Even Non-Antibiotic Drugs Can Promote Antibiotic Resistance

Five of the most widely used non-antibiotic pharmaceuticals promote antibiotic resistance, at least in test tubes, scientists have found. With just six drugs tested in this way, the problem is probably far more widespread and demonstrates the challenges of keeping bacterial diseases at bay.

Covid-19 was so shocking because we have become unaccustomed to widespread outbreaks of such a deadly infectious disease. Many of the great plagues that killed millions had bacterial causes and antibiotics have helped subdue them. The rise of antibiotic resistance threatens to change our supremacy over them, potentially killing more people than cancer by 2050.

“When we think of antibiotic resistance, we often link it to the intensive use of antibiotics for medical, veterinary or agricultural purposes,” said Dr Jianhua Guo of the University of Queensland in a statement. “We started wondering if non-antibiotic pharmaceuticals may also play a role in the spread of antibiotic resistance through bacterial transformation.

Guo and his PhD student Yue Wang tested six of the most widely used non-antibiotic prescription and non-prescription drugs to see if they changed the antibiotic resistance of Acinetobacter baylyi, a common hospital pathogen.

“We did find nonsteroidal anti-inflammatories (e.g. ibuprofen), a lipid-lowering drug, and a β-blocker significantly promoted the bacterial transformation,” Wang said.

The findings have been published in The ISME Journal. Some drugs required quite high concentrations before the effect was significant, but gemfibrozil and propranolol increased resistance at concentrations as low as can be found in wastewater.

Guo told IFLScience these drugs cause overproduction of reactive oxygen species (ROS), chemicals that damage the membranes of bacterial cells. Under some conditions this may kill the bacteria, making them antibacterials of their own. However, where the damage is more moderate, it just makes the membranes more permeable, increasing bacterial uptake of environmental DNA, including antibiotic-resistance genes shed by other bacteria.

Once DNA has been acquired by this process, known as horizontal gene transfer, natural selection takes over, with the resistant bacteria surviving exposure to antibiotics while others die out. Guo told IFLScience that adding molecules that scavenge and clean up ROS stops the build-up in resistance.

Guo acknowledged that what happens in the test tube doesn't always translate to a living environment, saying more animal tests are required. He also thinks pharmaceutical development needs to take the problem into account to mitigate drug side effects, saying “they are the iceberg of factors for promoting antibiotic resistance, and should not be ignored.”

Already an estimated 700,000 people die each year from infections resistant to the drugs with which we once subdued them, and that figure is expected to grow dramatically.