“Hospitals have been warned not to over-dilute cleaning chemicals amid fears that this could boost antibiotic resistance in bacteria” says the BBC News website today. A study in the US found that exposing the bacteria Staphylococcus aureus to low concentrations of a wide range of antiseptic and antibacterial solutions lead to the formation of strains that had “a higher number of ‘efflux pumps’, a feature found on the surface of their cells which allows them to get rid of toxic molecules”, the website says. These pumps can also remove certain antibiotics, such as ciprofloxacin, from the bacteria.
This study did show that there was a possibility of increasing “efflux pump” levels after exposure to low levels of certain cleaning chemicals (disinfectants and antiseptics known as biocides) and dyes. However, it did not investigate directly whether this has been responsible for the development of either antibiotic- or biocide-resistant bacteria in hospitals. Unlike antibiotics, biocides can be used in very high concentrations, and the findings of this study suggest it may be important to use sufficiently high concentrations of cleaning products. Further research into whether different kinds of cleaning products or ways of using them could avoid this potential source of antibiotic-resistant bacteria is warranted.
Where did the story come from?
Dr Aurélie Huet and colleagues from the John D. Dingell Department of Veterans Affairs (VA) Medical Center and Wayne State University School of Medicine in Detroit, USA, and the Université de Bretagne Occidentale in France carried out this research. The study was funded by VA Research Funds. It was published in the peer-reviewed scientific journal, Microbiology .
What kind of scientific study was this?
This was a laboratory study where researchers were investigating whether exposure of the Staphylococcus aureus bacteria to low levels of certain cleaning products (biocides) and dyes used in hospitals can lead to increased expression of the genes that are involved in drug resistance. These genes produce proteins called multidrug resistance (MDR) protein pumps. These proteins sit in the cell membrane of the bacteria and work by forcing unwanted toxins out of the cell, giving the bacteria a low level of resistance to the chemicals’ effects. In ‘superbugs’, such as MRSA, these MDR pumps also remove antibiotics from the cell, and this prevents the antibiotics from working properly.
The researchers took blood samples from patients and obtained eight strains of S. aureus bacteria. Five of these strains had been found to be resistant to the antibiotic methicillin, but three were susceptible to the antibiotic. This type of resistant bacteria is a cause of hospital-acquired infections, and is commonly known as methicillin-resistant S. aureus (MRSA). As a control, the researchers also obtained some S. aureus bacteria grown in the laboratory.
The researchers then exposed the different strains to low-to-moderate levels of various dyes and biocides (i.e. levels that were not high enough to kill the bacteria outright). The biocides and dyes used included pentamidine, cetrimide, chlorhexidine, norfloxacin and ethidium bromide, among others. In the first experiment, the bacteria were exposed to one of the dyes or biocides for two days, and any surviving bacteria were then isolated. In the second experiment, bacteria were exposed to increasing levels of the chemicals over a number of days; again, any surviving bacteria were isolated.
The researchers then took the ‘parent’ bacterial strain and the groups of surviving bacteria from both of these experiments and measured the levels of activity of the seven genes that produce MDR pump proteins. If the researchers identified bacteria that had increased the production of these proteins after exposure to the biocides and dyes, they looked at what genetic mutations had occurred to cause this increase. They also looked at how well the parent and the surviving mutated bacteria could pump out the dye, ethidium bromide.
What were the results of the study?
The researchers found that exposure of_ S. aureus_ to certain biocides and dyes led to the appearance of mutated forms of the bacteria that had increased levels of activity of one or more genes.
Some of the bacteria showed an increased resistance to the biocides and dyes that they were exposed to, but did not have an increase in the activity of the seven MDR pump genes that they looked at. This suggested that there may be other MDR genes responsible for this resistance.
When the researchers looked at the how well the mutant bacteria could pump out the dye ethidium bromide they found that although some of the mutated bacteria could pump out more dye than their parent bacteria, some could not.
What interpretations did the researchers draw from these results?
The researchers concluded that S. aureus bacteria that are repeatedly exposed to non-lethal concentrations of biocides can develop resistance to these chemicals by increasing the activity of MDR pump genes. Such bacteria might pose a threat to patients who are being treated with certain antibiotics that can also be pumped out of the bacteria by the same MDR pumps. They suggest that using cleaning agents that cannot be pumped out of bacteria by MDR pumps might reduce this effect.
What does the NHS Knowledge Service make of this study?
This study illustrates the possibility that exposing bacteria to low levels of certain cleaning chemicals and dyes can increase the resistance of the bacteria to these chemicals, and potentially to other chemicals such as antibiotics. It is not clear whether this type of exposure has been responsible for the development of antibiotic- or biocide-resistance in hospitals, and if so, what contribution it has made to this phenomenon relative to the overuse of antibiotics. This study does not suggest that cleaning should be stopped, but does suggest that it is important to use sufficiently high concentrations of these chemicals to kill any bacteria. Further research into whether different kinds of cleaning products or ways of using them could avoid this potential source of antibiotic-resistant bacteria is warranted.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
Channel 4 News, 5 October 2008
Metro, 5 October 2008
The Daily Telegraph, 6 October 2008
BBC News, 5 October 2008
Links to the science
Cochrane Database Syst Rev 2008, Issue 1
Microbiology 2008; 514:3144–3153