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      A Dalbavancin Lock Solution Can Reduce Enterococcal Biofilms After Freezing

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          Abstract

          Introduction

          We previously demonstrated the efficacy of a frozen dalbavancin–heparin (DH) lock solution against biofilms of staphylococci. However, as enterococci also commonly cause catheter-related bloodstream infections (C-RBSI), we assessed the bioactivity of frozen dalbavancin (D) and DH against enterococci.

          Methods

          Over 6 months, we compared the bioactivity of a solution of DH (1 mg/ml) with that of D in terms of cfu counts and metabolic activity against biofilms of Enterococcus faecalis and Enterococcus faecium (four strains each). For each solution, we individually compared results obtained at each time point (months 3 and 6) with baseline (month 0). We also compared the median DH value of each variable at baseline and at months 3 and 6 of freezing with the values obtained for D alone. We used both statistical and clinical criteria when results were within 25% of the reference value.

          Results

          At the end of the experiment (month 6), neither a statistically nor a clinically significant reduction in the bioactivity of D solution was observed in terms of cfu count and metabolic activity against enterococcal biofilms. Regarding the DH solution, we found both statistical and clinical significance in the median percentage reduction in metabolic activity between months 0 and 6 in E. faecalis strains (51.8% vs. 77.8%, P = 0.007). Moreover, after freezing, the DH solution lost significant bioactivity compared with the D solution, especially in E. faecalis.

          Conclusion

          A dalbavancin lock solution can be frozen for up to 6 months with no negative effect on its bioactivity against enterococcal biofilms. However, when combined with heparin, its efficacy was reduced. Therefore, we recommend that if lock therapy with frozen dalbavancin is used in the management of enterococcal C-RBSI, heparin should be added simultaneously at the time of catheter lock.

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          Most cited references23

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          Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America.

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            Comparison of multiple methods for quantification of microbial biofilms grown in microtiter plates.

            In the present study six assays for the quantification of biofilms formed in 96-well microtiter plates were optimised and evaluated: the crystal violet (CV) assay, the Syto9 assay, the fluorescein diacetate (FDA) assay, the resazurin assay, the XTT assay and the dimethyl methylene blue (DMMB) assay. Pseudomonas aeruginosa, Burkholderia cenocepacia, Staphylococcus aureus, Propionibacterium acnes and Candida albicans were used as test organisms. In general, these assays showed a broad applicability and a high repeatability for most isolates. In addition, the estimated numbers of CFUs present in the biofilms show limited variations between the different assays. Nevertheless, our data show that some assays are less suitable for the quantification of biofilms of particular isolates (e.g. the CV assay for P. aeruginosa).
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              In vitro activity of dalbavancin against biofilms of staphylococci isolated from prosthetic joint infections.

              The in vitro activity of dalbavancin was tested against biofilms of 171 staphylococci associated with prosthetic joint infection. Dalbavancin minimum biofilm bactericidal concentration (MBBC) values were: MBBC50 for Staphylococcus aureus and Staphylococcus epidermidis, 1μg/mL; MBBC90 for S. aureus, 2μg/mL; MBBC90 for S. epidermidis, 4μg/mL.
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                Author and article information

                Contributors
                mariaguembe@hotmail.com , maria.guembe@iisgm.com
                Journal
                Infect Dis Ther
                Infect Dis Ther
                Infectious Diseases and Therapy
                Springer Healthcare (Cheshire )
                2193-8229
                2193-6382
                16 January 2022
                16 January 2022
                April 2022
                : 11
                : 2
                : 743-755
                Affiliations
                [1 ]GRID grid.410526.4, ISNI 0000 0001 0277 7938, Department of Clinical Microbiology and Infectious Diseases, , Hospital General Universitario Gregorio Marañón, ; C/Dr. Esquerdo, 46, 28007 Madrid, Spain
                [2 ]GRID grid.410526.4, ISNI 0000 0001 0277 7938, Instituto de Investigación Sanitaria Gregorio Marañón, ; Madrid, Spain
                [3 ]GRID grid.4795.f, ISNI 0000 0001 2157 7667, Biology Department, School of Biology, , Universidad Complutense de Madrid, ; Madrid, Spain
                [4 ]GRID grid.512891.6, CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), ; Madrid, Spain
                [5 ]GRID grid.4795.f, ISNI 0000 0001 2157 7667, Medicine Department, School of Medicine, , Universidad Complutense de Madrid, ; Madrid, Spain
                [6 ]GRID grid.410526.4, ISNI 0000 0001 0277 7938, Hematology Department, , Hospital General Universitario Gregorio Marañón, ; Madrid, Spain
                [7 ]GRID grid.410526.4, ISNI 0000 0001 0277 7938, Pharmacy Department, , Hospital General Universitario Gregorio Marañón, ; Madrid, Spain
                Author information
                http://orcid.org/0000-0002-7607-5848
                Article
                579
                10.1007/s40121-021-00579-4
                8960518
                35034289
                acf1c449-82c2-4fe5-959f-aadab011684e
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 21 October 2021
                : 1 December 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004587, Instituto de Salud Carlos III;
                Award ID: MSII18/00008
                Award ID: PI18/00045
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100008433, Consejería de Educación, Juventud y Deporte, Comunidad de Madrid;
                Award ID: PEJD-2020-AI_BMD-17971
                Award Recipient :
                Categories
                Original Research
                Custom metadata
                © The Author(s) 2022

                biofilms,dalbavancin,enterococci,freezing,heparin,lock therapy
                biofilms, dalbavancin, enterococci, freezing, heparin, lock therapy

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