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,” but it’s more complex than that, because the issue is complex. At face value, overall reduction in antimicrobial use is a logical target, and it’s true that it is a big part of stewardship. However, what is an “antibiotic?” “Raised without antibiotics” and “Antibiotic-free” are flashy 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 their use is not ideal. The main thing that’s done to replace antibiotics and still maintain control of the disease is to add a lot of zinc to the piglets’ diets at that age.

  • The reason: zinc still kills bacteria, even though it’s not a conventional antibiotic.
  • The problem: bacteria don’t care whether we call it an antibiotic or not, just that it’s trying to kill them. So, they try to resist it.
  • The bigger problem: the way bacteria resist the action of zinc 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 most 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 might still be a concern, but it would be a better option than tetracycline. However, that’s not actually the case, and a recent paper in PLOS ONE (Ciesinski et al 2018) provides more information on the impact of zinc on other important drug-resistant bacteria.

In the study, researchers fed groups of pigs either low levels (i.e. basic dietary requirement) or high levels (antibacterial level) of zinc, and they investigated what happens with intestinal E. coli. They found significantly higher levels of multidrug-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, just the proportion of resistant strains.

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

  • I don’t know. Prevention of disease is important for a lot of 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) in terms of promoting resistance in bacteria in piglets and the corresponding risk to human health is still unclear.
  • Another unanswered question is the impact of high levels of zinc in manure, since that ultimately makes its way into the environment/ecosystem (just like some antibiotic residues).

However, the study 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 effects because “it makes sense.” We need sound 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.