Dr. Benjamin Tanner

Antibiotic resistance in bacteria is a terrible problem. Scientists have historically attributed the rise in antibiotic resistance among bacteria to two main causes: Low-level use of antibiotics in animal feed and inappropriate prescription of antibiotics by physicians. Recently, news articles with titles such as "Disinfectants May Promote Growth of Superbugs" have suggested that disinfectants may also contribute to antibiotic resistance. At the core of the matter is a phenomenon called "cross-resistance," where microbes exposed to sub-lethal levels of disinfectants undergo physiological or genetic changes that increase antibiotic resistance — without the bacteria even being exposed to the antibiotic to which they gain resistance. If cross-resistance were really taking place, then it would come as a huge surprise for cleaning professionals, disinfectant makers and users of facilities where disinfection currently plays a central role in breaking the cycle of infection. Fortunately, news about cross-resistance has been largely exaggerated. The reality is that while cross-resistance between certain disinfectants and certain antibiotics can be readily demonstrated by laboratory experiments, it is much, much more difficult to detect — and may not even occur — in actual facilities. Researchers have tried a number of approaches to detect the phenomenon in "real-life" without success. The Science: Laboratory Experiments A number of laboratory or in vitro studies have evaluated the effect of sub-lethal biocide exposure on antibiotic resistance. Most of these laboratory studies have utilized a study design called "stepwise training," where bacteria are grown in pure culture in increasing concentrations of a particular biocide, then exposed to a range of antibiotics at the end of the study to measure changes in its antibiotic resistance profile. Most stepwise training studies have centered on Triclosan, though Triclosan is a relatively uncommon active ingredient in surface disinfectants and is fundamentally more like an antibiotic than a typical biocide. That is, it appears to act on one target in a bacterium rather than multiple targets all at once (McMurray, Nature. 1998. 394:531-532). Since Triclosan is not frequently used as an active ingredient for surface disinfection, its discussion in this article is limited. With respect to surface disinfectants, the most relevant biocide that has been studied for cross-resistance potential is the quaternary ammonium compound (QAC) or quat. QACs are one of the most common active ingredients in disinfectants today, especially in health care and commercial settings. Laboratory studies have shown that exposure of a bacterium called Pseudomonas stutzeri to QACs over time can result in increased resistance to certain antibiotics and other biocides (Tattawasart, Journal of Hospital Infection. 1999. 42:219-29). And genes have been identified that appear to be linked to the development of QAC resistance and corresponding resistance to some antibiotics (Russel, Journal of Applied Microbiology. 2002. 92:121S-35S). The Science: Actual Usage A relatively small number of studies have evaluated the effect of biocide use on antibiotic resistance levels in real settings. No "smoking gun" studies showing cross-resistance are known at this time. Furthermore, no outbreaks of antibiotic-resistant microorganisms have been traced to sub-lethal disinfectant exposure in the environment. Of the few available studies, arguably the best designed and most comprehensive was done by Aiello, et al. in 2005. In this study, 224 households were randomized to use of a broad array of antimicrobial cleaning products for one year (Aiello, Emerging Infectious Diseases. 2005. 11:1565-70). Products included oxygenated bleach, a quaternary ammonium cleaner and a Triclosan-containing hand soap. Samples of bacteria from hands were collected at initiation of the study and after the one-year use period before being analyzed for antibiotic resistance. No linkage was found between antimicrobial use in the households and the rate of antibiotic-resistant bacteria isolated from hands. The findings of the 2005 Aiello, et al. study are generally representative of other real-world studies, though few have directly focused on the issue of cross-resistance. Interpretation One thing is clear: It is relatively easy to bring about cross-resistance in the laboratory using carefully designed and controlled experiments. However, it is difficult to bring about or observe such a phenomenon under more realistic conditions. Most of the research that has been done thus far to explore the phenomenon of cross-resistance could be considered primary in nature. That is, it has set out to answer fundamental questions or observe phenomena that were expected to be readily observable. Researchers such as Aiello, et al., who have asked these tough questions and carried out well-designed, rigorous studies to evaluate their hypotheses, should be praised. They have contributed greatly to the overall understanding of surface disinfection and its impact to antibiotic resistance. It would be foolhardy to think that cross-resistance does not take place to some extent in practice, but the current science suggests that the risk associated with not disinfecting contaminated surfaces far outweighs the risks associated with cross-resistance. Disinfection brings many benefits to facilities. A number of studies suggest that the use of disinfectants in strict compliance with label instructions yields a benefit to facility occupants by breaking the infection cycle (Cozad, American Journal of Infection Control. 2003. 31:243-254). For cleaning professionals who are hyper-aware of the cross-resistance issue, a safe bet is to utilize a surface disinfection technology that destroys many different components of a bacterium at once, leaving little opportunity for mutations and physiological changes that could result in cross-resistance to antibiotics. One example of such a technology is a steam vapor system. Steam vapor systems are finding more frequent use in hospitals, schools and foodservice applications. In the context of cross-resistance, steam vapor has a key advantage in that it is a chemical-free disinfection approach, where heat transferred to microorganisms on the surface destroys many target sites at once. Since nothing is left behind, there is virtually no risk of environmental development of cross-resistance. At least one device on the market has been tested extensively by independent laboratories (Tanner, American Journal of Infection Control. 2009. 37(1):20-27). Sodium hypochlorite or bleach is another example of a biocide that can be used regularly for indoor surface disinfection that acts against many different components of bacterial cells at once, reducing

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Dr. Benjamin Tanner

Principal of Antimicrobial Test Laboratories

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