Antimicrobial and Anticoagulant Activities of N-chlorotaurine, N,N-dichloro-2,2-dimethyltaurine, and N-monochloro-2,2-dimethyltaurine in Human Blood

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 2012 Jan 19

PMID 22252818

Citations 11

Authors

C Martini

A Hammerer-Lercher

M Zuck

A Jekle

D Debabov

M Anderson

M Nagl

Affiliations

Soon will be listed here.

Abstract

The aim of this study was to determine the potential application of N-chlorotaurine (NCT), N,N-dichloro-2,2-dimethyltaurine (NVC-422), and N-monochloro-2,2-dimethyltaurine (NVC-612) as catheter lock solutions for the prevention of catheter blockage and catheter-related bloodstream infections by testing their anticoagulant and broad-spectrum antimicrobial activities in human blood. NCT, NVC-422, NVC-612, and control compounds were serially diluted in fresh human blood to evaluate the effects on prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, and direct thrombin inhibition. Quantitative killing assays against pathogens, including methicillin-resistant Staphylococcus aureus, Escherichia coli, and Candida albicans, were performed in the presence of heparin and human blood. NCT and NVC-612 (1.38 mM each) and 1.02 mM NVC-422 prolonged prothrombin time (Quick value, 17 to 30%), activated partial thromboplastin time 3- to 4-fold to 76 to 125 s, and thrombin time 2- to 4-fold to 34 to 68 s. Fibrinogen decreased from 258 to 283 mg/dl (range of controls) to <40 mg/dl. No direct thrombin inhibition was observed by NVC-422 or NVC-612. Heparin did not influence the bactericidal activity of NCT. The microbicidal activities of NCT, NVC-422, and NVC-612 were maintained in diluted human blood. NCT, NVC-612, and NVC-422 have broad-spectrum antimicrobial activity in blood and anticoagulant activity targeting both intrinsic and extrinsic pathways of the coagulation system. These properties support their application as catheter lock solutions.

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References

Murina M, Roshchupkin D, Chudina N, Petrova A, Sergienko V . Antiaggregant effect of taurine chloramines in the presence of serum albumin. Bull Exp Biol Med. 2009; 147(6):704-7. DOI: 10.1007/s10517-009-0601-4. View

Henriques E, Fonseca N, Ramos M . On the modeling of snake venom serine proteinase interactions with benzamidine-based thrombin inhibitors. Protein Sci. 2004; 13(9):2355-69. PMC: 2280023. DOI: 10.1110/ps.04746804. View

Giese T, McGrath M, Stumm S, Schempp H, Elstner E, Meuer S . Differential effects on innate versus adaptive immune responses by WF10. Cell Immunol. 2004; 229(2):149-58. DOI: 10.1016/j.cellimm.2004.08.001. View

Stief T, Kurz J, Doss M, Fareed J . Singlet oxygen inactivates fibrinogen, factor V, factor VIII, factor X, and platelet aggregation of human blood. Thromb Res. 2000; 97(6):473-80. DOI: 10.1016/s0049-3848(99)00211-x. View

Murina M, Fesenko O, Sergienko V, Chudina N, Roshchupkin D . Antithrombotic activity of N,N-dichlorotaurine on mouse model of thrombosis in vivo. Bull Exp Biol Med. 2002; 134(1):36-8. DOI: 10.1023/a:1020600520233. View

Weber D, Rutala W . Central line-associated bloodstream infections: prevention and management. Infect Dis Clin North Am. 2011; 25(1):77-102. DOI: 10.1016/j.idc.2010.11.012. View

Casey A, Mermel L, Nightingale P, Elliott T . Antimicrobial central venous catheters in adults: a systematic review and meta-analysis. Lancet Infect Dis. 2008; 8(12):763-76. DOI: 10.1016/S1473-3099(08)70280-9. View

Kulawik D . Antimicrobial lock solutions: an approach to reduce catheter-related bacteremia. Nephrol Nurs J. 2010; 37(5):553-5. View

Rosenthal V, Maki D, Jamulitrat S, Medeiros E, Todi S, Gomez D . International Nosocomial Infection Control Consortium (INICC) report, data summary for 2003-2008, issued June 2009. Am J Infect Control. 2010; 38(2):95-104.e2. DOI: 10.1016/j.ajic.2009.12.004. View

10.

Casey A, Elliott T . Prevention of central venous catheter-related infection: update. Br J Nurs. 2010; 19(2):78, 80, 82 passim. DOI: 10.12968/bjon.2010.19.2.46289. View

11.

Low E, Nair S, Shiau T, Belisle B, Debabov D, Celeri C . N,N-Dichloroaminosulfonic acids as novel topical antimicrobial agents. Bioorg Med Chem Lett. 2008; 19(1):196-8. DOI: 10.1016/j.bmcl.2008.10.114. View

12.

Gottardi W, Nagl M . Chemical properties of N-chlorotaurine sodium, a key compound in the human defence system. Arch Pharm (Weinheim). 2002; 335(9):411-21. DOI: 10.1002/1521-4184(200212)335:9<411::AID-ARDP411>3.0.CO;2-D. View

13.

Stief T . Singlet oxygen potentiates thrombolysis. Clin Appl Thromb Hemost. 2007; 13(3):259-78. DOI: 10.1177/1076029607302404. View

14.

Veerasarn V, Boonnuch W, Kakanaporn C . A phase II study to evaluate WF10 in patients with late hemorrhagic radiation cystitis and proctitis. Gynecol Oncol. 2005; 100(1):179-84. DOI: 10.1016/j.ygyno.2005.08.014. View

15.

Iovino S, Krantz K, Blanco D, Fernandez J, Ocampo N, Najafi A . NVC-422 topical gel for the treatment of impetigo. Int J Clin Exp Pathol. 2011; 4(6):587-95. PMC: 3160610. View

16.

Mitchell M, Anderson B, Williams K, Umscheid C . Heparin flushing and other interventions to maintain patency of central venous catheters: a systematic review. J Adv Nurs. 2010; 65(10):2007-21. DOI: 10.1111/j.1365-2648.2009.05103.x. View

17.

Stief T, Aab A, HEIMBURGER N . Oxidative inactivation of purified human alpha-2-antiplasmin, antithrombin III, and C1-inhibitor. Thromb Res. 1988; 49(6):581-9. DOI: 10.1016/0049-3848(88)90255-1. View

18.

Steczko J, Ash S, Nivens D, Brewer L, Winger R . Microbial inactivation properties of a new antimicrobial/antithrombotic catheter lock solution (citrate/methylene blue/parabens). Nephrol Dial Transplant. 2009; 24(6):1937-45. PMC: 2684753. DOI: 10.1093/ndt/gfn776. View

19.

Wang L, Belisle B, Bassiri M, Xu P, Debabov D, Celeri C . Chemical characterization and biological properties of NVC-422, a novel, stable N-chlorotaurine analog. Antimicrob Agents Chemother. 2011; 55(6):2688-92. PMC: 3101424. DOI: 10.1128/AAC.00158-11. View

20.

Nagl M, Nguyen V, Gottardi W, Ulmer H, Hopfl R . Tolerability and efficacy of N-chlorotaurine in comparison with chloramine T for the treatment of chronic leg ulcers with a purulent coating: a randomized phase II study. Br J Dermatol. 2003; 149(3):590-7. DOI: 10.1046/j.1365-2133.2003.05432.x. View