Skip to main content
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems
  • Log in
  • My alerts
  • My Cart

Main menu

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About AAC
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • AAC Podcast
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems

User menu

  • Log in
  • My alerts
  • My Cart

Search

  • Advanced search
Antimicrobial Agents and Chemotherapy
publisher-logosite-logo

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About AAC
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • AAC Podcast
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
Experimental Therapeutics

Minocycline-EDTA-Ethanol Antimicrobial Catheter Lock Solution Is Highly Effective In Vitro for Eradication of Candida auris Biofilms

Ruth A. Reitzel, Joel Rosenblatt, Bahgat Z. Gerges, Nylev Vargas-Cruz, Issam I. Raad
Ruth A. Reitzel
aDepartment of Infectious Diseases, Infection Control, and Employee Health, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joel Rosenblatt
aDepartment of Infectious Diseases, Infection Control, and Employee Health, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bahgat Z. Gerges
aDepartment of Infectious Diseases, Infection Control, and Employee Health, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nylev Vargas-Cruz
aDepartment of Infectious Diseases, Infection Control, and Employee Health, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Issam I. Raad
aDepartment of Infectious Diseases, Infection Control, and Employee Health, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1128/AAC.02146-19
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

This article has a correction. Please see:

  • Erratum for Reitzel et al., “Minocycline-EDTA-Ethanol Antimicrobial Catheter Lock Solution Is Highly Effective In Vitro for Eradication of Candida auris Biofilms”
    - June 23, 2020

ABSTRACT

Candida auris is an emerging pathogen that can cause virulent central-line-associated bloodstream infections. Catheter salvage through the eradication of biofilms is a desirable therapeutic option. We compared taurolidine and minocycline-EDTA-ethanol (MEE) catheter lock solutions in vitro for the eradication of biofilms of 10 C. auris strains. MEE fully eradicated all C. auris biofilms, while taurolidine lock partially eradicated all of the C. auris biofilms. The superiority was significant for all C. auris strains tested (P = 0.002).

INTRODUCTION

The salvage of central lines in the setting of central-line-associated bloodstream infection (CLABSI) can be highly beneficial to patients that require continued vascular access for their medical care. The exchange of catheters at the same insertion site over guidewires in this setting frequently leads to recontamination of the new line and recurrence of the CLABSI. Another alternative is insertion of a fresh catheter at a new insertion site. This may be undesirable for cancer patients and other critically ill patients, because it subjects these patients to anxiety, particularly, for patients with coagulopathies or other adverse events (1).

Candida auris infections have steadily increased in prevalence since first identified in 2009, are frequently resistant to azoles and other classes of systemic antifungals (2), are readily spread through environmental exposure, and have been associated with high mortalities (3, 4). Consequently, catheter lock solutions suitable for salvaging central lines for patients requiring continued vascular access in the setting of C. auris candidemia is desirable.

Two broad-spectrum antimicrobial catheter lock solutions have recently been clinically evaluated for the salvage of vascular catheters in the setting of CLABSI. Saunders et al. evaluated catheter salvage in parenteral nutrition patients using a taurolidine catheter lock solution (5), and Chaftari et al. evaluated catheter salvage in cancer patients using a minocycline-EDTA-ethanol (MEE) catheter lock solution (6). In this in vitro study, we compared the efficacy of these two catheter lock solutions for eradicating biofilms of 10 different strains of C. auris.

Ten strains (AR 0381 to AR 0390) of Candida auris were obtained from the Centers for Disease Control and Prevention (CDC) Antibiotic Resistance Isolate Bank (ARIsolateBank). All isolates have been well characterized by susceptibilities and sequencing (7). Assessments of lock solutions were with a well-established in vitro biofilm eradication model (8, 9). Briefly, silicone discs colonized with 24-h biofilms were exposed to each lock for 60 min. Discs were then sonicated in saline to disrupt biofilms, and all sonicates were quantitatively cultured to assess any remaining viable organisms. Six replicates were run for each test group for each C. auris strain. Pairwise comparisons, using the Mann-Whitney U test, compared MEE with positive controls and taurolidine lock. All tests were two-sided and were considered significant at P values of <0.05. MEE consisted of 0.1% minocycline hydrochloride (Minocin; The Medicines Company, Parsippany, NJ), 3% EDTA (Letco Medical, Decatur, AL), and 25% ethanol (Akorn, Lake Forest, IL). The taurolidine catheter lock solution (TCH) consisted of 1.35% taurolidine (Enzo Life Sciences, Farmingdale, NY), 3.5% disodium citrate (Sigma-Aldrich, St. Louis, MO) and 1,000 IU/ml heparin (Sagent, Schaumburg, IL).

The medians and ranges for recoveries of viable organisms after lock exposure from the 10 C. auris biofilms are presented in Fig. 1. For all C. auris strains, robust biofilms formed for the positive controls. MEE was able to fully eradicate all 10 strains of C. auris biofilms following 60 min of exposure (P = 0.002 compared to control). TCH reduced the concentrations of viable C. auris organisms in all 10 biofilms but was unable to fully eradicate any of the biofilms. The superiority of MEE over TCH was statistically significant for each C. auris strain (P = 0.002).

FIG 1
  • Open in new tab
  • Download powerpoint
FIG 1

Biofilm eradication of Candida auris biofilms after exposure to lock solution. A total of 10 strains of C. auris biofilms were exposed to minocycline plus EDTA plus ethanol (MEE) or taurolidine plus citrate plus heparin (TCH) for 60 min. Quantitative recoveries of viable organisms still remaining in the biofilms were performed. Medians and ranges of the recovered viable organisms for each strain for each treatment group are reported (6 replicates for each group for each strain). MEE fully eradicated all 10 strains of C. auris and was significantly more efficacious than TCH (P = 0.002) for all strains.

Potent complete eradication of biofilms on catheters can help prevent relapses of candidemia from biofilms that retain viable pathogens. Taurolidine is reported to exhibit antimicrobial activity by attacking bacterial and fungal cell wall constituents (10). In a study of parenteral nutrition patients (5), catheter salvage was attempted in patients that had no prior taurolidine catheter lock use as well as in those that experienced breakthrough infections while using taurolidine catheter lock solutions. Salvage was successful in 45% of the pre-taurolidine-use cases and 33% of post-taurolidine-use cases. There were fungemias in both the pre- and post-taurolidine-use groups. In an in vitro study of potency of taurolidine against multiple Candida albicans strains, the MIC50 was found to be 2,048 mg/liter, reflecting weak potency (11). These outcomes are consistent with our findings of partial effectiveness of taurolidine catheter lock solution against all of the C. auris strains tested.

In a previous clinical catheter salvage study, MEE was 100% clinically effective in salvaging central lines for cancer patients with bacterial CLABSIs (6). In vitro studies showed this combination to be synergistically effective against other Candida species (12). Here, we found the MEE combination was also highly effective in eradicating Candida auris biofilms, with significant superiority over taurolidine. Clinical verification of the effectiveness of MEE for salvaging central lines in the setting of C. auris candidemias is warranted.

FOOTNOTES

    • Received 25 October 2019.
    • Returned for modification 16 November 2019.
    • Accepted 3 January 2020.
    • Accepted manuscript posted online 13 January 2020.
  • Copyright © 2020 American Society for Microbiology.

All Rights Reserved.

REFERENCES

  1. 1.↵
    1. Mermel LA,
    2. Allon M,
    3. Bouza E,
    4. Craven DE,
    5. Flynn P,
    6. O'Grady NP,
    7. Raad II,
    8. Rijnders BJA,
    9. Sherertz RJ,
    10. Warren DK
    . 2009. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 49:1–45. doi:10.1086/599376.
    OpenUrlCrossRefPubMedWeb of Science
  2. 2.↵
    1. Chowdhary A,
    2. Prakash A,
    3. Sharma C,
    4. Kordalewska M,
    5. Kumar A,
    6. Sarma S,
    7. Tarai B,
    8. Singh A,
    9. Upadhyaya G,
    10. Upadhyay S,
    11. Yadav P,
    12. Singh PK,
    13. Khillan V,
    14. Sachdeva N,
    15. Perlin DS,
    16. Meis JF
    . 2018. A multicentre study of antifungal susceptibility patterns among 350 Candida auris isolates (2009–17) in India: role of the ERG11 and FKS1 genes in azole and echinocandin resistance. J Antimicrob Chemother 73:891–899. doi:10.1093/jac/dkx480.
    OpenUrlCrossRef
  3. 3.↵
    1. Jeffery-Smith A,
    2. Taori SK,
    3. Schelenz S,
    4. Jeffery K,
    5. Johnson EM,
    6. Borman A,
    7. Manuel R,
    8. Brown CS
    . 2017. Candida auris: a review of the literature. Clin Microbiol Rev 31:e00029-17. doi:10.1128/CMR.00029-17.
    OpenUrlAbstract/FREE Full Text
  4. 4.↵
    1. Lamoth F,
    2. Kontoyiannis DP
    . 2018. The Candida auris alert: facts and perspectives. J Infect Dis 217:516–520. doi:10.1093/infdis/jix597.
    OpenUrlCrossRef
  5. 5.↵
    1. Saunders J,
    2. Naghibi M,
    3. Leach Z,
    4. Parsons C,
    5. King A,
    6. Smith T,
    7. Stroud M
    . 2015. Taurolidine locks significantly reduce the incidence of catheter-related blood stream infections in high-risk patients on home parenteral nutrition. Eur J Clin Nutr 69:282–284. doi:10.1038/ejcn.2014.32.
    OpenUrlCrossRef
  6. 6.↵
    1. Chaftari AM,
    2. Hachem R,
    3. Szvalb A,
    4. Taremi M,
    5. Granwehr B,
    6. Viola GM,
    7. Sapna A,
    8. Assaf A,
    9. Numan Y,
    10. Shah P,
    11. Gasitashvili K,
    12. Natividad E,
    13. Jiang Y,
    14. Slack R,
    15. Reitzel R,
    16. Rosenblatt J,
    17. Mouhayar E,
    18. Raad I
    . 2017. A novel nonantibiotic nitroglycerin-based catheter lock solution for prevention of intraluminal central venous catheter infections in cancer patients. Antimicrob Agents Chemother 61:e00091-17. doi:10.1128/AAC.00091-17.
    OpenUrlAbstract/FREE Full Text
  7. 7.↵
    CDC. 2018. Antibiotic resistance isolate bank. https://wwwn.cdc.gov/ARIsolateBank/.
  8. 8.↵
    1. Kuhn DM,
    2. George T,
    3. Chandra J,
    4. Mukherjee PK,
    5. Ghannoum MA
    . 2002. Antifungal susceptibility of Candida biofilms: unique efficacy of amphotericin B lipid formulations and echinocandins. Antimicrob Agents Chemother 46:1773–1780. doi:10.1128/aac.46.6.1773-1780.2002.
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    1. Rosenblatt J,
    2. Reitzel R,
    3. Vargas-Cruz N,
    4. Chaftari AM,
    5. Hachem R,
    6. Raad I
    . 2017. Comparative efficacies of antimicrobial catheter lock solutions for fungal biofilm eradication in an in vitro model of catheter-related fungemia. J Fungi (Basel) 3:E7. doi:10.3390/jof3010007.
    OpenUrlCrossRef
  10. 10.↵
    1. Jurewitsch B,
    2. Jeejeebhoy KN
    . 2005. Taurolidine lock: the key to prevention of recurrent catheter-related bloodstream infections. Clin Nutr 24:462–465. doi:10.1016/j.clnu.2005.02.001.
    OpenUrlCrossRefPubMed
  11. 11.↵
    1. Olthof ED,
    2. Rentenaar RJ,
    3. Rijs AJ,
    4. Wanten GJ
    . 2013. Absence of microbial adaptation to taurolidine in patients on home parenteral nutrition who develop catheter related bloodstream infections and use taurolidine locks. Clin Nutr 32:538–542. doi:10.1016/j.clnu.2012.11.014.
    OpenUrlCrossRefPubMed
  12. 12.↵
    1. Raad I,
    2. Hanna H,
    3. Dvorak T,
    4. Chaiban G,
    5. Hachem R
    . 2007. Optimal antimicrobial catheter lock solution, using different combinations of minocycline, EDTA, and 25-percent ethanol, rapidly eradicates organisms embedded in biofilm. Antimicrob Agents Chemother 51:78–83. doi:10.1128/AAC.00154-06.
    OpenUrlAbstract/FREE Full Text
PreviousNext
Back to top
Download PDF
Citation Tools
Minocycline-EDTA-Ethanol Antimicrobial Catheter Lock Solution Is Highly Effective In Vitro for Eradication of Candida auris Biofilms
Ruth A. Reitzel, Joel Rosenblatt, Bahgat Z. Gerges, Nylev Vargas-Cruz, Issam I. Raad
Antimicrobial Agents and Chemotherapy Mar 2020, 64 (4) e02146-19; DOI: 10.1128/AAC.02146-19

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Print

Alerts
Sign In to Email Alerts with your Email Address
Email

Thank you for sharing this Antimicrobial Agents and Chemotherapy article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Minocycline-EDTA-Ethanol Antimicrobial Catheter Lock Solution Is Highly Effective In Vitro for Eradication of Candida auris Biofilms
(Your Name) has forwarded a page to you from Antimicrobial Agents and Chemotherapy
(Your Name) thought you would be interested in this article in Antimicrobial Agents and Chemotherapy.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Minocycline-EDTA-Ethanol Antimicrobial Catheter Lock Solution Is Highly Effective In Vitro for Eradication of Candida auris Biofilms
Ruth A. Reitzel, Joel Rosenblatt, Bahgat Z. Gerges, Nylev Vargas-Cruz, Issam I. Raad
Antimicrobial Agents and Chemotherapy Mar 2020, 64 (4) e02146-19; DOI: 10.1128/AAC.02146-19
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Top
  • Article
    • ABSTRACT
    • INTRODUCTION
    • FOOTNOTES
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • PDF

KEYWORDS

Candida auris
minocycline-EDTA-ethanol
antimicrobial agents
biofilm
catheter lock solution

Related Articles

Cited By...

About

  • About AAC
  • Editor in Chief
  • Editorial Board
  • Policies
  • For Reviewers
  • For the Media
  • For Librarians
  • For Advertisers
  • Alerts
  • AAC Podcast
  • RSS
  • FAQ
  • Permissions
  • Journal Announcements

Authors

  • ASM Author Center
  • Submit a Manuscript
  • Article Types
  • Ethics
  • Contact Us

Follow #AACJournal

@ASMicrobiology

       

ASM Journals

ASM journals are the most prominent publications in the field, delivering up-to-date and authoritative coverage of both basic and clinical microbiology.

About ASM | Contact Us | Press Room

 

ASM is a member of

Scientific Society Publisher Alliance

 

American Society for Microbiology
1752 N St. NW
Washington, DC 20036
Phone: (202) 737-3600

Copyright © 2021 American Society for Microbiology | Privacy Policy | Website feedback

Print ISSN: 0066-4804; Online ISSN: 1098-6596