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Prudent use of antibiotics while reducing resistance

Prudent use of antibiotics enables direct professional input and availability of a wider range of tools to promote animal health, welfare and productivity.

The focus on reduction of antimicrobial resistant bacteria in humans and animals stimulates the discussion on how to efficiently produce pork meat without the use of antimicrobials as growth promoters. Considering prudent use provides a wide range of tools to promote animal health, welfare and productivity while reducing antibiotic resistance in food animals.

By James D. McKean, DVM, JD, extension veterinarian, associate director, Iowa Pork Industry Center, Lloyd Veterinary Medical Center, College of Veterinary Medicine, Ames, IA, USA

Worldwide scrutiny of human and veterinary antimicrobial usage focused on reduction of antimicrobial resistant microbes in human, animal and environmental compartments continues apace. Although antimicrobial products have been approved for efficacy, safety and manufacturing practices by the competent authority in licensing countries, since the late 1990s, efforts to reduce food animal antimicrobial use has been an accepted strategy to protect human use antimicrobials. The implementation rationale has varied, but is grounded in declining total usage to reduce or eliminate antimicrobial resistance (AMR), and obtain a positive impact on public health. Pressures from public health officials and politicians have been particularly focused on reductions in food animal production.

Food animal antimicrobials have demonstrated long-term benefits in disease treatment, prevention, control and production uses over a wide range of production environments and management strategies. Treatment regimens entail high levels of drug applied either as an injectable or water medication to individual or small groups following emergence of clinical signs.

Prevention and control strategies use medium to high dosages administered to larger populations in anticipation of clinical disease. Growth promotion has historically been obtained through lowlevel, continuous feed applications to target populations. Historically the mechanism(s) for growth and feed efficiency actions have been broadly categorised as: 1) metabolism altering;  2) nutrient sparing; and 3) general disease control effects. These categories don’t independently explain the range of impacts for low-level antimicrobials on performance. Likewise, growth promotion and feed efficiency, while linked as ‘performance’ effects, may have different pathways to accrue benefits.

Health, performance and welfare
In young poultry and recently weaned swine, the suppression of resident and environmental bacteria confers beneficial impacts on health, performance, and welfare. Unlike treatment activities that directly suppress or kill identified pathogens, low-level antimicrobials may not target specific flora of young swine/ poultry during stressful changes in diets, population dynamics, and environments, but provide non-specific protection as acclimation to these stressors occurs. This activity reflects positively on health, performance and welfare.

Early observations demonstrated that performance improvements were less dramatic when placed in ‘clean or new’ facilities but that the performance increasingly benefited from the inclusion of low-level feed antimicrobials as the environment aged. These observations have been repeated under modern management, and give credence to low-level feed additives as a credible and consistent health and welfare tool. Less uniformly accepted, based on cost/benefit analyses, has been low-level feed inclusion specifically for improved feed efficiency in older growing animals.

Continuous feed inclusions utilise larger quantities per animal than treatment, control and prevention regimens. This quantity of use, coupled with non-specific or less targeted and measurable effects have made low-level use an inviting target for the public.

The ban of all low-level feed inclusions (Sweden, 1986) demonstrated that animal health and welfare could be compromised at the production level, particularly in the weaned animal. The EUban of Avoparcin reduced Vancomycin Resistant Enterococci (VRE) prevalence in swine and poultry, but has not gone to zero in 15 years of non-use.

In some countries reduced human prevalence was concurrently reported. Conversely, in the USA, where Avoparcin was never approved or used in food animals, human VRE isolations remain high, presumably maintained by human therapeutic decisions. Following Avoparcin’s reduced prevalence, EU bans of Tylosin, Bacitracin, Spiramycin and Virginiamycin resulted in confirmation of detrimental health and welfare experiences. Increased severity of postweaning diarrhoeas and proliferative ileitis (Lawsonia intracellularis) followed in pigs. The removal of Bacitracins enhanced Clostridial enteritis in broilers. The cumulative result was an increase in treatment episodes and reduced pig and broiler health and welfare. Such treatment drugs, primarily tetracyclines, sulfas, macrolides, lincosamides and aminoglycosides, are all categorised as important human therapeutics. Remediation of adverse production effects through management have yet to be completely successful.

Prudent, judicious or appropriate?
Two different strategies are currently used for antimicrobial reduction in food animals – ban of specific antimicrobials from food animal use followed by regulatory pressures on general use for those remaining or reliance on professional oversight and management tools to reduce overall needs/usage. The growth promotant ban in the EU, elimination of specific treatment antimicrobials and the general reduction pressures on drug usage at national levels (Denmark, Netherlands, Germany) are consistent with the precautionary principle.

Beginning about 2000 numerous human and veterinary organisations formulated antimicrobial use policies that were predicated on voluntary reductions through professional oversight, education on right drug, right dose, right route and right regimen intensity and on management improvements to reduce usage, but to maintain flexibility for treatment, prevention, control and production purposes. These programmes were variously denominated, Prudent (WHO, OIE), Responsible (World Veterinary Association), Judicious (FDA and American Veterinary Medical  Association) and Appropriate (UK Department of Health). Most developed countries outside the EU have adopted some form of this concept. Veterinarians were designated the professionals to provide oversight of antimicrobial and management regimens.

Compared to their human medicine counterparts, veterinarians face potentially competing goals – preservation of animal health, productivity and welfare and avoidance of increased AMR populations which might negatively impact public health. Field-level approaches consist of increased reliance on prophylactic vaccinations, enhanced animal biosecurity, creation and maintenance of higher herd health status, strategic management changes (AIAO, geographic separation of weaned pigs, wean-finish production), better and more rapid diagnostics to focus treatment, and reductions of palliative treatments – all tied to professional (veterinary) management of specific threats.  This more nuanced approach requires heightened individual professionalism and evidence-based decisions-making, but provides clinicians with more flexibility to react to a broad range of fieldbased presentations which should positively impact animal health, productivity and welfare.

Issues for consideration
Management of AMR under prudent use rubrics is a complicated scientific and political conundrum. Experience and scientific exploration have highlighted important issues for consideration:

  • First, a strategy successful with one antimicrobial may not transfer to others (e.g. EU Avoparcin vs. growth promotion experiences).
  • Second, bacteria respond differently to antimicrobials in the same environment. Some may introduce specific AMR issues; others present no known impact on animal or public health.
  • Third, antimicrobial resistance markers are expected to survive long after antimicrobial use has ceased.
  • Fourth, reductions of AMR in food animals may not translate into measurable human health benefits.
  • Fifth, without ability to foresee direct public health benefits, restrictions on antimicrobials which protect animal health, welfare and productivity must be approached carefully. Increased animal suffering, clinical or subclinical disease or production losses resultant from reduced antimicrobial usage without potential for increased public health should be avoided.
  • Sixth, removal of selected antimicrobials in food animals may predictably drive use toward important human antimicrobials leading to increased resistance in animal populations.
  • Seventh, animal health benefits to lowlevel feed antimicrobials are most demonstrable to young swine/poultry health and welfare, and should be retained where possible. Nutrient-sparing effects in older animals may be more production related, and open for discussion.
  • Eighth, food animal antimicrobial uses produce predictable health and welfare effects. Alternate strategies and products should be refined to similar reproducibility over similar ranges to be considered as replacements for antimicrobials.

Judicious/Prudent use enables direct professional input and availability of a wider range of tools to promote animal health, welfare and productivity while reducing AMR in food animals. The admonition to ‘First, Do no harm’ should apply for all antimicrobial use strategies in humans and animals.