Impact of disinfectants on antibiotic resistance revealed

Australian scientists investigating the emergence of antimicrobial-resistant bacteria have found commonly used disinfectants and antiseptics may be giving dangerous pathogens a helping hand.

Acinetobacter baumannii is a bacterial pathogen that can cause blood, urinary tract and lung infections such as pneumonia, particularly within hospital settings.

It’s known as an ‘escape pathogen’ within healthcare settings – a cause of hospital infections among patients admitted for other reasons, which can be deadly for those who are critically ill.

It’s also the subject of studies into antimicrobial resistance, where pathogens build resilience to agents like antibiotics that are designed to eliminate them.

A recent study published in Nature Microbiology by a research group working across four Australian universities has found A. baumannii may be developing tolerance to antibiotics through a surprise mechanism – exposure to biocides.

Biocides are essential medicines commonly used in sanitation and infection control. They include hospital and household-grade antiseptics and disinfectants containing chlorhexidine, benzalkonium and the bleaching agent sodium hypochlorite.

But at low levels, it appears that these chemicals could be inadvertently causing bacteria to develop resistance.

“We’ve been using them for 50-60 years, but the funny thing is we don’t really know how they work,” says Associate Professor Amy Cain, a microbiologist at Macquarie University who led the study.

To understand the mechanism by which biocides work, Cain and her colleagues genomically evaluated the effect 10 low-concentration biocides had on A. baumannii. Rather than bursting the bacterial cells – as was assumed they would – nearly three-quarters of those chemicals tested instead dissipated their membrane potential, without actually damaging the bacterial cell’s membrane.

In effect, they ‘de-energised’ the cell and its ability to exchange material across its membrane. This loss of membrane potential diminishes the ability of antibiotics that target the interior of a cell – if the antibiotic can’t get inside the bacteria, it won’t find its target.

“They basically zapped the cells of energy, and this means that not only is the cell not able to function, but they can’t take up antibiotics as a secondary effect.

“If there are low levels of biocide around, then the cells can’t pick them up.”

While this is a lab-based study, Cain and her colleagues suggest their findings have implications for the use of sanitary agents, namely that repeated use of low-concentration biocide could create conditions that impede antibiotic treatment in hospitals.

“There’s no causative relationship yet – we haven’t studied that – but there is an implication that by over sterilising and allowing a buildup of biocides to occur, it might have an effect on antibiotic treatment later.”

The solution could be better regulation of these products.

Cain and her colleagues emphasise the importance of biocides in healthcare and households.

But some biocides are being reevaluated in light of new scientific understanding of their effects. One such chemical is triclosan. Triclosan was once a common additive to ‘antibacterial’ soap, but in 2016, both the European Union and US Food and Drug Administration banned its use after authorities agreed there was insufficient evidence of their effectiveness or safety in preventing the spread of illness or infection. In 2017, a group of 200 scientists and medical professionals called for greater stringency in the use of the product and other antimicrobial chemicals where evidence was lacking.

Although low-evidence biocides like triclosan are harder to come by in Australian handwash products today, this is more due to the regulatory policies of other jurisdictions like Europe and the US, says Dr Francesca Short. She’s a microbiologist at Monash University who collaborated on Cain’s paper. She’s also investigating the potential for greater biocide regulation in Australia.

“Triclosan is currently allowed in soaps in Australia. In a lot of countries it’s banned and it has very well documented links to antibiotic resistance,” Short says.

“It’s not used very much [in Australia] because it’s banned in so many other places and because a lot of consumers want to avoid it, so companies have stopped putting in their products.

“But you can still find it around a bit, so I think that’s an example of one that we would want to get out of soap straight away.”

Short has recently led a not-yet-reviewed study into the potential for biocides in commonly available supermarket and over-the-counter pharmacy products to drive antimicrobial resistance – or AMR – often containing agents like citric acid, ethanol and benzalkonium chloride in products like disinfectant wipes, toilet cleaners, sprays, hand soaps, washes and sanitisers.

She says while the Therapeutic Goods Administration is obliged to regulate some products, not all fall in the TGA’s remit. Along with Cain, she’s hoping to make progress in getting antimicrobial resistance considered more stringently.

“The TGA does regulate things that are claimed to prevent specific diseases, but just blanket anti-microbial activity isn’t considered in that sort of claim,” Short says.

“They regulate the terms  ‘household grade disinfectant’ and ‘hospital grade disinfectant’ and then there’s a bunch of tests you have to do to show how well your products works and claims like ‘kills COVID’ or ‘kills Staph aureus’ [a bacteria] – if you make that claim then your product’s regulated by the TGA.

“But if you just say kills 99.9% of bacteria, then it’s not.”

“I think that [for] products that are intended to kill microbes, if people are using them for hygiene and to prevent disease, then they probably should come on to the TGA.”

Amy Cain’s research in antimicrobial resistance is included in a story by Manuela Callari in Cosmos #100. Subscribe.