In Vitro Assessment of the Antimicrobial Efficacy of Optimized Nitroglycerin-Citrate-Ethanol as a Nonantibiotic, Antimicrobial Catheter Lock Solution for Prevention of Central Line-Associated Bloodstream Infections.
The rapid, broad-spectrum, biofilm-eradicating activity of the combination of 0.01% nitroglycerin, 7% citrate, and 20% ethanol and its potential as a nonantibiotic, antimicrobial catheter lock solution (ACLS) were previously reported. Here, a nitroglycerin-citrate-ethanol (NiCE) ACLS optimized for clinical assessment was developed by reducing the nitroglycerin and citrate concentrations and increasing the ethanol concentration. Biofilm-eradicating activity was sustained when the ethanol concentration was increased from 20 to 22% which fully compensated for reducing the citrate concentration from 7% to 4% as well as the nitroglycerin concentration from 0.01% to 0.0015% or 0.003%. The optimized formulations demonstrated complete and rapid (2 h) eradication of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate Staphylococcus aureus (VISA), methicillin-resistant Staphylococcus epidermidis (MRSE), vancomycin-resistant enterococci (VRE), multidrug-resistant (MDR) Pseudomonas aeruginosa, MDR Klebsiella pneumoniae, MDR Enterobacter cloacae, MDR Acinetobacter baumannii, MDR Escherichia coli, MDR Stenotrophomonas maltophilia, Candida albicans, and Candida glabrata biofilms. The optimized NiCE lock solutions demonstrated anticoagulant activities comparable to those of heparin lock solutions. NiCE lock solution was significantly more effective than taurolidine-citrate-heparin lock solution in eradicating biofilms of Staphylococcus aureus and Candida glabrata The optimized, nonantibiotic, heparin-free NiCE lock solution demonstrates rapid broad-spectrum biofilm eradication as well as effective anticoagulant activity, making NiCE a high-quality ACLS candidate for clinical assessment.
Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Ruth A
RA
Reitzel
Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA JSRosenblatt@mdanderson.org.
Joel
J
Rosenblatt
Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Cheryl
C
Hirsh-Ginsberg
School of Health Professions, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Kimberly
K
Murray
Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Anne-Marie
AM
Chaftari
Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Ray
R
Hachem
Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Issam
I
Raad
D040981:Acinetobacter baumannii / Q000187:drug effects / Q000254:growth & development; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000925:Anticoagulants / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development; D041221:Candida glabrata / Q000187:drug effects / Q000254:growth & development; D057785:Catheters / Q000382:microbiology; D002951:Citrates / Q000494:pharmacology*; D015169:Colony Count, Microbial; D016972:Enterobacter cloacae / Q000187:drug effects / Q000254:growth & development; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D000431:Ethanol / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000254:growth & development; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D005996:Nitroglycerin / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D000077559:Sodium Citrate; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000254:growth & development; D020615:Stenotrophomonas maltophilia / Q000187:drug effects / Q000254:growth & development; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology; D013829:Thiadiazines / Q000494:pharmacology; D065507:Vancomycin-Resistant Enterococci / Q000187:drug effects / Q000254:growth & development
D000890:Anti-Infective Agents; D000925:Anticoagulants; D002951:Citrates; D013829:Thiadiazines; D013654:Taurine; D000077559:Sodium Citrate; D000431:Ethanol; C012566:taurolidine; D006493:Heparin; D005996:Nitroglycerin