Antibiotic Lock Solutions Research Articles

Antibiotic lock solutions as adjunct therapy for catheter-related blood stream infections in pediatric hemodialysis patients.

The predominant use of intravenous catheters as primary access type in the pediatric hemodialysis population is associated with an increased risk of catheter related blood stream infections. While strict adherence to catheter placement and long-term care guidelines have helped to decrease the incidence of these infections, blood stream infections remain an infection burden in pediatric patients with long term hemodialysis catheters. The formation of biofilms on the surfaces of these catheters has been shown to be a source of microbes causing blood stream infections. One of the strategies for preventing bacterial colonization, inhibiting microbial multiplication, and suppressing the seeding of these microbes from biofilms upon maturation, has been the use of antibiotic-based lock solutions in-between dialysis treatments. Although clinical guidelines for the use of antibiotic lock solutions are yet to be developed, available evidence suggests a beneficial role of antibiotic lock solutions in the management of catheter related blood stream infections. Additionally, a clear understanding of how biofilms are formed and their role in the pathogenesis of catheter related bloodstream infection will facilitate the development of solutions that can prevent biofilm formation and inhibit their multiplication, maturation and seeding into the bloodstream.

P011 Antifungal lock therapy

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Objective Candida spp is the fourth leading cause of catheter-related blood stream infection (CRBSI). The standard treatment is prompt removal of the device (central venous catheter, CVC, or port or hemodialysis catheter) along with administration of systemic antifungal therapy. However, in patients with a lack of alternative intravenous access and in some critically ill patients, this standard of care is challenging. Our success with antibiotic lock solution in MDR GNB CRBSI, prompted us to consider similar therapy in Candida spp CRBSI.MethodsCatheter salvage using antifungal lock therapy was tried in a total of 15 cases in two centers. In 10 cases echinocandin (9 anidulafungin, 1 micafungin) and in 5 cases amphotericin b deoxycholate (AmB-d) were used to obtain an antifungal concentration of ∼ 1000 mcg/ml in the lock solutions. All these formulations had additional NAC, heparin, and normal saline. Systemic antifungal therapy was also administered concurrently.Success was defined as clearance of candidemia at 48 h and 14 days and/or till the use of the device was needed. Some of these patients had prior/co-infections with bacterial pathogens and they were managed with appropriate systemic antibiotics with antibiotic lock therapy.ResultsIn 11/15 episodes of CRBSI due to Candida species, catheter salvage was achieved. One case could not be assessed at 14 days as a port was removed in view of megaprosthesis in situ. In two cases this therapy failed and one patient lost to follow-up.See Figures 1 and 2 for details of all cases.ConclusionsAntifungal lock therapy using echinocandins and AmB-d appears to be a promising therapy in patients where catheter removal is difficult. However, this success neither means that this can become standard practice, nor should it make clinicians and hospital staff complacent about infection control practices.

Interventions for treating catheter-related bloodstream infections in people receiving maintenance haemodialysis.

Patients with kidney failure require vascular access to receive maintenance haemodialysis (HD), which can be achieved by an arteriovenous fistula or a central venous catheter (CVC). CVC use is related to frequent complications such as venous stenosis and infection. Venous stenosis occurs mainly due to trauma caused by the entrance of the catheter into the venous lumen and repeated contact with the vein wall. A biofilm, a colony of irreversible adherent and self-sufficient micro-organisms embedded in a self-produced matrix of exopolysaccharides, is associated with the development of infections in patients with indwelling catheters.Despite its clinical relevance, the treatment of catheter-related bloodstream infections (CRBSIs) in patients receiving maintenance HD remains controversial, especially regarding catheter management. Antibiotic lock solutions may sterilise the catheter, treat the infection and prevent unnecessary catheter procedures. However, such treatment may also lead to antibiotic resistance or even clinical worsening in certain more virulent pathogens. Catheter removal and delayed replacement may remove the source of infection, improving infectious outcomes, but this approach may also increase vascular access stenosis, thrombosis or both, or even central vein access failure. Catheter guidewire exchange attempts to remove the source of infection while maintaining access to the same vein and, therefore, may improve clinical outcomes and preserve central veins for future access. To assess the benefits and harms of different interventions for CRBSI treatment in patients receiving maintenance HD through a permanent CVC, such as systemic antibiotics alone or systemic antibiotics combined with either lock solutions or catheter guidewire exchange or catheter replacement. We searched the Cochrane Kidney and Transplant Register of Studies up to 21 December 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register were 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 controlled trials (RCTs) and quasi-RCTs evaluating the management of CRBSI in permanent CVCs in people receiving maintenance HD. Two authors independently selected studies for inclusion, assessed their risk of bias, and performed data extraction. Results were expressed as risk ratios (RR) or hazard ratios (HR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, with their 95% confidence intervals (CI). The certainty of the evidence was assessed using GRADE. We identified two RCTs and one quasi-RCT that enrolled 760 participants addressing the treatment of CRBSIs in people (children and adults) receiving maintenance HD through CVC. No two studies compared the same interventions. The quasi-RCT compared two different lock solutions (tissue plasminogen activator (TPA) and heparin) with concurrent systemic antibiotics. One RCT compared systemic antibiotics alone and in association with an ethanol lock solution, and the other compared systemic antibiotics with different catheter management strategies (guidewire exchange versus removal and replacement). The overall certainty of the evidence was downgraded due to the small number of participants, high risk of bias in many domains, especially randomisation, allocation, and other sources of bias, and missing outcome data. It is uncertain whether an ethanol lock solution used with concurrent systemic antibiotics improved CRBSI eradication compared to systemic antibiotics alone (RR 1.61, 95% CI 1.16 to 2.23) because the certainty of this evidence is very low. There were no reported differences between the effects of TPA and heparin lock solutions on cure rates (RR 0.92, 95% CI 0.74 to 1.15) or between catheter guidewire exchange versus catheter removal with delayed replacement, expressed as catheter infection-free survival (HR 0.88, 95% CI 0.43 to 1.79). To date, no results are available comparing other interventions. Outcomes such as venous stenosis and/or thrombosis, antibiotic resistance, death, and adverse events were not reported. Currently, there is no available high certainty evidence to support one treatment over another for CRBSIs. The benefit of using ethanol lock treatment in combination with systemic antibiotics compared to systemic antibiotics alone for CRBSIs in patients receiving maintenance HD remains uncertain due to the very low certainty of the evidence. Hence, further RCTs to identify the benefits and harms of CRBSI treatment options are needed. Future studies should unify CRBSI and cure definitions and improve methodological design.

Nitric Oxide-Releasing Lock Solution for the Prevention of Catheter-Related Infection and Thrombosis.

Although frequently used, venous catheters are often associated with serious complications such as infection and thrombosis. Lock solution therapies are clinically used to deter these issues but generally address only infection or thrombosis with limited success. Here, we report the development of a dual-functional lock therapy using nitric oxide (NO) donor molecule, S-nitrosoglutathione (GSNO). NO is a potent, broad-spectrum antimicrobial agent that also temporarily inhibits platelet activation, preventing thrombosis. Furthermore, NO has antibiofilm actions, an ability that traditional antibiotic lock solutions lack, thus limiting their efficacy. In this work, different concentrations of GSNO were characterized via NO analysis to determine a range of NO-releasing lock solution (NOreLS) concentrations to investigate and to demonstrate prolonged potential efficacy. Tested against clinically used vancomycin and gentamicin lock solutions, GSNO-based NOreLS repeatedly outperformed in models of different stages of catheter infections. NOreLS also prevented clot formation when exposed to whole blood, showing increased efficacy compared to a heparin lock solution. Moreover, NOreLS was demonstrated to be biocompatible via hemolysis and cytotoxicity assays. NOreLS has excellent potential for safely and effectively preventing infection and thrombosis related to catheter usage.

Hemodialysis Catheter-Related Infections: Incidence in Temporary Catheters locked with Vancomycin and Heparin vs. Heparin-only

Background: The increasing incidence of end stage renal disease (ESRD) patients initiating hemodialysis (HD) through a temporary HD catheter has caused the rise in catheter related infections and associated morbidity and mortality. An antibiotic lock solution (ALS) for the prevention of catheter-related bacteraemia is a promising strategy. The present randomized control study has evaluated the efficacy and safety of vancomycin as an ALS in 54 patients who required temporary double lumen catheters for HD.
 Methods: The patients were randomized to receive either (A) an ALS (vancomycin 5 mg/ml + heparin 5000 IU/ml) – group A; or (B) unfractionated heparin (5000 IU/ml) alone as a catheter lock control – group B. The study duration was of three months and was conducted at the Department of Nephrology, PIMS, Islamabad.
 Results: The primary endpoint of the study was catheter related blood stream infection (CRBSI). The vancomycin group (A) had one episode of infection (CRBSI rate = 1.23/1000 days) compared with six episodes in the heparin-locked control group (B) (CRBSI rate = 8.55/1000 days). Mean catheter survival was significantly (p<0.05) more in group A (30.48 ± 5.7days) compared to group B (26 ± 6.5 days). No thrombotic episodes or side effects were recorded.
 Conclusion: Vancomycin appeared to be a safe and effective ALS, preventing CRBSI and increasing survival of catheter in HD patients.

POS-626 IMPROVING CATHETER SURVIVAL IN CRBSI WITH ALCOHOL CATHETER LOCK SOLUTION

Despite the advocation of fistula first strategy, over 80 % of the incident dialysis patients initiate dialysis with tunnelled dialysis catheters (TDC) and 30 % remain catheter dependent. catheter related blood stream infection (CRBSI) is a dreaded complication of tunnelled dialysis catheters with reported incidence rate of 1.1 to 5.5 per 1000 catheter days. Conventionally the management of CRBSI includes IV antibiotics along with antibiotic catheter lock solution. Despite this 30-50 % of catheters require removal, especially in the setting of staphylococcal, pseudomonas, and fungal infection. Literature does mention benefit of alcohol catheter locks solution but there is no published data on its use. This study aimed to compare efficacy and safety of 70% alcohol lock solution (ACL) vs antibiotic lock solution in CRBSI management. All patients on dialysis with TDC as vascular access were followed for CRBSI. CRBSI was diagnosed if in appropriate clinical setting patient had two cultures (from venous hub and dialysis circuit or peripheral vein) positive for same organism and with no other obvious focus of infection.During CRBSI patients received appropriate antibiotics and either antibiotic lock instilled after each dialysis session or 70% alcohol lock which was instilled for 3 consecutive days. If patient became asymptomatic after 3 days, catheter was kept and if patient remained symptomatic even after 3 days of therapy or had hemodynamic compromise, catheter was removed. 225 catheters were followed for a duration of 24010 days. 34 patients developed CRBSI. Twenty two patients (Group A) received antibiotics and antibiotic lock and 12 patients (Group B) received antibiotics and ACL instead of antibiotic lock. Demographic and clinical profile of the group A & B is given in table 1. Group A had 11 males and 11 females with mean age of 61.36 ± 8.54 years. Group B had 5 males and 7 females with mean age of 58 ± 16.94 years. Of the 22 patients of CRBSI in group A,15 required catheter removal and of the 12 patients in group B, none required catheter removal (P= 0.0095 ). After a mean follow up of 84.16 ± 44.62 days, none of the patients in group B developed relapse of infection or any catheter dysfunction. Based on our pilot study, we found 70% alcohol lock solution to be far superior than antibiotic lock solution with no effect on catheter performance and life in short term follow-up. We recommend alcohol lock solution during management of CRBSI episodes.

Systematic Review and Meta-Analysis of Antibiotic and Antimicrobial Lock Solutions for Prevention of Hemodialysis Catheter-Related Infections.

Catheter-related bloodstream infection (CRBSI) with hemodialysis catheters are associated with increased mortality, morbidity and pose significant financial burden on healthcare. Antibiotic and antimicrobial locking solutions are effective in reducing risk of CRBSI. From inception to April 2020, we looked for relevant clinical controlled trials throughout the following databases: EBSCO, PubMed, Cochrane CENTRAL, MEDLINE, EMBASE, clinicaltrial.gov, and Google Scholar performing a metanalysis comparing antibiotic and antimicrobial lock solutions to heparin. Twenty-six studies with 4,967 patients reported the incidence of catheter-related bacteremia (CRB). The overall pooled risk ratio (RR) showed that the intervention group was associated with a significantly lower incidence of CRB by 30% compared with heparin (RR = 0.30, 95% confidence interval [CI] [0.25, 0.36], p < 0.001). Subgroup analysis showed that administration of antibiotic regimens led to a decreased risk of CRB episodes by 28% compared with the heparin group (RR = 0.28, 95% CI [0.21, 0.37], p < 0.0001). Antimicrobial solutions was associated with reduced risk of CRB by 32% compared with patients of the control group (RR = 0.32, 95% CI [0.25, 0.41], p < 0.0001). A test of subgroup differences was revealed no significant favoring of any of the two interventions. Both antibiotic and antimicrobial solutions are effective in reducing CRBSI.

Frequency and Microbiological Profile of Catheter-Related Infections in Hemodialysis Patients Receiving Gentamicin as Antimicrobial Lock Therapy for Prophylaxis

Antibiotic lock solution (ALS) in the lumen of catheter is a mean to decrease the possibility of catheter related blood stream infection (CRBSI). We conducted this study using Gentamicin as ALS to observe the frequency of catheter related infections (CRI) including CRBSI and exit site infection in this hemodialysis patients being dialyzed through tunneled and temporary hemodialysis catheters.&#x0D; Methods This descriptive, cross sectional study was conducted at Dr. Ziauddin Hospital, North Campus between January 2017- December 2017. Symptomatic patients for CRBSI were included in this study. Blood culture from the catheter ports and periphery and exit site swab if pus visible were sent for culture sensitivity. &#x0D; Results Total 138 patients of either gender with age more than 18 years to less than 80 years were evaluated. 44.9% were male and mean age of patients was 58.79±14.05 years. 70.3% patients were diabetic for 15.61±4.61 years and 11.6% were using immunosuppressive drugs. The overall mean catheter duration was 22.27±14.39 days and mean hemodialysis duration was 25.32±44.31 weeks. Tunneled catheter was placed in 40.6% and 46.4% had femoral temporary catheters. Blood culture was done for 51 cases and 21.5% were positive. Tip culture was positive in 33.3% patients. In our study, 23.18% patients were found to have catheter related infections, out of which 61.5% were found with gentamicin resistance including colonization.&#x0D; Conclusion We report a high frequency of catheter related infections despite using ALS as prophylaxis, with predominant organisms being gram positives and a high incidence of gentamycin resistance.

Meta-Analysis of Antibiotic and Non-Antibiotic Lock Solutions for Prevention of Hemodialysis Catheter-Related Infections

Meta-Analysis of Antibiotic and Non-Antibiotic Lock Solutions for Prevention of Hemodialysis Catheter-Related Infections

SAT-228 COMPARING ANTIBIOTIC LOCK THERAPY WITH SYSTEMIC ANTIBIOTICS TO PREVENT CENTRAL LINE ASSOCIATED BLOOD STREAM INFECTION (CLABSI)

Bangladesh is experiencing an overwhelming burden of central line–associated bloodstream infection (CLABSI) in haemodialysis (HD) patients. Most HD centres in Bangladesh are using systemic antibiotics to prevent CLABSI. However, Centers for Disease Control and Prevention (CDC) guideline does not recommend use of systemic antibiotic rather suggests use of antibiotic lock therapy in high risk situations. In this study we compared the efficacy of antibiotic lock therapy with systemic antibiotic to prevent CLABSI. This retrospective study was conducted in a tertiary hospital in Bangladesh. A total of 100 HD patients with a temporary catheter were included and divided in two groups. Group A (61 patients) received systemic antibiotic (Ceftazidime 1gm IV) and group B (39 patients) received antibiotic lock therapy after each HD. Antibiotic lock solution was prepared with vancomycin 5 mg/ml and heparin 2500 units/ml. All patients were advised to follow infection prevention measures as per CDC guidelines such as hand washing, frequent dressing, mupirocin ointments on nostrils. The incidence and source of infection in both groups were documented. The efficacy of antibiotic lock therapy in comparison to systemic antibiotic was measured. Basic demographics of patients are shown in table 1. Out of 100 patients 12 patients (12%) [group A=5(8.2%), group B=7(17.9%)] developed persistent fever after catheter insertion. In group A only 1 patient (1.6%) was suspected to develop CLABSI as no other source was found and fever only subsided after removal of catheter. The source of infection in other patients was chest (01), skin (01), UTI (01) and one patient was self discharged before source identification. In group B, 1 patient (2.6%) was suspected to develop CLABSI along with pneumonia and UTI as CXR showed consolidation and urine grew E. coli. Patient received intravenous antibiotics but only became afebrile after line removal. The source of infection in other patients was chest (03), gastroenteritis (01) and two patients discharged prior to source determination. Although the incidence of infection was significantly lower in IV Ceftazidime group compared to antibiotic lock group (8.2% vs 17.9%, p<0.05), there is no significant difference in the incidence of CLABSI between these groups (1.6% vs 2.6%, p=0.525). Interestingly, our study revealed that only 2 patients (2%) were suspected to develop CLABSI in our centre which is significantly lower than data from other centres in Bangladesh (Afroz et al., 2015). The enforcement of infection prevention measures might have contributed to this. Our study suggests that vancomycin lock is non-inferior to IV Ceftazidime in preventing CLABSI. Hence, IV Ceftazidime is not required for the prevention of CLABSI, rather it can be reserved for the treatment of systemic infections. Antibiotic lock therapy along with infection control measures is useful for the prevention of CLABSI and its use will prevent a large number of patients from unnecessary exposure to systemic antibiotics, hence reduce the development of antibiotic resistance and the economic impact of using long term prophylactic systemic antibiotics.

Cefazolin–gentamicin versus taurolidine–citrate for the prevention of infection in tunneled central catheters in hemodialysis patients: A quasi-experimental trial

BackgroundCatheter-related bloodstream infection (CR-BSI) is one of various complications related to hemodialysis (HD). As a result of the high rate of infection, the use of lock solutions for the prevention of CR-BSI has been studied. However, adverse effects of lock solution, such as increased emergence of strains resistant to antibiotics, which is an important concern, need to be investigated further. The aim of this study was to compare the efficacy of lock solution using a combination of cefazolin and gentamicin versus taurolidine and citrate in reducing CR-BSI in patients undergoing HD and to identify any adverse effects. MethodsA prospective observational study was performed at two dialysis centers. Patients using new tunneled central venous catheters (CVC) for HD were included. Patients with a tunneled CVC were assigned to receive either antibiotic lock solution (group 1: gentamicin 7mg/ml+cefazolin 12mg/ml+heparin 3500IU/ml) or lock solution with TauroLock-Hep500 (group 2: taurolidine citrate 4%+heparin 500 IU/ml) during the inter-dialysis period. The patients were allocated to these groups according to the hemodialysis center they were attending. ResultsA total of 145 CVCs were implanted in 127 patients and were followed for 15 months: 77 CVCs (65 patients) were placed in group 1 and 68 CVCs (62 patients) in group 2. There was no difference between the two groups with regard to CR-BSI (events per 1000 catheter-days: group 1=0.79, group 2=1.10; p=0.18) or exit site infection rates (events per 1000 catheter-days: group 1=2.45, group 2=1.83; p=0.37). The groups differed in ESI pathogens, with gram-positive oxacillin-resistant pathogens more frequent in group 1 (31.8% vs. 5.0%; p=0.003). The two groups were similar in mechanical complications. In the Cox regression analysis, the internal jugular vein site was a protective factor for all catheter removal complications (hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.19–0.91) and mechanical complications (HR 0.16, 95% CI 0.065–0.41); only ESI was a risk factor for all catheter removal complications (HR 1.79, 95% CI 1.04–3.07) and mechanical complications (HR 5.64, 95% CI 1.65–19.3). ConclusionsThe efficacy of both lock solutions was similar in preventing infections related to tunneled CVCs for HD. However, there were more oxacillin-resistant strains in patients who received antibiotic lock solution. Further studies are required to determine the optimal drug regimen and concentrations for lock solution and the associated adverse effects.

Prevention of hemodialysis catheter infections: Ointments, dressings, locks, and catheter hub devices

Tunneled central venous catheters used for the provision of hemodialysis are associated with excess morbidity and mortality. Catheter related exit site and blood stream infections are major risks of their use. Although catheter-avoidance is the best strategy to reduce infections and mortality in the hemodialysis population, the use of catheters remains unacceptably high. In this review, the existing clinical practice guidelines for the prevention of hemodialysis catheter associated infections are outlined, and a comprehensive evidenced-based summary of interventions is provided. This includes details about the use of topical antimicrobial ointments and dressings, intranasal ointment application, prophylactic use of antibiotic and non-antibiotic catheter lock solutions, and catheter hub devices for the prevention of catheter blood stream infections.

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.

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.

Investigation of the effects of various antibiotics against Klebsiella pneumoniae biofilms on in vitro catheter model

Klebsiella pneumoniae continues to be an important cause of community-acquired and nosocomial infection. This bacterium can cause catheter related infections by forming biofilm on the surface of catheter. The aim of our study is to determine the in vitro stability and efficacy of colistin, ciprofloxacin, tobramycin, doripenem and tigecycline alone, or in combination with clarithromycin or esomeprazole, as 24-h lock solutions against biofilm-embedded K. pneumoniae strains. The efficacy of antibiotic lock solutions was tested in an in vitro catheter biofilm model against K. pneumoniae. In our study, we observed that the use of doripenem and tobramycin as a lock solution had potent bactericidal effects. When colistin was used in combination with clarithromycin or esomeprazole, the combinations had a synergistic effect. No antagonistic effect was observed. The findings of our study have important information for effectiveness of tested antibiotic lock solution in the catheter-related infections with K. pneumoniae.

The incidence and costs of bacteremia due to lack of gentamicin lock solutions for dialysis catheters.

The use of antibiotic lock solutions as prophylaxis for catheter-associated blood stream infection (CRBSI) has been shown to be effective in previous randomized controlled trials. However, the cost-effectiveness of this approach had not been studied. In 2012, the routine gentamicin-heparin lock solution used in Auckland City Hospital was withdrawn from the market, leading to a change to heparin-only lock. This was then replaced with gentamicin-citrate lock in 2014. This situation allowed review of the CRBSI rate and financial impact of different catheter lock solutions. A retrospective audit was performed from 1 January 2011 to 31 December 2015 to investigate the rate of culture-proven CRBSI in patients with tunneled cuffed dialysis catheters. There were 89 cases of CRBSI involving 64 patients in the 5-year period. In comparison with the heparin-only lock, both gentamicin-heparin and gentamicin-citrate locks had a significantly lower rate of bacteremia, with rate ratios of 0.46 (confidence interval 0.30-0.72) and 0.11 (confidence interval 0.05-0.22), respectively. The inpatient costs as a consequence of the CRBSI were NZ$27792 per 1000 catheter days for heparin-only lock, NZ$10608.56 per 1000 catheter days for gentamicin-heparin lock, and NZ$ 1898.45 per 1000 catheter days for gentamicin-citrate lock. The lack of antibiotic lock solutions led to an increase in bacteremia rates and higher financial cost for inpatient management of bacteremia. Our findings highlight the importance of consistent supply of pharmaceuticals.

We Avoid Antibiotic Lock Solutions due to Fear of Antibiotic Resistance.

Hemodialysis catheter-related bacteremia (CRB) is the most common complication associated with catheter use in dialysis patients and portends a high morbidity and mortality. Current CDC and KDIGO guidelines recommend treating CRBs with systemic antibiotics in conjunction with catheter replacement, although the latter has limitations. Antibiotic lock solutions (ABLs) are very effective in both prevention and treatment of CRBs in hemodialysis patients and may be a preferred alternative to catheter replacement especially in patients where catheter salvage is a priority. Previous smaller observational studies have raised concerns of a potential increase in antibiotic resistance associated with the widespread use of ABLs. Review of the recent literature does not support this claim.

Comparison of telavancin and vancomycin lock solutions in eradication of biofilm-producing staphylococci and enterococci from central venous catheters

Results of a study of the activity of antibiotic lock solutions of vancomycin and telavancin against biofilm-forming strains of Staphylococcus epidermidis, Enterococcus faecalis, and Staphylococcus aureus are reported. An established in vitro central venous catheter model was used to evaluate lock solutions containing vancomycin (5 mg/mL) or telavancin (5 mg/mL), with and without preservative-containing heparin sodium (with 0.45% benzyl alcohol) 2500 units/mL, heparin, and 0.9% sodium chloride solution. Lock solutions were introduced after 24-hour bacterial growth in catheters incubated at 35 °C. After 72 hours of exposure to the lock solutions, catheters were drained, flushed, and cut into segments for quantification of colony-forming units. Against S. epidermidis, vancomycin and telavancin (with or without heparin) had similar activity. Against E. faecalis, vancomycin alone was more active than telavancin alone (p < 0.01). Against S. aureus, vancomycin plus heparin had activity similar to that of vancomycin alone; both lock agents had greater activity than telavancin (p < 0.02). The addition of heparin was associated with reduced activity of the vancomycin lock solution against S. epidermidis and E. faecalis (p < 0.01). Telavancin activity was not significantly changed with the addition of heparin. In a central venous catheter model, vancomycin and telavancin activity was similar in reducing biofilm-producing S. epidermidis. However, vancomycin was more active than telavancin against E. faecalis and S. aureus. None of the tested agents eradicated biofilm-forming strains. The addition of preservative-containing heparin sodium 2500 units/mL to vancomycin was associated with reduced activity against S. epidermidis and E. faecalis.

Comparative in vitro efficacies of various antipseudomonal antibiotics based catheter lock solutions on eradication of Pseudomonas aeruginosa biofilms

Antibiotic lock technique (ALT) may be an adjunct therapy in treating catheter-related infections. The aim of this study was to determine the in vitro stability and efficacy of colistin, meropenem and levofloxacin alone or in combination with clarithromycin or heparin lock solutions against biofilm embedded Pseudomonas aeruginosa strains. The efficacy of antibiotic lock solutions was tested in an in vitro catheter biofilm model against P. aeruginosa isolated from catheter-related bacteremia. We observed that the use of meropenem, levofloxacin or colistin as a lock solution had potent bactericidal effects and could be prevented bacterial regrowth at 96 or 72 hours, respectively. When the tested antibiotics were used in combination with clarithromycin, the combinations were significantly more effective and rapid in eliminating P. aeruginosa colonization in biofilm than each of the antibiotics were used alone. Moreover, tested antibiotics in combination with heparin were not significantly different for killing effect against PA-1 and PA-27853 compared with that of each antibiotics alone. Tested catheter lock solutions may have promising adjuvants for treating infections caused by P. aeruginosa.

Antibiotic lock for the prevention of catheter-related infection in neonates.

Use of a central venous catheter (CVC) in neonates is associated with an increase in nosocomial infection. Numerous strategies exist to prevent catheter-related bloodstream infection (CRBSI); however, CRBSI continues to be a major problem. Antibiotic locking catheters is a new and promising treatment that potentially prevents this severe condition. To assess the effectiveness of antibiotic lock versus no antibiotic lock or alternative antibiotic lock in the prevention of catheter-related infections in newborn infants of any gestational age during their initial stay in the neonatal unit and to study any relevant adverse effects from antibiotic lock therapy. Methods followed those of the Cochrane Neonatal Review Group (CNRG).We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2014, Issue 5); MEDLINE (via PubMed); EMBASE (hosted by EBCHOST); CINAHL; abstracts from Pediatric Academic Societies, European Society for Paediatric Research and trials registries; and references cited in our short listed articles using keywords and MeSH headings, up to April 2015. We considered all trials utilising random or quasi-random participant allocation. Participants included all newborn infants of any postmenstrual age who required any type of CVC. We compared an antibiotic lock technique with no antibiotic lock or placebo, such as heparinised saline, for any duration of time. We extracted data using the standard methods of the CNRG. Two review authors independently assessed the relevance and risk of bias of the retrieved records. We expressed our dichotomous results using risk ratio (RR) with their 95% confidence intervals (CIs). We assessed for heterogeneity using the I(2) statistic. We included three trials (271 infants) in this review. Two of the three included studies had an overall low risk of bias and the remaining study had high risk of selection and performance biases. The use of an antibiotic lock decreased the incidence of confirmed catheter-related infection (typical RR 0.15, 95% CI 0.06 to 0.40; 3 studies, 271 infants) (high-quality evidence). The typical absolute risk reduction (ARR) was 18.5% and the number needed to treat for an additional beneficial outcome (NNTB) was 5. The effect of use of an antibiotic lock on suspected catheter infection was imprecise (typical RR 0.65, 95% CI 0.22 to 1.92) (moderate quality evidence). Confirmed and suspect infection rates combined were lower in the antibiotic lock group (absolute rates, RR 0.25, 95% CI 0.12 to 0.49; rate per 1000 catheter days, RR 0.17, 95% CI 0.07 to 0.40). The ARR was 20.5% and the NNTB was 5. None of the studies report resistance to the antibiotic used during the lock treatment. There was no significant difference in the detectable serum levels of antibiotic. When the data from two studies were pooled, there were significantly fewer episodes of hypoglycaemia in the treatment arm (typical RR 0.51, 95% CI 0.28 to 0.92). There was no statistically significant difference for mortality due to sepsis between the control and intervention group. Based on a small number of trials and neonates, antibiotic lock solution appeared to be effective in preventing CRBSI in the neonatal population. However, as each included study used a different antibiotics and antibiotic resistance could not be reliably assessed, the evidence to-date is insufficient to determine the effects of antibiotic lock on infections in neonates.