Hospital superbugs are evolving to survive hand sanitizers

Popular hand sanitizers may be heading the way of antibiotics, according to a study published this week in Science Translational Medicine.

Bacteria gathered from two hospitals in Australia between 1997 and 2015 appeared to gradually get better at surviving the alcohol used in hand sanitizers, researchers found. The bacteria’s boost in booze tolerance seemed in step with the hospitals’ gradually increasing use of alcohol-based sanitizers within that same time period—an increase aimed at improving sanitation and thwarting the spread of those very bacteria. Yet the germ surveillance data as well as a series of experiments the researchers conducted in mice suggest that the effort might be backfiring and that the hooch hygiene may actually be encouraging the spread of drug-resistant pathogens.

The researchers, led by infectious disease expert Paul Johnson and microbiologist Timothy Stinear of the University of Melbourne, summarized the findings, writing:

We have proposed here that the significant positive relationship between time and increasing alcohol tolerance is a response of the bacteria to increased exposure to alcohols in disinfectant preparations and that the more tolerant strains are able to displace their less alcohol-tolerant predecessors.

Johnson, Stinear, and colleagues cracked open the research after noting a puzzling pattern in hospital-acquired infections. While healthcare settings were upping their sanitation game with alcohol-based rubs, certain nefarious germs seemed to be in decline—methicillin-resistant Staphylococcus aureus, MRSA, for instance—yet another set of germs seemed to be thriving. Those would be Enterococci bacteria, which are usually harmless occupants of the human gut but can become opportunistic pathogens that lurk in hospitals and pounce on vulnerable patients.

A species called Enterococcus faecium is of particular concern as it has become a leading cause of hospital-acquired infections and often carries resistance to multiple antibiotics, including a last-line drug called vancomycin.

To understand why these germs seemed to be in such high spirits, the researchers examined a collection of 139 E. faecium bacteria collected from infected patients in two Australian hospitals between 1997 and 2015. First, they subjected the germs to low levels of isopropanol, a type of alcohol found in hand sanitizers.

Hand sanitizers often contain 70 percent or more isopropanol or ethanol, which usually annihilates bacteria. The alcohols essentially shred the microbes’ outer membranes, causing molecular mayhem and the germs’ innards to leak out. In high concentrations, the alcohols are quickly fatal.

Stiff drink

To keep from simply massacring their isolates, the researchers poured them to a watered-down 23-percent isopropanol mixture. This wiped out some, but not all, of the germs. But when they compared the isolates in batches based on when they were collected, they saw a clear shift. The bacteria collected between 2009 and 2015 had a tenfold higher survival rate than those collected before 2004.

The researchers noted that hospitals began guzzling the alcohol-based sanitizers in 2002. In fact, they went from using 100 liters of alcohol-based hand rubs per month in 2001 to using 1,000 liters per month in 2015—a tenfold increase.

Of course, the hospitals don’t use weak-sauce, 23-percent alcohol sanitizers; they use the deadly 70-percent concentrations. To see if the bacteria’s shift in tolerance was at all relevant to sanitation and infection risks in the hospitals, the researchers turned to mice.

First, the researchers coated the floors of mouse cages with E. faecium strains, either strains that were easily killed by alcohol or ones that had relatively high levels of tolerance. Then, they mopped the floors with a 70-percent alcohol solution and unleashed the mice to play in the cages for an hour. Afterward, the researchers scanned the rodents’ poops to see how many of them had managed to pick up E. faecium from the cages, despite the cleaning.

In repeated experiments (and with mock water treatments as controls), the researchers found that the more alcohol-tolerant bacteria were better at surviving the floor cleaning and infecting the mice than their less-tolerant counterparts.

The researchers did genetic comparisons to try to rule out that the alcohol-tolerant isolates were just more infectious than the others—the isolates didn’t seem to be. The team also went on the hunt for genetic changes that might explain the germs’ ability to hold their liquor. In the case of antibiotic resistance, for example, single genes or mutations can sometimes explain a microbe’s survival. But in this case, alcohol tolerance appears more complicated, involving many genes that act together to harden germs. Some of those genes seem to be involved in metabolism.

Researchers will need to do far more work to verify and understand alcohol tolerance. But for now, the researchers conclude that:

The development of alcohol-tolerant strains of E. faecium has the potential to undermine the effectiveness of alcohol-based disinfectant standard precautions and may, in part, explain the increase in [vancomycin-resistant Enterococci] infection that is now widely reported in hospitals in Europe, Asia, the Americas, and Australia.

Science Translational Medicine, 2018. DOI: 10.1126/scitranslmed.aar6115  (About DOIs).