Ethylzingerone, a Novel Compound with Antifungal Activity.

Preservatives increase the shelf life of cosmetic products by preventing growth of contaminating microbes, including bacteria and fungi. In recent years, the Scientific Committee on Consumer Safety (SCCS) has recommended the ban or restricted use of a number of preservatives due to safety concerns. Here, we characterize the antifungal activity of ethylzingerone (hydroxyethoxyphenyl butanone [HEPB]), an SCCS-approved new preservative for use in rinse-off, oral care, and leave-on cosmetic products. We show that HEPB significantly inhibits growth of Candida albicans, Candida glabrata, and Saccharomyces cerevisiae, acting fungicidally against C. albicans Using transcript profiling experiments, we found that the C. albicans transcriptome responded to HEPB exposure by increasing the expression of genes involved in amino acid biosynthesis while activating pathways involved in chemical detoxification/oxidative stress response. Comparative analyses revealed that C. albicans phenotypic and transcriptomic responses to HEPB treatment were distinguishable from those of two widely used preservatives, triclosan and methylparaben. Chemogenomic analyses, using a barcoded S. cerevisiae nonessential mutant library, revealed that HEPB antifungal activity strongly interfered with the biosynthesis of aromatic amino acids. The trp1Δ mutants in S. cerevisiae and C. albicans were particularly sensitive to HEPB treatment, a phenotype rescued by exogenous addition of tryptophan to the growth medium, providing a direct link between HEPB mode of action and tryptophan availability. Collectively, our study sheds light on the antifungal activity of HEPB, a new molecule with safe properties for use as a preservative in the cosmetic industry, and exemplifies the powerful use of functional genomics to illuminate the mode of action of antimicrobial agents.

Hydroxyethoxy phenyl butanone, a new cosmetic preservative, does not cause bacterial cross-resistance to antimicrobials.

Introduction. Biocide-induced cross-resistance to antimicrobials in bacteria has been described and is a concern for regulators. We have recently reported on a new protocol to predict the propensity of biocide to induce phenotypic resistance in bacteria.Aim. To measure bacterial propensity to develop antimicrobial resistance following exposure to a new cosmetic preservative developed by L'Oréal R and I.Methodology. Well-established antimicrobials including triclosan (TRI) and benzalkonium chloride (BZC) and a new molecule hydroxyethoxy phenyl butanone (HEPB) were investigated for their antimicrobial efficacy, effect on bacterial growth, and their potential to induce resistance to chemotherapeutic antibiotics using a new predictive protocol.Results. The use of this predictive protocol with Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa showed that TRI and BZC significantly affected bacterial growth, MICs and minimum bactericidal concentrations (MBCs). There was no change in antibiotic susceptibility profile following exposure to BZC, but E. coli became intermediate resistant to tobramycin following treatment with TRI (0.00002 % w/v). HEPB did not change the antimicrobial susceptibility profile in P. aeruginosa and S. aureus but E. coli became susceptible to gentamicin. TRI exposure resulted in bacterial susceptibility profile alteration consistent with the literature and confirmed the use of TRI as a positive control in such a test.Conclusion. Data produced on the propensity of a molecule to induce bacterial resistance is useful and appropriate when launching a new preservative.

Impact of antimicrobial wipes compared with hypochlorite solution on environmental surface contamination in a health care setting: A double-crossover study.

OBJECTIVE: Antimicrobial wipes are increasingly used in health care settings. This study evaluates, in a clinical setting, the efficacy of sporicidal wipes versus a cloth soaked in a 1,000 ppm chlorine solution. INTERVENTION: A double-crossover study was performed on 2 different surgical and cardiovascular wards in a 1,000-bed teaching hospital over 29 weeks. The intervention period that consisted of surface decontamination with the preimpregnated wipe or cloth soaked in chlorine followed a 5-week baseline assessment of microbial bioburden on surfaces. Environmental samples from 11 surfaces were analyzed weekly for their microbial content. RESULTS: A total of 1,566 environmental samples and 1,591 ATP swabs were analyzed during the trial. Overall, there were significant differences in the recovery of total aerobic bacteria (P < .001), total anaerobic bacteria (P < .001), and ATP measurement (P < .001) between wards and between the different parts of the crossover study. Generally, the use of wipes produced the largest reduction in the total aerobic and anaerobic counts when compared with the baseline data or the use of 1,000 ppm chlorine. Collectively, the introduction of training plus daily wipe disinfection significantly reduced multidrug-resistant organisms recovered from surfaces. Reversion to using 1,000 ppm chlorine resulted in the number of sites positive for multidrug-resistant organisms rising again. CONCLUSIONS: This double-crossover study is the first controlled field trial comparison of using preimpregnated wipes versus cotton cloth dipped into a bucket of hypochlorite to decrease surface microbial bioburden. The results demonstrate the superiority of the preimpregnated wipes in significantly decreasing microbial bioburden from high-touch surfaces.

Use of a predictive protocol to measure the antimicrobial resistance risks associated with biocidal product usage.

BACKGROUND: In this study we assessed the propensity of biocide exposure in the development of antimicrobial resistance in bacteria. METHODS: Our protocol is based on reporting changes in established antimicrobial susceptibility profiles in biocides and antibiotics after during use exposure to a product. The during use exposure reflects worse conditions of product use during application. It differs from the term low concentration, which usually reflects a concentration below the minimal inhibitory concentration, but not necessarily a concentration that occurs in practice. RESULTS: Our results showed that exposure to triclosan (0.0004%) was associated with a high risk of developing resistance and cross-resistance in Staphylococcus aureus and Escherichia coli. This was not observed with exposure to chlorhexidine (0.00005%) or a hydrogen peroxide-based biocidal product (in during use conditions). Interestingly, exposure to a low concentration of hydrogen peroxide (0.001%) carried a risk of emerging resistance to antibiotics if the presence of the oxidizing agent was maintained. We observed a number of unstable clinical resistances to antibiotics after exposure to the cationic biocide and oxidizing agent, notably to tobramycin and ticarcillin-clavulanic acid. CONCLUSIONS: Using a decision tree based on the change in antimicrobial susceptibility test results, we were able to provide information on the effect of biocide exposure on the development of bacterial resistance to antimicrobials. Such information should address the call from the U.S. Food and Drug Administration and European Union Biocidal Products Regulation for manufacturers to provide information on antimicrobial resistance and cross-resistance in bacteria after the use of their product.

Pathogen transfer and high variability in pathogen removal by detergent wipes.

BACKGROUND: The rise in health care-associated infections has placed a greater emphasis on cleaning and disinfection practices. The majority of policies advocate using detergent-based products for routine cleaning, with detergent wipes increasingly being used; however, there is no information about their ability to remove and subsequently transfer pathogens in practice. METHODS: Seven detergent wipes were tested for their ability to remove and transfer Staphylococcus aureus, Acinetobacter baumannii, and Clostridium difficile spores using the 3-stage wipe protocol. RESULTS: The ability of the detergent wipes to remove S aureus, A baumannii, and C difficile spores from a stainless steel surface ranged from 1.50 log10 (range, 0.24-3.25), 3.51 log10 (range, 3.01-3.81), and 0.96 log10 (range, 0.26-1.44), respectively, following a 10-second wiping time. All wipes repeatedly transferred significant amounts of bacteria/spores over 3 consecutive surfaces, although the percentage of total microorganisms transferred from the wipes after wiping was low for a number of products. CONCLUSIONS: Detergent-based wipe products have 2 major drawbacks: their variability in removing microbial bioburden from inanimate surfaces and a propensity to transfer pathogens between surfaces. The use of additional complementary measures such as combined detergent/disinfectant-based products and/or antimicrobial surfaces need to be considered for appropriate infection control and prevention.