Chlorhexidine leads to the evolution of antibiotic-resistant Pseudomonas aeruginosa

ElDein, Moustafa A. Tag; Yassin, Aymen S.; El–Tayeb, O. M.; Kashef, Mona T.

doi:10.1007/s10096-021-04292-5

Cited by 31 publications

(23 citation statements)

References 43 publications

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“…Also, benzalkonium chloride-adapted Pseudomonas aeruginosa showed cross- resistance to polymyxin [ 10 ]. Repeated exposure of P. aeruginosa to chlorhexidine caused chlorhexidine resistance with cross-resistance to different antibiotics [ 11 ]. The U.S. Food and Drug Administration (FDA) suspended the use of triclosan in soap preparations because of its ability to trigger antibiotic cross-resistance [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of povidone-iodine and propanol-based mecetronium ethyl sulphate on antimicrobial resistance and virulence in Staphylococcus aureus

Barakat

Rasmy

Hosny

et al. 2022

Antimicrob Resist Infect Control

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Background Reports are available on cross-resistance between antibiotics and biocides. We evaluated the effect of povidone-iodine (PVP-I) and propanol-based mecetronium ethyl sulphate (PBM) on resistance development, antibiotics cross-resistance, and virulence in Staphylococcus aureus. Methods The minimum inhibitory concentration (MIC) of PVP-I and PBM were determined against S. aureus ATCC 25923 using the agar-dilution method. Staphylococcus aureus ATCC 25923 was subjected to subinhibitory concentrations of the tested biocides in ten consecutive passages followed by five passages in a biocide-free medium; MIC was determined after each passage and after the fifth passage in the biocide-free medium. The developed resistant mutant was tested for cross-resistance to different antibiotics using Kirby-Bauer disk diffusion method. Antibiotic susceptibility profiles as well as biocides’ MIC were determined for 97 clinical S. aureus isolates. Isolates were categorized into susceptible and resistant to the tested biocides based on MIC distribution pattern. The virulence of the biocide-resistant mutant and the effect of subinhibitory concentrations of biocides on virulence (biofilm formation, hemolysin activity, and expression of virulence-related genes) were tested. Results PVP-I and PBM MIC were 5000 μg/mL and 664 μg/mL. No resistance developed to PVP-I but a 128-fold increase in PBM MIC was recorded, by repeated exposure. The developed PBM-resistant mutant acquired resistance to penicillin, cefoxitin, and ciprofloxacin. No clinical isolates were PVP-I-resistant while 48.5% were PBM-resistant. PBM-resistant isolates were more significantly detected among multidrug-resistant isolates. PVP-I subinhibitory concentrations (¼ and ½ of MIC) completely inhibited biofilm formation and significantly reduced hemolysin activity (7% and 0.28%, respectively). However, subinhibitory concentrations of PBM caused moderate reduction in biofilm activity and non-significant reduction in hemolysin activity. The ½ MIC of PVP-I significantly reduced the expression of hla, ebps, eno, fib, icaA, and icaD genes. The virulence of the biocide-resistant mutant was similar to that of parent strain. Conclusion PVP-I is a highly recommended antiseptic for use in healthcare settings to control the evolution of high-risk clones. Exposure to PVP-I causes no resistance-development risk in S. aureus, with virulence inhibition by subinhibitory concentrations. Also, special protocols need to be followed during PBM use in hospitals to avoid the selection of resistant strains.

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Section: Introductionmentioning

confidence: 99%

Effect of povidone-iodine and propanol-based mecetronium ethyl sulphate on antimicrobial resistance and virulence in Staphylococcus aureus

Barakat

Rasmy

Hosny

et al. 2022

Antimicrob Resist Infect Control

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“…Thus, phenotypic differences in membrane composition could endow individual bacteria with a higher tolerance, for example through changes to the surface charge or membrane permeability. In support of this idea are several reports that found genetic alterations pertaining membrane components allow the adaptation to cationic antimicrobials (Nordholt et al 2021;Nagai et al 2003;Wand et al 2017;Kim et al 2018;Herrera, Hankins, and Trent 2010;Tag ElDein et al 2021). Another general defense mechanism against QACs and CHX is multi-drug efflux (Buffet-Bataillon et al 2012;Gregorchuk et al 2021;Nordholt et al 2021).…”

Section: Discussionmentioning

confidence: 84%

Time-kill kinetics reveal heterogeneous tolerance to disinfectants

Nordholt

Lewerenz

Schreiber

2022

Preprint

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Disinfection is an important strategy to limit the spread of infections. Failure of disinfection may facilitate evolution of resistance against disinfectants and antibiotics through the processes of cross-resistance and co-resistance. The best possible outcome of disinfection minimizes the number of surviving bacteria and the chance for resistance evolution. Resistance describes the ability to grow in previously inhibitory concentrations of an antimicrobial, whereas tolerance is associated with enhanced survival of lethal doses. Individual bacteria from the same population can display considerable heterogeneity in their ability to survive treatment (i.e. tolerance) with antimicrobials, which can result in unexpected treatment failure. Here, we investigated how phenotypic heterogeneity affects the ability of E. coli to survive treatment with six different substances commonly used as active substances in disinfectants, preservatives and antiseptics. A mathematical model which assumes that phenotypic heterogeneity underlies the observed disinfection kinetics was used to infer whether time-kill kinetics were caused by a tolerant subpopulation. The analysis identified bimodal kill kinetics for benzalkonium chloride (BAC), didecyldimethylammonium chloride (DDAC), and isopropanol (Iso). In contrast, kill kinetics by chlorhexidine (CHX), glutaraldehyde (GTA), and hydrogen peroxide (H2O2) were best explained by unimodal kill kinetics underpinned by a broad distribution of tolerance times for CHX as opposed to a narrow distribution of tolerance times for GTA and H2O2. These findings have implications for the risk of disinfection failure, with potential consequences for the evolution of antimicrobial resistance and tolerance.

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“…However, low-level CHX-resistant species may become more consequential when introduced to CHX-exposed environments (mucosa, disinfected surfaces) with residual levels of inhibitory CHX. Under these conditions, low-level CHX resistant species can be selected for and out compete CHX susceptible species, as suggested from past clinical studies 5 , 49 – 51 or even enhance antibiotic cross-resistance 16 , 51 .…”

Section: Discussionmentioning

confidence: 99%

“…Bacterial CHX resistance is often correlated with antiseptic over-usage/contamination and its common addition to many personal hygiene and cleaning products 14 . CHX is a growing concern due to its frequent co-association with species that have resistance to peptide antimicrobials such as colistin, and ceragenins in Enterobacteria 8 , 13 , 15 , suggesting CHX may promote antimicrobial cross-resistance 16 .…”

Section: Introductionmentioning

confidence: 99%

Applying fluorescent dye assays to discriminate Escherichia coli chlorhexidine resistance phenotypes from porin and mlaA deletions and efflux pumps

Gregorchuk

Reimer

Slipski

et al. 2022

Sci Rep

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Bacterial resistance to the antiseptic chlorhexidine (CHX), is a growing problem, recently shown to be caused by deleterious mutations to the phospholipid transport system component (mlaA) as well as efflux pump overexpression. Comparisons of CHX resistance mechanisms, such as porin deletions (ompCF), and over-expressed efflux pumps (acrB, qacE, aceI), are lacking and may be distinguishable using antiseptic rapid fluorescent dye testing assays. Using E. coli K-12 CHX adapted isolates (CHXR1), gene deletion mutants, and over-expressed transformants the phenotypes of these CHX resistance genes were compared using antimicrobial susceptibility tests (AST), rapid fluorescent propidium iodide dye-based membrane integrity assays (RFDMIA), and scanning electron microscopy (SEM). AST findings showed CHXR1, ΔacrB, ΔompCF, and transformants pCA24N-aceI and pCA24N-mlaA conferred greater (two to fourfold) MIC changes when compared to matched controls. Examination of these mutants/transformants using CHX RFDMIA showed that porin dual-deletions (ΔompCF) and mlaA alterations (ΔmlaA; pCA24N-mlaA, CHXR1) were distinguishable from controls. Results for over-expressed (pMS119EH-aceI) and deleted (ΔacrB) efflux pump RFDMIA could not be distinguished with propidium iodide, only with ethidium bromide, suggesting propidium iodide is better suited for detecting porin and mlaA associated CHX resistance mechanisms. SEM of CHXR1 and unadapted E. coli cells exposed to increasing CHX concentrations revealed that CHX does not visibly damage cell envelope integrity at any tested concentration but did identify elongated CHXR1 cells. ΔmlaA confers similar levels of CHX resistance as efflux overexpression and porin deletions, however, only outer membrane-altering porin and mlaA deletions can be reliably distinguished using RFDMIA.

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Chlorhexidine leads to the evolution of antibiotic-resistant Pseudomonas aeruginosa

Cited by 31 publications

References 43 publications

Effect of povidone-iodine and propanol-based mecetronium ethyl sulphate on antimicrobial resistance and virulence in Staphylococcus aureus

Effect of povidone-iodine and propanol-based mecetronium ethyl sulphate on antimicrobial resistance and virulence in Staphylococcus aureus

Time-kill kinetics reveal heterogeneous tolerance to disinfectants

Applying fluorescent dye assays to discriminate Escherichia coli chlorhexidine resistance phenotypes from porin and mlaA deletions and efflux pumps

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