Antimicrobial Catheter Lock Solution Research Articles

Evaluation of Cellular and Systemic Toxicity of Dielectric Barrier Discharge Plasma-Treated N-Acetylcysteine as Potential Antimicrobial Catheter Lock Solution

Intravenous catheter-related bloodstream infections are a cause of remarkable problems. Catheter lock solutions are used to keep catheter patency and prevent catheter-related bloodstream infections. The leakage of catheter lock solution to the bloodstream raises toxicity concerns. Plasma-treated liquids carry the potential to act as catheter lock solutions by virtue of their strong antimicrobial effects. The present study investigates the tolerance of the proposed solution in vitro and in vivo. N-acetylcysteine (NAC) solution was treated with atmospheric-air DBD plasma and antimicrobial assays were performed. The cytotoxicity of the plasma-treated NAC solution was evaluated on an EA.hy926 cell line. Intravenous administration of plasma-treated NAC solution in different doses was given to Sprague Dawley rats. One week after infusion with plasma-treated NAC solution, first, the blood samples were collected, and then liver, kidney, tail vein, heart, and lung tissue samples were collected from euthanized rats for histopathological examination. The cytotoxicity of plasma-treated NAC solution depended on plasma treatment time, contact time, and cell number. A strong antimicrobial effect with no cytotoxicity of plasma-treated NAC solution was observed in endothelial cells. Based on blood tests and histopathological examination, no signs of systemic toxicity were observed that can be correlated to the plasma-treated-NAC solution. This solution has the potential to be used as a catheter lock solution with strong antimicrobial properties, keeping catheter patency.

Tetrasodium EDTA Is Effective at Eradicating Biofilms Formed by Clinically Relevant Microorganisms from Patients’ Central Venous Catheters

Central venous access devices (CVADs) are an essential component of modern health care. However, their prolonged use commonly results in microbial colonization, which carries the potential risk of hospital-acquired bloodstream infections. These infections complicate the treatment of already sick individuals and cost the existing health care systems around the world millions of dollars. The microbes that colonize CVADs typically form multicellular biofilms that are difficult to dislodge and are resistant to antimicrobial treatments. Clinicians are searching for better ways to extend the working life span of implanted CVADs, by preventing colonization and reducing the risk of bloodstream infections. In this study, we analyzed 210 bacterial and fungal isolates from colonized CVADs or human bloodstream infections from two hospitals geographically separated in the east and west of Canada and screened the isolates for biofilm formation in vitro Twenty isolates, representing 12 common, biofilm-forming species, were exposed to 4% tetrasodium EDTA, an antimicrobial lock solution that was recently approved in Canada for use as a medical device. The EDTA solution was effective at eradicating surface-attached biofilms from each microbial species, indicating that it could likely be used to prevent biofilm growth within CVADs and to eliminate established biofilms. This new lock solution fits with antibiotic stewardship programs worldwide by sparing the use of important antibiotic agents, targeting prevention rather than the expensive treatment of hospital-acquired infections.IMPORTANCE The colonization of catheters by microorganisms often precludes their long-term use, which can be a problem for human patients that have few body sites available for new catheters. The colonizing organisms often form biofilms, and increasingly these organisms are resistant to multiple antibiotics, making them difficult to treat. In this article, we have taken microorganisms that are associated with biofilm formation in catheters from two Canadian hospitals and tested them with tetrasodium EDTA, a new antimicrobial catheter lock solution. Tetrasodium EDTA was effective at eliminating Gram-positive, Gram-negative, and fungal species and represents a promising alternative to antibiotic treatment with less chance of the organisms developing resistance. We expect that our results will be of interest to researchers and clinicians and will lead to improved patient care.

Locking Hemodialysis Catheters With Trimethoprim-Ethanol-Ca-EDTA to Prevent Bloodstream Infections: A Randomized, Evaluator-blinded Clinical Trial.

Central line-associated bloodstream infections (CLABSIs) often result from intraluminal microbial colonization and are associated with morbidity, mortality, and substantial costs. The use of antimicrobial catheter lock solutions may reduce the incidence of CLABSI. Patients undergoing hemodialysis (HD) through a prevalent central venous catheter (CVC) were randomly assigned to have their CVC locked between dialysis sessions with an antimicrobial catheter lock solution that contained trimethoprim 5 mg/mL, ethanol 25%, and Ca-EDTA 3% (investigational medical device [IMD]) or heparin 5000 U/mL active control heparin (ACH). Exit site care was standardized by protocol-driven use of skin antiseptics and occlusive dressings. The composite primary endpoint consisted of the incidence of CLABSI and intracatheter thrombolytic treatment (TT). Given the viscosity and odor of the IMD, blinding was impossible. Therefore, a blinded endpoint committee adjudicated the incidence of CLABSI. A total of 270 patients on HD were enrolled and followed for 43738 CVC-days. Despite the low CLABSI incidence of 0.41/1000 CVC-days in patients randomized to ACH, the IMD further reduced the incidence 4.56-fold to 0.09/1000 CVC-days (P < .03). The product was well tolerated, and the frequency and severity of adverse events were comparable between groups. Intracatheter instillation of thrombolytics was more frequent in patients who received the IMD (12% ACH, 40% IMD; P < .001), but rates of catheter removal did not differ (13% ACH, 11% IMD). Overall, dialysis adequacy was comparable between groups. In patients on chronic HD, a trimethoprim, ethanol, and Ca-EDTA lock solution significantly reduced the incidence of CLABSI. NCT01989091.

Non-Antibiotic Antimicrobial Catheter Lock Solutions in Patients on Home Parenteral Nutrition.

Patients on home parenteral nutrition (HPN) are dependent on central venous access for long-term sustenance, and catheter-related bloodstream infections (CRBSIs) are a major cause of morbidity and mortality in this patient population. As such, there is much interest in finding new methods for preventing CRBSIs in patients on HPN. As it is thought that these infections are preceded by microbial colonization of the catheter, one approach is to use antimicrobial catheter lock solutions. Although antibiotic catheter lock solutions have been present for decades, their use has been mostly limited to the treatment of CRBSIs due to concern for promoting microbial resistance. Recently, however, with the advent of non-antibiotic antimicrobial catheter lock solutions, this approach is gaining popularity as a promising method to decrease rates of CRBSI in HPN patients.

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

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.

Antimicrobial lock solutions for preventing catheter-related infections in haemodialysis.

Patients undergoing haemodialysis (HD) through a central venous catheter (CVC) are exposed to several risks, being a catheter-related infection (CRI) and a CVC lumen thrombosis among the most serious. Standard of care regarding CVCs includes their sealing with heparin lock solutions to prevent catheter lumen thrombosis. Other lock solutions to prevent CRI, such as antimicrobial lock solutions, have proven useful with antibiotics solutions, but not as yet for non-antibiotic antimicrobial solutions. Furthermore, it is uncertain if these solutions have a negative effect on thrombosis incidence. To assess the efficacy and safety of antimicrobial (antibiotic, non-antibiotic, or both) catheter lock solutions for preventing CRI in participants undergoing HD with a CVC. We searched the Cochrane Kidney and Transplant Specialised Register up to 18 December 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. We included all randomised or quasi-randomised control trials (RCTs) comparing antimicrobial (antibiotic and non-antibiotic) lock solutions to standard lock solutions, in participants using a CVC for HD, without language restriction. Two authors independently assessed studies for eligibility, and two additional authors assessed for risk of bias and extracted data. We expressed results as rate ratios (RR) per 1000 catheter-days or 1000 dialysis sessions with 95% confidence intervals (CI). Statistical analyses were performed using the random-effects model. Thirty-nine studies, enrolling 4216 participants, were included in this review, however only 30 studies, involving 3392 participants, contained enough data to be meta-analysed. Risk of bias was low or unclear for most domains in the majority of the included studies.Studies compared antimicrobial lock solutions (antibiotic and non-antibiotic) to standard sealing solutions (usually heparin) of the CVC for HD. Fifteen studies used antibiotic lock solutions, 21 used non-antibiotic antimicrobial lock solutions, and 4 used both (antibiotic and non-antibiotic) lock solutions. Studies reported the incidence of CRI, catheter thrombosis, or both.Antimicrobial lock solutions probably reduces CRI per 1000 catheter-days (27 studies: RR 0.38, 95% CI 0.27 to 0.53; I2 = 54%; low certainty evidence), however antimicrobial lock solutions probably makes little or no difference to the risk of thrombosis per 1000 catheter days (14 studies: RR 0.79, 95% CI 0.52 to 1.22; I2 = 83%; very low certainty evidence). Subgroup analysis of antibiotic and the combination of both lock solutions showed that both probably reduced CRI per 1000 catheter-days (13 studies: RR 0.30, 95% CI: 0.22 to 0.42; I2 = 47%) and risk of thrombosis per 1000 catheter-days (4 studies: RR 0.26, 95% CI: 0.14 to 0.49; I2 = 0%), respectively. Non-antibiotic antimicrobial lock solutions probably reduced CRI per 1000 catheter-days for tunnelled CVC (9 studies: RR 0.60, 95% CI 0.40 to 0.91) but probably made little or no difference with non-tunnelled CVC (4 studies: RR 0.93, 95% CI 0.48 to 1.81). Subgroup analyses showed that antibiotic (5 studies: RR 0.76, 95% CI 0.42 to 1.38), non-antibiotic (8 studies: RR 0.85, 95% CI 0.44 to 1.66), and the combination of both lock solutions (3 studies: RR 0.63, 95% CI 0.22 to 1.81) made little or no difference to thrombosis per 1000 catheter-days compared to control lock solutions. Antibiotic antimicrobial and combined (antibiotic-non antibiotic) lock solutions decreased the incidence of CRI compared to control lock solutions, whereas non-antibiotic lock solutions reduce CRI only for tunnelled CVC. The effect on thrombosis incidence is uncertain for all antimicrobial lock solutions. Our confidence in the evidence is low and very low; therefore, better-designed studies are needed to confirm the efficacy and safety of antimicrobial lock solutions.

Postmarketing experience with Neutrolin\xae (taurolidine, heparin, calcium citrate) catheter lock solution in hemodialysis patients

Catheter-related bloodstream infections (CRBSI) are major complications for patients with life-threatening conditions requiring chronic vascular catheterization. The wide range of etiologic microbes and the ongoing development of resistance to antimicrobials with specific mechanisms of action make this an appropriate target for applying a nonspecific antimicrobial therapeutic. Taurolidine hydrolyzes into two antimicrobial moieties, formaldehyde and methylene glycol, which react with microbial surfaces. Neutrolin® (taurolidine, heparin, calcium citrate) was recently introduced in Germany as an antimicrobial catheter lock solution. This postmarketing experience collected data on 201 patients at 20 centers from January 2014 through September 2016. Likely CRBSI was observed in 13 episodes in 47,118 days (0.2759 per 1000 days [0.1468, 0.4718]). Thrombosed catheter was observed in seven catheters in 47,118 days (0.1486 per 1000 days [0.0595, 0.3061]). No adverse drug reactions that led to the discontinuation of Neutrolin® use were reported. Two patients experienced occasional transient dysgeusia. Neutrolin®, when used in conjunction with guideline-based catheter care, showed reduction in the rate of both CRBSI and catheter thrombosis relative to recent historical controls.

Taurolidine-citrate-heparin lock reduces catheter-related bloodstream infections in intestinal failure patients dependent on home parenteral support: a randomized, placebo-controlled trial

Background: In patients with intestinal failure who are receiving home parenteral support (HPS), catheter-related bloodstream infections (CRBSIs) inflict health impairment and high costs.Objective: This study investigates the efficacy and safety of the antimicrobial catheter lock solution, taurolidine-citrate-heparin, compared with heparin 100 IE/mL on CRBSI occurrence.Design: Forty-one high-risk patients receiving HPS followed in a tertiary HPS unit were randomly assigned in a double-blinded, placebo-controlled trial. External, stratified randomization was performed according to age, sex, and prior CRBSI incidence. The prior CRBSI incidence in the study population was 2.4 episodes/1000 central venous catheter (CVC) days [95% Poisson confidence limits (CLs): 2.12, 2.71 episodes/1000 CVC days]. The maximum treatment period was 2 y or until occurrence of a CRBSI or right-censoring because of CVC removal. The exact permutation tests were used to calculate P values for the log-rank tests.Results: Twenty patients received the taurolidine-citrate-heparin lock and 21 received the heparin lock, with 9622 and 6956 treatment days, respectively. In the taurolidine-citrate-heparin arm, no CRBSIs occurred, whereas 7 CRBSIs occurred in the heparin arm, with an incidence of 1.0/1000 CVC days (95% Poisson CLs: 0.4, 2.07/1000 CVC days; P = 0.005). The CVC removal rates were 0.52/1000 CVC days (95% Poisson CLs: 0.17, 1.21/1000 CVC days) and 1.72/1000 CVC days (95% Poisson CLs: 0.89, 3.0/1000 CVC days) in the taurolidine-citrate-heparin and heparin arm, respectively, tending to prolong CVC survival in the taurolidine arm (P = 0.06). Costs per treatment year were lower in the taurolidine arm (€2348) than in the heparin arm (€6744) owing to fewer admission days related to treating CVC-related complications (P = 0.02).Conclusions: In patients with intestinal failure who are life dependent on HPS, the taurolidine-citrate-heparin catheter lock demonstrates a clinically substantial and cost-beneficial reduction of CRBSI occurrence in a high-risk population compared with heparin. This trial was registered at clinicaltrials.gov as NCT01948245.

Comparative Efficacies of Antimicrobial Catheter Lock Solutions for Fungal Biofilm Eradication in an in Vitro Model of Catheter-Related Fungemia.

Fungal catheter-related bloodstream infections (CRBSIs)—primarily due to Candida species—account for over 12% of all CRBSIs, and have been progressively increasing in prevalence. They present significant health and economic burdens, and high mortality rates. Antimicrobial catheter lock solutions are an important prophylactic option for preventing fungal CRBSIs. In this study, we compared the effectiveness of two FDA-approved catheter lock solutions (heparin and saline) and three experimental antimicrobial catheter lock solutions—30% citrate, taurolidine-citrate-heparin (TCH), and nitroglycerin-citrate-ethanol (NiCE)—in an in vitro model of catheters colonized by fungi. The fungi tested were five different strains of Candida clinical isolates from cancer patients who contracted CRBSIs. Time-to-biofilm-eradication was assessed in the model with 15, 30, and 60 min exposures to the lock solutions. Only the NiCE lock solution was able to fully eradicate all fungal biofilms within 60 min. Neither 30% citrate nor TCH was able to fully eradicate any of the Candida biofilms in this time frame. The NiCE lock solution was significantly superior to TCH in eradicating biofilms of five different Candida species (p = 0.002 for all).

Comparative efficacies of Antimicrobial Catheter Lock Solutions for Fungal Biofilm Eradication in an in vitro model of Catheter-Related Fungemia

Fungal catheter-related bloodstream infections (CRBSIs), primarily due to Candidaspecies, account for over 12% of all CRBSIs and have been progressively increasing in prevalence. They present significant health and economic burdens and high rates of mortality. Antimicrobial catheter lock solutions are an important prophylactic option for preventing fungal CRBSIs. In this study we compared the effectiveness of two FDA-approved catheter lock solutions (heparin and saline) and three experimental antimicrobial catheter lock solutions, 30% Citrate, Taurolidine-Citrate-Heparin (TCH), and Nitroglycerin-Citrate-Ethanol (NiCE). All solutions were tested in an in vitro model of yeast biofilm eradication. The yeast tested were five different strains of Candidaclinical isolates from cancer patients who contracted CRBSIs. Time-to-biofilm-eradication was assessed in the model with 15, 30 and 60 minute exposures to the lock solutions. Only the NiCE lock solution was able to fully eradicate all fungal biofilms within 60 minutes. Neither 30% citrate nor TCH was able to fully eradicate any of the Candida biofilms in this time frame. The NiCE lock solution was significantly superior to TCH in eradicating biofilms of five different Candidaspecies (P = 0.002 for all). NiCE lock showed significant efficacy compared with all solutions tested indicating NiCE has the potential to be used as an antifungal lock solution in high-risk settings where CRBSI caused by Candida is predominant. J. Rosenblatt, Infective Technologies, LLC: Co-Inventor of the Nitroglycerin-Citrate-Ethanol catheter lock solution technology which is owned by the University of Texas MD Anderson Cancer Center (UTMDACC) and has been licensed by Novel Anti-Infective Technologies, LLC in which Dr. Rosenblatt is a and Shareholder, Licensing agreement or royalty; UT MD Anderson Cancer Center: Co-Inventor of the Nitroglycerin-Citrate-Ethanol catheter lock solution technology which is owned by the University of Texas MD Anderson Cancer Center (UTMDACC) and has been licensed by Novel Anti-Infective Technologies, LLC in which Dr. Rosenblatt is a s and Scientific Advisor, Licensing agreement or royalty; I. Raad, Merck: Grant Investigator, Research grant; Allergan: Grant Investigator, Research grant; Infective Technologies, LLC: Co-Inventor of the Nitroglycerin-Citrate-Ethanol catheter lock solution technology which is owned by the University of Texas MD Anderson Cancer Center (UTMDACC) and has been licensed by Novel Anti-Infective Technologies, LLC in which Dr. Raad is a s and Shareholder, Licensing agreement or royalty

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.

Risk of Catheter-Related Bloodstream Infection in Elderly Patients on Hemodialysis

Elderly patients require tunneled central vein dialysis catheters more often than younger patients. Little is known about the risk of catheter-related bloodstream infection in this population. This study identified 464 patients on hemodialysis with tunneled central vein dialysis catheters between 2005 and 2007 and excluded patients who accrued <21 catheter-days during this period. Outpatient and inpatient catheter-related bloodstream infection data were collected. A Cox proportional hazards regression analysis adjusting for sex, ancestry, comorbidites, dialysis vintage, dialysis unit, immunosuppression, initial catheter site, and first antimicrobial catheter lock solution was performed for risk of catheter-related bloodstream infection between nonelderly (18-74 years) and elderly (≥ 75 years) patients. In total, 374 nonelderly and 90 elderly patients with mean (SD) ages of 54.8 (12.3) and 81.3 (4.9) years and dialysis vintages of 1.8 (3.3) and 1.5 (2.9) years (P=0.47), respectively, were identified. Mean at-risk catheter-days were 272 (243) in nonelderly and 318 (240) in elderly patients. Between age groups, there were no significant differences in initial catheter site, type of catheter lock solution, or microbiology results. A total of 208 catheter-related bloodstream infection events occurred (190 events in nonelderly and 18 events in elderly patients), with a catheter-related bloodstream infection incidence per 1000 catheter-days of 1.97 (4.6) in nonelderly and 0.55 (1.6) in elderly patients (P<0.001). Relative to nonelderly patients, the hazard ratio for catheter-related bloodstream infection in the elderly was 0.33 (95% confidence interval, 0.20 to 0.55; P<0.001) after multivariate analysis. Elderly patients on hemodialysis using tunneled central vein dialysis catheters are at lower risk of catheter-related bloodstream infection than their younger counterparts. For some elderly patients, tunneled central vein dialysis catheters may represent a suitable dialysis access option in the setting of nonmaturing arteriovenous fistulae or poorly functioning synthetic grafts.

Infection and Hemodialysis Access: An Updated Review.

The incidence of end-stage renal disease (ESRD) has almost doubled over past 2 decades. Despite decreasing overall hospital admission rates for ESRD population, the rate of infection-related hospitalizations has steadily increased. Infection remains the second most common cause of mortality in this patient population. Specifically, in the hemodialysis (HD) patients, the vascular access related infections are the most common identifiable source of infection. This concise review provides an update on the bacteremia related to vascular access primarily the catheters (Catheter Related Blood Stream Infection- CRBSI) in HD patients emphasizing on the determinants ranging from the epidemiology to pathogenesis, risk factors, cost implications and prevention. Staphylococcus aureus, coagulase negative Staphylococci, and Enterococci are the most common causative microorganisms implicated in CRBSI. The pathogenesis of CRBSI includes organism entry into the blood stream followed by adherence to catheter, colonization and biofilm formation. Vascular access type, catheter position, and prior bacteremic episodes are strongly associated with blood stream infection. Preventive measures should be multidisciplinary in nature and should include avoidance of central venous catheters, best practices for catheter care, surveillance, antimicrobial catheter lock solutions, and use of antibiotic impregnated catheters.

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

Antimicrobial 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-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Pseudomonas aeruginosa, and Candida albicans biofilms in an in vitro model 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.

Absence of microbial adaptation to taurolidine in patients on home parenteral nutrition who develop catheter related bloodstream infections and use taurolidine locks

Some home parenteral nutrition (HPN) patients develop catheter related bloodstream infections (CRBSI) despite using an anti-microbial catheter lock solution taurolidine. The aim of this study was to assess whether long-term use of taurolidine leads to selective growth of microorganisms with increased taurolidine minimum inhibitory concentrations (MICs). Bloodstream infections among 158 HPN patients with long-term taurolidine catheter locking were analyzed retrospectively. CRBSI-diagnosis was based on clinical symptoms, culture results, and absence of other sources of infections. CRBSIs were classified as definitive, probable or possible and exit site/tunnel/port or luminal infections. MICs were determined by broth microdilution. Between January 2009 and April 2011, 14 patients developed at least one luminal CRBSI episode during long-term taurolidine catheter locking (median (range) = 451 (78-1394) days). Coagulase-negative Staphylococcus species or Staphylococcus aureus predominated among CRBSI-causing Gram-positive bacteria. Taurolidine MICs were 512 mg/l or less in 50% of these isolates (MIC50). Taurolidine MIC50 for Klebsiella pneumoniae and Escherichia coli, the most common CRBSI-causing Gram-negative bacteria, were 256 and 512 mg/l, respectively. Taurolidine MIC50 among CRBSI-causing Candida albicans were 2048 mg/l. Adaptation of microorganisms to taurolidine has not yet emerged as a factor in the pathogenesis of CRBSI in HPN patients with long-term taurolidine catheter locking.

Chelator-Based Catheter Lock Solutions in Eradicating Organisms in Biofilm

Two different chelator-based antimicrobial catheter lock solutions, methylene blue-citrate-parabens (MB-CIT) and minocycline-EDTA-25% ethanol (M-EDTA-25% ETOH), were compared in 2-h biofilm eradication experiments. Eradication of both mature and immature Gram-positive, Gram-negative, and fungal biofilms was assessed. M-EDTA-25% ETOH was able to fully eradicate all biofilms within 2 h. MB-CIT was only effective against immature biofilms but was unable to fully eradicate most of the mature biofilms tested.

N-Acetylcysteine Lock Solution Prevents Catheter-Associated Bacteremia in Rabbits

Indwelling vascular catheters are the most common cause of nosocomial bloodstream infections. One approach to infection prevention is the use of antimicrobial catheter lock solutions, although their widespread use is limited due to concern regarding the emergence of antimicrobial resistance. The primary purpose of this study was to determine the efficacy of N-acetylcysteine (NAC) lock solution in preventing peripheral bacteremia using an in vivo model of catheter-associated infection. Twenty-four hours after inoculating a clinical isolate of Staphylococcus aureus into the lumen of tunneled external jugular catheters in rabbits, a catheter lock solution that contained NAC vs. heparinized saline alone was allowed to dwell for two consecutive periods of 72 hours. Surveillance peripheral and centrally collected blood cultures were obtained. Distal intravascular segments of the catheters were removed at day 7 and cultured using a sonication method. At 7 days after catheter insertion, none of the NAC-treated rabbits (0/8) developed peripheral bacteremia with S. aureus whereas 4/7 controls did (p=0.026). The bacterial yield from catheter tip cultures was not statistically different between the two arms. These promising data encourage further clinical evaluation of an NAC lock solution for prevention of catheter-associated bacteremia in patients.

Antimicrobial Catheter Locks

In this issue of JASN , Campos et al. report a well performed, prospective, randomized clinical trial demonstrating the benefit of an antimicrobial catheter lock solution (ACL) containing minocycline and EDTA (M-EDTA) in the prevention of hemodialysis catheter-related bacteremia.[1][1] It is unclear

Novel antimicrobial catheter lock solution: A new direction in which chelators replace heparin*

University of Texas M.D., Anderson Cancer Center, Houston, TX I.R. received grant support from Cook Medical and has royalties with American Medical Systems, Cook Medical, Greatlakes Pharmaceutical, and Telleflex. G.P.B. has not disclosed any potential conflicts of interest.

Catheter-related bloodstream infections: catheter management according to pathogen

Central-line access is an essential part of modern healthcare practice; however, catheter-related bloodstream infection is a major problem that causes substantial morbidity and mortality, and excess length of stay and cost. The risk of infection depends on the type of device, the site of insertion, the underlying conditions and the appropriate prevention measures taken during catheter insertion. Management of catheter-related bloodstream infection involves deciding on catheter removal, antimicrobial catheter lock solution and the type and duration of systemic antimicrobial therapy. Systemic antimicrobial use is essential but, although generally effective in controlling sepsis, it often fails to sterilise the line, increasing the incidence of complications or recurrence. The decision regarding whether the catheter should be removed or retained is therefore crucial. One of the major factors to be considered is the type of organism involved in the catheter-related infection. This review outlines the epidemiology, pathogenesis, diagnosis, microbiology and management of catheter-related infections, mainly focusing on the management of the intravascular device according to the pathogen.