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Helo S, Bonakdar Hashemi M, Ziegelmann MJ, Lybbert DT, Piraino J, Guillen Lozoya AH, Köhler TS. Chlorhexidine gluconate application, diabetes, revision surgery, and extended operative time increase risk for penile implant infection. J Sex Med 2025; 22:508-516. [PMID: 39916374 DOI: 10.1093/jsxmed/qdaf009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 11/20/2024] [Accepted: 01/20/2025] [Indexed: 04/12/2025]
Abstract
BACKGROUND Chlorhexidine gluconate (CHG) (0.05%) has recently been suggested as a dip and irrigation solution at time of inflatable penile prosthesis (IPP) surgery. AIM This study evaluated infection rates before and after implementing CHG protocol while investigating concurrent risk factors contributing to post operative infections. METHODS A retrospective, consecutive cohort study was performed that included patients who underwent insertion of a Coloplast Titan IPP including both virgin and revision cases between 2021 and 2024. Cases performed from January 2021 to August 2022 utilized rifampin/gentamicin for dip and vancomycin/gentamicin for irrigation (ABX), whereas those from October 2022 to May 2024 utilized CHG for both dip and irrigation. Perioperative risk factors including dip and irrigation solution used at time of surgery were compared between groups. OUTCOMES We defined the incidence of postoperative infection and risk factors associated with infection in each group. RESULTS The incidence of infection was significantly higher in the 0.05% CHG group (13/377) compared to the ABX group (0/320) (P < .001). When analyzed separately by subgroup, virgin cases treated with CHG for dip and irrigation demonstrated a significantly higher infection rate (7/315) compared to those in the ABX group (0/280) (P = .012). Similarly, in revision cases, the CHG group also exhibited a significantly higher infection rate (0/40) than the ABX group (6/62) (P = .043).Univariable analysis of the CHG cohort identified three significant risk factors for infection: diabetes mellitus (DM), extended operative time (OP), and revision surgery (P = .003, .001, and < .001, respectively). Multivariable regression analysis revealed that patients with DM had a 5.7-fold increased risk of infection (OR: 5.70, P = .004), while those undergoing revision surgery faced a 5.3-fold higher risk (OR: 5.26, P = .004). Additionally, each minute increase in OP was associated with a 1% higher infection risk (OR: 1.01 per minute, P = .007). These associations remained significant after adjusting for all variables in the model. CLINICAL IMPLICATIONS Prosthetic surgeons should be cautious about adopting 0.05% CHG for both dip and irrigation in the absence of strong clinical evidence demonstrating its non-inferiority to antibiotic solutions. STRENGTHS AND LIMITATIONS This is the first clinical study reporting infection rates after IPP surgery using 0.05% CHG for both dip and irrigation. While retrospective and non-randomized, we present a relatively large sample size of patients. CONCLUSIONS Our findings identify four risk factors for penile prosthesis infection: usage of the 0.05% CHG solution for dip and irrigation solution of Coloplast hydrophilic-coated devices, DM, revision surgery, and extended OP.
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Affiliation(s)
- Sevann Helo
- Mayo Clinic Department of Urology, Rochester, MN 55905, United States
| | | | | | - Daniel T Lybbert
- Mayo Clinic Department of Urology, Rochester, MN 55905, United States
| | - Javier Piraino
- Mayo Clinic Department of Urology, Rochester, MN 55905, United States
| | | | - Tobias S Köhler
- Mayo Clinic Department of Urology, Rochester, MN 55905, United States
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Bartsch S, Kohnert E, Kreutz C, Woelber JP, Anderson A, Burkhardt AS, Hellwig E, Buchalla W, Hiller KA, Ratka-Krueger P, Cieplik F, Al-Ahmad A. Chlorhexidine digluconate mouthwash alters the oral microbial composition and affects the prevalence of antimicrobial resistance genes. Front Microbiol 2024; 15:1429692. [PMID: 38983634 PMCID: PMC11231401 DOI: 10.3389/fmicb.2024.1429692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 06/07/2024] [Indexed: 07/11/2024] Open
Abstract
Introduction Chlorhexidine (CHX) is a commonly used antiseptic in situations of limited oral hygiene ability such as after periodontal surgery. However, CHX is also considered as a possible factor in the emergence of cross-resistance to antibiotics. The aim of this study was to analyze the changes in the oral microbiota and the prevalence of antimicrobial resistance genes (ARGs) due to CHX treatment. Materials and methods We analyzed the oral metagenome of 20 patients who applied a 0.2% CHX mouthwash twice daily for 4 weeks following periodontal surgical procedures. Saliva and supragingival plaque samples were examined before, directly after 4 weeks, and another 4 weeks after discontinuing the CHX treatment. Results Alpha-diversity decreased significantly with CHX use. The Bray-Curtis dissimilarity increased in both sample sites and mainly streptococci showed a higher relative abundance after CHX treatment. Although no significant changes of ARGs could be detected, an increase in prevalence was found for genes that encode for tetracycline efflux pumps. Conclusion CHX treatment appears to promote a caries-associated bacterial community and the emergence of tetracycline resistance genes. Future research should focus on CHX-related changes in the microbial community and whether the discovered tetracycline resistance genes promote resistance to CHX.
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Affiliation(s)
- Sibylle Bartsch
- Center for Dental Medicine, Department of Operative Dentistry and Periodontology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg im Breisgau, Germany
| | - Eva Kohnert
- Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg im Breisgau, Germany
| | - Clemens Kreutz
- Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg im Breisgau, Germany
| | - Johan P. Woelber
- Policlinic of Operative Dentistry, Periodontology, and Pediatric Dentistry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Annette Anderson
- Center for Dental Medicine, Department of Operative Dentistry and Periodontology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg im Breisgau, Germany
| | - Ann-Sophie Burkhardt
- Center for Dental Medicine, Department of Operative Dentistry and Periodontology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg im Breisgau, Germany
| | - Elmar Hellwig
- Center for Dental Medicine, Department of Operative Dentistry and Periodontology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg im Breisgau, Germany
| | - Wolfgang Buchalla
- Department of Conservative Dentistry and Periodontology, University Hospital Regensburg, Regensburg, Germany
| | - Karl-Anton Hiller
- Department of Conservative Dentistry and Periodontology, University Hospital Regensburg, Regensburg, Germany
| | - Petra Ratka-Krueger
- Center for Dental Medicine, Department of Operative Dentistry and Periodontology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg im Breisgau, Germany
| | - Fabian Cieplik
- Center for Dental Medicine, Department of Operative Dentistry and Periodontology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg im Breisgau, Germany
- Department of Conservative Dentistry and Periodontology, University Hospital Regensburg, Regensburg, Germany
| | - Ali Al-Ahmad
- Center for Dental Medicine, Department of Operative Dentistry and Periodontology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg im Breisgau, Germany
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Lu F, Xia K, Su J, Yi J, Luo Z, Xu J, Gu Q, Chen B, Zhou H. Biochemical and structural characterization of chlorhexidine as an ATP-assisted inhibitor against type 1 methionyl-tRNA synthetase from Gram-positive bacteria. Eur J Med Chem 2024; 268:116303. [PMID: 38458107 DOI: 10.1016/j.ejmech.2024.116303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Revised: 02/27/2024] [Accepted: 03/02/2024] [Indexed: 03/10/2024]
Abstract
Methionyl-tRNA synthetase (MetRS) catalyzes the attachment of l-methionine (l-Met) to tRNAMet to generate methionyl-tRNAMet, an essential substrate for protein translation within ribosome. Owing to its indispensable biological function and the structural discrepancies with human counterpart, bacterial MetRS is considered an ideal target for developing antibacterials. Herein, chlorhexidine (CHX) was identified as a potent binder of Staphylococcus aureus MetRS (SaMetRS) through an ATP-aided affinity screening. The co-crystal structure showed that CHX simultaneously occupies the enlarged l-Met pocket (EMP) and the auxiliary pocket (AP) of SaMetRS with its two chlorophenyl groups, while its central hexyl linker swings upwards to interact with some conserved hydrophobic residues. ATP adopts alternative conformations in the active site cavity, and forms ionic bonds and water-mediated hydrogen bonds with CHX. Consistent with this synergistic binding mode, ATP concentration-dependently enhanced the binding affinity of CHX to SaMetRS from 10.2 μM (no ATP) to 0.45 μM (1 mM ATP). While it selectively inhibited two representative type 1 MetRSs from S. aureus and Enterococcus faecalis, CHX did not show significant interactions with three tested type 2 MetRSs, including human cytoplasmic MetRS, in the enzyme inhibition and biophysical binding assays, probably due to the conformational differences between two types of MetRSs at their EMP and AP. Our findings on CHX may inspire the design of MetRS-directed antimicrobials in future.
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Affiliation(s)
- Feihu Lu
- Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China; Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China
| | - Kaijiang Xia
- Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China; Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China
| | - Jingtian Su
- Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China; Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China
| | - Jia Yi
- Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China; Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China
| | - Zhiteng Luo
- Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China; Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China
| | - Jun Xu
- Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China
| | - Qiong Gu
- Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China
| | - Bingyi Chen
- Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China; Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
| | - Huihao Zhou
- Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China; Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
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Večerková L, Mašková L, Knejzlík Z, Kašpar O, Tokárová V. Development of spray-dried powder hand sanitiser with prolonged effectivity. Sci Rep 2024; 14:4827. [PMID: 38413707 PMCID: PMC10899249 DOI: 10.1038/s41598-024-55503-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 02/24/2024] [Indexed: 02/29/2024] Open
Abstract
Since the outbreak of the COVID-19 pandemic, the use of hand sanitisers has become an inseparable part of our personal hygiene. However, the short-term effect and the need for frequent application are shortcomings that impair the overall protection. Another aspect is that repeated use of some products (typically alcohol-based) may cause skin irritation or eventually more severe health problems. This work proposes spray-drying as a suitable method for the preparation of swellable chitosan carriers, allowing for encapsulation and sustained release of antibacterial chlorhexidine digluconate as a model active substance. After application to hands, micron-sized particles preferentially accommodate space between epidermal ridges, protected against attrition. Thanks to their small size (d < 10 µm), particles are comfortable to carry since they are not recognisable by somatosensory receptors. The performance of formulations with various amounts of chlorhexidine and cross-linker was tested and compared with selected commercial disinfectants available on the Czech market (ethanol gel and alcoholic solution with chlorhexidine) against E. coli and S. epidermidis. The real-life performance was investigated with twelve volunteers performing various activities for up to 2 h. Finally, a replica of the human index finger with accurately captured micro-topology was proposed and compared with volunteers' fingers concerning the total amount of adhered and detached particles.
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Affiliation(s)
- Lucie Večerková
- Department of Chemical Engineering, University of Chemistry and Technology Prague, Technická 5, 166 28, Prague 6, Czech Republic
| | - Lucie Mašková
- Department of Chemical Engineering, University of Chemistry and Technology Prague, Technická 5, 166 28, Prague 6, Czech Republic
| | - Zdeněk Knejzlík
- Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo náměstí 542/2, 160 00, Prague 6, Czech Republic
| | - Ondřej Kašpar
- Department of Chemical Engineering, University of Chemistry and Technology Prague, Technická 5, 166 28, Prague 6, Czech Republic
| | - Viola Tokárová
- Department of Chemical Engineering, University of Chemistry and Technology Prague, Technická 5, 166 28, Prague 6, Czech Republic.
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Anderson DM, Logan MG, Patty SS, Kendall AJ, Borland CZ, Pfeifer CS, Kreth J, Merritt JL. Microbiome imaging goes à la carte: Incorporating click chemistry into the fluorescence-activating and absorption-shifting tag (FAST) imaging platform. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.10.02.560575. [PMID: 37873282 PMCID: PMC10592883 DOI: 10.1101/2023.10.02.560575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/25/2023]
Abstract
The human microbiome is predominantly composed of facultative and obligate anaerobic bacteria that live in hypoxic/anoxic polymicrobial biofilm communities. Given the oxidative sensitivity of large fractions of the human microbiota, green fluorescent protein (GFP) and related genetically-encoded fluorophores only offer limited utility for live cell imaging due the oxygen requirement for chromophore maturation. Consequently, new fluorescent imaging modalities are needed to study polymicrobial interactions and microbiome-host interactions within anaerobic environments. The fluorescence-activating and absorption shifting tag (FAST) is a rapidly developing genetically-encoded fluorescent imaging technology that exhibits tremendous potential to address this need. In the FAST system, fluorescence only occurs when the FAST protein is complexed with one of a suite of cognate small molecule fluorogens. To expand the utility of FAST imaging, we sought to develop a modular platform (Click-FAST) to democratize fluorogen engineering for personalized use cases. Using Click-FAST, investigators can quickly and affordably sample a vast chemical space of compounds, potentially imparting a broad range of desired functionalities to the parental fluorogen. In this work, we demonstrate the utility of the Click-FAST platform using a novel fluorogen, PLBlaze-alkyne, which incorporates the widely available small molecule ethylvanillin as the hydroxybenzylidine head group. Different azido reagents were clicked onto PLBlaze-alkyne and shown to impart useful characteristics to the fluorogen, such as selective bacterial labeling in mixed populations as well as fluorescent signal enhancement. Conjugation of an 80 Å PEG molecule to PLBlaze-alkyne illustrates the broad size range of functional fluorogen chimeras that can be employed. This PEGylated fluorogen also functions as an exquisitely selective membrane permeability marker capable of outperforming propidium iodide as a fluorescent marker of cell viability.
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Affiliation(s)
- David M Anderson
- Division of Biomaterial and Biomedical Sciences, Oregon Health & Science University, Portland, OR, USA
| | - Matthew G Logan
- Division of Biomaterial and Biomedical Sciences, Oregon Health & Science University, Portland, OR, USA
| | - Sara S Patty
- Division of Biomaterial and Biomedical Sciences, Oregon Health & Science University, Portland, OR, USA
| | - Alexander J Kendall
- Division of Biomaterial and Biomedical Sciences, Oregon Health & Science University, Portland, OR, USA
| | - Christina Z Borland
- Division of Biomaterial and Biomedical Sciences, Oregon Health & Science University, Portland, OR, USA
| | - Carmem S Pfeifer
- Division of Biomaterial and Biomedical Sciences, Oregon Health & Science University, Portland, OR, USA
| | - Jens Kreth
- Division of Biomaterial and Biomedical Sciences, Oregon Health & Science University, Portland, OR, USA
- Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, USA
| | - Justin L Merritt
- Division of Biomaterial and Biomedical Sciences, Oregon Health & Science University, Portland, OR, USA
- Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, USA
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6
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Weber J, Bonn EL, Auer DL, Kirschneck C, Buchalla W, Scholz KJ, Cieplik F. Preprocedural mouthwashes for infection control in dentistry-an update. Clin Oral Investig 2023:10.1007/s00784-023-04953-z. [PMID: 37079156 PMCID: PMC10116478 DOI: 10.1007/s00784-023-04953-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Accepted: 03/17/2023] [Indexed: 04/21/2023]
Abstract
OBJECTIVES Aerosols and splatter are routinely generated in dental practice and can be contaminated by potentially harmful bacteria or viruses such as SARS-CoV-2. Therefore, preprocedural mouthwashes containing antiseptic agents have been proposed as a potential measure for infection control in dental practice. This review article aims to summarize the clinical (and, if insufficient, preclinical) evidence on preprocedural mouthwashes containing antiseptic agents and to draw conclusions for dental practitioners. METHODS Literature on preprocedural mouthwashes for reduction of bacterial or viral load in dental aerosols was searched and summarized. RESULTS Preprocedural mouthwashes, particularly those containing chlorhexidine digluconate (CHX), cetylpyridinium chloride (CPC), or essential oils (EO), can significantly reduce the bacterial load in dental aerosols. With respect to viruses such as HSV-1, there are too little clinical data to draw any clear recommendations. On the other hand, clinical data is consolidating that CPC-containing mouthwashes can temporarily reduce the intraoral viral load and infectivity in SARS-CoV-2 positive individuals. Nevertheless, potential risks and side effects due to regular antiseptic use such as ecological effects or adaptation of bacteria need to be considered. CONCLUSIONS The use of preprocedural mouthwashes containing antiseptics can be recommended according to currently available data, but further studies are needed, particularly on the effects on other viruses besides SARS-CoV-2. When selecting a specific antiseptic, the biggest data basis currently exists for CHX, CPC, EO, or combinations thereof. CLINICAL RELEVANCE Preprocedural mouthwashes containing antiseptics can serve as part of a bundle of measures for protection of dental personnel despite some remaining ambiguities and in view of potential risks and side effects.
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Affiliation(s)
- Johanna Weber
- Department of Conservative Dentistry and Periodontology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany
- Department of Orthodontics, University Hospital Regensburg, Regensburg, Germany
| | - Eva L Bonn
- Department of Conservative Dentistry and Periodontology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany
| | - David L Auer
- Department of Conservative Dentistry and Periodontology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany
| | | | - Wolfgang Buchalla
- Department of Conservative Dentistry and Periodontology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany
| | - Konstantin J Scholz
- Department of Conservative Dentistry and Periodontology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany
| | - Fabian Cieplik
- Department of Conservative Dentistry and Periodontology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
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Basiry D, Entezari Heravi N, Uluseker C, Kaster KM, Kommedal R, Pala-Ozkok I. The effect of disinfectants and antiseptics on co- and cross-selection of resistance to antibiotics in aquatic environments and wastewater treatment plants. Front Microbiol 2022; 13:1050558. [PMID: 36583052 PMCID: PMC9793094 DOI: 10.3389/fmicb.2022.1050558] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 11/21/2022] [Indexed: 12/14/2022] Open
Abstract
The outbreak of the SARS-CoV-2 pandemic led to increased use of disinfectants and antiseptics (DAs), resulting in higher concentrations of these compounds in wastewaters, wastewater treatment plant (WWTP) effluents and receiving water bodies. Their constant presence in water bodies may lead to development and acquisition of resistance against the DAs. In addition, they may also promote antibiotic resistance (AR) due to cross- and co-selection of AR among bacteria that are exposed to the DAs, which is a highly important issue with regards to human and environmental health. This review addresses this issue and provides an overview of DAs structure together with their modes of action against microorganisms. Relevant examples of the most effective treatment techniques to increase the DAs removal efficiency from wastewater are discussed. Moreover, insight on the resistance mechanisms to DAs and the mechanism of DAs enhancement of cross- and co-selection of ARs are presented. Furthermore, this review discusses the impact of DAs on resistance against antibiotics, the occurrence of DAs in aquatic systems, and DA removal mechanisms in WWTPs, which in principle serve as the final barrier before releasing these compounds into the receiving environment. By recognition of important research gaps, research needs to determine the impact of the majority of DAs in WWTPs and the consequences of their presence and spread of antibiotic resistance were identified.
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Affiliation(s)
- Daniel Basiry
- Department of Chemistry, Bioscience and Environmental Engineering, Faculty of Science and Technology, University of Stavanger, Stavanger, Norway
| | - Nooshin Entezari Heravi
- Department of Chemistry, Bioscience and Environmental Engineering, Faculty of Science and Technology, University of Stavanger, Stavanger, Norway
| | - Cansu Uluseker
- School of Biosciences, University of Birmingham, Birmingham, United Kingdom
| | - Krista Michelle Kaster
- Department of Chemistry, Bioscience and Environmental Engineering, Faculty of Science and Technology, University of Stavanger, Stavanger, Norway
| | - Roald Kommedal
- Department of Chemistry, Bioscience and Environmental Engineering, Faculty of Science and Technology, University of Stavanger, Stavanger, Norway
| | - Ilke Pala-Ozkok
- Department of Chemistry, Bioscience and Environmental Engineering, Faculty of Science and Technology, University of Stavanger, Stavanger, Norway
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Pałka Ł, Nowakowska-Toporowska A, Dalewski B. Is Chlorhexidine in Dentistry an Ally or a Foe? A Narrative Review. Healthcare (Basel) 2022; 10:764. [PMID: 35627901 PMCID: PMC9141996 DOI: 10.3390/healthcare10050764] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 04/11/2022] [Accepted: 04/19/2022] [Indexed: 12/17/2022] Open
Abstract
Chlorhexidine has been one of the most effective and popular antiseptic substances used in medicine for decades. In dentistry, it has been used in endodontics, periodontology, surgery, and general dentistry. It is also widely used daily by patients in mouth rinses, gels, or toothpastes. Because of its multiple uses, we should follow all types of research reporting its potential adverse effects. This article aims to review the most up-to-date studies regarding chlorhexidine and its possible side effects, in the period of the SARS-CoV-2 pandemic, as the use of different antiseptic substances has rapidly increased.
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Affiliation(s)
| | | | - Bartosz Dalewski
- Department of Dental Prosthetics, Pomeranian Medical University, 70-204 Szczecin, Poland;
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Transcriptomic Stress Response in Streptococcus mutans following Treatment with a Sublethal Concentration of Chlorhexidine Digluconate. Microorganisms 2022; 10:microorganisms10030561. [PMID: 35336136 PMCID: PMC8950716 DOI: 10.3390/microorganisms10030561] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 03/01/2022] [Accepted: 03/02/2022] [Indexed: 01/27/2023] Open
Abstract
Despite the widespread use of antiseptics such as chlorhexidine digluconate (CHX) in dental practice and oral care, the risks of potential resistance toward these antimicrobial compounds in oral bacteria have only been highlighted very recently. Since the molecular mechanisms behind antiseptic resistance or adaptation are not entirely clear and the bacterial stress response has not been investigated systematically so far, the aim of the present study was to investigate the transcriptomic stress response in Streptococcus mutans after treatment with CHX using RNA sequencing (RNA-seq). Planktonic cultures of stationary-phase S. mutans were treated with a sublethal dose of CHX (125 µg/mL) for 5 min. After treatment, RNA was extracted, and RNA-seq was performed on an Illumina NextSeq 500. Differentially expressed genes were analyzed and validated by qRT-PCR. Analysis of differential gene expression following pathway analysis revealed a considerable number of genes and pathways significantly up- or downregulated in S. mutans after sublethal treatment with CHX. In summary, the expression of 404 genes was upregulated, and that of 271 genes was downregulated after sublethal CHX treatment. Analysis of differentially expressed genes and significantly regulated pathways showed regulation of genes involved in purine nucleotide synthesis, biofilm formation, transport systems and stress responses. In conclusion, the results show a transcriptomic stress response in S. mutans upon exposure to CHX and offer insight into potential mechanisms that may result in development of resistances.
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10
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Kanclerz P, Myers WG. Chlorhexidine and other alternatives for povidone-iodine in ophthalmic surgery: review of comparative studies. J Cataract Refract Surg 2022; 48:363-369. [PMID: 34538779 DOI: 10.1097/j.jcrs.0000000000000754] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 06/20/2021] [Indexed: 11/25/2022]
Abstract
Povidone-iodine (PVI) is a universally accepted antiseptic agent used in ophthalmic surgery. Insufficient antisepsis in patients with self-reported allergies to iodine has led to devastating complications. The aim of this study was to review the current evidence for alternatives to PVI in ocular surgery. Aqueous chlorhexidine has been used as a primary antiseptic agent in Sweden for several years and has proven efficiency and safety; in a study of a large series of intravitreal injections in Australia, the endophthalmitis rates were similar to those after the use of PVI. The evidence related to using other disinfectants such as picloxydine, hypochlorous acid solution, and polyhexanide is scarce. Single studies have shown lower patient discomfort after conjunctival lavage with chlorhexidine or hypochlorous acid than with PVI. No evidence was found to suggest changing from PVI to other antiseptic agents. Disinfectant solutions other than PVI or chlorhexidine will require further investigations to show their utility in ocular surgery.
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Affiliation(s)
- Piotr Kanclerz
- From the Hygeia Clinic, Gdańsk, Poland (Kanclerz); Helsinki Retina Research Group, University of Helsinki, Helsinki, Finland (Kanclerz); Northwestern University, Chicago, Illinois (Myers)
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Saadatpour F, Mohammadipanah F. Enhancement of bactericidal effect of Chlorhexidine using choline augmentation as a natural additive. Am J Infect Control 2022; 50:39-48. [PMID: 34058268 DOI: 10.1016/j.ajic.2021.05.012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 05/22/2021] [Accepted: 05/22/2021] [Indexed: 11/01/2022]
Abstract
BACKGROUND The long-term use of Chlorhexidine (CHG) at high concentrations has detrimental effects on health and the environment. This research was aimed to evaluate the antibacterial capacity of CHG in the presence of choline as a natural additive to reduce the amount CHG required for the activity. METHODS The newly obtained formulation was evaluated for its stability and efficiency under physicochemical stresses. The checkerboard test was also performed to evaluate the type of CHG-additive interaction in a combinational state. RESULTS The MIC of CHG was reduced up to five-fold in combination with choline at the concentration of 50mg/L and five log cfu/mL at 3 minutes of exposure. Chlorhexidine activity in combination with choline was preserved 20% more in the presence of interfering substances. The activity between CHG and choline was demonstrated as synergistic with FICI of 0.375. At sub MIC concentrations of both CHG (≤20 mg/L) and choline (≤6 mg/L) the observed interaction was synergy. While the significant interaction at high concentrations for both compounds was indifferent manner. The lysis effect of the CHG 20 mg/L was diminished in the presence of choline. CONCLUSIONS Our suggested CHG formulation demonstrated rapid antimicrobial efficacy which can be a useful adjunct to infection control strategies currently employed in healthcare facilities. In conclusion, CHG can be combined with natural compounds as additives for enhanced synergistic antimicrobial activity.
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Kling KE, Maddox CW, Manfra Marretta S, Nowicki C, Schaeffer DJ. Effect of TrisEDTA and Chlorhexidine 0.12% on an In Vitro-Defined Biofilm Representing the Subgingival Plaque Biofilm of the Dog. J Vet Dent 2021; 39:9-20. [PMID: 34866484 DOI: 10.1177/08987564211058496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
This study was designed to investigate the effects of chlorhexidine 0.12%, TrisEDTA (tromethamine ethylenediamintetraacetic acid), and a combination of chlorhexidine 0.12% and TrisEDTA on an in vitro plaque biofilm model comprised of three bacterial species commonly found in canine subgingival plaque. Porphyromonas gulae, Actinomyces canis, and Neisseria canis were grown in a biofilm on polished hydroxyapatite coated titanium alloy pucks for 72 h prior to exposure to one of four test solutions: TrisEDTA, chlorhexidine 0.12%, a combination of TrisEDTA and chlorhexidine 0.12%, or sterile deionized water as a control. Following exposure to the test solution, a sample was collected of the biofilm either immediately or following 24 h of additional incubation in a broth medium. Lower numbers of CFU/mL of Porphyromonas gulae resulted when the biofilm was treated with a solution of chlorhexidine 0.12% and TrisEDTA compared to with chlorhexidine 0.12% alone, TrisEDTA alone, or the control and so this solution can be said to be synergistic against Porphyromonas gulae in this controlled in vitro model. Greater reductions in the numbers of CFU/mL of Actinomyces canis and Neisseria canis resulted from treatment with chlorhexidine 0.12% alone than if treated with the combination of TrisEDTA and chlorhexidine 0.12%. When treated biofilm samples were allowed 24 h of additional growth in fresh media, greater variance resulted and this variance highlights the complex dynamics involved in bacterial growth within a biofilm.
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Sethi DK, Felgate H, Diaz M, Faust K, Kiy C, Clarke P, Härtel C, Rupp J, Webber MA. Chlorhexidine gluconate usage is associated with antiseptic tolerance in staphylococci from the neonatal intensive care unit. JAC Antimicrob Resist 2021; 3:dlab173. [PMID: 34806010 PMCID: PMC8599896 DOI: 10.1093/jacamr/dlab173] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 10/18/2021] [Indexed: 12/20/2022] Open
Abstract
Background Intravascular catheters are essential for care in Neonatal Intensive Care Units (NICUs) but predispose infants to catheter-associated infections including late-onset sepsis, commonly caused by CoNS. Antiseptics are applied to prevent infection with chlorhexidine (CHG) and octenidine (OCT) the most common agents used. Objectives To investigate the association between antiseptic use and bacterial susceptibility. Methods CoNS isolates were collected from two NICUs with differing antiseptic regimens: Norwich, UK (using CHG) and Lubeck, Germany (using OCT). CoNS were isolated from different body sites of babies upon admission, and weekly thereafter. Antiseptic susceptibility testing was performed, and a selection underwent genome sequencing. Results A total of 1274 isolates were collected. UK isolates (n = 863) were significantly less susceptible than German isolates (n = 411) to both CHG (mean MIC: 20.1 mg/L versus 8.9 mg/L) and OCT (mean MIC: 2.3 mg/L versus 1.6 mg/L). UK isolates taken on admission were more susceptible to CHG than subsequent isolates. No cross-resistance between the agents was seen. Genome sequencing of 122 CoNS showed the most common species to be Staphylococcus epidermidis and Staphylococcus haemolyticus and phylogenetic analysis suggested antiseptic tolerance evolved multiple times in independent lineages. There was no evidence of dominant antiseptic tolerant clones and carriage of genes previously implicated in antimicrobial susceptibility (qac, smr, norA/B), did not correlate with CHG or OCT susceptibility. Conclusions Long-term CHG use may select for CHG and OCT tolerance in CoNS. This highlights the different potential for separate antiseptic regimens to select for resistance development. This could be an important factor in developing future infection control policies.
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Affiliation(s)
- Dheeraj K Sethi
- Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, UK.,Norwich Medical School, University of East Anglia (UEA), Norwich, UK
| | - Heather Felgate
- Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, UK
| | - Maria Diaz
- Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, UK
| | - Kirstin Faust
- Department of Pediatrics, University of Lübeck, Lübeck, Germany
| | - Cemsid Kiy
- Department of Pediatrics, University of Lübeck, Lübeck, Germany
| | - Paul Clarke
- Norwich Medical School, University of East Anglia (UEA), Norwich, UK.,Neonatal Unit, Norfolk and Norwich University Hospital (NNUH), Norwich NR4 7UY, UK
| | - Christoph Härtel
- Department of Pediatrics, University of Würzburg, Würzburg, Germany
| | - Jan Rupp
- Department of Infectious Diseases and Microbiology, University of Lübeck, Lübeck, Germany
| | - Mark A Webber
- Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, UK.,Norwich Medical School, University of East Anglia (UEA), Norwich, UK
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Buxser S. Has resistance to chlorhexidine increased among clinically-relevant bacteria? A systematic review of time course and subpopulation data. PLoS One 2021; 16:e0256336. [PMID: 34411140 PMCID: PMC8376095 DOI: 10.1371/journal.pone.0256336] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 08/03/2021] [Indexed: 12/03/2022] Open
Abstract
Chlorhexidine (CHX) was introduced for use as an antimicrobial more than 70 years ago. CHX has been and continues to be used broadly for disinfecting surfaces in medical and food service facilities as well as directly on skin of humans and animals. Considering its widespread use over many decades, questions of resistance to CHX have been raised. Additionally, questions of possible coincident resistance to the biocide and resistance to clinically relevant antibiotics have also been raised. A number of important questions remain, including is there consistent evidence of resistance, what is the degree of resistance, especially among clinically isolated microbial strains, and what is the degree of resistance compared to the typical concentrations of the biocide used? Data for microbial species isolated over the last 70+ years were compiled to construct as complete a picture as practical regarding possible resistance, especially among species in which resistance to commonly used antibiotics has been noted to be increasing. This is a compilation and analysis of individual MIC values for CHX reported in the literature, not a compilation of the conclusions individual authors reached. The data were analyzed using straight-forward and robust statistical procedures to detect changes in susceptibility to CHX over time, i.e. linear regression. Linear regression was supplemented with the use of nonlinear least squares regression analysis to detect the presence of population parameters associated with subpopulations of microbial strains which exhibit increased resistance to CHX. Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii were all found to have an increased resistance to CHX over time with the most profound change detected in A. baumannii. Additionally, subpopulations with log-normal distributions were found consistent with the presence of a baseline subpopulation of susceptible strains and a subpopulation with increased resistance to CHX. However, the CHX-resistant subpopulations did not correlate exactly with antibiotic resistance, so details of the relationship remain to be addressed. Increased resistance over time was not detected for Escherichia coli, Enterobacter faecalis, Staphylococcus aureus, or Candida albicans, although a subpopulation with greater than baseline resistance to CHX was detected among strains of E. faecalis and C. albicans. A difference in susceptibility to CHX was also detected between methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) S. aureus strains. The levels of resistance to CHX detected were all markedly lower than concentrations routinely used in medical and food service applications. Reaching conclusions regarding the relationship between antibiotic and CHX resistance was complicated by the limited overlap between tests of CHX and antibiotic resistance for several species. The results compiled here may serve as a foundation for monitoring changes in resistance to CHX and possible relationships between the use of CHX and resistance to antibiotics commonly used in clinical medicine.
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Affiliation(s)
- Stephen Buxser
- Select Bio Consult, LLC, Indianapolis, Indiana, United States of America
- * E-mail:
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15
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Biguanides drugs: Past success stories and promising future for drug discovery. Eur J Med Chem 2021; 224:113726. [PMID: 34364161 DOI: 10.1016/j.ejmech.2021.113726] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 07/27/2021] [Accepted: 07/27/2021] [Indexed: 12/13/2022]
Abstract
Biguanides have attracted much attention a century ago and showed resurgent interest in recent years after a long period of dormancy. They constitute an important class of therapeutic agents suitable for the treatment of a wide spectrum of diseases. Therapeutic indications of biguanides include antidiabetic, antimalarial, antiviral, antiplaque, and bactericidal applications. This review presents an extensive overview of the biological activity of biguanides and different mechanisms of action of currently marketed biguanide-containing drugs, as well as their pharmacological properties when applicable. We highlight the recent developments in research on biguanide compounds, with a primary focus on studies on metformin in the field of oncology. We aim to provide a critical overview of all main bioactive biguanide compounds and discuss future perspectives for the design of new drugs based on the biguanide fragment.
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17
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Reda B, Hollemeyer K, Trautmann S, Volmer DA, Hannig M. First insights into chlorhexidine retention in the oral cavity after application of different regimens. Clin Oral Investig 2021; 25:6109-6118. [PMID: 33825020 PMCID: PMC8531059 DOI: 10.1007/s00784-021-03910-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Accepted: 03/23/2021] [Indexed: 11/29/2022]
Abstract
Objectives This in situ study aimed to determine and compare the chlorhexidine (CHX) retention in the oral cavity after the application of different CHX pharmaceutical regimens. Methods Five volunteers used different CHX treatment regimens including mouth rinses, dental spray and toothpaste gel. After the application of the different CHX regimens, 2-μl samples were taken from saliva and buccal mucosa pellicle as well as the dental pellicle samples formed on standardized enamel surfaces. Sample collection was conducted at six time points within 12 h. Retention of CHX was measured using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Results CHX retention values in the oral mucosa pellicle were significantly higher than those in saliva. CHX remained in the mucosal pellicle at microgrammes per millilitre levels for 12 h after mouth rinsing, 10 h after spray application and 2 h after using the toothpaste. CHX was detected in the dental pellicle for at least 12 h after application of mouth rinsing and spray. Retention of CHX after mouth rinsing or spray application was significantly higher than the retention after using toothpaste. Conclusions Oral mucosa was the favourable site for CHX retention. Higher mouth rinse concentration and longer rinsing time produced a slight increase in CHX retention. CHX spray provided considerable retention values, whereas toothpaste gel delivered the lowest retention after application. MALDI-TOF was a sensitive method with excellent limits of quantification for CHX detection.
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Affiliation(s)
- Bashar Reda
- Clinic of Operative Dentistry, Periodontology and Preventive Dentistry, University Hospital, Saarland University, Building 73, 66421, Homburg, Saar, Germany
| | - Klaus Hollemeyer
- Physical Chemistry and Didactics of Chemistry, Saarland University, Campus B2 2, 66123, Saarbrücken, Germany
| | - Simone Trautmann
- Clinic of Operative Dentistry, Periodontology and Preventive Dentistry, University Hospital, Saarland University, Building 73, 66421, Homburg, Saar, Germany
| | - Dietrich A Volmer
- Department of Chemistry, Bioanalytical Chemistry, Humboldt University of Berlin, Brook-Taylor-Strasse 2, 12489, Berlin, Germany
| | - Matthias Hannig
- Clinic of Operative Dentistry, Periodontology and Preventive Dentistry, University Hospital, Saarland University, Building 73, 66421, Homburg, Saar, Germany.
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Kathuria D, Raul AD, Wanjari P, Bharatam PV. Biguanides: Species with versatile therapeutic applications. Eur J Med Chem 2021; 219:113378. [PMID: 33857729 DOI: 10.1016/j.ejmech.2021.113378] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Revised: 03/04/2021] [Accepted: 03/08/2021] [Indexed: 12/18/2022]
Abstract
Biguanides are compounds in which two guanidine moieties are fused to form a highly conjugated system. Biguanides are highly basic and hence they are available as salts mostly hydrochloride salts, these cationic species have been found to exhibit many therapeutic properties. This review covers the research and development carried out on biguanides and accounts the various therapeutic applications of drugs containing biguanide group-such as antimalarial, antidiabetic, antiviral, anticancer, antibacterial, antifungal, anti-tubercular, antifilarial, anti-HIV, as well as other biological activities. The aim of this review is to compile all the medicinal chemistry applications of this class of compounds so as to pave way for the accelerated efforts in finding the drug action mechanisms associated with this class of compounds. Importance has been given to the organic chemistry of these biguanide derivatives also.
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Affiliation(s)
- Deepika Kathuria
- University Center for Research and Development, Chandigarh University, Gharuan, Punjab, 140413, India
| | - Akshay D Raul
- Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S. A. S. Nagar, 160 062, Punjab, India
| | - Pravin Wanjari
- Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S. A. S. Nagar, 160 062, Punjab, India
| | - Prasad V Bharatam
- Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S. A. S. Nagar, 160 062, Punjab, India.
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Chen YD, Shu C, Duan ZH, Xu JJ, Li XJ, Chen F, Luo QJ, Li XD. Synthesis and characterization of an anti-caries and remineralizing fluorine-containing cationic polymer PHMB-F. Biomater Sci 2021; 9:2009-2019. [PMID: 33349819 DOI: 10.1039/d0bm01627f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Dental caries have become a major global public health problem. Plaque control and remineralization of initial enamel lesions are paramount for the prevention and control of caries. Polyhexamethylene biguanide (PHMB) is a type of cationic amphipathic antibacterial agent with broad-spectrum antibacterial properties and good biological safety. Fluoride delays demineralization and promotes the remineralization of hard dental tissues. However, a high concentration is needed for it to function as an antibacterial agent. In order to create a PHMB with the benefits associated with fluoride, we synthesized a fluorine-containing cationic polymer, PHMB-F. Fourier transform-infrared spectroscopy and solid state nuclear magnetic resonance characterization confirmed the successful synthesis of PHMB-F. Antibacterial tests showed that PHMB-F had better antiseptic efficacy for Streptococcus mutans compared with just PHMB. Moreover, positively-charged PHMB-F allows fluoride ions to exist closer to the enamel surface with negative potential, which markedly lowers the ion concentrations in the microenvironment adjacent to hard dental tissues needed to maintain equilibrium. Thus, only low concentrations of PHMB-F are required for enamel remineralization.
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Affiliation(s)
- Y D Chen
- The Affiliated Hospital of Stomatology, School of Stomatology, Zhejiang University School of Medicine, Hangzhou, 310006, P. R. China.
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Impact of preoperative chlorhexidine gluconate (CHG) application methods on preoperative CHG skin concentration. Infect Control Hosp Epidemiol 2020; 42:464-466. [PMID: 32993846 DOI: 10.1017/ice.2020.448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Elective surgical patients routinely bathe with chlorhexidine gluconate (CHG) at home days prior to their procedures. However, the impact of home CHG bathing on surgical site CHG concentration is unclear. We examined 3 different methods of applying CHG and hypothesized that different application methods would impact resulting CHG skin concentration.
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21
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Holinga GJ, McGuire JE. In vitro antimicrobial effects of chlorhexidine diacetate versus chlorhexidine free base dressings. J Wound Care 2020; 29:S22-S28. [PMID: 32412890 DOI: 10.12968/jowc.2020.29.sup5a.s22] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
OBJECTIVE The aim of this study was to investigate the in vitro antimicrobial performance of a chlorhexidine diacetate dressing and a chlorhexidine free base dressing to determine if the free base form of chlorhexidine has the potential to be an effective alternative to the chlorhexidine salts used in conventional, chlorhexidine-based antimicrobial dressings. METHOD Dressing samples were inoculated with clinically relevant pathogenic microorganisms including Gram-positive and Gram-negative bacteria, yeasts and fungus, and subsequently evaluated for in vitro log10 reduction at 1-, 3-, and 7-day time points. Chlorhexidine mole content was also calculated as a function of dressing surface area for both sample types to allow for formulation-independent comparison between the dressings. RESULTS The chlorhexidine free base dressing demonstrated >0.5 log10 superior mean antimicrobial efficacy at 67% of the experimental time points and equivalent mean antimicrobial efficacy (≤0.5 log10 different) at the remaining time points when compared with the chlorhexidine diacetate dressing. The chlorhexidine free base dressing was also found to contain 36% less chlorhexidine mole content than the chlorhexidine diacetate dressing. CONCLUSION Our results suggest that a dressing formulated with chlorhexidine free base can deliver in vitro antimicrobial performance at both a magnitude and rate that meets or exceeds that of a chlorhexidine diacetate-based dressing, while also allowing for a reduction in total chlorhexidine content per dressing. These findings could be of particular interest to researchers developing new antimicrobial technologies as well as to infection preventionists when evaluating antimicrobial products for use on clinical patients at elevated risk of infection.
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Systematic Analysis of Efflux Pump-Mediated Antiseptic Resistance in Staphylococcus aureus Suggests a Need for Greater Antiseptic Stewardship. mSphere 2020; 5:5/1/e00959-19. [PMID: 31941819 PMCID: PMC6968660 DOI: 10.1128/msphere.00959-19] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
S. aureus remains a significant cause of disease within hospitals and communities. To reduce the burden of S. aureus infections, antiseptics are ubiquitously used in our daily lives. Furthermore, many antiseptic compounds are dual purpose and are found in household products. The increased abundance of antiseptic compounds has selected for S. aureus strains that carry efflux pumps that increase resistance to antiseptic compounds; however, the effect of carrying multiple pumps within S. aureus is unclear. We demonstrated that an isogenic strain carrying multiple efflux pumps had an additive resistance phenotype to cetrimide. Moreover, in a strain carrying qacA and norA, increased chlorhexidine tolerance was observed after the strain was preexposed to subinhibitory concentrations of a different common-use antiseptic. Taken together, our findings demonstrate cooperation between antiseptic resistance efflux pumps and suggest that their protective phenotype may be exacerbated by priming with subinhibitory concentrations of household antiseptics. Staphylococcus aureus-associated infections can be difficult to treat due to multidrug resistance. Thus, infection prevention is critical. Cationic antiseptics, such as chlorhexidine (CHX) and benzalkonium chloride (BKC), are liberally used in health care and community settings to prevent infection. However, increased administration of antiseptics has selected for S. aureus strains that show reduced susceptibilities to cationic antiseptics. This increased resistance has been associated with carriage of specific efflux pumps (QacA, QacC, and NorA). Since prior published studies focused on different strains and on strains carrying only a single efflux gene, the relative importance of these various systems to antiseptic resistance is difficult to ascertain. To overcome this, we engineered a collection of isogenic S. aureus strains that harbored norA, qacA, and qacC, individually or in combination. MIC assays showed that qacA was associated with increased resistance to CHX, cetrimide (CT), and BKC, qacC was associated with resistance to CT and BKC, and norA was necessary for basal-level resistance to the majority of tested antiseptics. When all three pumps were present in a single strain, an additive effect was observed in the MIC for CT. Transcriptional analysis revealed that expression of qacA and norA was significantly induced following exposure to BKC. Alarmingly, in a strain carrying qacA and norA, preexposure to BKC increased CHX tolerance. Overall, our results reveal increased antiseptic resistance in strains carrying multiple efflux pumps and indicate that preexposure to BKC, which is found in numerous daily-use products, can increase CHX tolerance. IMPORTANCES. aureus remains a significant cause of disease within hospitals and communities. To reduce the burden of S. aureus infections, antiseptics are ubiquitously used in our daily lives. Furthermore, many antiseptic compounds are dual purpose and are found in household products. The increased abundance of antiseptic compounds has selected for S. aureus strains that carry efflux pumps that increase resistance to antiseptic compounds; however, the effect of carrying multiple pumps within S. aureus is unclear. We demonstrated that an isogenic strain carrying multiple efflux pumps had an additive resistance phenotype to cetrimide. Moreover, in a strain carrying qacA and norA, increased chlorhexidine tolerance was observed after the strain was preexposed to subinhibitory concentrations of a different common-use antiseptic. Taken together, our findings demonstrate cooperation between antiseptic resistance efflux pumps and suggest that their protective phenotype may be exacerbated by priming with subinhibitory concentrations of household antiseptics.
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Reda B, Hollemeyer K, Trautmann S, Hannig M, Volmer DA. Determination of chlorhexidine retention in different oral sites using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Arch Oral Biol 2019; 110:104623. [PMID: 31830639 DOI: 10.1016/j.archoralbio.2019.104623] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Revised: 11/19/2019] [Accepted: 11/23/2019] [Indexed: 11/17/2022]
Abstract
OBJECTIVE The aim of this study was to determine chlorhexidine retention in different oral sites after a one-time 30 s mouth rinsing. DESIGN Five volunteers were asked to rinse their mouth with 10 ml of 0.2 % chlorhexidine digluconate for 30 s. After rinsing, samples were collected from the interdental area, buccal dental pellicle, anterior labial and posterior buccal mucosa, and saliva with a microbrush at five-time points within 24 h. Retention of chlorhexidine was measured using matrix-assisted laser desorption/ionization-time of flight mass spectrometry with a quantification limit of 15 ng/ml. RESULTS Chlorhexidine remained in the oral cavity at micrograms per milliliter levels for 11 h after mouth rinsing and was even detected 24 h after application. The results showed a distinct decline of intraoral chlorhexidine levels during the first 6 h after rinsing and it was then retained at low concentrations for at least 24 h. CONCLUSIONS The dental pellicle and oral mucosa were favorable sites for chlorhexidine retention. The novel method used for chlorhexidine determination offered excellent quantification limits and readily permitted quantification of chlorhexidine.
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Affiliation(s)
- Bashar Reda
- Clinic of Operative Dentistry, Periodontology and Preventive Dentistry, Saarland University, Kirrberger Strasse 73, 66421 Homburg, Saarland, Germany.
| | - Klaus Hollemeyer
- Institute of Bioanalytical Chemistry, Saarland University, 66123 Saarbrücken, Saarland, Germany.
| | - Simone Trautmann
- Clinic of Operative Dentistry, Periodontology and Preventive Dentistry, Saarland University, Kirrberger Strasse 73, 66421 Homburg, Saarland, Germany.
| | - Matthias Hannig
- Clinic of Operative Dentistry, Periodontology and Preventive Dentistry, Saarland University, Kirrberger Strasse 73, 66421 Homburg, Saarland, Germany.
| | - Dietrich A Volmer
- Institute of Bioanalytical Chemistry, Saarland University, 66123 Saarbrücken, Saarland, Germany.
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Biswas D, Tiwari M, Tiwari V. Molecular mechanism of antimicrobial activity of chlorhexidine against carbapenem-resistant Acinetobacter baumannii. PLoS One 2019; 14:e0224107. [PMID: 31661500 PMCID: PMC6818764 DOI: 10.1371/journal.pone.0224107] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Accepted: 10/04/2019] [Indexed: 02/07/2023] Open
Abstract
Acinetobacter baumannii causes hospital-acquired infections, especially in those with impaired immune function. Biocides or disinfectants are widely used antibacterial agents used to eradicate the effect of A. baumannii on inanimate objects and health care environments. In the current study, the antimicrobial activity of chlorhexidine has been investigated against carbapenem-resistant (RS-307, RS-7434, RS-6694, and RS-122), and sensitive (ATCC-19606 and RS-10953) strains of A. baumannii. We have determined growth kinetics, antimicrobial susceptibility, ROS production, lipid peroxidation, cell viability using flow cytometry assay (FACS), and membrane integrity by scanning electron microscope (SEM). The effect of chlorhexidine on the bacterial membrane has also been investigated using Fourier transform infrared (FTIR) spectroscopy. The present study showed that 32μg/ml chlorhexidine treatment results in the decreased bacterial growth, CFU count and cell viability. The antibacterial activity of chlorhexidine is due to the elevated ROS production and higher lipid peroxidation. These biochemical changes result in the membrane damage and alteration in the membrane proteins, phospholipids, carbohydrates, nucleic acids as evident from the FTIR and SEM data. Therefore, chlorhexidine has the potential to be used in the hospital setups to remove the spread of A. baumannii.
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Affiliation(s)
- Deepika Biswas
- Department of Biochemistry, Central University of Rajasthan, Ajmer, India
| | - Monalisa Tiwari
- Department of Biochemistry, Central University of Rajasthan, Ajmer, India
| | - Vishvanath Tiwari
- Department of Biochemistry, Central University of Rajasthan, Ajmer, India
- * E-mail: ,
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Huang SS. Chlorhexidine-based decolonization to reduce healthcare-associated infections and multidrug-resistant organisms (MDROs): who, what, where, when, and why? J Hosp Infect 2019; 103:235-243. [PMID: 31494130 DOI: 10.1016/j.jhin.2019.08.025] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Accepted: 08/29/2019] [Indexed: 10/26/2022]
Abstract
Body surface decolonization with chlorhexidine bathing and nasal mupirocin has become a simple solution for prevention of healthcare-associated infections. The clinical trial evidence for this practice will be reviewed to understand who benefits from this practice, for what reasons, and at what times. The method of bathing and nasal decolonization will also be discussed as proper application is needed for maximal effectiveness. Finally, the conflict between current effectiveness and future potential for fueling resistance is considered.
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Affiliation(s)
- S S Huang
- Division of Infectious Diseases and Health Policy Research Institute, University of California Irvine School of Medicine, Irvine, California, USA.
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Baines SL, Jensen SO, Firth N, Gonçalves da Silva A, Seemann T, Carter GP, Williamson DA, Howden BP, Stinear TP. Remodeling of pSK1 Family Plasmids and Enhanced Chlorhexidine Tolerance in a Dominant Hospital Lineage of Methicillin-Resistant Staphylococcus aureus. Antimicrob Agents Chemother 2019; 63:e02356-18. [PMID: 30783008 PMCID: PMC6496109 DOI: 10.1128/aac.02356-18] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Accepted: 02/08/2019] [Indexed: 12/29/2022] Open
Abstract
Staphylococcus aureus is a significant human pathogen whose evolution and adaptation have been shaped in part by mobile genetic elements (MGEs), facilitating the global spread of extensive antimicrobial resistance. However, our understanding of the evolutionary dynamics surrounding MGEs, in particular, how changes in the structure of multidrug resistance (MDR) plasmids may influence important staphylococcal phenotypes, is incomplete. Here, we undertook a population and functional genomics study of 212 methicillin-resistant S. aureus (MRSA) sequence type 239 (ST239) isolates collected over 32 years to explore the evolution of the pSK1 family of MDR plasmids, illustrating how these plasmids have coevolved with and contributed to the successful adaptation of this persistent MRSA lineage. Using complete genomes and temporal phylogenomics, we reconstructed the evolution of the pSK1 family lineage from its emergence in the late 1970s and found that multiple structural variants have arisen. Plasmid maintenance and stability were linked to IS256- and IS257-mediated chromosomal integration and disruption of the plasmid replication machinery. Overlaying genomic comparisons with phenotypic susceptibility data for gentamicin, trimethoprim, and chlorhexidine, it appeared that pSK1 has contributed to enhanced resistance in ST239 MRSA isolates through two mechanisms: (i) acquisition of plasmid-borne resistance mechanisms increasing the rates of gentamicin resistance and reduced chlorhexidine susceptibility and (ii) changes in the plasmid configuration linked with further enhancement of chlorhexidine tolerance. While the exact mechanism of enhanced tolerance remains elusive, this research has uncovered a potential evolutionary response of ST239 MRSA to biocides, one of which may contribute to the ongoing persistence and adaptation of this lineage within health care institutions.
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Affiliation(s)
- Sarah L Baines
- Department of Microbiology & Immunology, The University of Melbourne at The Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
- Doherty Applied Microbial Genomics, Department of Microbiology & Immunology, The University of Melbourne at The Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
| | - Slade O Jensen
- Microbiology and Infectious Diseases, School of Medicine, Ingham Institute for Applied Medical Research, University of Western Sydney, Sydney, New South Wales, Australia
| | - Neville Firth
- School of Life and Environmental Sciences, University of Sydney, Sydney, New South Wales, Australia
| | - Anders Gonçalves da Silva
- Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology & Immunology, The University of Melbourne at The Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
| | - Torsten Seemann
- Department of Microbiology & Immunology, The University of Melbourne at The Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
- Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology & Immunology, The University of Melbourne at The Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
- Doherty Applied Microbial Genomics, Department of Microbiology & Immunology, The University of Melbourne at The Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
| | - Glen P Carter
- Department of Microbiology & Immunology, The University of Melbourne at The Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
- Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology & Immunology, The University of Melbourne at The Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
| | - Deborah A Williamson
- Department of Microbiology & Immunology, The University of Melbourne at The Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
- Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology & Immunology, The University of Melbourne at The Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
- Doherty Applied Microbial Genomics, Department of Microbiology & Immunology, The University of Melbourne at The Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
| | - Benjamin P Howden
- Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology & Immunology, The University of Melbourne at The Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
- Doherty Applied Microbial Genomics, Department of Microbiology & Immunology, The University of Melbourne at The Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
- Infectious Diseases Department, Austin Health, Melbourne, Victoria, Australia
| | - Timothy P Stinear
- Department of Microbiology & Immunology, The University of Melbourne at The Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
- Doherty Applied Microbial Genomics, Department of Microbiology & Immunology, The University of Melbourne at The Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia
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Cieplik F, Jakubovics NS, Buchalla W, Maisch T, Hellwig E, Al-Ahmad A. Resistance Toward Chlorhexidine in Oral Bacteria - Is There Cause for Concern? Front Microbiol 2019; 10:587. [PMID: 30967854 PMCID: PMC6439480 DOI: 10.3389/fmicb.2019.00587] [Citation(s) in RCA: 216] [Impact Index Per Article: 36.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Accepted: 03/07/2019] [Indexed: 12/20/2022] Open
Abstract
The threat of antibiotic resistance has attracted strong interest during the last two decades, thus stimulating stewardship programs and research on alternative antimicrobial therapies. Conversely, much less attention has been given to the directly related problem of resistance toward antiseptics and biocides. While bacterial resistances toward triclosan or quaternary ammonium compounds have been considered in this context, the bis-biguanide chlorhexidine (CHX) has been put into focus only very recently when its use was associated with emergence of stable resistance to the last-resort antibiotic colistin. The antimicrobial effect of CHX is based on damaging the bacterial cytoplasmic membrane and subsequent leakage of cytoplasmic material. Consequently, mechanisms conferring resistance toward CHX include multidrug efflux pumps and cell membrane changes. For instance, in staphylococci it has been shown that plasmid-borne qac ("quaternary ammonium compound") genes encode Qac efflux proteins that recognize cationic antiseptics as substrates. In Pseudomonas stutzeri, changes in the outer membrane protein and lipopolysaccharide profiles have been implicated in CHX resistance. However, little is known about the risk of resistance toward CHX in oral bacteria and potential mechanisms conferring this resistance or even cross-resistances toward antibiotics. Interestingly, there is also little awareness about the risk of CHX resistance in the dental community even though CHX has been widely used in dental practice as the gold-standard antiseptic for more than 40 years and is also included in a wide range of oral care consumer products. This review provides an overview of general resistance mechanisms toward CHX and the evidence for CHX resistance in oral bacteria. Furthermore, this work aims to raise awareness among the dental community about the risk of resistance toward CHX and accompanying cross-resistance to antibiotics. We propose new research directions related to the effects of CHX on bacteria in oral biofilms.
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Affiliation(s)
- Fabian Cieplik
- Department of Conservative Dentistry and Periodontology, University Medical Center Regensburg, Regensburg, Germany
| | - Nicholas S Jakubovics
- Centre for Oral Health Research, School of Dental Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Wolfgang Buchalla
- Department of Conservative Dentistry and Periodontology, University Medical Center Regensburg, Regensburg, Germany
| | - Tim Maisch
- Department of Dermatology, University Medical Center Regensburg, Regensburg, Germany
| | - Elmar Hellwig
- Department of Operative Dentistry and Periodontology, Center for Dental Medicine, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany
| | - Ali Al-Ahmad
- Department of Operative Dentistry and Periodontology, Center for Dental Medicine, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany
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Opstrup MS, Jemec GBE, Garvey LH. Chlorhexidine Allergy: On the Rise and Often Overlooked. Curr Allergy Asthma Rep 2019; 19:23. [PMID: 30874959 DOI: 10.1007/s11882-019-0858-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
PURPOSE OF REVIEW In recent years, the risk of allergy to chlorhexidine is increasingly recognised. In this review, we discuss why the allergy is so easily overlooked and point out several preventative initiatives that can minimise the risk of both chlorhexidine sensitisation and allergy development and accidental re-exposure in patients with chlorhexidine allergy. Testing for chlorhexidine allergy is also discussed. RECENT FINDINGS Numerous reports have been published from many different specialties. Symptoms range from mild skin symptoms to life-threatening anaphylaxis. Testing for chlorhexidine allergy is based on skin testing and in vitro testing. Recently, it was found that both skin prick testing and specific IgE have high sensitivities and specificities. This review gives an overview of chlorhexidine allergy with a special focus on preventative initiatives and testing.
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Affiliation(s)
- Morten Schjørring Opstrup
- Department of Dermatology, Zealand University Hospital, Roskilde, Denmark. .,Danish Anaesthesia Allergy Centre, Allergy Clinic, Department of Dermatology and Allergy, Copenhagen University Hospital Gentofte, Kildegårdsvej 28, 2900, Hellerup, Denmark.
| | - Gregor Borut Ernst Jemec
- Department of Dermatology, Zealand University Hospital, Roskilde, Denmark.,Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Lene Heise Garvey
- Danish Anaesthesia Allergy Centre, Allergy Clinic, Department of Dermatology and Allergy, Copenhagen University Hospital Gentofte, Kildegårdsvej 28, 2900, Hellerup, Denmark.,Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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Hashemi MM, Holden BS, Coburn J, Taylor MF, Weber S, Hilton B, Zaugg AL, McEwan C, Carson R, Andersen JL, Price JC, Deng S, Savage PB. Proteomic Analysis of Resistance of Gram-Negative Bacteria to Chlorhexidine and Impacts on Susceptibility to Colistin, Antimicrobial Peptides, and Ceragenins. Front Microbiol 2019; 10:210. [PMID: 30833936 PMCID: PMC6388577 DOI: 10.3389/fmicb.2019.00210] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Accepted: 01/24/2019] [Indexed: 12/19/2022] Open
Abstract
Use of chlorhexidine in clinical settings has led to concerns that repeated exposure of bacteria to sub-lethal doses of chlorhexidine might result in chlorhexidine resistance and cross resistance with other cationic antimicrobials including colistin, endogenous antimicrobial peptides (AMPs) and their mimics, ceragenins. We have previously shown that colistin-resistant Gram-negative bacteria remain susceptible to AMPs and ceragenins. Here, we investigated the potential for cross resistance between chlorhexidine, colistin, AMPs and ceragenins by serial exposure of standard strains of Gram-negative bacteria to chlorhexidine to generate resistant populations of organisms. Furthermore, we performed a proteomics study on the chlorhexidine-resistant strains and compared them to the wild-type strains to find the pathways by which bacteria develop resistance to chlorhexidine. Serial exposure of Gram-negative bacteria to chlorhexidine resulted in four- to eight-fold increases in minimum inhibitory concentrations (MICs). Chlorhexidine-resistant organisms showed decreased susceptibility to colistin (8- to 32-fold increases in MICs) despite not being exposed to colistin. In contrast, chlorhexidine-resistant organisms had the same MICs as the original strains when tested with representative AMPs (LL-37 and magainin I) and ceragenins (CSA-44 and CSA-131). These results imply that there may be a connection between the emergence of highly colistin-resistant Gram-negative pathogens and the prevalence of chlorhexidine usage. Yet, use of chlorhexidine may not impact innate immune defenses (e.g., AMPs) and their mimics (e.g., ceragenins). Here, we also show that chlorhexidine resistance is associated with upregulation of proteins involved in the assembly of LPS for outer membrane biogenesis and virulence factors in Pseudomonas aeruginosa. Additionally, resistance to chlorhexidine resulted in elevated expression levels of proteins associated with chaperones, efflux pumps, flagella and cell metabolism. This study provides a comprehensive overview of the evolutionary proteomic changes in P. aeruginosa following exposure to chlorhexidine and colistin. These results have important clinical implications considering the continuous application of chlorhexidine in hospitals that could influence the emergence of colistin-resistant strains.
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Affiliation(s)
- Marjan M Hashemi
- Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, United States
| | - Brett S Holden
- Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, United States
| | - Jordan Coburn
- Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, United States
| | - Maddison F Taylor
- Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, United States
| | - Scott Weber
- Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, United States
| | - Brian Hilton
- Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, United States
| | - Aaron L Zaugg
- Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, United States
| | - Colten McEwan
- Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, United States
| | - Richard Carson
- Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, United States
| | - Joshua L Andersen
- Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, United States
| | - John C Price
- Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, United States
| | - Shenglou Deng
- Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, United States
| | - Paul B Savage
- Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, United States
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Gili NJ, Noren T, Törnquist E, Crafoord S, Bäckman A. Preoperative preparation of eye with chlorhexidine solution significantly reduces bacterial load prior to 23-gauge vitrectomy in Swedish health care. BMC Ophthalmol 2018; 18:167. [PMID: 29996791 PMCID: PMC6042411 DOI: 10.1186/s12886-018-0844-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Accepted: 07/03/2018] [Indexed: 11/10/2022] Open
Abstract
Background Bacteria in the conjunctiva present a potential risk of vitreous cavity infection during 23-gauge pars plana vitrectomy (PPV). Current preoperative procedures used in Sweden include irrigation with chlorhexidine solution (CHX) 0.05% only and no iodine solutions. We evaluated the bacterial diversity and load before and after this single antibacterial measure. Methods In a prospective, consecutive cohort we investigated bacterial growth in samples from 40 eyes in 39 consecutive individuals subjected to vitrectomy. A conjunctival specimen was collected from each preoperative patient before and after irrigating of eye with CHX, 0.05% solution. Iodine was not used during any part of the surgery. One drop of chloramphenicol was administered prior to surgery. Samples from vitreous cavity were collected at the beginning and end of vitrectomy. All conjunctival specimens were cultured for different species and quantified using colony forming units (CFU). Results There was a significant 82% reduction in the total number of CFUs for all bacteria in all eyes (P < 0.0001), and 90% reduction for coagulase negative staphylococci (CoNS) alone (P = 0.0002). The number of eyes with positive bacterial growth in conjunctival samples decreased from 33 to 18 after irrigation with CHX (P = 0.0023). The most common bacteria prior to surgery were CoNS (70%), Propionibacterium acnes (55%) and Corynebacterium species (36%). No case of post-vitrectomy endophthalmitis was reported during mean follow-up time, which was 4.6 ± 2.3 (range; 1.5 to 9) months. Conclusions Patients undergoing PPV harbored bacteria in conjunctiva capable of causing post-vitrectomy endophthalmitis. Preoperative preparation with CHX significantly reduced the bacterial load in the conjunctival samples subsequently leading to very low inoculation rates in recovered vitreous samples. Thus, CHX used as a single disinfectant agent might be an effective preoperative procedure for eye surgery in Sweden. This is a relatively small study but the results could be a reference for other intraocular surgeries.
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Affiliation(s)
- Nasser J Gili
- Department of Ophthalmology, Örebro University Hospital, SE-701 85, Örebro, Sweden.
| | - Torbjörn Noren
- Faculty of Medicine and Health, Örebro University, Örebro, Sweden.,Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden
| | - Eva Törnquist
- Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden
| | - Sven Crafoord
- Department of Ophthalmology, Örebro University Hospital, SE-701 85, Örebro, Sweden
| | - Anders Bäckman
- Faculty of Medicine and Health, Örebro University, Örebro, Sweden.,Department of Clinical Research Laboratory, Örebro University Hospital, Örebro, Sweden
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Antimicrobial Resistance to Agents Used for Staphylococcus aureus Decolonization: Is There a Reason for Concern? Curr Infect Dis Rep 2018; 20:26. [PMID: 29882094 DOI: 10.1007/s11908-018-0630-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
PURPOSE OF REVIEW Chlorhexidine gluconate (CHG) and mupirocin are increasingly used for Staphylococcus aureus decolonization to prevent healthcare-associated infections; however, increased use of these agents has led to concerns for growing resistance and reduced efficacy. In this review, we describe current understanding of reduced susceptibility to CHG and mupirocin in S. aureus and their potential clinical implications. RECENT FINDINGS While emergence of S. aureus tolerant or resistant to topical antimicrobial agents used for decolonization is well described, the clinical impact of reduced susceptibility is not clear. Important challenges are that standardized methods of resistance testing and interpretation are not established, and the risk for selection for co- or cross-resistance using universal, as opposed to targeted decolonization, is unclear. Evidence continues to support S. aureus decolonization in certain patient groups, although further studies are needed to determine the long-term impact of CHG and mupirocin resistance on efficacy. Strategies to mitigate further development of reduced susceptibility and the consequences of selection pressures through universal decolonization on resistance will benefit from further investigation.
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Roode GJ, Bütow KW. A Descriptive Study of Chlorhexidine as a Disinfectant in Cleft Palate Surgery. Clin Med Res 2018; 16:9-15. [PMID: 29724746 PMCID: PMC6108510 DOI: 10.3121/cmr.2018.1385] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Revised: 02/20/2018] [Accepted: 03/23/2018] [Indexed: 11/18/2022]
Abstract
OBJECTIVES Chlorhexidine is seen as the golden standard of disinfectants. It is widely used to clean surgical sites; however, many studies indicate resistance of pathogens to chlorhexidine. One study indicated that pathogenic microorganisms were isolated from the soft palate cleft region in 57% of patients with facial clefts. The objectives of our study were to determine (1) if chlorhexidine application is effective in removing pathogens from the surgical site in these patients, and (2) if any pathogens are isolated, determine if they are resistant to other antimicrobials. DESIGN A descriptive observational study. SETTINGS A private practice that specializes in facial cleft surgery, with a country-wide patient base. All procedures were executed by one oral and maxillofacial surgeon. PARTICIPANTS All patients (N=50) who presented for primary repair of the soft palate cleft were included in the study. INCLUSION CRITERIA written consent from parent(s), and patient cleared as systemically healthy by a pediatric physician. EXCLUSION CRITERIA patient(s) with systemic infections (eg, flu) and/or any local infections (eg, tonsillitis). There were 25 males and 25 females with an average age of 7 months and 16 days included in the study. METHODS Swabs were taken from the surgical site of all 50 patients with cleft soft palate and were sent for culture, identification and antimicrobial sensitivity. The swabs were taken before disinfecting the site as well as after 2 minutes of disinfecting the surgical site with chlorhexidine. Results were compared against each other. RESULTS Positive cultures with 28 different pathogenic microorganisms that were identified in 47 patients before cleaning the surgical site with the chlorhexidine. The most dominant pathogens were K. pneumonia (n=22), H. influenza (n=18) and S. aureus (n=10). Of the pathogens found, 13 (46%) were still present on the swabs taken after disinfecting with chlorhexidine. K. pneumonia (n= 13), H. influenza (n=11) and S. aureus (n=9) were still the most prevalent pathogens. CONCLUSIONS This study demonstrated that 61 of the total of 113 pathogens isolated (54%), survived after 2 minutes of disinfecting the surgical and surrounding area with chlorhexidine, thus intensifying the chances of post-operative infection.
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Affiliation(s)
- Gieljam Johannes Roode
- Senior lecturer, Department of Anatomy, University of Pretoria, P/Bag x 323, Arcadia, 0007, South Africa,
| | - Kurt-Wilhelm Bütow
- Consultant Professor, Department of Maxillo-Facial and Oral Surgery, University of Pretoria, PO Box 1266, Pretoria, 0001, South Africa;
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Increased Usage of Antiseptics Is Associated with Reduced Susceptibility in Clinical Isolates of Staphylococcus aureus. mBio 2018; 9:mBio.00894-18. [PMID: 29844113 PMCID: PMC5974466 DOI: 10.1128/mbio.00894-18] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Hospital-acquired infection is a major cause of morbidity and mortality, and regimes to prevent infection are crucial in infection control. These include the decolonization of vulnerable patients with methicillin-resistant Staphylococcus aureus (MRSA) carriage using antiseptics, including chlorhexidine and octenidine. Concern has been raised, however, regarding the possible development of biocide resistance. In this study, we assembled a panel of S. aureus isolates, including isolates collected before the development of chlorhexidine and octenidine and isolates, from a major hospital trust in the United Kingdom during a period when the decolonization regimes were altered. We observed significant increases in the MIC and minimum bactericidal concentration (MBC) of chlorhexidine in isolates from periods of high usage of chlorhexidine. Isolates with increased MICs and MBCs of octenidine rapidly emerged after octenidine was introduced in the trust. There was no apparent cross-resistance between the two biocidal agents. A combination of variable-number tandem repeat (VNTR) analysis, PCR for qac genes, and whole-genome sequencing was used to type isolates and examine possible mechanisms of resistance. There was no expansion of a single strain associated with decreased biocide tolerance, and biocide susceptibility did not correlate with carriage of qac efflux pump genes. Mutations within the NorA or NorB efflux pumps, previously associated with chlorhexidine export, were identified, however, suggesting that this may be an important mechanism of biocide tolerance. We present evidence that isolates are evolving in the face of biocide challenge in patients and that changes in decolonization regimes are reflected in changes in susceptibility of isolates. Infection in hospitals remains a major cause of death and disease. One way in which we combat this is by decolonizing at-risk patients from carriage of bacteria which can cause disease such as MRSA. This is done with antiseptics, including chlorhexidine and octenidine. There is concern, however, that bacteria may be able to become resistant to these antiseptics. In this study, we looked at isolates of MRSA and found that there was a correlation between the use of antiseptics and increased resistance in the isolates. We also suggest that the mechanism by which these more tolerant isolates may become resistant to antiseptics is that of changing a transport pump that exports these agents. This information suggests that we need to study the impact of antiseptics on clinically important bacteria more closely.
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Differential Effects of Chlorhexidine Skin Cleansing Methods on Residual Chlorhexidine Skin Concentrations and Bacterial Recovery. Infect Control Hosp Epidemiol 2018; 39:405-411. [PMID: 29493475 DOI: 10.1017/ice.2017.312] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND Bathing intensive care unit (ICU) patients with 2% chlorhexidine gluconate (CHG)-impregnated cloths decreases the risk of healthcare-associated bacteremia and multidrug-resistant organism transmission. Hospitals employ different methods of CHG bathing, and few studies have evaluated whether those methods yield comparable results. OBJECTIVE To determine whether 3 different CHG skin cleansing methods yield similar residual CHG concentrations and bacterial densities on skin. DESIGN Prospective, randomized 2-center study with blinded assessment. PARTICIPANTS AND SETTING Healthcare personnel in surgical ICUs at 2 tertiary-care teaching hospitals in Chicago, Illinois, and Boston, Massachusetts, from July 2015 to January 2016. INTERVENTION Cleansing skin of one forearm with no-rinse 2% CHG-impregnated polyester cloth (method A) versus 4% CHG liquid cleansing with rinsing on the contralateral arm, applied with either non-antiseptic-impregnated cellulose/polyester cloth (method B) or cotton washcloth dampened with sterile water (method C). RESULTS In total, 63 participants (126 forearms) received method A on 1 forearm (n=63). On the contralateral forearm, 33 participants received method B and 30 participants received method C. Immediately and 6 hours after cleansing, method A yielded the highest residual CHG concentrations (2500 µg/mL and 1250 µg/mL, respectively) and lowest bacterial densities compared to methods B or C (P<.001). CONCLUSION In healthy volunteers, cleansing with 2% CHG-impregnated cloths yielded higher residual CHG concentrations and lower bacterial densities than cleansing with 4% CHG liquid applied with either of 2 different cloth types and followed by rinsing. The relevance of these differences to clinical outcomes remains to be determined. Infect Control Hosp Epidemiol 2018;39:405-411.
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Reduced Chlorhexidine and Daptomycin Susceptibility in Vancomycin-Resistant Enterococcus faecium after Serial Chlorhexidine Exposure. Antimicrob Agents Chemother 2017; 62:AAC.01235-17. [PMID: 29038276 PMCID: PMC5740357 DOI: 10.1128/aac.01235-17] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2017] [Accepted: 10/10/2017] [Indexed: 12/22/2022] Open
Abstract
Vancomycin-resistant Enterococcus faecium strains (VREfm) are critical public health concerns because they are among the leading causes of hospital-acquired bloodstream infections. Chlorhexidine (CHX) is a bisbiguanide cationic antiseptic that is routinely used for patient bathing and other infection control practices. VREfm are likely frequently exposed to CHX; however, the long-term effects of CHX exposure have not been studied in enterococci. In this study, we serially exposed VREfm to increasing concentrations of CHX for a period of 21 days in two independent experimental evolution trials. Reduced CHX susceptibility emerged (4-fold shift in CHX MIC). Subpopulations with reduced daptomycin (DAP) susceptibility were detected, which were further analyzed by genome sequencing and lipidomic analysis. Across the trials, we identified adaptive changes in genes with predicted or experimentally confirmed roles in chlorhexidine susceptibility (efrE), global nutritional stress response (relA), nucleotide metabolism (cmk), phosphate acquisition (phoU), and glycolipid biosynthesis (bgsB), among others. Moreover, significant alterations in membrane phospholipids were identified for some populations with reduced DAP susceptibility. Our results are clinically significant because they identify a link between serial subinhibitory CHX exposure and reduced DAP susceptibility. In addition, the CHX-induced genetic and lipidomic changes described in this study offer new insights into the mechanisms underlying the emergence of antibiotic resistance in VREfm.
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Current and Emerging Topical Antibacterials and Antiseptics: Agents, Action, and Resistance Patterns. Clin Microbiol Rev 2017; 30:827-860. [PMID: 28592405 DOI: 10.1128/cmr.00112-16] [Citation(s) in RCA: 209] [Impact Index Per Article: 26.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Bacterial skin infections represent some of the most common infectious diseases globally. Prevention and treatment of skin infections can involve application of a topical antimicrobial, which may be an antibiotic (such as mupirocin or fusidic acid) or an antiseptic (such as chlorhexidine or alcohol). However, there is limited evidence to support the widespread prophylactic or therapeutic use of topical agents. Challenges involved in the use of topical antimicrobials include increasing rates of bacterial resistance, local hypersensitivity reactions (particularly to older agents, such as bacitracin), and concerns about the indiscriminate use of antiseptics potentially coselecting for antibiotic resistance. We review the evidence for the major clinical uses of topical antibiotics and antiseptics. In addition, we review the mechanisms of action of common topical agents and define the clinical and molecular epidemiology of antimicrobial resistance in these agents. Moreover, we review the potential use of newer and emerging agents, such as retapamulin and ebselen, and discuss the role of antiseptic agents in preventing bacterial skin infections. A comprehensive understanding of the clinical efficacy and drivers of resistance to topical agents will inform the optimal use of these agents to preserve their activity in the future.
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Salgueiro AM, Santos MD, Saraiva JA, Almeida F, Sousa I, Tedim J, Nogueira HI, Evtuguin DV. Ultra-high pressure modified cellulosic fibres with antimicrobial properties. Carbohydr Polym 2017; 175:303-310. [DOI: 10.1016/j.carbpol.2017.07.081] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2017] [Revised: 07/21/2017] [Accepted: 07/28/2017] [Indexed: 11/24/2022]
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Kampf G. Acquired resistance to chlorhexidine – is it time to establish an ‘antiseptic stewardship’ initiative? J Hosp Infect 2016; 94:213-227. [DOI: 10.1016/j.jhin.2016.08.018] [Citation(s) in RCA: 196] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Accepted: 08/18/2016] [Indexed: 01/12/2023]
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Merani R, McPherson ZE, Luckie AP, Gilhotra JS, Runciman J, Durkin S, Muecke J, Donaldson M, Aralar A, Rao A, Davies PE. Aqueous Chlorhexidine for Intravitreal Injection Antisepsis: A Case Series and Review of the Literature. Ophthalmology 2016; 123:2588-2594. [PMID: 27720552 DOI: 10.1016/j.ophtha.2016.08.022] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Revised: 08/18/2016] [Accepted: 08/18/2016] [Indexed: 11/27/2022] Open
Abstract
PURPOSE To determine the incidence of endophthalmitis in a large clinical series using aqueous chlorhexidine for antisepsis before intravitreal injection and to review the ophthalmic literature regarding chlorhexidine efficacy and safety. DESIGN Multicenter retrospective case series. PARTICIPANTS All patients receiving intravitreal injections from 7 retinal specialists. METHODS An audit of intravitreal injections performed by retinal specialists who exclusively used aqueous chlorhexidine 0.05% or 0.1% for prophylaxis of infective endophthalmitis was undertaken. The incidence of endophthalmitis was determined from August 1, 2011, to February 28, 2015. A literature review was performed to critically appraise the ocular safety and efficacy of aqueous chlorhexidine. MAIN OUTCOME MEASURES Incidence of endophthalmitis after intravitreal injections. RESULTS A total of 40 535 intravitreal injections were performed by 7 retinal specialists across 3 centers. Chlorhexidine was well tolerated, and only 1 patient with a suspected allergic reaction was noted. Three cases of endophthalmitis were identified with 1 culture-positive case. The 0.0074% (1 in 13 512) per-injection rate of endophthalmitis in this series compares favorably with previous series in which povidone-iodine has been used. CONCLUSIONS Aqueous chlorhexidine was associated with a low rate of postinjection endophthalmitis and was well tolerated by patients.
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Affiliation(s)
- Rohan Merani
- Save Sight Institute, University of Sydney, NSW, Australia; Australian School of Advanced Medicine, Macquarie University, NSW, Australia; Concord Repatriation General Hospital, Concord NSW, Australia; Retina Associates, Chatswood, NSW, Australia
| | | | | | - Jagjit S Gilhotra
- South Australian Institute of Ophthalmology, Royal Adelaide Hospital, Adelaide, SA, Australia; Adelaide Eye and Retina Centre, Adelaide, SA, Australia
| | - Jim Runciman
- Adelaide Eye and Retina Centre, Adelaide, SA, Australia
| | - Shane Durkin
- Adelaide Eye and Retina Centre, Adelaide, SA, Australia
| | - James Muecke
- Adelaide Eye and Retina Centre, Adelaide, SA, Australia
| | | | | | - Anupam Rao
- Hornsby Ku-ring-gai Hospital, Hornsby, NSW, Australia
| | - Peter E Davies
- The University of Newcastle, Newcastle, NSW, Australia; Newcastle Eye Hospital, Newcastle, NSW, Australia.
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Vatkar NA, Hegde V, Sathe S. Vitality of Enterococcus faecalis inside dentinal tubules after five root canal disinfection methods. J Conserv Dent 2016; 19:445-9. [PMID: 27656064 PMCID: PMC5026105 DOI: 10.4103/0972-0707.190019] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
Aim: To compare the vitality of Enterococcus faecalis within dentinal tubules after subjected to five root canal disinfection methods. Materials and Methods: Dentin blocks (n = 60) were colonized with E. faecalis. After 4 weeks of incubation, the dentin blocks were divided into one control and five test groups (n = 10 each). The root canals of test groups were subjected to one of the disinfection methods, namely, normal saline (NS), sodium hypochlorite (NaOCl), chlorhexidine digluconate (CHX), neodymium-doped yttrium aluminum garnet (Nd: YAG) laser, and diode laser. The effect of disinfection methods was assessed by LIVE/DEAD BacLight stain under the confocal laser scanning microscopy to determine the “zone of dead bacteria” (ZDB). Mean values were calculated for ZDB and the difference between groups was established. Results: Penetration of E. faecalis was seen to a depth of >1000 μm. Viable bacteria were detected with NS irrigation. NaOCl and CHX showed partial ZDB. When the root canals were disinfected with Nd: YAG and diode lasers, no viable bacteria were found. Conclusion: E. faecalis has the ability to colonize inside dentinal tubules to a depth of >1000 μm. In contrast to conventional irrigants, both Nd: YAG and diode lasers were effective in eliminating the vitality of E. faecalis. NS, NaOCl, and CHX showed viable bacteria remaining in dentinal tubules.
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Affiliation(s)
- Niranjan Ashok Vatkar
- Department of Endodontics, M.A. Rangoonwala Dental College and Hospital, Pune, Maharashtra, India
| | - Vivek Hegde
- Department of Endodontics, M.A. Rangoonwala Dental College and Hospital, Pune, Maharashtra, India
| | - Sucheta Sathe
- Department of Endodontics, M.A. Rangoonwala Dental College and Hospital, Pune, Maharashtra, India
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Santezi C, Tanomaru JM, Bagnato VS, Júnior OBO, Dovigo LN. Potential of curcumin-mediated photodynamic inactivation to reduce oral colonization. Photodiagnosis Photodyn Ther 2016; 15:46-52. [DOI: 10.1016/j.pdpdt.2016.04.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2016] [Revised: 03/31/2016] [Accepted: 04/12/2016] [Indexed: 10/21/2022]
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Abstract
Healthcare-associated infections (HAIs) are an important cause of morbidity and mortality in the USA. They are associated with a substantial increase in health care costs each year. Fortunately, many HAIs are preventable, and their eradication is a national priority. Chlorhexidine (CHG) bathing has been used as an infection prevention measure, either alone or bundled with other interventions, with mostly beneficial results. The recent surge in its use as an agent of choice for skin antisepsis has lead to concerns over emerging resistance among microorganisms. Moreover, compliance with CHG-bathing protocols is not routinely monitored. Policies developed to determine the best infection prevention practice must consider that a "one-size-fits-all" strategy may lead to the selection of CHG-tolerant microorganisms, thereby emphasizing the need for more robust guidelines and additional studies on the role of chlorhexidine bathing for the prevention of HAIs.
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Yadiki JV, Jampanapalli SR, Konda S, Inguva HC, Chimata VK. Comparative Evaluation of the Antimicrobial Properties of Glass Ionomer Cements with and without Chlorhexidine Gluconate. Int J Clin Pediatr Dent 2016; 9:99-103. [PMID: 27365927 PMCID: PMC4921875 DOI: 10.5005/jp-journals-10005-1342] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Accepted: 11/11/2015] [Indexed: 11/23/2022] Open
Abstract
Background: Chlorhexidine gluconate is a widely used antimicrobial agent. Adding chlorhexidine and quaternary ammonium compounds to filling materials, such as composite resins, acrylic resins, and glass ionomer cements increases the antibacterial property of restorative materials. This study includes antibacterial property of glass ionomer restorative cements with chlorhexidine gluconate. Aim: The primary objective of our study was to compare the antimicrobial properties of two commercially available glass ionomer cements with and without chlorhexidine gluconate on strains of mutans streptococci. Materials and methods: Two glass ionomers (Fuji II Conventional and Fuji IX) were used. Chlorhexidine gluconate was mixed with glass ionomer cements, and antimicrobial properties against mutans streptococci were assessed by agar diffusion. The tested bacterial strain was inhibited and the antimicrobial properties decreased with time. Results: The highest amount of antimicrobial activity with mean inhibitory zone was found in Fuji II with chlorhexidine gluconate followed by Fuji IX with chlorhexidine gluconate, Fuji II without chlorhexidine gluconate, and Fuji IX without chlorhexidine gluconate. Conclusion: The results of the study confirmed that the addition of 5% chlorhexidine gluconate to Fuji II and Fuji IX glass ionomer cements resulted in a restorative material that had increased antimicrobial properties over the conventional glass ionomer cements alone for Streptococcus mutans. How to cite this article: Yadiki JV, Jampanapalli SR , Konda S, Inguva HC, Chimata VK. Comparative Evaluation of the Antimicrobial Properties of Glass Ionomer Cements with and without Chlorhexidine Gluconate. Int J Clin Pediatr Dent 2016;9(2):99-103.
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Affiliation(s)
- Josna Vinutha Yadiki
- Assistant Professor, Department of Pedodontics and Preventive Dentistry, Army College of Dental Sciences, Secunderabad, Telangana, India
| | - Sharada Reddy Jampanapalli
- Professor and Head, Department of Pedodontics and Preventive Dentistry Government Dental College and Hospital, Hyderabad Telangana, India
| | - Suhasini Konda
- Associate Professor, Department of Pedodontics and Preventive Dentistry Government Dental College and Hospital, Hyderabad Telangana, India
| | - Hema Chandrika Inguva
- Assistant Professor, Department of Pedodontics and Preventive Dentistry Government Dental College and Hospital, Hyderabad Telangana, India
| | - Vamsi Krishna Chimata
- Assistant Professor, Department of Pedodontics and Preventive Dentistry, Terna Dental College, Mumbai, Maharashtra, India
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Mohammadi Z, Jafarzadeh H, Shalavi S. Antimicrobial efficacy of chlorhexidine as a root canal irrigant: a literature review. J Oral Sci 2016; 56:99-103. [PMID: 24930745 DOI: 10.2334/josnusd.56.99] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Abstract
Use of an appropriate root canal irrigant is essential during endodontic treatment, due to the complex and unpredictable anatomy of the root canal system and limitations in the mechanical instrumentation techniques used to obtain a clean, bacteria-free canal. Several irrigants, such as sodium hypochlorite, chlorhexidine, hydrogen peroxide, and normal saline, have been proposed as canal system irrigants in endodontic treatment. The widely used endodontic irrigant chlorhexidine is a positively charged lipophilic/hydrophobic molecule that interacts with phospholipids and lipopolysaccharides on the bacterial cell membrane. In endodontics, its mode of antibacterial activity is determined by its concentration (0.2% or 2%). This article reviews findings from available endodontic studies on the antibacterial, antifungal, and antibiofilm activities of chlorhexidine.
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Affiliation(s)
- Zahed Mohammadi
- Iranian Center for Endodontic Research, Shahid Beheshti University of Medical Sciences
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Sathiyamurthy S, Banerjee J, Godambe SV. Antiseptic use in the neonatal intensive care unit - a dilemma in clinical practice: An evidence based review. World J Clin Pediatr 2016; 5:159-171. [PMID: 27170926 PMCID: PMC4857229 DOI: 10.5409/wjcp.v5.i2.159] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2015] [Revised: 11/24/2015] [Accepted: 01/19/2016] [Indexed: 02/06/2023] Open
Abstract
Infants in the neonatal intensive care unit are highly susceptible to healthcare associated infections (HAI), with a substantial impact on mortality, morbidity and healthcare costs. Effective skin disinfection with topical antiseptic agents is an important intervention in the prevention or reduction of HAI. A wide array of antiseptic preparations in varying concentrations and combinations has been used in neonatal units worldwide. In this article we have reviewed the current evidence of a preferred antiseptic of choice over other agents for topical skin disinfection in neonates. Chlorhexidine (CHG) appears to be a promising antiseptic agent; however there exists a significant concern regarding the safety of all agents used including CHG especially in preterm and very low birth weight infants. There is substantial evidence to support the use of CHG for umbilical cord cleansing and some evidence to support the use of topical emollients in reducing the mortality in infants born in developing countries. Well-designed large multicentre randomized clinical trials are urgently needed to guide us on the most appropriate and safe antiseptic to use in neonates undergoing intensive care, especially preterm infants.
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Varying activity of chlorhexidine-based disinfectants against Klebsiella pneumoniae clinical isolates and adapted strains. J Hosp Infect 2016; 93:42-8. [DOI: 10.1016/j.jhin.2015.12.019] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Accepted: 12/29/2015] [Indexed: 11/15/2022]
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Chlorhexidine Induces VanA-Type Vancomycin Resistance Genes in Enterococci. Antimicrob Agents Chemother 2016; 60:2209-21. [PMID: 26810654 DOI: 10.1128/aac.02595-15] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2015] [Accepted: 01/20/2016] [Indexed: 11/20/2022] Open
Abstract
Chlorhexidine is a bisbiguanide antiseptic used for infection control. Vancomycin-resistantE. faecium(VREfm) is among the leading causes of hospital-acquired infections. VREfm may be exposed to chlorhexidine at supra- and subinhibitory concentrations as a result of chlorhexidine bathing and chlorhexidine-impregnated central venous catheter use. We used RNA sequencing to investigate how VREfm responds to chlorhexidine gluconate exposure. Among the 35 genes upregulated ≥10-fold after 15 min of exposure to the MIC of chlorhexidine gluconate were those encoding VanA-type vancomycin resistance (vanHAX) and those associated with reduced daptomycin susceptibility (liaXYZ). We confirmed thatvanAupregulation was not strain or species specific by querying other VanA-type VRE. VanB-type genes were not induced. ThevanHpromoter was found to be responsive to subinhibitory chlorhexidine gluconate in VREfm, as was production of the VanX protein. UsingvanHreporter experiments withBacillus subtilisand deletion analysis in VREfm, we found that this phenomenon is VanR dependent. Deletion ofvanRdid not result in increased chlorhexidine susceptibility, demonstrating thatvanHAXinduction is not protective against chlorhexidine. As expected, VanA-type VRE is more susceptible to ceftriaxone in the presence of sub-MIC chlorhexidine. Unexpectedly, VREfm is also more susceptible to vancomycin in the presence of subinhibitory chlorhexidine, suggesting that chlorhexidine-induced gene expression changes lead to additional alterations in cell wall synthesis. We conclude that chlorhexidine induces expression of VanA-type vancomycin resistance genes and genes associated with daptomycin nonsusceptibility. Overall, our results indicate that the impacts of subinhibitory chlorhexidine exposure on hospital-associated pathogens should be further investigated in laboratory studies.
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Magina S, Santos MD, Ferra J, Cruz P, Portugal I, Evtuguin D. High Pressure Laminates with Antimicrobial Properties. MATERIALS 2016; 9:ma9020100. [PMID: 28787897 PMCID: PMC5456506 DOI: 10.3390/ma9020100] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Accepted: 02/04/2016] [Indexed: 12/22/2022]
Abstract
High-pressure laminates (HPLs) are durable, resistant to environmental effects and good cost-benefit decorative surface composite materials with special properties tailored to meet market demand. In the present work, polyhexamethylene biguanide (PHMB) was incorporated for the first time into melamine-formaldehyde resin (MF) matrix on the outer layer of HPLs to provide them antimicrobial properties. Chemical binding of PHMB to resin matrix was detected on the surface of produced HPLs by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). Antimicrobial evaluation tests were carried out on the ensuing HPLs doped with PHMB against gram-positive Listeria innocua and gram-negative Escherichia coli bacteria. The results revealed that laminates prepared with 1.0 wt % PHMB in MF resin were bacteriostatic (i.e., inhibited the growth of microorganisms), whereas those prepared with 2.4 wt % PHMB in MF resin exhibited bactericidal activity (i.e., inactivated the inoculated microorganisms). The results herein reported disclose a promising strategy for the production of HPLs with antimicrobial activity without affecting basic intrinsic quality parameters of composite material.
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Affiliation(s)
- Sandra Magina
- CICECO-Aveiro Institute of Materials and Chemistry Department, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
| | - Mauro D Santos
- CICECO-Aveiro Institute of Materials and Chemistry Department, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
| | - João Ferra
- EuroResinas-Indústrias Químicas SA, Plataforma Industrial de Sines-Lote Industrial I, Monte Feio, 7520-064 Sines, Portugal.
| | - Paulo Cruz
- SONAE Indústria de Revestimentos SA (SIR), Lugar do Espido-Via Norte, Apartado 1096, 4470-177 Maia, Portugal.
| | - Inês Portugal
- CICECO-Aveiro Institute of Materials and Chemistry Department, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
| | - Dmitry Evtuguin
- CICECO-Aveiro Institute of Materials and Chemistry Department, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
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50
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Khan S, Khan AU, Hasan S. Genotoxic assessment of chlorhexidine mouthwash on exfoliated buccal epithelial cells in chronic gingivitis patients. J Indian Soc Periodontol 2016; 20:584-591. [PMID: 29238137 PMCID: PMC5713080 DOI: 10.4103/jisp.jisp_9_17] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Background: Chlorhexidine (CHX) is the gold standard of all chemical plaque control agents and the most commonly prescribed mouthwash. However, several studies have shown cytotoxic and genotoxic effects of CHX on various eukaryotic cells. In this study, we have used micronuclei as a biomarker of DNA damage in buccal epithelial cells of chronic gingivitis patients who were given adjunct 0.2% CHX for plaque control. Materials and Methods: Chronic gingivitis patients who were exclusively on mechanical plaque control methods were taken as control (Group A) (n = 101), and chronic gingivitis patients who along with mechanical plaque control measures were taking 0.2% chlorhexidine mouthwash as adjunct were taken as cases (Group B) (n = 255). The Group B was further divided into 5 subgroups (B1, B2, B3, B4, B5) (n = 51) on increasing duration of usage of CHX from ≤1 week to 24 weeks. Buccal epithelial cells were gently scrapped from the buccal mucosa using soft toothbrush. The epithelial cells were collected in buffer solution and centrifuged at 8000 rpm for 5 min. The buccal epithelial cells were air dried, fixed, and stained with 5% Giemsa stain on preheated glass microscopic slides and observed under microscope to screen 2000 nucleated cells per individual for number of micronucleated cells and micronuclei as genotoxic measure. Results: The mean number of micronucleated cells was found to be 0.41 ± 0.71 for Group A as compared values ranging from 1.65 ± 2.09 (Group B1) to 11.7 ± 1.87 (Group B5) in different subgroups of Group B, and similarly, the mean number of micronuclei was found to be 0.48 ± 0.80 for Group A as compared to values ranging from 2.57 ± 1.64 (Group B1) to 14.5 ± 2.49 (Group B5) in different subgroups of Group B using analysis of variance (P < 0.001). Conclusion: We conclude that CHX mouthwash is genotoxic to buccal epithelial cells and there is incremental trend in genotoxicity as the duration of usage is increased.
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Affiliation(s)
- Saif Khan
- Department of Periodontics and Community Dentistry, Dr. Z A Dental College and Hospital, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
| | - Asad Ullah Khan
- Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
| | - Sadaf Hasan
- Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
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