Antimicrobial Use Reduction for Animal Production: Opportunity or Liability for the Poultry Industry?

A nice overview of the problem of antimicrobial use in animal production is given on the EFFORT website, a European initiative for reducing antimicrobial resistance:

 

The introduction of antimicrobial agents in the 1940s for human clinical medicine but also in animal husbandry changed the options for treatment completely. Successful treatment of infections which were previously considered lethal became possible. In veterinary medicine, the use of antimicrobials has improved animal health, welfare and the efficiency of production.

 

However, the benefits of antimicrobial discovery were soon hampered as even before the moment penicillin was introduced, resistant strains of bacteria had been detected. The use of antimicrobials invariably leads to selection of bacteria that are resistant against the substance used. Resistance can then spread in populations and the environment.

 

In human medicine, antimicrobial resistance (AMR) leads to increased morbidity and mortality. The European Centre for Disease Prevention and Control (ECDC) estimates that AMR results annually in 25,000 deaths and related costs of over 1.5 billion € in healthcare expenses and productivity losses due to work absenteeism. In the USA, an estimated 23,000 deaths and two million illnesses were conservatively estimated by the US Centers for Disease Control.

 

Also in veterinary medicine the efficacy of antimicrobial treatments is declining and from several bacterial diseases (e.g. swine dysenteria) multidrug resistant strains are circulating making, these infections untreatable resulting in a high economic burden for the producers and animal welfare problems. Due to overuse of certain classes antimicrobials (e.g. tetracyclines) and beneficial pharmacological characteristics an undesirable shift towards new drugs is observed, which should preferably be reserved for human use only.

 

Part of the problem of treatment failure is amplified by the fact that new and effective antimicrobials are not currently being developed at a sufficient rate nor will they be developed at a higher rate in the near future. Antimicrobial resistance therefore poses a major threat to the continued efficacy of antimicrobial agents in both human and veterinary medicine.

 

As described above, spread of resistant microorganisms in the food chain can potentially have dramatic consequences. From emergence of resistance and along the transmission pathways, there are knowledge gaps that need to be addressed to allow for the development of science-based measures. The ultimate aim of these measures is to decrease, or at least, minimise the further development and spread of antimicrobial resistance (1,3).

 

This message of antimicrobial use pressure might not be completely adopted yet by the agricultural and poultry industries, but fighting these tendencies is a losing battle. Some will consider pressure on use as a serious risk for health, welfare and especially profitability of the poultry industry, but others will look at the challenge as an opportunity.

 

Respiratory and systemic infections. Before the ban on antimicrobial growth promoters (AGP) in some countries and in most countries still using AGP, respiratory (E. coli, Mycoplasma) and systemic infections (E. coli, S. aureus) were and are the most common indications for antimicrobial usage. Still there is a decreasing trend of use, as control strategies include increasingly effective vaccinations against E. coli and Ornithobacterium rhinotracheale (ORT). As often diseases are multifactorial, these vaccinations must include also those targeting respiratory viral pathogens such as Newcastle disease virus (NDV) and infectious bronchitis virus (IBV). Attempts for better control of emerging diseases such as infections with Enterococcus spp. seem promising.

 

One of the main difficulties though, and thus also one of the main indications of use remaining in this area, are Mycoplasma spp. infections. Immunity against Mycoplasma infections is not well understood; although some recent experiences with live vaccines are giving hope to design more solid programs where antimicrobial use can be optimised.

 

Intestinal issues. The main problem for the poultry industry will reside in finding antibiotic-free or low-use-antibiotic answers to gut health issues. Without AGP, about 70-80% of therapeutic antimicrobials are used for gut health issues, generally called dysbacteriosis, clostridiosis or bacterial enteritis (BE), all of these names referring to the same syndrome, globally affecting the poultry industry. As with several respiratory/systemic infections, these issues are multifactorial. At the start of the Bacterial Enteritis Vicious Circle (BEVC), a relative oversupply of nutrients in the gut creates an environment in the lumen of the gut that will help some members of the gut microbiota to abundantly replicate in disfavour of some other groups. In creating this oversupply, next to the genetic predilection of meat-type birds to high feed intakes, mostly coccidiosis is involved, and often mycotoxins, enteric viruses or other gut stressors will allow the intestinal microbiota to have contact with the gut associated lymphoid tissue (GALT), further exacerbating intestinal pathophysiological changes such as villous fusion, goblet cell proliferation, tight junction alterations, excessive GALT activation, decrease of gut peristaltic and anti-peristaltic capacities.

 

These changes will further, through a number of pathways, increase the availability of poorly absorbable nutrients to some bacterial groups. The result will be increased losses through poor utilization of feed and loss of nutrients due to overcoming morphological changes as well as activation of the GALT, which is the most important part of the immune system of a bird in terms of relative size of immune cells involved.

 

Before the ban of AGP, we were not so much aware of this BEVC creating potential losses in poultry. AGP will work to reduce fuelling the BEVC at the second step by reducing the number of potential harmful microbiota and maybe also by altering the immune reactions at the third step (4).

 

Understanding this vicious circle is crucial to understand the potential that some of the alternatives proposed to replace AGP have. In fact, only focusing on reducing microbial proliferation in the second step of BEVC seems to be not fully satisfying as need for retreatments often occur. This seems logical in the sense that not taking away underlying causes of initiating BEVC during the first step will of course lead to relapses. In presence of AGP this does not happen as they are given continuously, although here the use of AGP seems to cover up a constant irritation of the gut, and today it seems that better solutions can be provided by not only trying to ‘replace’ the AGP antimicrobial action but also looking on how to tackle the issues in other steps of the cycle. This seems in line even with the fact that also AGP results were not fully explained by the antimicrobial action (often expressed as activity against Clostridium perfringens) only. This understanding leads to solutions, with less antibiotics but with improved end results both in terms of welfare, health and very importantly, technical performance of poultry produced on industrial scale. This is clearly an opportunity for the poultry industry, not only in areas with ban of AGP but also when AGP are used.

 

Figure 1. Model of resistance emergence and the crucial roles of antibiotic and infection control in preventing outbreaks, epidemics and pandemics (EFFORT, 2014).

 

 

Figure 2. Bacterial Enteritis Vicious Circle (De Gussem, 2010).

 

Pressure on antimicrobial use seems to be a challenge, but has already led to better understanding why and when antimicrobials are used. In the end, reduction of use will be unavoidable, but will not lead to production problems, on the contrary, it is expected that, especially in gut health, the improvements that will be made to prevent use of antibiotics will lead to performance that better approaches the genetic potential the modern meat-type birds present.

 

1. EFFORT (2014) http://www.effort-against-amr.eu/page/the-effort-project/background-challenges.php. Accessed 21st July 2014.

2. De Gussem (2010) Macroscopic scoring system for bacterial enteritis in broiler chickens and turkeys. WVPA Meeting Merelbeke, Belgium. http://www.vetworks.eu/gut-health/. Accessed 21st July 2014.
 
3. Laxminarayan et al., (2013)Antibiotic resistance-the need for global solutions Lancet infect Dis13:1057-98.

4. Niewold T. (2007) The Nonantibiotic Anti-Inflammatory Effect of Antimicrobial Growth Promoters, the Real Mode of Action? A Hypothesis. Poultry Science 86 (4): 605-609.