combat resistant infections should not be used for prophylaxis. 4. The antibiotic should be present in the wound in effective concentrations at the time of the incision and be maintained only as long as the risk of new bacterial contamination exists.     

Pharmacokinetic/pharmacodynamic relationships of antimicrobial drugs used in veterinary medicine

The rise in incidence of antimicrobial resistance, consumer demands and improved understanding of antimicrobial action has encouraged international agencies to review the use of antimicrobial drugs. More detailed understanding of relationships between the pharmacokinetics (PK) of antimicrobial drugs in target animal species and their action on target pathogens [pharmacodynamics (PD)] has led to greater sophistication in design of dosage schedules which improve the activity and reduce the selection pressure for resistance in antimicrobial therapy. This, in turn, may be informative in the pharmaceutical development of antimicrobial drugs and in their selection and clinical utility. PK/PD relationships between area under the concentration time curve from zero to 24 h (AUC(0-24)) and minimum inhibitory concentration (MIC), maximum plasma concentration (C(max)) and MIC and time during which plasma concentrations exceed the MIC have been particularly useful in optimizing efficacy and minimizing resistance. Antimicrobial drugs have been classified as concentration-dependent where increasing concentrations at the locus of infection improve bacterial kill, or time-dependent where exceeding the MIC for a prolonged percentage of the inter-dosing interval correlates with improved efficacy. For the latter group increasing the absolute concentration obtained above a threshold does not improve efficacy. The PK/PD relationship for each group of antimicrobial drugs is 'bug and drug' specific, although ratios of 125 for AUC(0-24):MIC and 10 for C(max):MIC have been recommended to achieve high efficacy for concentration-dependent antimicrobial drugs, and exceeding MIC by 1-5 multiples for between 40 and 100% of the inter-dosing interval is appropriate for most time-dependent agents. Fluoroquinolones, aminoglycosides and metronidazole are concentration-dependent and beta-lactams, macrolides, lincosamides and glycopeptides are time-dependent. For drugs of other classes there is limited and conflicting information on their classification. Resistance selection may be reduced for concentration-dependent antimicrobials by achieving an AUC(0-24):MIC ratio of greater than 100 or a C(max):MIC ratio of greater than 8. The relationships between time greater than MIC and resistance selection for time-dependent antimicrobials have not been well characterized.     

Corynebacterium urealyticum urinary tract infection in dogs and cats: 7 cases (1996-2003)

OBJECTIVE: To identify clinical features of Corynebacterium urealyticum urinary tract infection in dogs and cats and antimicrobial susceptibility patterns of C urealyticum isolates. DESIGN: Retrospective study. ANIMALS: 5 dogs and 2 cats. PROCEDURE: Medical records of dogs and cats for which C urealyticum was isolated from urine samples were reviewed. Isolates from clinical cases, along with previously lyophilized unsubtyped isolates of Corynebacterium spp collected between 1977 and 1995, were examined and, if subtyped as C urealyticum, tested for antimicrobial susceptibility. RESULTS: Signalment of infected animals was variable. Prior micturition disorders were common, and all animals had signs of lower urinary tract disease at the time C urealyticum infection was diagnosed. Median urine pH was 8.0; WBCs and bacteria were variably seen in urine sediment. In vitro antimicrobial susceptibility testing of 14 C urealyticum isolates revealed that all were susceptible or had intermediate susceptibility to chloramphenicol, tetracycline, and vancomycin and most were susceptible to enrofloxacin. Thickening of the bladder wall and accumulation of sediment were common ultrasonographic findings. Contrast radiography or cystoscopy revealed findings consistent with encrusting cystitis in 3 dogs. Infection resolved in 2 dogs following surgical debridement of bladder plaques and antimicrobial administration. In 2 other dogs and 1 cat treated with antimicrobials, infection with C urealyticum resolved, but urinary tract infection with a different bacterial species developed. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that preexisting urinary tract disorders are common in dogs and cats with C urealyticum infection. Treatment with appropriate antimicrobials in combination with surgical debridement might eliminate C urealyticum 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.     

Overview of the use of antimicrobial drugs for the treatment of bacterial infections in horses

The use of antimicrobials in veterinary medicine is under great scrutiny with the emergence of antimicrobial resistance in the human population. Equine veterinarians rely on antimicrobials as an essential tool for the treatment of infections in horses, but there is much criticism of some use, particularly prophylaxis. While the appropriate use of antimicrobials can be justified in equine medicine, the misuse cannot. The definition of appropriate use is complex and involves the indication for therapy, antimicrobial selection, dosing regimen and timing and route of administration, duration of therapy and modification of therapy based on microbial susceptibility and clinical response. The aim of this article is to provide guidance on these factors to assist equine veterinarians in determining what constitutes appropriate antimicrobial use in horses.     

Calf-related Drug Use on Holstein Dairy Farms in Southwestern Ontario

Calf-related drug use was studied on 104 randomly selected Holstein dairy farms in southwestern Ontario between October 1980 and July 1983. About 20% of dairy farmers were observed to administer antimicrobials preventively to healthy newborn calves (primarily as commercial “cocktails” of various antimicrobials, vitamins and minerals given in an oral bolus form) at some time during the year. About 30% of the farmers were observed to use vitamins (primarily vitamins A,D and E) preventively. The pattern of types of antimicrobials used preventively appeared to be different from the pattern seen for therapeutic use. Chloramphenicol was the single most commonly used therapeutic antimicrobial in this population of calves, accounting for some 30% of overall therapeutic antimicrobial use. In this study population, the prophylactic use of antimicrobials was associated with a decreased risk of being treated for pneumonia, and of dying, but an increased risk of being treated for scours. Case fatality rates for calves treated therapeutically varied, depending on the antimicrobial used and the routine of treatment. Calves treated with penicillin consistently suffered the highest case fatality rates. Case fatality rates for calves treated with chloramphenicol were considerably higher for calves treated once per day than for calves treated twice per day. For instance, calves first treated for scours with chloramphenicol, if treated once per day, suffered a case fatality rate of 22%. For scouring calves treated twice per day the case fatality rate was just under five percent. Clinical field trials of specific antimicrobials used preventively and therapeutically are required to delineate the conditions under which they might be useful.     

Antimicrobial therapy of selected diseases in turkeys,laying hens,and minor poultry species in Canada

This paper identifies common poultry diseases requiring antimicrobial therapy, antimicrobials deemed efficacious to treat these diseases, and antimicrobial resistance (AMR) in these commodity-pathogen combinations, and describes current residue issues and minor use minor species (MUMS) guidelines. Veterinarians with turkey/layer expertise and diagnosticians were surveyed to determine the bacterial and protozoal diseases diagnosed in the last 5 years. Avian pathogenic Escherichia coli, Staphylococcus aureus, and Ornithobacterium rhinotracheale were the 3 most frequently diagnosed pathogens of turkeys. In layers, E. coli-peritonitis, and Clostridium perfringens/Eimeria spp. infections were the most common diagnoses. A literature review identified 32 antimicrobials as efficacious and/or recommended for treating these diseases. Surveillance and monitoring indicate the presence of enteric resistant organisms from some of these avian species (including resistance to antimicrobials of very high importance to human medicine). This paper highlights the need for surveillance of pathogen frequency, antimicrobial use (AMU), and AMR particularly in turkeys.     

Antimicrobial resistance in beef and dairy cattle production

Observational studies of cattle production systems usually find that cattle from conventional dairies harbor a higher prevalence of antimicrobial resistant (AMR) enteric bacteria compared to organic dairies or beef-cow operations; given that dairies usually use more antimicrobials, this result is not unexpected. Experimental studies have usually verified that application of antimicrobials leads to at least a transient expansion of AMR bacterial populations in treated cattle. Nevertheless, on dairy farms the majority of antibiotics are used to treat mastitis and yet AMR remains relatively low in mastitis pathogens. Other studies have shown no correlation between antimicrobial use and prevalence of AMR bacteria including documented cases where the prevalence of AMR bacteria is non-responsive to antimicrobial applications or remains relatively high in the absence of antimicrobial use or any other obvious selective pressures. Thus, there are multi-factorial events and pressures that influence AMR bacterial populations in cattle production systems. We introduce a heuristic model that illustrates how repeated antimicrobial selection pressure can increase the probability of genetic linkage between AMR genes and niche- or growth-specific fitness traits. This linkage allows persistence of AMR bacteria at the herd level because subpopulations of AMR bacteria are able to reside long-term within the host animals even in the absence of antimicrobial selection pressure. This model highlights the need for multiple approaches to manage herd health so that the total amount of antimicrobials is limited in a manner that meets animal welfare and public health needs while reducing costs for producers and consumers over the long-term.     

Effects of administration of antimicrobials in feed on growth rate and feed efficiency of pigs in multisite production systems

OBJECTIVE: To evaluate effect of various regimens for administration of antimicrobials in feed on growth rate and feed efficiency (feed/gain) of pigs in multisite production systems. DESIGN: Controlled trial. ANIMALS: 24,099 growing pigs in 3 multisite production systems. PROCEDURE: 10 trials involving various regimens for administration of antimicrobials in feed were evaluated. Trial 1 compared effects of 2 antimicrobial regimens on finishing pig performance. Trials 2 through 10 compared growth rate and feed efficiency of nursery and finishing pigs given antimicrobials in feed with values for control pigs not given antimicrobials. RESULTS: In trial 1, no significant differences were observed between the 2 antimicrobial regimens. In the remaining trials, growth rate of nursery pigs fed antimicrobials was significantly improved, compared with growth rate of control pigs. However, growth rate of finishing pigs and feed efficiency of nursery and finishing pigs were not significantly improved by adding antimicrobials to the feed. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that use of antimicrobials in the feed to promote growth should be limited to the nursery phase in multisite pig production systems. Use of antimicrobials in the feed of finishing pigs should be limited to therapeutic applications in which a diagnosis of bacterial infection susceptible to the antimicrobial to be used has been confirmed.     

Prophylactic and metaphylactic antimicrobial use in Belgian fattening pig herds

The monitoring of antimicrobial use is an essential step to control the selection and spread of antimicrobial resistance. Between January and October 2010 data on prophylactic and metaphylactic antimicrobial use were collected retrospectively on 50 closed or semi-closed pig herds. Ninety-three percent of the group treatments were prophylactic whereas only 7% were methaphylactic. The most frequently used antimicrobials orally applied at group level were colistin (30.7%), amoxicillin (30.0%), trimethoprim-sulfonamides (13.1%), doxycycline (9.9%) and tylosin (8.1%). The most frequently applied injectable antimicrobials were tulathromycin (45.0%), long acting ceftiofur (40.1%) and long acting amoxicillin (8.4%). The treatment incidences (TI) based on the used daily dose pig (UDD(pig) or the actually administered dose per day per kg pig of a drug) for all oral and injectable antimicrobial drugs was on average 200.7 per 1000 pigs at risk per day (min=0, max=699.0), while the TI based on the animal daily dose pig (ADD(pig) or the national defined average maintenance dose per day per kg pig of a drug used for its main indication) was slightly higher (average=235.8, min=0, max=1322.1). This indicates that in reality fewer pigs were treated with the same amount of antimicrobials than theoretically possible. Injectable products were generally overdosed (79.5%), whereas oral treatments were often underdosed (47.3%). In conclusion, this study shows that prophylactic group treatment was applied in 98% of the visited herds and often includes the use of critically important and broad-spectrum antimicrobials. In Belgium, the guidelines for prudent use of antimicrobials are not yet implemented.     

Principles of antimicrobial therapy.

The most compelling reason for practicing judicious antimicrobial use is to facilitate therapeutic success. The definition of therapeutic success has changed in recent years, however; not only does success include eradication of infection, but it must now include avoidance of resistance. If the goal of antimicrobial therapy is to achieve sufficient concentrations at the site of infection such that the infecting organism is killed, therapy should be successful.     

Post operative infection, pyrexia and perioperative antimicrobial drug use in surgical colic patients

Reasons for performing study: Infections are common complications in post operative colic patients. It is the impression of some surgeons that pyrexia in the early post operative period is a sign of infection and appropriate timing of perioperative antimicrobials will decrease the incidence of post operative infection. Objective: To determine the association between 1) post operative pyrexia and development of infection and 2) perioperative antimicrobial drug use and infection rate in post operative colic patients. Methods: Medical records of patients undergoing surgical treatment for colic were reviewed. Horses recovering from surgery and surviving >48 h were included. Data relating to case details, duration of surgery, post operative infection, peri‐ and post operative antimicrobial administration, presence, intensity and duration of pyrexia, were recorded. Data were analysed using standard statistical methods for simple comparisons between groups and by logistic regression for more complex comparisons. Results: One‐hundred‐and‐thirteen horses were included in the final analyses, 48 (43%) of which were diagnosed with a post operative infection. Duration of surgery and anaesthesia were associated with post operative infection. Eighty‐five percent of horses (n = 96) exhibited pyrexia (rectal temperature >38.3°C) post operatively. Peak temperature >39.2°C, time post surgery to peak temperature >48 h and duration of pyrexia >48 h were significantly associated with infection. In a combined model, time to first pyrexic >48 h post surgery, peak temperature and time to peak >48 h were equally weighted and the model's positive predictive value for post operative infection was 72%. Timing and dose rate of preoperative antimicrobials were not associated with infection but duration of post operative antimicrobial drug use was. Conclusion and clinical relevance: Slight to mild pyrexia (38–39.4°C) in the early post operative period is not necessarily associated with impending bacterial infection in colic patients and the use of antimicrobials in these patients may be costly and unnecessary.