Susceptibility of vancomycin-resistant and -sensitive Enterococcus faecium obtained from Danish hospitals to benzalkonium chloride, chlorhexidine and hydrogen peroxide biocides

Alotaibi, Sulaiman Mohammed I; Ayibieke, Alafate; Pedersen, Annemette Frøling; Jakobsen, Lotte; Pinholt, Mette; Gumpert, Heidi; Hammerum, Anette M.; Westh, Henrik; Ingmer, Hanne

doi:10.1099/jmm.0.000642

Cited by 47 publications

(31 citation statements)

References 36 publications

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“…The high reproducibility points towards the reliable description of susceptibility patterns for cationic biocides by applying a test system based on vacuum dried plates. Overall, MIC and MBC values of BAC, DDAC, and CHX were in accordance with previously reported data on E. faecium, which were generated by broth microdilution according to ISO 20776-1 [13,21], modified broth microdilution and subsequent macrodilution [22,23], or agar dilution [14]. Interestingly, compared to data published by Morrissey et al [21], MIC values of CHX were quite low (2-4 mg/L vs. 16 mg/L) in our subpopulation of E. faecium isolates, which might display geographic variability.…”

Section: Cationic Biocide Susceptibility Profiles Of Vancomycin Resissupporting

confidence: 89%

“…The MBC 95 of BAC and the MIC 95 of CHX were twice as high in VSE compared to VRE. This observation is in contrast to previous findings, where vancomycin resistance was associated with reduced susceptibility to cationic biocides, such as BAC and CHX [13,14]. While our study focused on clinical E. faecium isolates from wards with low CHX usage, the study conducted by Alotaibi et al investigated isolates from Danish hospital wards, where CHX is heavily used [13], which might be one reason for the observed difference in study outcomes.…”

Section: Cationic Biocide Susceptibility Profiles Of Vancomycin Resiscontrasting

confidence: 62%

“…This observation is in contrast to previous findings, where vancomycin resistance was associated with reduced susceptibility to cationic biocides, such as BAC and CHX [13,14]. While our study focused on clinical E. faecium isolates from wards with low CHX usage, the study conducted by Alotaibi et al investigated isolates from Danish hospital wards, where CHX is heavily used [13], which might be one reason for the observed difference in study outcomes. Last but not least, BAC and CHX susceptibility of VRE and VSE differed only in one doubling dilution step, which is within the acceptable range in terms of comparability of results according to ISO 20776-2.…”

Section: Cationic Biocide Susceptibility Profiles Of Vancomycin Resiscontrasting

confidence: 62%

“…Thus, the first aim of our study was to evaluate the comparability of susceptibility profiles for chosen biocides obtained with broth microdilution method according to ISO 20776-1 and a newly developed microtiter-plate containing vacuum dried cationic biocides (MERLIN Diagnostika GmbH, Bornheim-Hersel, Germany). Subsequently, we used the novel test system to determine biocide susceptibility of vancomycin-resistant (VRE) and susceptible enterococci (VSE) as vancomycin resistance has been linked to reduced susceptibility to cationic biocides such as CHX and benzalkonium chloride (BAC) in the past [13,14].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of a Newly Developed Vacuum Dried Microtiter Plate for Rapid Biocide Susceptibility Testing of Clinical Enterococcus faecium Isolates

et al. 2020

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We investigated the suitability of a newly developed biocide susceptibility test system based on microtiter plates containing vacuum dried biocides as a fast and reliable screening method. The evaluated substances included the cationic biocides benzalkonium chloride (BAC), chlorhexidine dihydrochloride (CHX), cetylpyridinium chloride, didecyldimethylammonium chloride, and octenidine dihydrochloride. Testing a selection of Escherichia coli and enterococci, the biocide microtiter plates provided results comparable to those obtained from broth microdilution according to ISO 20776-1. Broad MIC ranges allowed for testing gram-positive and gram-negative species with the same plate design. In the second part of our study, we applied the established method to analyze the susceptibility of 90 clinical Enterococcus faecium isolates from a German university hospital, as previous studies have indicated a link between reduced susceptibility to substances such as CHX and BAC and vancomycin resistance. We therefore determined MIC and minimum bactericidal concentrations (MBC) for 48 non-clonal vancomycin susceptible and 42 non-clonal vancomycin resistant isolates, but MIC95 and MBC95 were quite similar in both groups. Our easy to handle and ready to use test system enables the routine surveillance of bacterial tolerance towards disinfectants in hospitals. As a result, hygiene measures can be adapted and nosocomial infections controlled despite increasing prevalence of antibiotic-resistant bacteria.

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Section: Cationic Biocide Susceptibility Profiles Of Vancomycin Resissupporting

confidence: 89%

Section: Cationic Biocide Susceptibility Profiles Of Vancomycin Resiscontrasting

confidence: 62%

Section: Cationic Biocide Susceptibility Profiles Of Vancomycin Resiscontrasting

confidence: 62%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Evaluation of a Newly Developed Vacuum Dried Microtiter Plate for Rapid Biocide Susceptibility Testing of Clinical Enterococcus faecium Isolates

et al. 2020

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“…Chlorhexidine and iodine, which the World Health Organization (WHO) recognizes as essential antiseptics for human medicine (10), are among the most common antiseptics used in teat disinfectants (11). Increased tolerance to chlorhexidine has been reported in both Gram-positive and Gram-negative hospital-associated pathogens (12)(13)(14), illustrating the pressing need to discover novel animal-only antimicrobials for mastitis prevention and treatment.…”

mentioning

confidence: 99%

Multiple Bactericidal Mechanisms of the Zinc Ionophore PBT2

Harbison-Price

Ferguson

Heikal

et al. 2020

mSphere

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Globally, more antimicrobials are used in food-producing animals than in humans, and the extensive use of medically important human antimicrobials poses a significant public health threat in the face of rising antimicrobial resistance (AMR). The development of novel ionophores, a class of antimicrobials used exclusively in animals, holds promise as a strategy to replace or reduce essential human antimicrobials in veterinary practice. PBT2 is a zinc ionophore with recently demonstrated antibacterial activity against several Gram-positive pathogens, although the underlying mechanism of action is unknown. Here, we investigated the bactericidal mechanism of PBT2 in the bovine mastitis-causing pathogen, Streptococcus uberis. In this work, we show that PBT2 functions as a Zn2+/H+ ionophore, exchanging extracellular zinc for intracellular protons in an electroneutral process that leads to cellular zinc accumulation. Zinc accumulation occurs concomitantly with manganese depletion and the production of reactive oxygen species (ROS). PBT2 inhibits the activity of the manganese-dependent superoxide dismutase, SodA, thereby impairing oxidative stress protection. We propose that PBT2-mediated intracellular zinc toxicity in S. uberis leads to lethality through multiple bactericidal mechanisms: the production of toxic ROS and the impairment of manganese-dependent antioxidant functions. Collectively, these data show that PBT2 represents a new class of antibacterial ionophores capable of targeting bacterial metal ion homeostasis and cellular redox balance. We propose that this novel and multitarget mechanism of PBT2 makes the development of cross-resistance to medically important antimicrobials unlikely. IMPORTANCE More antimicrobials are used in food-producing animals than in humans, and the extensive use of medically important human antimicrobials poses a significant public health threat in the face of rising antimicrobial resistance. Therefore, the elimination of antimicrobial crossover between human and veterinary medicine is of great interest. Unfortunately, the development of new antimicrobials is an expensive high-risk process fraught with difficulties. The repurposing of chemical agents provides a solution to this problem, and while many have not been originally developed as antimicrobials, they have been proven safe in clinical trials. PBT2, a zinc ionophore, is an experimental therapeutic that met safety criteria but failed efficacy checkpoints against both Alzheimer’s and Huntington’s diseases. It was recently found that PBT2 possessed potent antimicrobial activity, although the mechanism of bacterial cell death is unresolved. In this body of work, we show that PBT2 has multiple mechanisms of antimicrobial action, making the development of PBT2 resistance unlikely.

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Antimicrobial Biocides Susceptibility and Tolerance-Associated Genes in Enterococcus faecalis and Enterococcus faecium Isolates Collected from Human and Environmental Sources

et al. 2022

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Susceptibility of vancomycin-resistant and -sensitive Enterococcus faecium obtained from Danish hospitals to benzalkonium chloride, chlorhexidine and hydrogen peroxide biocides

Cited by 47 publications

References 36 publications

Evaluation of a Newly Developed Vacuum Dried Microtiter Plate for Rapid Biocide Susceptibility Testing of Clinical Enterococcus faecium Isolates

Evaluation of a Newly Developed Vacuum Dried Microtiter Plate for Rapid Biocide Susceptibility Testing of Clinical Enterococcus faecium Isolates

Multiple Bactericidal Mechanisms of the Zinc Ionophore PBT2

Antimicrobial Biocides Susceptibility and Tolerance-Associated Genes in Enterococcus faecalis and Enterococcus faecium Isolates Collected from Human and Environmental Sources

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