scholarly journals Glyceryl Trinitrate Complements Citrate and Ethanol in a Novel Antimicrobial Catheter Lock Solution To Eradicate Biofilm Organisms

2013 ◽  
Vol 57 (8) ◽  
pp. 3555-3560 ◽  
Author(s):  
Joel Rosenblatt ◽  
Ruth Reitzel ◽  
Tanya Dvorak ◽  
Ying Jiang ◽  
Ray Y. Hachem ◽  
...  
Keyword(s):  
Glyceryl Trinitrate ◽  
Methicillin Resistant ◽  
Content Type ◽  
Lock Solution ◽  
Test Organisms ◽  
History Of ◽  
Lock Therapy ◽  
Catheter Lock ◽  
Clinically Significant

ABSTRACTAntimicrobial catheter lock therapy is practiced to prevent lumenal-sourced infections of central venous catheters. Citrate has been used clinically as an anticoagulant in heparin-free catheter locks. Ethanol has also been widely studied as an antimicrobial lock solution component. This study reports on the synergy of glyceryl trinitrate (GTN) with citrate and ethanol in rapidly eradicating methicillin-resistantStaphylococcus aureus, methicillin-resistantStaphylococcus epidermidis,Pseudomonas aeruginosa, andCandida albicansbiofilms in anin vitromodel for catheter biofilm colonization. GTN has a long history of intravenous use as a hypotensive agent. It is potentially attractive as a component of a catheter lock solution because its physiologic half-life is quite short and its metabolic pathways are known. A lock containing 7% citrate and 20% ethanol required 0.01% GTN to fully eradicate biofilms of all test organisms within 2 h in the model. This GTN concentration is below the levels where clinically significant hypotensive effects are expected.

scholarly journals Efficacy of Ethanol against Candida albicans and Staphylococcus aureus Polymicrobial Biofilms

2012 ◽  
Vol 57 (1) ◽  
pp. 74-82 ◽  
Author(s):  
Brian M. Peters ◽  
Raven M. Ward ◽  
Hallie S. Rane ◽  
Samuel A. Lee ◽  
Mairi C. Noverr
Keyword(s):  
Staphylococcus Aureus ◽  
Candida Albicans ◽  
Bacterial Pathogen ◽  
Content Type ◽  
Environmental Surfaces ◽  
Lock Solution ◽  
Lock Therapy ◽  
Catheter Lock ◽  
Therapy Model

ABSTRACTCandida albicans, an opportunistic fungus, andStaphylococcus aureus, a bacterial pathogen, are two clinically relevant biofilm-forming microbes responsible for a majority of catheter-related infections, with such infections often resulting in catheter loss and removal. Not only do these pathogens cause a substantial number of nosocomial infections independently, but also they are frequently found coexisting as polymicrobial biofilms on host and environmental surfaces. Antimicrobial lock therapy is a current strategy to sterilize infected catheters. However, the robustness of this technique against polymicrobial biofilms has remained largely untested. Due to its antimicrobial activity, safety, stability, and affordability, we tested the hypothesis that ethanol (EtOH) could serve as a potentially efficacious catheter lock solution againstC. albicansandS. aureusbiofilms. Therefore, we optimized the dose and time necessary to achieve killing of both monomicrobial and polymicrobial biofilms formed on polystyrene and silicone surfaces in a static microplate lock therapy model. Treatment with 30% EtOH for a minimum of 4 h was inhibitory for monomicrobial and polymicrobial biofilms, as evidenced by XTT {sodium 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide inner salt} metabolic activity assays and confocal microscopy. Experiments to determine the regrowth of microorganisms on silicone after EtOH treatment were also performed. Importantly, incubation with 30% EtOH for 4 h was sufficient to kill and inhibit the growth ofC. albicans, while 50% EtOH was needed to completely inhibit the regrowth ofS. aureus. In summary, we have systematically defined the dose and duration of EtOH treatment that are effective against and prevent regrowth ofC. albicansandS. aureusmonomicrobial and polymicrobial biofilms in anin vitrolock therapy model.

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

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Ruth A. Reitzel ◽  
Joel Rosenblatt ◽  
Bahgat Z. Gerges ◽  
Nylev Vargas-Cruz ◽  
Issam I. Raad
Keyword(s):  
Therapeutic Option ◽  
Bloodstream Infections ◽  
Central Line ◽  
Emerging Pathogen ◽  
Candida Auris ◽  
Content Type ◽  
Lock Solution ◽  
Highly Effective ◽  
Catheter Lock

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).

scholarly journals In VitroAssessment of the Antimicrobial Efficacy of Optimized Nitroglycerin-Citrate-Ethanol as a Nonantibiotic, Antimicrobial Catheter Lock Solution for Prevention of Central Line-Associated Bloodstream Infections

2016 ◽  
Vol 60 (9) ◽  
pp. 5175-5181 ◽  
Author(s):  
Ruth A. Reitzel ◽  
Joel Rosenblatt ◽  
Cheryl Hirsh-Ginsberg ◽  
Kimberly Murray ◽  
Anne-Marie Chaftari ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Broad Spectrum ◽  
Clinical Assessment ◽  
Candida Glabrata ◽  
Ethanol Concentration ◽  
Methicillin Resistant ◽  
Content Type ◽  
Lock Solution ◽  
Catheter Lock ◽  
Heparin Lock

ABSTRACTThe 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-resistantStaphylococcus aureus(MRSA), vancomycin-intermediateStaphylococcus aureus(VISA), methicillin-resistantStaphylococcus epidermidis(MRSE), vancomycin-resistant enterococci (VRE), multidrug-resistant (MDR)Pseudomonas aeruginosa, MDRKlebsiella pneumoniae, MDREnterobacter cloacae, MDRAcinetobacter baumannii, MDREscherichia coli, MDRStenotrophomonas maltophilia,Candida albicans, andCandida glabratabiofilms. 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 ofStaphylococcus aureusandCandida 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.

scholarly journals In Vitro and In Vivo Activity of a Novel Catheter Lock Solution against Bacterial and Fungal Biofilms

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
J. Chandra ◽  
L. Long ◽  
N. Isham ◽  
P. K. Mukherjee ◽  
G. DiSciullo ◽  
...  
Keyword(s):  
Rabbit Model ◽  
Bloodstream Infections ◽  
Central Line ◽  
Resistant Bacteria ◽  
Content Type ◽  
Lock Solution ◽  
Catheter Lock ◽  
Adhesion Phase

ABSTRACT Central-line-associated bloodstream infections are increasingly recognized to be associated with intraluminal microbial biofilms, and effective measures for the prevention and treatment of bloodstream infections remain lacking. This report evaluates a new commercially developed antimicrobial catheter lock solution (ACL), containing trimethoprim (5 mg/ml), ethanol (25%), and calcium EDTA (Ca-EDTA) (3%), for activity against bacterial and fungal biofilms, using in vitro and in vivo (rabbit) catheter biofilm models. Biofilms were formed by bacterial (seven different species, including vancomycin-resistant Enterococcus [VRE]) or fungal (Candida albicans) species on catheter materials. Biofilm formation was evaluated by quantitative culture (CFU) and scanning electron microscopy (SEM). Treatment with ACL inhibited the growth of adhesion-phase biofilms in vitro after 60 min (VRE) or 15 min (all others), while mature biofilms were completely inhibited after exposure for 2 or 4 h, compared to control. Similar results were observed for drug-resistant bacteria. Compared to the heparinized saline controls, ACL lock therapy significantly reduced the catheter bacterial (3.49 ± 0.75 versus 0.03 ± 0.06 log CFU/catheter; P = 0.016) and fungal (2.48 ± 1.60 versus 0.55 ± 1.19 log CFU/catheter segment; P = 0.013) burdens in the catheterized rabbit model. SEM also demonstrated eradication of bacterial and fungal biofilms in vivo on catheters exposed to ACL, while vigorous biofilms were observed on untreated control catheters. Our results demonstrated that ACL was efficacious against both adhesion-phase and mature biofilms formed by bacteria and fungi in vitro and in vivo.

scholarly journals 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

2013 ◽  
Vol 57 (4) ◽  
pp. 1998-2000 ◽  
Author(s):  
R. Estes ◽  
J. Theusch ◽  
A. Beck ◽  
D. Pitrak ◽  
Kathleen M. Mullane
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Bloodstream Infections ◽  
Central Line ◽  
Methicillin Resistant ◽  
Content Type ◽  
Lock Therapy ◽  
Antibiotic Lock ◽  
Mrsa Colonization

ABSTRACTCentral venous catheters commonly develop central line-associated bloodstream infections.In vitroantibiotic lock therapy (ALT) was simulated on 10 methicillin-resistantStaphylococcus aureus(MRSA) clinical isolates imbedded in biofilm-coated silicon disks. Five days of 4-h daily exposures to daptomycin (2.5 mg/ml) in 25% ethanol or minocycline (3 mg/ml) plus 25% ethanol and 30 mg/ml EDTA resulted in significantly greater elimination of MRSA colonization than treatment with minocycline alone.

scholarly journals Full and Broad-SpectrumIn VivoEradication of Catheter-Associated Biofilms Using Gentamicin-EDTA Antibiotic Lock Therapy

2012 ◽  
Vol 56 (12) ◽  
pp. 6310-6318 ◽  
Author(s):  
Ashwini Chauhan ◽  
David Lebeaux ◽  
Jean-Marc Ghigo ◽  
Christophe Beloin
Keyword(s):  
Metal Binding ◽  
Venous Access ◽  
Access Port ◽  
Content Type ◽  
Length Of Treatment ◽  
Lock Solution ◽  
Lock Therapy ◽  
Antibiotic Lock

ABSTRACTBiofilms that develop on indwelling devices are a major concern in clinical settings. While removal of colonized devices remains the most frequent strategy for avoiding device-related complications, antibiotic lock therapy constitutes an adjunct therapy for catheter-related infection. However, currently used antibiotic lock solutions are not fully effective against biofilms, thus warranting a search for new antibiotic locks. Metal-binding chelators have emerged as potential adjuvants due to their dual anticoagulant/antibiofilm activities, but studies investigating their efficiency were mainlyin vitroor else focused on their effects in prevention of infection. To assess the ability of such chelators to eradicate mature biofilms, we used anin vivomodel of a totally implantable venous access port inserted in rats and colonized by eitherStaphylococcus aureus,Staphylococcus epidermidis,Escherichia coli, orPseudomonas aeruginosa. We demonstrate that use of tetrasodium EDTA (30 mg/ml) as a supplement to the gentamicin (5 mg/ml) antibiotic lock solution associated with systemic antibiotics completely eradicated Gram-positive and Gram-negative bacterial biofilms developed in totally implantable venous access ports. Gentamicin-EDTA lock was able to eliminate biofilms with a single instillation, thus reducing length of treatment. Moreover, we show that this combination was effective for immunosuppressed rats. Lastly, we demonstrate that a gentamicin-EDTA lock is able to eradicate the biofilm formed by a gentamicin-resistant strain of methicillin-resistantS. aureus. Thisin vivostudy demonstrates the potential of EDTA as an efficient antibiotic adjuvant to eradicate catheter-associated biofilms of major bacterial pathogens and thus provides a promising new lock solution.

scholarly journals In Vitro Study To Evaluate the Bioactivity of Freezing a Heparin-Based Dalbavancin Lock Solution

2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Marta Rubia ◽  
Andrea Cordero ◽  
María Jesús Pérez-Granda ◽  
Emilia Cercenado ◽  
Cristina Pascual ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Metabolic Activity ◽  
Staphylococcus Epidermidis ◽  
Anticoagulant Activity ◽  
In Vitro Study ◽  
Methicillin Resistant ◽  
Content Type ◽  
Clinical Criteria ◽  
Lock Solution

ABSTRACT The use of dalbavancin as a catheter lock solution must be addressed in depth before implementation in clinical practice. We assessed whether a heparin-based dalbavancin lock solution could be frozen in single-dose vials for 6 months without affecting its bioactivity against biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE). Over 6 months, we tested the bioactivity of a frozen solution of dalbavancin (≈1 mg/ml) plus heparin (60 IU) in terms of CFU counts and metabolic activity against biofilms of Staphylococcus aureus ATCC 43300 (MRSA) and Staphylococcus epidermidis ATCC 35984 (MRSE). The Anti-Xa assay was also performed to assess whether the anticoagulant activity of heparin was reduced under freezing. Every month, we compared the mean value of each variable with that obtained at baseline (before freezing, month 0) using both clinical criteria (values were within 25% of the baseline value) and statistical criteria (linear mixed models). At the end of the experiment (month 6), neither a clinically nor a statistically significant reduction in the bioactivity of dalbavancin-heparin solution was observed in terms of CFU counts and metabolic activity against biofilm of MRSA. Regarding MRSE, considering the clinical criteria, neither CFU counts nor metabolic activity decreased significantly. However, the reduction was statistically significant for all variables. Anti-Xa values (mean [standard deviation] international units per milliliter) for heparin in combination with dalbavancin were within 25% of the heparin-water value. A heparin-based dalbavancin lock solution can be frozen for up to 6 months with no effect on its bioactivity against MRSA and MRSE biofilms.

scholarly journals Nitroglycerin-Citrate-Ethanol Catheter Lock Solution Is Highly Effective for In Vitro Eradication of Candida auris Biofilm

2019 ◽  
Vol 63 (7) ◽  
Author(s):  
Nylev Vargas-Cruz ◽  
Ruth A. Reitzel ◽  
Joel Rosenblatt ◽  
Anne-Marie Chaftari ◽  
Rita Wilson Dib ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Bloodstream Infections ◽  
Central Line ◽  
Candida Auris ◽  
Content Type ◽  
Lock Solution ◽  
Amphotericin B Deoxycholate ◽  
Catheter Lock

ABSTRACT Candida auris poses emerging risks for causing severe central line-associated bloodstream infections. We tested in vitro the ability of antifungal lock solutions to rapidly eradicate C. auris biofilms. Liposomal amphotericin B, amphotericin B deoxycholate, fluconazole, voriconazole, micafungin, caspofungin, and anidulafungin failed to completely eradicate all 10 tested C. auris biofilms. Conversely, nitroglycerin-citrate-ethanol (NiCE) catheter lock solution completely eradicated all replicates for all of C. auris biofilms tested.

scholarly journals In VitroActivities of Daptomycin-, Vancomycin-, and Teicoplanin-Loaded Polymethylmethacrylate against Methicillin-Susceptible, Methicillin-Resistant, and Vancomycin-Intermediate Strains of Staphylococcus aureus

2011 ◽  
Vol 55 (12) ◽  
pp. 5480-5484 ◽  
Author(s):  
Yuhan Chang ◽  
Wen-Chien Chen ◽  
Pang-Hsin Hsieh ◽  
Dave W. Chen ◽  
Mel S. Lee ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
High Performance ◽  
Low Dose ◽  
Antibacterial Activities ◽  
High Dose ◽  
Bone Cements ◽  
Antibacterial Effects ◽  
Methicillin Resistant ◽  
Content Type

ABSTRACTThe objective of this study was to evaluate the antibacterial effects of polymethylmethacrylate (PMMA) bone cements loaded with daptomycin, vancomycin, and teicoplanin against methicillin-susceptibleStaphylococcus aureus(MSSA), methicillin-resistantStaphylococcus aureus(MRSA), and vancomycin-intermediateStaphylococcus aureus(VISA) strains. Standardized cement specimens made from 40 g PMMA loaded with 1 g (low-dose), 4 g (middle-dose) or 8 g (high-dose) antibiotics were tested for elution characteristics and antibacterial activities. The patterns of release of antibiotics from the cement specimens were evaluated usingin vitrobroth elution assay with high-performance liquid chromatography. The activities of broth elution fluid against differentStaphylococcus aureusstrains (MSSA, MRSA, and VISA) were then determined. The antibacterial activities of all the tested antibiotics were maintained after being mixed with PMMA. The cements loaded with higher dosages of antibiotics showed longer elution periods. Regardless of the antibiotic loading dose, the teicoplanin-loaded cements showed better elution efficacy and provided longer inhibitory periods against MSSA, MRSA, and VISA than cements loaded with the same dose of vancomycin or daptomycin. Regarding the choice of antibiotics for cement loading in the treatment ofStaphylococcus aureusinfection, teicoplanin was superior in terms of antibacterial effects.

scholarly journals Comparison of Borate Bioactive Glass and Calcium Sulfate as Implants for the Local Delivery of Teicoplanin in the Treatment of Methicillin-Resistant Staphylococcus aureus-Induced Osteomyelitis in a Rabbit Model

2015 ◽  
Vol 59 (12) ◽  
pp. 7571-7580 ◽  
Author(s):  
Wei-Tao Jia ◽  
Qiang Fu ◽  
Wen-Hai Huang ◽  
Chang-Qing Zhang ◽  
Mohamed N. Rahaman
Keyword(s):  
Staphylococcus Aureus ◽  
Bioactive Glass ◽  
Calcium Sulfate ◽  
Rabbit Model ◽  
Local Delivery ◽  
Methicillin Resistant ◽  
Content Type ◽  
Borate Bioactive Glass ◽  
Phosphate Buffered Saline

ABSTRACTThere is growing interest in biomaterials that can cure bone infection and also regenerate bone. In this study, two groups of implants composed of 10% (wt/wt) teicoplanin (TEC)-loaded borate bioactive glass (designated TBG) or calcium sulfate (TCS) were created and evaluated for their ability to release TECin vitroand to cure methicillin-resistantStaphylococcus aureus(MRSA)-induced osteomyelitis in a rabbit model. When immersed in phosphate-buffered saline (PBS), both groups of implants provided a sustained release of TEC at a therapeutic level for up to 3 to 4 weeks while they were gradually degraded and converted to hydroxyapatite. The TBG implants showed a longer duration of TEC release and better retention of strength as a function of immersion time in PBS. Infected rabbit tibiae were treated by debridement, followed by implantation of TBG or TCS pellets or intravenous injection with TEC, or were left untreated. Evaluation at 6 weeks postimplantation showed that the animals implanted with TBG or TCS pellets had significantly lower radiological and histological scores, lower rates of MRSA-positive cultures, and lower bacterial loads than those preoperatively and those of animals treated intravenously. The level of bone regeneration was also higher in the defects treated with the TBG pellets. The results showed that local TEC delivery was more effective than intravenous administration for the treatment of MRSA-induced osteomyelitis. Borate glass has the advantages of better mechanical strength, more desirable kinetics of release of TEC, and a higher osteogenic capacity and thus could be an effective alternative to calcium sulfate for local delivery of TEC.

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