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Unintended consequences of early antibiotic introduction

Kavishti Kokaram for Progressive Dairy Published on 30 July 2021

As more research is being done on calf health, it is being discovered that common calf management practices that introduce antibiotics during critical development periods might be doing more harm than good.

Some of these practices include feeding waste milk with high levels of antibiotics, using medicated feed additives in nutrition plans and aggressive antibiotic usage in disease control. While these practices might have seemed effective in accomplishing their goal – keeping calves healthy – we now know that early introduction of antibiotics also can have serious downsides.

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Prompts antimicrobial resistance 

Calves are extremely susceptible to disease because they are born without a fully developed immune system. In early months of life, a calf’s immune system is slow to respond to pathogen challenges, often resulting in a weak response and limited protection. While antibiotics have helped provide some protection, the old adage, “too much of a good thing,” might render these tools futile in the future.

Recent evidence suggests that feeding waste milk, and other practices that introduce antibiotics to a calf’s system at subtherapeutic levels, promotes the presence of antimicrobial-resistant bacteria in the calf’s gut. Extensive research has shown that the overuse of antimicrobials, such as antibiotics, is the primary driver behind antimicrobial resistance, which occurs when bacterial populations shift to make antibiotics ineffective. Scientists have identified two ways bacteria develop resistance: biofilm production and gene transfer.

Biofilm production is bacteria’s most basic response to a threat, in which they develop a glycolipid barrier – or membrane – based on a change in gene expression. Research has shown that bacteria in a biofilm cannot be readily reached by the host’s immune system or by antibiotics. When antibiotics are introduced into a calf’s system, it triggers bacteria to change their expression and build this defense to protect themselves. Once formed, biofilm can attach to the lungs and other tissue surface areas within the body, and it becomes extremely difficult to remove the bacteria from the calf’s system, which then continues to be a constant threat to the calf’s health.

In addition to biofilm, there is the natural process that occurs when the genetic makeup of bacteria is altered through various mechanisms of sharing genetic material in a population. This makes the bacteria no longer susceptible to antimicrobials designed to prevent their growth or kill them. When this resistance is developed, antimicrobials stop working or have reduced efficacy, animals do not respond to treatment and the health of the animals continues to be at risk.

When antibiotics are introduced in the first few days of a calf’s life, it is very likely that they might become less effective throughout the animal’s life due to the development of antimicrobial resistance and biofilm formation. This presents a challenge to many dairy farmers when they discover that routine antibiotics no longer cure sick animals on their operations.

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Impacts rumen development

If you have invested in the best genetics for your future herd, the last thing you want to do is hinder the ability of those genetics to flourish. When it comes to the development of the rumen, we know good bacteria play a crucial role and are essential to the health of the gut microbiome. There is a delicate balance that needs to be kept between minimizing exposure to harmful bacteria and maximizing the role of beneficial bacteria for rumen development and efficient feed conversion. Certain calf management practices, like pasteurizing waste milk and colostrum, exist to maintain this balance and protect calves. While this process reduces the harmful bacterial load that poses a threat to health, it does not remove the antibiotic residue present in waste milk or colostrum. Antibiotics are unable to differentiate bad bacteria from good. As a result, introduction of antibiotics to an animal’s system threatens all bacteria.

Studies that have looked specifically at resistance in calves have not measured the impact to rumen development. Only a handful of studies have attempted to quantify the influence of antibiotics on rumen development in pre-weaned calves, and most have been inconclusive. These results are also based on the assumption that antibiotics kill both good and bad bacteria, underscoring the need for additional research in this critical area.

Quorum-sensing solutions

As research into the downsides of early antibiotic introduction continues, new scientific discoveries are leading to solutions that will assist in antimicrobial stewardship and our ability to target specific bacteria strains. The term “quorum sensing” describes the unique biochemical communication system of bacteria. Groundbreaking discoveries that revolve around the way bacteria communicate are significant. These advancements in understanding how communication occurs have resulted in new approaches on how we can fight bacteria differently and more directly.

Bacteria use quorum sensing to communicate by releasing protein signal molecules to determine their population density and influence the expression of various factors. When a significant concentration of bacteria is detected, genes that regulate behaviors such as virulence (the ability of a pathogen to cause disease) or biofilm formation are activated. This occurs only when bacteria have reached a certain population size, so quorum sensing is key to the coordination of bacterial population behavior.

By disrupting the communication of bacteria, their ability to cause harm or build biofilm defenses is inhibited. Creating this disruption gives the calf’s immune system time to develop and clear out bacteria on her own, while also reducing the risk of harm from these bacteria, decreasing the need for antibiotics and increasing her resilience to future attacks. Additionally, targeted disruption of quorum sensing will not adversely affect good bacteria in the rumen, allowing natural processes that convert food into energy and efficient rumen development to continue without interruption.

As the unintended consequences of antibiotic usage are explored further, it is important to identify alternative practices and solutions that can help reduce the need for antibiotics in our operations. By saving antibiotics for times when they are truly required, the possibility of reducing antimicrobial resistance and increasing the efficacy of these tools is enabled. Disrupting quorum sensing gives us a new tactic to combat bacterial populations. While it will not fully replace antibiotics, it will assist us in making great strides toward reducing antibiotic usage and will resonate strongly with today’s consumers.  end mark

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References omitted but are available upon request. Click here to email an editor.

Kavishti Kokaram, DVM, is a technical services veterinarian at AHV North America. Email Kavishti Kokaram.

 5 tips to keep calves healthy and minimize antibiotic impact

 Check out these tips to maintain calf health from day one to reduce antibiotic impact in your herd:

  1.  Start building a strong gut microbiome with proper colostrum feeding – 10% of a calf’s bodyweight of high-quality, pasteurized colostrum in the first two hours of life.
  2. Avoid feeding waste milk to calves, if possible, especially in the first two weeks of life, to prevent subtherapeutic levels of antibiotics from entering the calf through the milk.
  3. Maintain a clean, stress-free environment to promote calf health. Ensure all buckets, bottles and other equipment are thoroughly cleaned and disinfected between use. Provide calves with clean, well-ventilated housing.
  4. Feed calves a high level of nutrition to ensure they have enough energy to maintain their immune systems and fight off disease challenges without antibiotic usage.
  5. If a calf is sick, look to other tools in your toolbox before reaching for antibiotics.

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