Phenotypic Adaptation to Antiseptics and Effects on Biofilm Formation Capacity and Antibiotic Resistance in Clinical Isolates of Early Colonizers in Dental Plaque

Auer, David L.; Mao, Xiaodong; Anderson, Anne B. M.; Muehler, Denise; Wittmer, Annette; Ohle, Christiane von; Wolff, Diana; Frese, Cornelia; Hiller, Karl‐Anton; Maisch, Tim; Buchalla, Wolfgang; Hellwig, Elmar; Al‐Ahmad, Ali

doi:10.3390/antibiotics11050688

Cited by 13 publications

(21 citation statements)

References 92 publications

(126 reference statements)

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“…Furthermore, a relevant observation was that this resistance increased, especially for S. mutans and L. acidophilus , during the observation time of the RCTs 14,16 . These results are in agreement with various in vitro reports that found an intensification in microbial resistance to chlorhexidine during extended exposure 22–26 . Interestingly, it was found that in the presence of V. parvula , S. mutans presented an increment in subsistence following exposure to diverse antimicrobials 25 .…”

Section: Discussionsupporting

confidence: 89%

Bacterial resistance to antiseptics used in dentistry: A systematic scoping review of randomized clinical trials

Medina

Bedoya-García

2022

Int J Dental Hygiene

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The menace of antibiotic resistance has had robust relevance recently. This concern has led to the creation of public policies and alternative antimicrobial management. 1 Contrariwise, less consideration has been assumed to the directly interconnected trouble of resistance regarding antiseptics. 1,2 This is noteworthy because microbial resistance to antiseptics such as benzalkonium chloride and biocides (triclosan, chlorhexidine, and cetylpyridinium chloride), including the induction of cross-resistance between them and some antibiotics, has long been recognized in the medical management of different diseases. 3,4 These antiseptics have also been widely used in dentistry as oral rinses and gels, including oral care formulations. The use of antiseptics has also been extended to improve the oral hygiene conditions of hospitalized patients. 5,6 Thus, present protocols of prevention in dentistry are pointed at decreasing dental biofilm in an attempt to diminish the occurrence of periodontal diseases and caries. 7 On the

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Section: Discussionsupporting

confidence: 89%

Bacterial resistance to antiseptics used in dentistry: A systematic scoping review of randomized clinical trials

Medina

Bedoya-García

2022

Int J Dental Hygiene

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“…After the cultivation of the surviving microorganisms, the bacterial colonies visible on the plates were classified according to chemical and morphological criteria and transferred into pure cultures. Such modified microdilution methods have been used by other authors to investigate the adaption of bacteria to antiseptics after frequent exposure to subinhibitory concentrations [ 6 , 9 , 15 , 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, it was shown by our group that microorganisms display the ability to adapt to antiseptics and are thereby able to also increase their biofilm formation. While major changes in antibiotic susceptibility could not be detected [ 15 ], the frequent treatment with subinhibitory CHX concentrations led to a genetic adaptation in the sense of the upregulation of efflux pumps in the bacteria [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…A threshold value of the MIC for defining the resistance against CHX has not yet been established [ 20 ], but the adaption of oral bacteria to the antiseptic has been observed [ 15 ]. Different mechanisms of action are discussed for such adaptations, including changes in the membrane that complicate the penetration of CHX into the inside of the cell and the expression of multidrug efflux pumps [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

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Antibiotic Resistance of Selected Bacteria after Treatment of the Supragingival Biofilm with Subinhibitory Chlorhexidine Concentrations

et al. 2022

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Due to increasing rates of antibiotic resistance and very few novel developments of antibiotics, it is crucial to understand the mechanisms of resistance development. The aim of the present study was to investigate the adaptation of oral bacteria to the frequently used oral antiseptic chlorhexidine digluconate (CHX) and potential cross-adaptation to antibiotics after repeated exposure of supragingival plaque samples to subinhibitory concentrations of CHX. Plaque samples from six healthy donors were passaged for 10 days in subinhibitory concentrations of CHX, while passaging of plaque samples without CHX served as control. The surviving bacteria were cultured on agar plates and identified with Matrix-assisted Laser Desorption/Ionization-Time of Flight-Mass spectrometry (MALDI-TOF). Subsequently, the minimum inhibitory concentrations (MIC) of these isolates toward CHX were determined using a broth-microdilution method, and phenotypic antibiotic resistance was evaluated using the epsilometertest. Furthermore, biofilm-forming capacities were determined. Repeated exposure of supragingival plaque samples to subinhibitory concentrations of CHX led to the selection of oral bacteria with 2-fold up to 4-fold increased MICs toward CHX. Furthermore, these isolates showed up to 12-fold increased MICs towards some antibiotics such as erythromycin and clindamycin. Conversely, biofilm-forming capacity was decreased. In summary, this study shows that oral bacteria are able to adapt to CHX, while also decreasing their susceptibility to antibiotics.

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“…Therefore, it seems reasonable that bacteria in deeper layers of biofilms will be exposed to subinhibitory antiseptic concentrations upon application of antiseptic-containing mouthwash ( Cieplik et al, 2019a ; Mao et al, 2020 ; Schwarz et al, 2021 ; Muehler et al, 2022 ). Previous studies have shown that repeated exposure to subinhibitory concentrations of CHX or CPC in vitro may lead to phenotypic adaptation of bacteria to these antiseptics ( Kitagawa et al, 2016 ; Cieplik et al, 2019a ; Verspecht et al, 2019 ; Mao et al, 2020 ; Schwarz et al, 2021 ; Auer et al, 2022 ). Furthermore, selection pressure due to antiseptic treatment may lead to selection of antibiotic-resistant strains ( Wand et al, 2017 ; Verspecht et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Ecological Effects of Daily Antiseptic Treatment on Microbial Composition of Saliva-Grown Microcosm Biofilms and Selection of Resistant Phenotypes

et al. 2022

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Antiseptics are widely used in dental practice and included in numerous over-the-counter oral care products. However, the effects of routine antiseptic use on microbial composition of oral biofilms and on the emergence of resistant phenotypes remain unclear. Microcosm biofilms were inoculated from saliva samples of four donors and cultured in the Amsterdam Active Attachment biofilm model for 3 days. Then, they were treated two times daily with chlorhexidine digluconate (CHX) or cetylpyridinium chloride (CPC) for a period of 7 days. Ecological changes upon these multiple antiseptic treatments were evaluated by semiconductor-based sequencing of bacterial 16S rRNA genes and identification of amplicon sequence variants (ASVs). Furthermore, culture-based approaches were used for colony-forming units (CFU) assay, identification of antiseptic-resistant phenotypes using an agar dilution method, and evaluation of their antibiotic susceptibilities. Both CHX and CPC showed only slight effects on CFU and could not inhibit biofilm growth despite the two times daily treatment for 7 days. Both antiseptics showed significant ecological effects on the microbial compositions of the surviving microbiota, whereby CHX led to enrichment of rather caries-associated saccharolytic taxa and CPC led to enrichment of rather gingivitis-associated proteolytic taxa. Antiseptic-resistant phenotypes were isolated on antiseptic-containing agar plates, which also exhibited phenotypic resistance to various antibiotics. Our results highlight the need for further research into potential detrimental effects of antiseptics on the microbial composition of oral biofilms and on the spread of antimicrobial resistance in the context of their frequent use in oral healthcare.

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Phenotypic Adaptation to Antiseptics and Effects on Biofilm Formation Capacity and Antibiotic Resistance in Clinical Isolates of Early Colonizers in Dental Plaque

Cited by 13 publications

References 92 publications

Bacterial resistance to antiseptics used in dentistry: A systematic scoping review of randomized clinical trials

Bacterial resistance to antiseptics used in dentistry: A systematic scoping review of randomized clinical trials

Antibiotic Resistance of Selected Bacteria after Treatment of the Supragingival Biofilm with Subinhibitory Chlorhexidine Concentrations

Ecological Effects of Daily Antiseptic Treatment on Microbial Composition of Saliva-Grown Microcosm Biofilms and Selection of Resistant Phenotypes

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