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Antimicrobial activity of hemodialysis catheter lock solutions in relation to other compounds with antiseptic properties.

ABSTRACT: Proper protection of vascular access after haemodialysis is one of the key measures for the prevention of catheter-related infections. Various substances with bactericidal and anticoagulant properties are used to fill catheters, but due to the unsatisfactory clinical effects and occurrence of adverse reactions, the search for new substances is still ongoing. In the present paper, we compared the in vitro antimicrobial activity of solutions used for tunnelled catheter locking (taurolidine, trisodium citrate) and solutions of substances that could potentially be used for this purpose (sodium bicarbonate, polyhexanide-betaine). The studies have been conducted on bacteria that most commonly cause catheter-related infections. The values of both minimum inhibitory concentration and minimum biofilm eradication concentration of the substances were determined. The ability of the tested substances to eradicate biofilm from the dialysis catheter surface was also evaluated. The results showed that polyhexanide-betaine inhibited the growth of all microbes comparably to taurolidine, even after ≥ 32-fold dilution. The activity of trisodium citrate and sodium bicarbonate was significantly lower. Polyhexanide exhibited the highest activity in the eradication of bacterial biofilm on polystyrene plates. The biofilm formed on a polyurethane dialysis catheter was resistant to complete eradication by the test substances. Polyhexanide-betaine and taurolidine showed the highest activity. Inhibition of bacterial growth regardless of species was observed not only at the highest concentration of these compounds but also after dilution 32-128x (taurolidine) and 32-1024x (polyhexanide-betaine). Therefore, it can be assumed that taurolidine application as a locking solution prevents catheter colonization and systemic infection development. Taurolidine displays high antimicrobial efficacy against Gram-positive cocci as well as Gram-negative bacilli. On the contrary, the lowest antibacterial effect displayed product contained sodium bicarbonate. The inhibitions of bacterial growth were not satisfactory to consider it as a substance for colonization prevention. Polyhexanidine-betaine possessed potent inhibitory and biofilm eradication properties comparing to all tested products. PHMB is applied as a wound irrigation solution worldwide. However, based on our results, we assume that the PHMB is a promising substance for catheter locking solutions thanks to its safety and high antimicrobial properties.

SUBMITTER: Piatkowska E

PROVIDER: S-EPMC8496847 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThere is no ideal lock solution that prevents hemodialysis (HD) catheter loss due to catheter-related thrombosis (CRT) and catheter-related bloodstream infection (CRBSI). Catheter loss is associated with increased hospitalization and high inpatient costs. Sodium bicarbonate (NaHCO3) demonstrates anti-infective and anticoagulation properties with a good safety profile, making it an ideal lock solution development target.The objective of this study was to determine the safety and efficacy of using sodium bicarbonate catheter lock solution (SBCLS) as a means of preventing HD catheter loss due to CRT and CRBSI.MethodsThe study took place in a community hospital in Brooklyn, NY, USA. All admitted patients ≥18 years of age who needed HD treatment through CVC were included in the study. 451 patients included in the study were provided SBCLS or NSCLS post-dialysis. Catheter loss due to CRT or CRBSI was evaluated over a period of 546 days.ResultsA total of 452 patients met the criteria; 1 outlier was excluded, 226 were in the NSCLS group and 225 were in the SBCLS group. There were no significant differences between groups in comorbidities at the outset. The NSCLS group had CRT and CRBSI rates of 4.1 and 2.6/1000 catheter days (CD), respectively, compared with 0.17/1000 CD for both outcomes in the SBCLS group. SBCLS patients had a significantly reduced catheter loss rate due to CRT (P < 0.0001) and CRBSI (P = 0.0004). NSCLS patients had higher odds of losing their catheter due to CRT {odds ratio [OR] 26.6 [95% confidence interval (CI) 3.57-198.52]} and CRBSI [OR 15.9 (95% CI 2.09-121.61)] during the study period.ConclusionThe novel approach of using SBCLS was found to be safe and was statistically superior to normal saline in preventing HD catheter loss due to CRT and CRBSI. NaHCO3 solution is inexpensive, readily available in various settings and holds the potential to decrease hospitalization, length of stay and dialysis-related costs.Trial registrationMaimonides Medical Center Investigational Review Board, Study IRB 2015-06-25-CIH. ClinicalTrials.gov identifier: NCT03627884.

Project description:BackgroundCatheter-related bloodstream infections (CRBSIs) are a significant cause of morbidity and mortality in critically ill patients, contributing to prolonged hospital stays and increased costs. Whether taurolidine lock solutions (TLS) are beneficial for the prevention of CRBSIs remains controversial. In this meta-analysis, we aim to assess the efficacy of TLS for preventing CRBSIs.MethodsWe conducted a systematic search of PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Eligible studies included randomized controlled trials that reported on the effects of TLS for preventing CRBSIs. The primary outcome in these studies was catheter-related bloodstream infections, with microbial distribution of CRBSI and catheter-associated thrombosis as secondary outcomes. Data were combined using random-effects models owing to significant clinical heterogeneity.ResultsSix randomized controlled trials (RCTs) conducted from 2004 through 2013 involving 431 patients and 86,078 catheter-days were included in the review. TLS were significantly associated with a lower incidence of CRBSIs when compared to heparin lock solutions (Risk Ratio [RR], 0.34; 95% Confidence Interval [CI], 0.21-0.55). Use of TLS significantly decreased the incidence of CRBSIs from gram-negative (G-) bacteria (P = 0.004; RR, 0.27; CI, 0.11-0.65), and was associated with a non-significant decrease in gram-positive (G+) bacterial infections (P = 0.07; RR, 0.41; CI, 0.15-1.09). No significant association was observed with TLS and catheter-associated thrombosis (RR, 1.99; CI, 0.75-5.28).ConclusionsThe use of TLS reduced the incidence of CRBSIs without obvious adverse effects or bacterial resistance. However, the susceptibility of G+ and G- bacteria to taurolidine and the risk for catheter-associated thrombosis of TLS are indeterminate due to limited data. The results should be treated with caution due to the limited sample sizes and methodological deficiencies of included studies. Therefore, additional well-designed and adequately powered RCTs are needed to confirm these findings.

Project description:IntroductionCentral venous access devices (CVADs) are commonly used for the treatment of paediatric cancer patients. Catheter locking is a routine intervention that prevents CVAD-associated adverse events, such as infection, occlusion and thrombosis. While laboratory and clinical data are promising, tetra-EDTA (T-EDTA) has yet to be rigorously evaluated or introduced in cancer care as a catheter lock.Methods and analysisThis is a protocol for a two-arm, superiority type 1 hybrid effectiveness-implementation randomised controlled trial conducted at seven hospitals across Australia and New Zealand. Randomisation will be in a 3:2 ratio between the saline (heparinised saline and normal saline) and T-EDTA groups, with randomly varied blocks of size 10 or 20 and stratification by (1) healthcare facility; (2) CVAD type and (3) duration of dwell since insertion. Within the saline group, there will be a random allocation between normal and heparin saline. Participants can be re-recruited and randomised on insertion of a new CVAD. Primary outcome for effectiveness will be a composite of CVAD-associated bloodstream infections (CABSI), CVAD-associated thrombosis or CVAD occlusion during CVAD dwell or at removal. Secondary outcomes will include CABSI, CVAD-associated-thrombosis, CVAD failure, incidental asymptomatic CVAD-associated-thrombosis, other adverse events, health-related quality of life, healthcare costs and mortality. To achieve 90% power (alpha=0.05) for the primary outcome, data from 720 recruitments are required. A mixed-methods approach will be employed to explore implementation contexts from the perspective of clinicians and healthcare purchasers.Ethics and disseminationEthics approval has been provided by Children's Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC) (HREC/22/QCHQ/81744) and the University of Queensland HREC (2022/HE000196) with subsequent governance approval at all sites. Informed consent is required from the substitute decision-maker or legal guardian prior to participation. In addition, consent may also be obtained from mature minors, depending on the legislative requirements of the study site. The primary trial and substudies will be written by the investigators and published in peer-reviewed journals. The findings will also be disseminated through local health and clinical trial networks by investigators and presented at conferences.Trial registration numberACTRN12622000499785.

Project description:BACKGROUND:Non-tunneled hemodialysis catheters are currently used for critically ill patients with acute kidney injury requiring extracorporeal renal replacement therapy. Strategies to prevent catheter dysfunction and infection with catheter locks remain controversial. METHODS:In a multicenter, randomized, controlled, double-blind trial, we compared two strategies for catheter locking of non-tunneled hemodialysis catheters, namely trisodium citrate at 4% (intervention group) versus unfractionated heparin (control group), in patients aged 18 years or older admitted to the intensive care unit and in whom a first non-tunneled hemodialysis catheter was to be inserted by the jugular or femoral vein. The primary endpoint was length of event-free survival of the first non-tunneled hemodialysis catheter. Secondary endpoints were: rate of fibrinolysis, incidence of catheter dysfunction and incidence of catheter-related bloodstream infection (CRBSI), all per 1000 catheter-days; number of hemorrhagic events requiring transfusion, length of stay in intensive care and in hospital; 28-day mortality. RESULTS:Overall, 396 randomized patients completed the trial: 199 in the citrate group and 197 in the heparin group. There was no significant difference in baseline characteristics between groups. The duration of event-free survival of the first non-tunneled hemodialysis catheter was not significantly different between groups: 7 days (IQR 3-10) in the citrate group and 5 days (IQR 3-11) in the heparin group (p = 0.51). Rates of catheter thrombosis, CRBSI, and adverse events were not statistically different between groups. CONCLUSIONS:In critically ill patients, there was no significant difference in the duration of event-free survival of the first non-tunneled hemodialysis catheter between trisodium citrate 4% and heparin as a locking solution. Catheter thrombosis, catheter-related infection, and adverse events were not statistically different between the two groups. Trial registration Registered with Clinicaltrials.gov under the number NCT01962116. Registered 14 October 2013.

Project description:ESKAPE bacteria are a major cause of multidrug-resistant infections, and new drugs are urgently needed to combat these pathogens. Given the importance of iron in bacterial physiology and pathogenicity, iron uptake and metabolism have become attractive targets for the development of new antibacterial drugs. In this scenario, the FDA-approved iron mimetic metal Gallium [Ga(III)] has been successfully repurposed as an antimicrobial drug. Ga(III) disrupts ferric iron-dependent metabolic pathways, thereby inhibiting microbial growth. This work provides the first comparative assessment of the antibacterial activity of Ga(NO3)3 (GaN), Ga(III)-maltolate (GaM), and Ga(III)-protoporphyrin IX (GaPPIX), belonging to the first-, second- and third-generation of Ga(III) formulations, respectively, on ESKAPE species, including reference strains and multidrug-resistant (MDR) clinical isolates. In addition to the standard culture medium Mueller Hinton broth (MHB), iron-depleted MHB (DMHB) and RPMI-1640 supplemented with 10% human serum (HS) (RPMI-HS) were also included in Ga(III)-susceptibility tests, because of their different nutrient and iron contents. All ESKAPE species were resistant to all Ga(III) compounds in MHB and DMHB (MIC > 32 μM), except Staphylococcus aureus and Acinetobacter baumannii, which were susceptible to GaPPIX. Conversely, the antibacterial activity of GaN and GaM was very evident in RPMI-HS, in which the low iron content and the presence of HS better mimic the in vivo environment. In RPMI-HS about 50% of the strains were sensitive (MIC < 32) to GaN and GaM, both compounds showing a similar spectrum of activity, although GaM was more effective than GaN. In contrast, GaPPIX lost its antibacterial activity in RPMI-HS likely due to the presence of albumin, which binds GaPPIX and counteracts its inhibitory effect. We also demonstrated that the presence of multiple heme-uptake systems strongly influences GaPPIX susceptibility in A. baumannii. Interestingly, GaN and GaM showed only a bacteriostatic effect, whereas GaPPIX exerted a bactericidal activity on susceptible strains. Altogether, our findings raise hope for the future development of Ga(III)-based compounds in the treatment of infections caused by multidrug-resistant ESKAPE pathogens.

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Antimicrobial activity of hemodialysis catheter lock solutions in relation to other compounds with antiseptic properties.

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