Disinfectant resistant superbugs?

A couple days ago, a new scientific study was published, about Enterococcus bacteria with increased alcohol tolerance. One day later, Reuters quoted it using a bit more shocking title; „Superbugs now also becoming resistant to alcohol disinfectants”.

It really sounds terrific. How bad it really is?

The study was focused on a specific bacteria strain, Enterococcus faecium. 139 samples, collected over the last 19 years were analyzed.

Vanomycin Resistante Enterococci (VRE). Source: CDC PHIL James Archer

Effectiveness of an alcohol-based handrub (ABHR) can be described with a so called “log₁₀ reduction”. If a handrub can reach 4 log₁₀ reduction, it means that only 1 of 10⁴ (1 of 10 000) bacteria can survive the disinfection procedure.

Testing the alcohol tolerance, researchers treated the bacteria with 23% propan-2-ol (isopropyl alcohol or isopropanol) for 5 minutes. Samples varied widely in regards of alcohol tolerance, in a 4.7 log₁₀ range.

All samples were collected in Australia, where healthcare facilities have used alcohol-based handrub since 2002, and has become more and more popular since then. When pre-2004 and post-2009 samples were compared, a 0.97 log₁₀ mean difference was found. No relationship was found between antibiotic (vanomycin) resistance and increased alcohol tolerance.

Log₁₀ CFU reduction by 23% isopropyl alcohol on E. faecium isolates. (Source: Pidot et al. 2018)

The good news, the “full strength” propan-2-ol is 70%, instead of the 23% what was used in the study. Applying 70% propan-2-ol, in vitro bacterial killing was complete; more than 8 log₁₀ reduction (1:100 000 000) was reached and there was no difference between the isolates. According to the EN1500 standard, all disinfectants required to be more effective in vivo than 60% propan-2-ol.

Then why increased alcohol tolerance is a problem? As the study highlights, there might be surfaces on the hands, that do not receive high enough concentration or required contact time. No mutations were able to make any change in tolerance after exposure to 25% propan-2-ol. It means that increased tolerance is an issue only if ABHR is applied in suboptimal concentration.

In a previous study, the research group examined how VRE can be eliminated from hands by handrub. 20 volunteers’ hands were artificially contaminated with special VRE clones (AUS-0085 or AUS-0021), then participants disinfected their hands with an ABHR (containing 70% propan-2-ol and 0.5% chlorhexidine). An average 3.71±1.46 and 3.64±1.24 log₁₀ reduction was reached, respectively. The interesting thing in this study was what great difference in reduction was achieved by participants. In the case of the AUS-0085 clone, participant J reached only 1.58, while participant L had 6.08 log₁₀ reduction (see Figure 1.), using the same handrub. These results suggest that hand hygiene technique has a huge clinical relevance.

Interpersonal variability in handrub effectiveness. (Source: Graysonet al. 2012)

Alcohols kill bacteria by disrupting membrane functions, as alcohol can penetrate into the phospholipid bilayer. What mechanisms help bacteria to be more resistant? It’s an interesting question, we will discuss it in a different post, later on.

CONCLUSION

Prevalence of more alcohol tolerant bacterial strains is not really surprising, as wide use of alcohol-based handrub (ABHR) put alcohol tolerance under selection pressure. This study proposed an explanation, that mean resistance to alcohol were increased due to the disappearance of less tolerant isolates. We definitely should keep an eye on this phenomenon, yet for now, ABHR remain the preferred and number one solution to prevent nosocomial infections (1). The study emphasizes that ABHR remain in important, general defense against healthcare-associated infections. We should ensure that everyone apply the right amount of handrub with right technique and adequate application time.