Bacteria are smarter than we give them credit for.
Or maybe we’re not a bright as we think we are.

Antimicrobial stewardship is sometimes (wrongly) assumed to simply be the practice of ‘using fewer antimicrobials’. It’s more complex than that, because the issue is complex. At face value, using overall reduction in antimicrobial use is a logical target, and it’s true that it is a big aspect of stewardship.

However, what is an ‘antibiotic’?

“Raised without antibiotics” and “Antibiotic-free” are good marketing terms, but what do they mean in terms of antimicrobial resistance? That’s less clear.

In pig production, control of post weaning E. coli diarrhea is a big problem. Prophylactic antibiotics are effective for this, but that’s not ideal. The main thing that’s done to replace antibiotics is to add a lot of zinc to the piglets’ diets at that age.

  • The reason….zinc kills bacteria.
  • The problem…bacteria don’t care whether we call it an antibiotic, just that it’s trying to kill them. So, they try to resist it.
  • The bigger problem….the way the resist it can be linked to the way they resist conventional antibiotics.

We (and others) have previously shown that addition of high levels of zinc to the diet of piglets selects as well for MRSA (methicillin-resistant Staphylococcus aureus) as tetracycline, the commonly used antibiotic for prevention of post-weaning diarrhea. If zinc selects for MRSA but not other resistant bugs, while tetracycline selects for a broader range of resistance, zinc use still might be of concern, but it would be a better option than tetracycline. However, that’s not the case and a recent paper in PLOS ONE (Ciesinski et al 2018) provides more information on the impact on other important resistant bacteria.

In that study, they took a typical approach of feeding groups of pigs either low levels (dietary requirements) or high levels (antibacterial levels) of zinc, and they investigated what happens with E. coli. They found significantly higher levels of multi drug resistant E. coli in association with feeding high levels of zinc: 5.8-14% in the control group compared to 29-30% in the high level zinc group. This appeared to be because the resistant strains persisted better than susceptible strains, as numbers of E. coli didn’t increase, but the proportion of resistant strains did.

Does this mean we shouldn’t be feeding high levels of zinc to piglet?

  • I don’t know. Prevention of disease is important for various reasons, including piglet welfare, reduced need to use therapeutic antibiotics (which are often more important drug classes than those used for prevention) and the need for economic production of safe food.
  • Whether antibiotics or zinc are better (or less worse) for resistance in piglets and the corresponding human risk is still unclear.
  • Another unanswered question is the impact of high levels of zinc in manure, since that ultimately makes its way into the ecosystem (just like some antibiotic residues).

However, it provides more evidence that ‘common sense isn’t evidence’ when it comes to antimicrobial resistance. We can’t assume things will have positive or negative aspects because ‘it makes sense’. We need proper research to figure out the best ways to optimize and improve antimicrobial use, minimizing resistance while maximizing the care of people and animals.
That’s antimicrobial stewardship.

JSW

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