Hospital Superbug Becoming Resistant to Alcohol Disinfectants

Some bacteria are growing resistant to hospital alcohol sanitizers, according to a new report from Australia. | Dilated Time

Scientists have discovered that a drug-resistant bacterial species that commonly causes hospital infections is becoming increasingly resistant to the alcohols used in hospital sanitizers, a finding that carries major implications for the control of bacterial infections in healthcare facilities. The research was published in the August 1 issue of Science Translational Medicine.

The results are based on an analysis of samples of the species Enterococcus faecium gathered from two Australian hospitals over a 19-year period. The alcohol-tolerant bacteria also spread more quickly to mice living in contaminated cages that were then wiped down with alcohol, a discovery that could help explain the recent resurgence in E. faecium hospital infections.

The study does not mean hospital sanitizers are ineffective for infection control, but the authors say that global efforts to mitigate bacterial resistance should consider how microbes can adapt not only to drugs but also to alcohols and other ingredients used in disinfectants.

The specter of bacterial antibiotic resistance poses a serious challenge to public health authorities and facilities worldwide. Infections that were once easily treated with antibiotics such as penicillin are becoming resistant to all but the most powerful drug combinations, increasing the cost of treatment and the risk of side effects in patients. The CDC estimated that care for the superbug methicillin-resistant Staphylococcus aureus (MRSA) can cost up to $60,000 per patient and up to $9.7 billion annually.

Hospitals have therefore expanded their antimicrobial measures and adopted stringent sanitation procedures to counter the rising tide of drug resistance. These protocols often include the use of disinfectant hand rubs and washes that contain at least 70% isopropyl or ethyl alcohol, a similar concentration used in some store-bought hand sanitizers.

The introduction of these disinfectants has aligned with declines in MRSA and other hospital infections. A 2014 study found that MRSA infections in U.S. hospitals declined 54% between 2005 and 2011, a pattern also seen in other countries such as Australia.

However, cases of E. faecium that are resistant to the first-line antibiotic vancomycin (or VRE) have been steadily climbing both in Australia and worldwide despite the introduction of these procedures, said Paul Johnson, director of research at Austin Health in Heidelberg, Australia and a coauthor of the new study.

"MRSA was being so well controlled with the new national hand hygiene program [in Australia], but we also started to notice a gradual increase in VRE infections," he said. "This seemed like a paradox because both infections should be controlled using standard hand hygiene."

Suspecting that E. faecium could be adapting to the widespread usage of alcohol disinfectants, Sacha Pidot, a molecular microbiologist at the Peter Doherty Institute of Infection and Immunity in Melbourne, Australia and colleagues gathered 139 isolated bacterial samples, or isolates, that had previously been collected between 1997 and 2015 from two hospitals in Melbourne, Australia.

The authors then performed an alcohol-killing test, where they exposed each isolate to a diluted quantity of isopropyl alcohol for five minutes and recorded how many bacteria were killed off during the treatment.

The isolates gathered after 2009 were on average more tolerant to the isopropyl alcohol compared to isolates collected before 2004. The later isolates were also more resistant to ethanol, another form of alcohol.

To test the clinical relevance of their findings, Pidot's team then created a model of E. faecium surface transmission. They seeded an isolate collected in 2012 and another gathered in 1998 onto the floors of mouse cages and cleaned each cage with wipes containing isopropyl alcohol.

The alcohol-tolerant 2012 isolate was better able to withstand the cleaning regimen compared to the 1998 isolate. Furthermore, the 2012 isolate more effectively colonized the guts of mice that were housed in the cages after cleaning.

The research group also performed an analysis of the bacterial genome, which revealed that the tolerant isolates harbored several mutations in genes involved in metabolism that granted increased alcohol resistance.

One limitation of the study is that the authors do not fully understand the evolutionary forces that are pushing E. faecium to develop alcohol tolerance, according to Tim Stinear, a microbiologist at the Peter Doherty Institute of Infection and Immunity in Melbourne, Australia and a coauthor of the new study.

"One possibility that we propose in this research article is the use of alcohol that's led to this new VRE that's more tolerant," he said. "But it might also be that this bacterium is doing another trick, it's becoming better able to live in the low pH of our gut, an adaptation that coincidentally confers resistance to alcohol."

Stinear also stressed that more research is necessary to determine if E. faecium is developing alcohol tolerance in other countries with hand hygiene programs.

The new findings are of "considerable importance," according to Willem van Schaik, a professor of microbiology and infection at the University of Birmingham in United Kingdom. Van Schaik, who is not affiliated with the new research, highlighted how the mouse transmission model suggests that alcohol-tolerant bacteria could better colonize human patients.

The study does not mean hospital sanitizers are ineffective for infection control, but the authors say that global efforts to mitigate bacterial resistance should consider how microbes can adapt not only to drugs but also to alcohols and other ingredients used in disinfectants.

"I find this part of the study exceptionally important as it can provide a mechanistic explanation for the increasing prevalence of E. faecium in hospitals," he said.

Van Schaik said the genetic findings were more difficult to interpret and that future work should aim to refine scientific understanding of the mechanisms of alcohol tolerance.

Van Schaik also emphasized that the study does not mean hospitals should stop using alcohol-based hand sanitizers, which are effective against the vast majority of bacterial pathogens. However, manufacturers may want to consider refining the formulations of antibacterial washes and including different alcohol types such as 1-propanol to retain their effectiveness, he said.

Johnson had a similar message, cautioning against the idea that alcohol hand rubs could be losing their effectiveness as a public health measure.

"Alcohol hand hygiene programs have been highly successful, particularly at controlling MRSA but also other types of hospital infections, and I would strongly advocate that we continue," he said.

"However, with certain pathogens like VRE, we may have to consider not relying on what we call standard precautions, where we prevent cross infection in everybody by using hand hygiene. We might need to specifically add additional control measures for VRE outbreaks."