Hostname: page-component-586b7cd67f-t7czq Total loading time: 0 Render date: 2024-11-28T08:26:31.493Z Has data issue: false hasContentIssue false

Advances in the prevention and management of central-line–associated bloodstream infections: The role of chelator-based catheter locks

Published online by Cambridge University Press:  24 June 2019

Anne-Marie Chaftari*
Affiliation:
Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas
George M. Viola
Affiliation:
Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas
Joel Rosenblatt
Affiliation:
Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas
Ray Hachem
Affiliation:
Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas
Issam Raad
Affiliation:
Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas
*
Author for correspondence: Anne-Marie Chaftari, MD, Anderson Cancer Center, Infectious Diseases, Infection Control and Employee Health, 1515 Holcombe Blvd. Unit 1460 Houston, TX 77030. Email: [email protected]

Abstract

The proper functioning of central lines is imperative for the management of patients with cancer or on hemodialysis. However, these lifelines can become infected and can malfunction.

Chelators such as citrate and EDTA have been widely studied alone or in combination with other antimicrobial agents in catheter lock solutions to prevent catheter-related bloodstream infections and to maintain catheter patency. Given their anticoagulation, antiplatelet aggregation, antibiofilm, antimicrobial activity, safety profile, as well as their low cost, chelators have long been considered alternatives to heparin and a vital component of catheter lock solutions. In this review, we present a detailed summary of the properties of chelators and in vitro and in vivo studies of chelator-containing lock solutions.

Type
Review
Copyright
© 2019 by The Society for Healthcare Epidemiology of America. All rights reserved. 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Shanks, RM, Sargent, JL, Martinez, RM, Graber, ML, O’Toole, GA. Catheter lock solutions influence staphylococcal biofilm formation on abiotic surfaces. Nephrol Dial Transpl 2006;21:22472255.CrossRefGoogle ScholarPubMed
Green, JV, Orsborn, KI, Zhang, M, et al. Heparin-binding motifs and biofilm formation by Candida albicans. J Infect Dis 2013;208:16951704.CrossRefGoogle Scholar
Shanks, RM, Donegan, NP, Graber, ML, et al. Heparin stimulates Staphylococcus aureus biofilm formation. Infect Immun 2005;73:45964606.10.1128/IAI.73.8.4596-4606.2005CrossRefGoogle ScholarPubMed
Pronovost, P, Needham, D, Berenholtz, S, et al. An intervention to decrease catheter-related bloodstream infections in the ICU. N Engl J Med 2006;355:27252732.CrossRefGoogle ScholarPubMed
Pronovost, PJ, Goeschel, CA, Colantuoni, E, et al. Sustaining reductions in catheter-related bloodstream infections in Michigan intensive care units: observational study. BMJ 2010;340:c309.CrossRefGoogle ScholarPubMed
Raad, I, Costerton, W, Sabharwal, U, Sacilowski, M, Anaissie, E, Bodey, GP. Ultrastructural analysis of indwelling vascular catheters: a quantitative relationship between luminal colonization and duration of placement. J Infect Dis 1993;168:400407.CrossRefGoogle ScholarPubMed
Safdar, N, Maki, DG. The pathogenesis of catheter-related bloodstream infection with noncuffed short-term central venous catheters. Intens Care Med 2004;30:6267.CrossRefGoogle ScholarPubMed
Salzman, MB, Isenberg, HD, Shapiro, JF, Lipsitz, PJ, Rubin, LG. A prospective study of the catheter hub as the portal of entry for microorganisms causing catheter-related sepsis in neonates. J Infect Dis 1993;167:487490.CrossRefGoogle ScholarPubMed
Mermel, LA. What is the evidence for intraluminal colonization of hemodialysis catheters? Kidney Int 2014;86:2833.CrossRefGoogle ScholarPubMed
Viola, GM, Rosenblatt, J, Raad, II. Drug eluting antimicrobial vascular catheters: progress and promise. Advanced drug delivery reviews 2016.10.1016/j.addr.2016.07.011CrossRefGoogle Scholar
McNaught, AD, Wilkinson, A. Compendium of Chemical Terminology, 2nd ed, (The “Gold Book”). Oxford, UK: Blackwell Scientific; 1997. See also the corrected version online created by M. Nic, J. Jirat, and B. Kosata. IUPAC website. http://goldbook.iupac.org. Accessed May 29, 2019.Google Scholar
Davie, EW, Fujikawa, K, Kisiel, W. The coagulation cascade: initiation, maintenance, and regulation. Biochemistry 1991;30:1036310370.CrossRefGoogle ScholarPubMed
Flemming, HC, Wingender, J, Griebe, T, Mayer, C. Chapter 2: Physico-chemical properties of biofilms. In: Biofilms: Recent Advances in Their Study and Control. Boca Raton, FL: CRC Press; 2000.10.1201/9781482293968CrossRefGoogle Scholar
Flemming, HC, Wingender, J, Szewzyk, U, Steinberg, P, Rice, SA, Kjelleberg, S. Biofilms: an emergent form of bacterial life. Nat Rev Microbiol 2016;14:563575.CrossRefGoogle ScholarPubMed
Ma, Z, Jacobsen, FE, Giedroc, DP. Coordination chemistry of bacterial metal transport and sensing. Chem Rev 2009;109:46444681.CrossRefGoogle Scholar
Aslam, S, Trautner, BW, Ramanathan, V, Darouiche, RO. Pilot trial of N-acetylcysteine and tigecycline as a catheter-lock solution for treatment of hemodialysis catheter-associated bacteremia. Infect Control Hosp Epidemiol 2008;29:894897.CrossRefGoogle ScholarPubMed
Raad, I, Hanna, H, Jiang, Y, et al. Comparative activities of daptomycin, linezolid, and tigecycline against catheter-related methicillin-resistant Staphylococcus bacteremic isolates embedded in biofilm. Antimicrob Agents Chemother 2007;51:16561660.CrossRefGoogle ScholarPubMed
Estes, R, Theusch, J, Beck, A, Pitrak, D, Mullane, KM. Activity of daptomycin with or without 25 percent ethanol compared to combinations of minocycline, EDTA, and 25 percent ethanol against methicillin-resistant Staphylococcus aureus isolates embedded in biofilm. Antimicrob Agents Chemother 2013;57:19982000.CrossRefGoogle ScholarPubMed
Passerini de Rossi, B, Feldman, L, Pineda, MS, Vay, C, Franco, M. Comparative in vitro efficacies of ethanol-, EDTA- and levofloxacin-based catheter lock solutions on eradication of Stenotrophomonas maltophilia biofilms. J Med Microbiol 2012;61:12481253.CrossRefGoogle ScholarPubMed
Harris, DC. EDTA Titrations. Quantitative Chemical Analysis, 8th edition. New York: W. H. Freeman & Co.; 2010.Google Scholar
Brown, MJ, Willis, T, Omalu, B, Leiker, R. Deaths resulting from hypocalcemia after administration of edetate disodium: 2003–2005. Pediatrics 2006;118:e534e536.CrossRefGoogle ScholarPubMed
Meltzer, LE, Kitchell, JR, Palmon, F J r. The long-term use, side effects, and toxicity of disodium ethylenediamine tetraacetic acid (EDTA). Am J Med Sci 1961;242:1117.CrossRefGoogle ScholarPubMed
Lamas, GA, Goertz, C, Boineau, R, et al. Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: the TACT randomized trial. JAMA 2013;309:12411250.CrossRefGoogle ScholarPubMed
Raad, II, Fang, X, Keutgen, XM, Jiang, Y, Sherertz, R, Hachem, R. The role of chelators in preventing biofilm formation and catheter-related bloodstream infections. Curr Opin Infect Dis 2008;21:385392.CrossRefGoogle ScholarPubMed
Raad, II, Hachem, RY, Hanna, HA, et al. Role of ethylene diamine tetra-acetic acid (EDTA) in catheter lock solutions: EDTA enhances the antifungal activity of amphotericin B lipid complex against Candida embedded in biofilm. Int J Antimicrob Agents 2008;32:515518.CrossRefGoogle ScholarPubMed
Percival, SL, Kite, P, Eastwood, K, et al. Tetrasodium EDTA as a novel central venous catheter lock solution against biofilm. Infect Control Hosp Epidemiol 2005;26:515519.CrossRefGoogle ScholarPubMed
Kite, P, Eastwood, K, Sugden, S, Percival, SL. Use of in vivo–generated biofilms from hemodialysis catheters to test the efficacy of a novel antimicrobial catheter lock for biofilm eradication in vitro. J Clin Microbiol 2004;42:30733076.CrossRefGoogle ScholarPubMed
Raad, I, Chatzinikolaou, I, Chaiban, G, et al. In vitro and ex vivo activities of minocycline and EDTA against microorganisms embedded in biofilm on catheter surfaces. Antimicrob Agents Chemother 2003;47:35803585.CrossRefGoogle ScholarPubMed
Raad, I, Rosenblatt, J, Reitzel, R, Jiang, Y, Dvorak, T, Hachem, R. Chelator-based catheter lock solutions in eradicating organisms in biofilm. Antimicrob Agents Chemother 2013;57:586588.CrossRefGoogle ScholarPubMed
Raad, I, Buzaid, A, Rhyne, J, et al. Minocycline and ethylenediaminetetraacetate for the prevention of recurrent vascular catheter infections. Clin Infect Dis 1997;25:149151.CrossRefGoogle ScholarPubMed
Chatzinikolaou, I, Zipf, TF, Hanna, H, et al. Minocycline-ethylene-diamine-tetra-acetate lock solution for the prevention of implantable port infections in children with cancer. Clin Infect Dis 2003;36:116119.CrossRefGoogle ScholarPubMed
Bleyer, AJ, Mason, L, Russell, G, Raad, II, Sherertz, RJ. A randomized, controlled trial of a new vascular catheter flush solution (minocycline-EDTA) in temporary hemodialysis access. Infect Control Hosp Epidemiol 2005;26:520524.CrossRefGoogle Scholar
Campos, RP, do Nascimento MM, Chula DC, Riella MC. Minocycline-EDTA lock solution prevents catheter-related bacteremia in hemodialysis. J Am Soc Nephrol 2011;22:19391945.CrossRefGoogle ScholarPubMed
Luiz, MV, Scavone, C, Tzanno, C. The CLOCK trial, a double-blinded randomized controlled trial: Trisodium citrate 30% and minocycline 3 mg/mL plus EDTA 30 mg/mL are effective and safe for catheter patency maintenance among CKD 5D patients on hemodialysis. Hemodialysis Int 2017;21:294304.CrossRefGoogle ScholarPubMed
Kanaa, M, Wright, MJ, Akbani, H, Laboi, P, Bhandari, S, Sandoe, JA. Cathasept line lock and microbial colonization of tunneled hemodialysis catheters: a multicenter randomized controlled trial. Am J Kidney Dis 2015;66:10151023.CrossRefGoogle ScholarPubMed
Nori, US, Manoharan, A, Yee, J, Besarab, A. Comparison of low-dose gentamicin with minocycline as catheter lock solutions in the prevention of catheter-related bacteremia. Am J Kidney Dis 2006;48:596605.CrossRefGoogle ScholarPubMed
Raad, I, Chaftari, AM, Zakhour, R, et al. Successful salvage of central venous catheters in patients with catheter-related or central-line–associated bloodstream infections by using a catheter lock solution consisting of minocycline, EDTA, and 25% ethanol. Antimicrob Agents Chemother 2016;60:34263432.CrossRefGoogle ScholarPubMed
Martin, RB. Citrate binding of Al3+ and Fe3+. J Inorg Biochem 1986;28:181187.CrossRefGoogle ScholarPubMed
Warner, RC, Weber, I. The cupric and ferric citrate complexes. J Am Chem Soc 1953;75:50865094.Google Scholar
Glusker, JP. Citrate conformation and chelation: enzymic implications. Acct Chem Res 1980;13:345352.CrossRefGoogle Scholar
Joshi-Tope, G, Francis, AJ. Mechanisms of biodegradation of metal-citrate complexes by Pseudomonas fluorescens. J Bacteriol 1995;177:19891993.CrossRefGoogle ScholarPubMed
Meyer, JL. Formation constants for interaction of citrate with calcium and magnesium ions. Anal Biochem 1974;62:295300.CrossRefGoogle ScholarPubMed
Lanford, OE, Quinan, JR. A spectrophotometric study of the reaction of ferric iron and citric acid. J Am Chem Soc 1948;70:29002903.CrossRefGoogle Scholar
Weijmer, MC, Debets-Ossenkopp, YJ, Van De Vondervoort, FJ, ter Wee, PM. Superior antimicrobial activity of trisodium citrate over heparin for catheter locking. Nephrol Dial Transpl 2002;17:21892195.CrossRefGoogle ScholarPubMed
Hermite, L, Quenot, JP, Nadji, A, et al. Sodium citrate versus saline catheter locks for nontunneled hemodialysis central venous catheters in critically ill adults: a randomized controlled trial. Intens Care Med 2012;38:279285.CrossRefGoogle Scholar
Correa Barcellos, F, Pereira Nunes, B, Jorge Valle, L, et al. Comparative effectiveness of 30% trisodium citrate and heparin lock solution in preventing infection and dysfunction of hemodialysis catheters: a randomized controlled trial (CITRIM trial). Infection 2017;45:139145.CrossRefGoogle Scholar
Power, A, Duncan, N, Singh, SK, et al. Sodium citrate versus heparin catheter locks for cuffed central venous catheters: a single-center randomized controlled trial. Am J Kidney Dis 2009;53:10341041.CrossRefGoogle ScholarPubMed
Bonkain, F, Racape, J, Goncalvez, I, et al. Prevention of tunneled cuffed hemodialysis catheter-related dysfunction and bacteremia by a neutral-valve closed-system connector: a single-center randomized controlled trial. Am J Kidney Dis 2013;61:459465.CrossRefGoogle ScholarPubMed
Silva, J, Antunes, J, Carvalho, T, Ponce, P. Efficacy of preventing hemodialysis catheter infections with citrate lock. Hemodial Int 2012;16:545552.CrossRefGoogle ScholarPubMed
Weijmer, MC, van den Dorpel, MA, Van de Ven, PJ, et al. Randomized, clinical trial comparison of trisodium citrate 30% and heparin as catheter-locking solution in hemodialysis patients. J Am Soc Nephrol 2005;16:27692777.CrossRefGoogle ScholarPubMed
Moran, J, Sun, S, Khababa, I, Pedan, A, Doss, S, Schiller, B. A randomized trial comparing gentamicin/citrate and heparin locks for central venous catheters in maintenance hemodialysis patients. Am J Kidney Dis 2012;59:102107.CrossRefGoogle ScholarPubMed
Filiopoulos, V, Hadjiyannakos, D, Koutis, I, et al. Approaches to prolong the use of uncuffed hemodialysis catheters: results of a randomized trial. Am J Nephrol 2011;33:260268.CrossRefGoogle ScholarPubMed
Dogra, GK, Herson, H, Hutchison, B, et al. Prevention of tunneled hemodialysis catheter-related infections using catheter-restricted filling with gentamicin and citrate: a randomized controlled study. J Am Soc Nephrol 2002;13:21332139.CrossRefGoogle ScholarPubMed
Dotson, B, Lynn, S, Savakis, K, Churchwell, MD. Physical compatibility of 4% sodium citrate with selected antimicrobial agents. Am J Health Syst Pharm 2010;67:11951198.CrossRefGoogle ScholarPubMed
Justo, JA, Bookstaver, PB. Antibiotic lock therapy: review of technique and logistical challenges. Infect Drug Resist 2014;7:343363.Google ScholarPubMed
Klek, S, Szczepanek, K, Hermanowicz, A, Galas, A. Taurolidine lock in home parenteral nutrition in adults: results from an open-label randomized controlled clinical trial. JPEN 2015;39:331335.CrossRefGoogle ScholarPubMed
Handrup, MM, Moller, JK, Schroder, H. Central venous catheters and catheter locks in children with cancer: a prospective randomized trial of taurolidine versus heparin. Pediatr Blood Cancer 2013;60:12921298.CrossRefGoogle ScholarPubMed
Dumichen, MJ, Seeger, K, Lode, HN, et al. Randomized controlled trial of taurolidine citrate versus heparin as catheter lock solution in paediatric patients with haematological malignancies. J Hosp Infect 2012;80:304309.CrossRefGoogle ScholarPubMed
Maki, DG, Ash, SR, Winger, RK, Lavin, P. A novel antimicrobial and antithrombotic lock solution for hemodialysis catheters: a multi-center, controlled, randomized trial. Crit Care Med 2011;39:613620.CrossRefGoogle ScholarPubMed
Solomon, LR, Cheesbrough, JS, Ebah, L, et al. A randomized double-blind controlled trial of taurolidine-citrate catheter locks for the prevention of bacteremia in patients treated with hemodialysis. Am J Kidney Dis 2010;55:10601068.CrossRefGoogle ScholarPubMed
Betjes, MG, van Agteren, M. Prevention of dialysis catheter-related sepsis with a citrate-taurolidine-containing lock solution. Nephrol Dial Transpl 2004;19:15461551.CrossRefGoogle ScholarPubMed
Allon, M. Prophylaxis against dialysis catheter-related bacteremia with a novel antimicrobial lock solution. Clin Infect Dis 2003;36:15391544.CrossRefGoogle ScholarPubMed
Bisseling, TM, Willems, MC, Versleijen, MW, Hendriks, JC, Vissers, RK, Wanten, GJ. Taurolidine lock is highly effective in preventing catheter-related bloodstream infections in patients on home parenteral nutrition: a heparin-controlled prospective trial. Clin Nutr 2010;29:464468.CrossRefGoogle ScholarPubMed
Murray, EC, Deighan, C, Geddes, C, Thomson, PC. Taurolidine-citrate-heparin catheter lock solution reduces staphylococcal bacteraemia rates in haemodialysis patients. QJM 2014;107:9951000.CrossRefGoogle ScholarPubMed
Shah, CB, Mittelman, MW, Costerton, JW, et al. Antimicrobial activity of a novel catheter lock solution. Antimicrob Agents Chemother 2002;46:16741679.CrossRefGoogle ScholarPubMed
Toure, A, Lauverjat, M, Peraldi, C, et al. Taurolidine lock solution in the secondary prevention of central venous catheter-associated bloodstream infection in home parenteral nutrition patients. Clin Nutr 2012;31:567570.CrossRefGoogle ScholarPubMed
Zwiech, R, Adelt, M, Chrul, S. A Taurolidine-citrate-heparin lock solution effectively eradicates pathogens from the catheter biofilm in hemodialysis patients. Am J Therapeut 2016;23:e363368.CrossRefGoogle ScholarPubMed
Takla, TA, Zelenitsky, SA, Vercaigne, LM. Effect of ethanol/trisodium citrate lock on microorganisms causing hemodialysis catheter-related infections. J Vasc Access 2007;8:262267.CrossRefGoogle ScholarPubMed
Warning on tricitrasol dialysis catheter anticoagulant. USFDA website. http://www.hdcn.com/00/004fdci.htm. Published 2000. Accessed, May 29, 2019.Google Scholar
Grudzinski, L, Quinan, P, Kwok, S, Pierratos, A. Sodium citrate 4% locking solution for central venous dialysis catheters—an effective, more cost-efficient alternative to heparin. Nephrol Dial Transpl 2007;22:471476.CrossRefGoogle Scholar
Landry, DL, Braden, GL, Gobeille, SL, Haessler, SD, Vaidya, CK, Sweet, SJ. Emergence of gentamicin-resistant bacteremia in hemodialysis patients receiving gentamicin lock catheter prophylaxis. Clin J Am Soc Nephrol 2010;5:17991804.Google ScholarPubMed
Abbas, SA, Haloob, IA, Taylor, SL, et al. Effect of antimicrobial locks for tunneled hemodialysis catheters on bloodstream infection and bacterial resistance: a quality improvement report. Am J Kidney Dis 2009;53:492502.CrossRefGoogle ScholarPubMed
Chaftari, AM, Hachem, R, Szvalb, A, et al. A novel nonantibiotic nitroglycerin based catheter lock solution for the prevention of intraluminal central venous catheter infections in cancer patients. Antimicrob Agents Chemother 2017.CrossRefGoogle Scholar
Zacharioudakis, IM, Zervou, FN, Arvanitis, M, Ziakas, PD, Mermel, LA, Mylonakis, E. Antimicrobial lock solutions as a method to prevent central line-associated bloodstream infections: a meta-analysis of randomized controlled trials. Clin Infect Dis 2014;59:17411749.CrossRefGoogle ScholarPubMed
Zhao, Y, Li, Z, Zhang, L, et al. Citrate versus heparin lock for hemodialysis catheters: a systematic review and meta-analysis of randomized controlled trials. Am J Kidney Dis 2014;63:479490.CrossRefGoogle ScholarPubMed
Chapla, K, Oza-Gajera, BP, Yevzlin, AS, Shin, JI, Astor, BC, Chan, MR. Hemodialysis catheter locking solutions and the prevention of catheter dysfunction: a meta-analysis. J Vasc Access 2015;16:107112.CrossRefGoogle ScholarPubMed
Feely, T, Copley, A, Bleyer, AJ. Catheter lock solutions to prevent bloodstream infections in high-risk hemodialysis patients. Am J Nephrol 2007;27:2429.CrossRefGoogle ScholarPubMed