Clinical Outcome of Patients with Escherichia coli Isolated from Catheter Lumens and/or Peripheral Blood Cultures: A Retrospective Analysis.

BACKGROUND: Escherichia coli commonly causes catheter-related bloodstream infection (C-RBSI) in specific populations. The differential time to positivity (DTTP) technique is the recommended conservative procedure for diagnosing C-RBSIs. METHODS: We conducted a retrospective study of episodes in which E. coli was isolated from catheter lumens obtained using the DTTP technique. Microbiological and clinical data were obtained based on the DTTP technique as either catheter colonization, C-RBSI, or non-C-RBSI. RESULTS: A total of 89 catheter blood cultures were included, classified as follows: catheter colonization, 33.7%; C-RBSI, 9.0%; and non-C-RBSI, 57.3%. Only 15.7% of the catheters were withdrawn, with no positive catheter-tip cultures. We found no statistically significant differences in catheter type, antibiotic treatment, or clinical outcome among the groups, except for the frequency of catheter lock therapy or in the frequency of successful treatment. Mortality was associated with C-RBSI in only one patient. CONCLUSION: E. coli bacteremia diagnosed by the DTTP technique was classified as non-catheter-related in most patients. As the majority of the catheters were retained, E. coli bacteremia could not be microbiologically confirmed as catheter-related by the catheter-tip culture. Future studies are needed to assess the profitability of the DTTP technique for diagnosing E. coli C-RBSIs.

Addressing catheter lock therapy: Does heparin reduce the bioactivity of dalbavancin when together in solution during freezing?

INTRODUCTION: The possible use of dalbavancin as a catheter lock solution was previously demonstrated by our study group. However, it was needed to assess whether heparin could affect dalbavancin bioactivity during freezing storage. METHODS: We tested the bioactivity of a dalbavancin+heparin (DH) vs. dalbavancin (D) against Staphylococcal biofilms comparing DH median value of cfu counts and metabolic activity with that obtained for D before and during storage under freezing up to 6 months. RESULTS: Despite there was a slight decrease in the median percentage reduction of metabolic activity at month 3 in Staphylococcus epidermidis between DH and D (97.6 vs. 100, p=0.037), considering the clinical criteria, no significant reduction in any of the variables tested was observed at the end of the experiment between D and DH solutions. CONCLUSION: The addition of heparin to a dalbavancin lock solution did not affect its bioactivity against staphylococcal biofilms irrespective of its preservation time under freezing.

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.

Combination of Systemic and Lock-Therapies with Micafungin Eradicate Catheter-Based Biofilms and Infections Caused by Candida albicans and Candida parapsilosis in Neutropenic Rabbit Models.

Vascular catheter-related infections, primarily caused by Candida albicans and Candida parapsilosis, pose significant challenges due to the formation of biofilms on catheters, leading to refractory disease and considerable morbidity. We studied the efficacy of micafungin in systemic and lock therapies to eliminate catheter-based biofilms and deep tissue infections in experimental central venous catheter (CVC)-related candidemia in neutropenic rabbits. Silastic CVCs in rabbits were inoculated with 1 × 103 CFU/mL of C. albicans or C. parapsilosis, establishing catheter-based biofilm, and subjected to various treatments. Neutropenic rabbits treated with a combination of lock therapy and systemic micafungin demonstrated the most significant reduction in fungal burden, from 5.0 × 104 to 1.8 × 102 CFU/mL of C. albicans and from 5.9 × 104 to 2.7 × 102 CFU/mL of C. parapsilosis (p ≤ 0.001), in the CVC after 24 h, with full clearance of blood cultures after 72 h from treatment initiation. The combination of lock and systemic micafungin therapy achieved eradication of C. albicans from all studied tissues (0.0 ± 0.0 log CFU/g) vs. untreated controls (liver 7.5 ± 0.22, spleen 8.3 ± 0.25, kidney 8.6 ± 0.07, cerebrum 6.3 ± 0.31, vena cava 6.6 ± 0.29, and CVC wash 2.3 ± 0.68 log CFU/g) (p ≤ 0.001). Rabbits treated with a combination of lock and systemic micafungin therapy demonstrated a ≥2 log reduction in C. parapsilosis in all treated tissues (p ≤ 0.05) except kidney. Serum (1→3)-ß-D-glucan levels demonstrated significant decreases in response to treatment. The study demonstrates that combining systemic and lock therapies with micafungin effectively eradicates catheter-based biofilms and infections caused by C. albicans or C. parapsilosis, particularly in persistently neutropenic conditions, offering promising implications for managing vascular catheter-related candidemia and providing clinical benefits in cases where catheter removal is not feasible.

Use of 2% taurolidine lock solution for treatment and prevention of catheter-related bloodstream infections in neonates: a feasibility study.

BACKGROUND: Taurolidine lock, a technique used to prevent or treat catheter-related bloodstream infection (CRBSI), is effective in adult and paediatric patients but has been described rarely in neonates. The aim of this descriptive retrospective study, was to determine the feasibility and direct outcomes of prophylactic and therapeutic taurolidine locks in term and preterm neonates. METHODS: We implemented the use of therapeutic taurolidine lock in addition to antibiotic treatment with the aim of catheter salvage in critical neonates with difficult vascular access (group 1). In addition, we introduced taurolidine lock as a preventive measure in neonates with a central venous catheter (CVC) at high risk of developing CRBSI (group 2). Every 24 h (in the treatment group) a 2% taurolidine solution was injected and the catheter locked for at least 120 min, until infection clearance (group 1). In the preventive group, the catheter was locked for 30 min every 48 h until CVC removal (group 2). FINDINGS: Thirty-seven neonates who received taurolidine were included in this study. We did not observe any major adverse events. In group 1 (21 cases), clinical symptom disappearance and bacteraemia clearance were achieved without catheter removal in 18 cases (85.7%); in the other three neonates the catheter was removed shortly after the start of the locks as it was possible to replace the CVC. In group 2 (16 neonates), no CRBSI was observed during the duration of the catheter placement. CONCLUSIONS: In this retrospective study, taurolidine was successfully used in neonates both for prevention and treatment of CRBSI, without major undesired effects. A larger cohort and a randomized clinical trial is warranted in order to establish its efficacy and safety in neonates.

First case of persistent Stenotrophomonas maltophilia bacteraemia due to septic thrombosis successfully treated with a cefiderocol-containing regimen.

INTRODUCTION: There is scarce evidence in literature of what should be the best antimicrobial treatment for bloodstream infections (BSIs) sustained by Stenotrophomonas maltophilia, a peculiar pathogen that intrinsically withstands to most of the available antibiotics. RESULTS AND CONCLUSION: Here, we describe a challenging case of a persistent S. maltophilia BSI due to septic thrombosis successfully treated with the addition of the novel siderophore cephalosporin cefiderocol to an only partially effective levofloxacin regimen. Additionally, an intra-lock therapy with trimethoprim/sulfamethoxazole was selected as a strategy to prevent recurrence of infection since complete source control was not possible. The serum bactericidal assay was also used to corroborate the in vivo efficacy of the adopted combination therapy.

Effectiveness of Antimicrobial Lock Therapy for the Treatment of Catheter-Related and Central-Line-Associated Bloodstream Infections in Children: A Single Center Retrospective Study.

Antimicrobial lock solutions (ALT) in combination with systemic antibiotics can represent a valid option to attempt central venous catheter (CVC) salvage in the case of catheter-related and central-line-associated bloodstream infections (CRBSI and CLABSI). However, data concerning the effectiveness and safety of ALT in children are limited. We aimed to share our center's experience in order to contribute to investigations into the causes of ALT failure in the pediatric population. All children consecutively admitted to Meyer Children's Hospital, University of Florence, Italy, from 1 April 2016 to 30 April 2022, who received salvage ALT to treat an episode of CRBSI/CLABSI, were reviewed. According to ALT failure or success, children were compared with the aim of identifying the risk factors for unsuccessful ALT outcome. Data from 28 children, 37 CLABSI/CRBSI episodes, were included. ALT was associated with clinical and microbiologic success in 67.6% (25/37) of children. No statistically significant differences were observed between the two groups, successes and failures, considering age, gender, reason for use, duration, insertion, type and presence of insertion site infection of the CVC, laboratory data and number of CRBSI episodes. Nevertheless, a trend towards a higher success rate was observed for a dwell time of 24 h for the entire duration of ALT (88%; 22/25 vs. 66.7%; 8/12; p = 0.1827), while the use of taurolidine and the infections sustained by MDR bacteria were associated with a tendency toward greater failure (25%; 3/12 vs. 4%; 1/25; p = 0.1394; 60%; 6/10 vs. 33.3%; 8/24; p = 0.2522). No adverse events, except one CVC occlusion, were observed. ALT combined with systemic antibiotics appears to be an effective and safe strategy for treating children with CLABSI/CRBSI episodes.

Treatment of long-term catheter-related bloodstream infections with short-course Daptomycin lock and systemic therapy associated with Taurolidine-lock: A multicenter experience.

PURPOSE: Few studies describe the efficacy of antibiotic lock therapy (ALT) in long-term catheter-related bloodstream (CRBSI) infections. We applied local protocols combining Daptomycin (DPT) and Taurolidine ALT, associated with systemic antibiotic treatment (SAT), for conservative management of coagulase-negative Staphylococci (CoNS) CRBSI. METHODS: Patients admitted for CoNS-associated CRBSI and treated with DPT and Taurolidine as ALT were retrospectively analyzed. Success was defined as catheter retention 30 days after ending treatment. Catheter removal within 30 days was considered as failure. RESULTS: From April 2018 to September 2021, 22 subjects with CoNS-associated-CRBSI were included (95% with cancer, mean age 64 years, 59% male). Staphylococcus epidermidis was isolated in 82% of cases. Mean duration of DPT was 3.9 and 3 days as ALT and SAT, respectively. SAT also included Rifampin for 3 days. Taurolidine ALT was started on day 4 and was combined with oral SAT, that is, either Linezolid or Tedizolid. Mean duration of Taurolidine was 10.5 days, while total antibiotic treatment lasted 13.5 days. Clinical success and failure rates were 95% and 5%, respectively. DISCUSSION: Short course DPT as ALT, combined with SAT and Taurolidine ALT, allowed high rates of conservative management of catheters in case of CoNS-associated-CRBSI.

Role of short-dwell daily ethanol-lock therapy in the management of hemodialysis tunneled cuffed catheter-related bloodstream infection.

BACKGROUND: Catheter-Related Blood Stream Infection (CRBSI) is the major limitation of using Tunneled cuffed catheter (TCC) for long-term Hemodialysis. The standard therapy of CRBSI involves systemic antibiotics with catheter replacement/removal. As antibiotic alone is rarely effective therapy for CRBSI, biofilm eradication using antimicrobial locking solutions is a promising modality for CRBSI treatment, hence catheter salvage. The present study evaluated the efficacy and safety of Ethanol-lock therapy (ELT) in combination with systemic antibiotics for the management of CRBSI associated with hemodialysis TCC. METHOD: 56 patients with CRBSI were treated with 70% ELT (1 h daily for 5 days) along with systemic antibiotics. Seventeen patients with CRBSI who didn't consent to ELT were treated with antibiotics alone. The effect of ELT was evaluated as clinical cure (fever resolution and negative surveillance cultures), infection-free TCC survival duration and adverse events of ELT among patients with CRBSI. The parameters were compared with 17 patients treated with antibiotics alone. RESULTS: ELT was successful in 50 out of 56 patients (89.28%); compared to 41.17% (seven out of 17) with antibiotics alone (p < 0.001). Mean TCC survival was also significantly higher with ELT combined with systemic antibiotics (126.23 ± 18.67 days) compared to antibiotics alone (38.76 ± 9.91) (p = 0.006). No systemic adverse effects were noted with ELT; two patients receiving ELT had catheter breakage during the study period. CONCLUSION: We conclude that short-dwell daily ELT with systemic antibiotics is an effective therapy for CRBSI in hemodialysis patients with TCC.

Lock terapia na prevenção e tratamento da infecção da corrente sanguínea associada ao cateter vascular: revisão integrativa / Terapia de bloqueo en la prevención y tratamiento de infecciones del torrente sanguíneo asociadas al catéter vascular: revisión integradora / Lock therapy in prevention and treatment of catheter-associated bloodstream infection: integrative review

Resumo Objetivo Sintetizar o conhecimento sobre o uso da lock terapia na prevenção e no tratamento da infecção da corrente sanguínea associada ao dispositivo de acesso vascular central de longa permanência em pacientes adultos e idosos hospitalizados. Métodos Revisão integrativa com busca nas bases de dados CINAHL, Cochrane Central, Embase, LILACS, PubMed, Scopus e Web of Science, no período de 1º janeiro de 2010 a 28 de setembro de 2021 sem restrições de idioma. Os dados foram analisados de forma descritiva. Resultados Foram identificados 16 estudos sendo seis (37,5%) sobre o uso da lock terapia como prevenção de infecção associada ao dispositivo de acesso vascular central e dez (62,5%) sobre tratamento. Os artigos sobre prevenção relataram o uso de soluções não antibióticas. Nove dos dez estudos que abordaram a lock terapia como tratamento, utilizaram soluções antibióticas. Dois estudos avaliaram a eficácia da lock terapia em curta duração (de três a quatro dias), sete em maior duração (entre 10 e 14 dias) e um não especificou a duração. Cada estudo descreveu uma técnica de intervenção e o tempo de permanência da solução intraluminal. Em relação ao risco de viés, foram avaliados como baixo risco: cinco ensaios clínicos randomizados, dois ensaios clínicos sem randomização e oito estudos observacionais. Apenas um estudo observacional foi classificado como risco moderado. Conclusão Na prevenção, identificou-se o uso de soluções não antibióticas como o etanol. Para o tratamento, foi utilizada a daptomicina endovenosa. Enquanto os estudos incluídos nessa revisão sobre prevenção não demonstraram evidência estatística, os dez estudos sobre tratamento demonstraram que a lock terapia é um complemento eficaz ao tratamento sistêmico, apresentando boas taxas de salvamento do cateter.

Resumen Objetivo Sintetizar el conocimiento sobre el uso de la terapia de bloqueo en la prevención y tratamiento de infecciones del torrente sanguíneo asociadas al dispositivo de acceso vascular central de larga permanencia en pacientes adultos y adultos mayores hospitalizados. Métodos Revisión integradora con búsqueda en las bases de datos CINAHL, Cochrane Central, Embase, LILACS, PubMed, Scopus y Web of Science, en el período del 1 de enero de 2010 al 28 de septiembre de 2021 sin restricción de idioma. Los datos fueron analizados de forma descriptiva. Resultados Se identificaron 16 estudios, de los cuales seis (37,5 %) trataban sobre el uso de la terapia de bloqueo como prevención de infecciones asociadas al dispositivo de acceso vascular central y diez (62,5 %) sobre tratamiento. En los artículos sobre prevención se relató el uso de soluciones no antibióticas. En nueve de los diez estudios que abordaban la terapia de bloqueo como tratamiento, se utilizaron soluciones antibióticas. En dos estudios se evaluó la eficacia de la terapia de bloqueo de corta duración (de tres a cuatro días), siete de mayor duración (entre 10 y 14 días) y uno sin especificar la duración. En cada estudio se describió una técnica de intervención y el tiempo de permanencia de la solución intraluminal. Con relación al riesgo de sesgo, fueron evaluados con riesgo bajo: cinco ensayos clínicos aleatorizados, dos ensayos clínicos no aleatorizados y ocho estudios observacionales. Solo un estudio observacional fue clasificado con riesgo moderado. Conclusión Para la prevención, se identificó el uso de soluciones no antibióticas como el etanol. Para el tratamiento, se utilizó la daptomicina intravenosa. Aunque los estudios incluidos en esta revisión sobre prevención no hayan demostrado evidencia estadística, los diez estudios sobre tratamiento demostraron que la terapia de bloqueo es un complemento eficaz para el tratamiento sistémico y presentó buenos índices de salvamento del catéter.

Abstract Objective To synthesize knowledge on the use of lock therapy for prevention and treatment of long-term central vascular access devices-associated bloodstream infection in hospitalized adult and elderly patients. Methods Integrative review conducted in CINAHL, Cochrane Central, Embase, LILACS, PubMed, Scopus, and Web of Science databases, from January 1st, 2010 to September 28th, 2021, without language restrictions. Data were analyzed descriptively. Results Sixteen studies were identified, six (37.5%) on the use of lock therapy for prevention of bloodstream infection associated with central vascular access devices, and ten (62.5%) on treatment. The articles on prevention reported the use of non-antibiotic solutions. Nine of the ten studies that addressed lock therapy as treatment used antibiotic solutions. Two studies assessed the effectiveness of lock therapy in a short duration (three to four days), seven in a longer duration (between 10 and 14 days), and one did not specify the length of time. Each study described an intervention technique and the length of stay of the intraluminal solution. Regarding the risk of bias, five randomized clinical trials, two non-randomized clinical trials, and eight observational studies were rated as low risk. Only one observational study was classified as moderate risk. Conclusion The use of non-antibiotic solutions such as ethanol was identified for prevention of bloodstream infection. For treatment, intravenous daptomycin was used. While the studies included in this review on prevention did not show statistical evidence, the ten studies on treatment demonstrated that lock therapy is an effective complement to systemic treatment, showing good catheter salvage rates.

Multidisciplinary management of disseminated Exophiala dermatitidis mycosis in an infant with mixed phenotype acute leukemia: a case report.

BACKGROUND: Exophiala dermatitidis is a dematiaceous fungus isolated from various environmental sources. Systemic E. dermatitidis infections can lead to fatal outcomes, and treatment has not yet been standardized. Although E. dermatitidis is also known to cause cutaneous infection, it has not been previously reported to appear as ecthyma gangrenosum (EG), an uncommon cutaneous lesion in neutropenic patients that is mainly caused by Pseudomonas aeruginosa. CASE PRESENTATION: A 2-month-old male infant with mixed-phenotype acute leukemia presented with prolonged fever unresponsive to antibacterial and antifungal agents during myelosuppression due to remission induction therapy. He also presented with skin lesions on the left wrist and left lower quadrant of the abdomen. The abdominal lesion gradually turned black and necrotic, which was consistent with the findings of the EG. E. dermatitidis was isolated from the blood, stool, wrist skin, and endotracheal aspirate. During hematopoietic recovery, consolidation in both lungs was evident. Multiagent antifungal treatment failed to eliminate E. dermatitidis from blood. In order to salvage the central venous catheter, ethanol lock therapy (ELT) was adopted, following which the blood culture became negative. The abdominal lesion that evolved as a necrotic mass connecting the small intestine and subcutaneous tissue adjacent to the skin was surgically resected. After these interventions, the general condition improved. CONCLUSION: Disseminated E. dermatitidis mycosis in the neutropenic infant was successfully managed with a multidisciplinary treatment consisting of multiagent antifungal treatment, ELT, and surgery.

Use of Meropenem and Other Antimicrobial Lock Therapy in the Treatment of Catheter-Related Blood Stream Infections in Neonates: A Retrospective Study.

(1) Background: Newborns admitted to Neonatal Intensive Care Units (NICUs) often require the placement of central vascular catheters (CVC), which are a major risk factor for hospital infection. Numerous strategies exist to prevent central line-associated blood stream infections (CLABSIs) and catheter-related bloodstream infections (CRBSIs), with only a few offering options to save the catheter when it is impossible to replace. CRBSIs continue to be a major problem for neonates in NICUs. Most CRBSIs are resistant to systemic antibiotics due to the presence of intraluminal bacterial biofilm. Therefore, catheter removal is frequently necessary when a CRBSI occurs. The so-called Antibiotic Lock Therapy (ALT) is an antimicrobial therapeutic strategy which seems to be promising in neonates when catheter removal is difficult due to critical conditions. To date, evidence about the use of ALT in the neonatal period is still fragmentary, since only poor and heterogeneous data exist. (2) Methods: We report our successful experience with ALT in seriously ill neonates with CRBSI for whom the replacement of the catheter could have been life threatening. (3) Results: ALT repetitively performed for at least 12 h was effective in 11 out of 13 infants (84.6%). It was not effective in two infants in whom ALT was performed for only 6 h. Moreover, we present new data about the stability testing of meropenem for its use during ALT in neonates. (4) Conclusions: When CRBSI occurs-bearing in mind that the optimal management is catheter removal if antibiotic therapy is not effective within 48 h-ALT seems to be a valid alternative therapy when removal is impractical due to critical conditions.

Catheter salvage strategies in children with central venous catheter-related or -associated bloodstream infections: a systematic review and meta-analysis.

BACKGROUND: Optimal management of central venous catheter-related, or -associated, bloodstream infections (CRBSI or CLABSI) in children is not established. AIM: To evaluate success of catheter salvage strategies in paediatric patients. METHODS: Studies were retrieved from medical databases and article reference lists. Data were collected relating to clinical outcomes of two treatments: systemic antibiotics alone or in association with antimicrobial lock therapy (ALT). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from a mixed logistic effects model. Heterogeneity was summarized using I2 statistics. Publication bias was investigated by Egger's regression test and funnel plots. FINDINGS: From 345 identified publications, 19 met inclusion criteria (total of 914 attempted salvage strategies). To achieve successful catheter salvage, in CRBSI the addition of ALT was superior to systemic antibiotics alone (OR: -0.40; 95% CI: -1.41, 0.62): 77% (95% CI: 69, 85; I2 = 42.5%; P = 0.12) and 68% of success (95% CI: 59, 77; I2 = 0; P < 0.05), respectively. CRBSI recurrence was less common in studies that used ALT compared with systemic antibiotics alone: 5% (95% CI: 0, 13; I2 = 59.7%; P = 0.03) and 18% of recurrence (95% CI: 9, 28; I2 = 0; P < 0.05), respectively. Recurrences were low with both antibiotic locks and ethanol lock. No clear benefits of ALT addition compared to systemic antibiotic only were found in CLABSI (OR: -0.81; 95% CI: -0.80, 2.43). CONCLUSION: The addition of an antimicrobial lock solution to systemic antibiotic may be beneficial for successful catheter salvage in paediatric patients with CRBSI, depending on aetiology, whereas no statistically significant difference between systemic antibiotic with or without addition of an antimicrobial lock solution was found regarding CLABSI.

"Locking in" a rare pathogen.

Since its identification as a unique species in 1982, Escherichia hermannii has only recently been implicated as a pathogenic organism in human diseases. Literature search indicates removal of hemodialysis catheter as being essential to the success of treatment for bacteremia with this organism. However, having no alternative access for hemodialysis led to the attempt to salvage the catheter with the use of Antibiotic lock therapy. This case highlights Antibiotic lock therapy as an indication in Escherichia hermanii Catheter related Bloodstream infection.

A Dalbavancin Lock Solution Can Reduce Enterococcal Biofilms After Freezing.

INTRODUCTION: We previously demonstrated the efficacy of a frozen dalbavancin-heparin (DH) lock solution against biofilms of staphylococci. However, as enterococci also commonly cause catheter-related bloodstream infections (C-RBSI), we assessed the bioactivity of frozen dalbavancin (D) and DH against enterococci. METHODS: Over 6 months, we compared the bioactivity of a solution of DH (1 mg/ml) with that of D in terms of cfu counts and metabolic activity against biofilms of Enterococcus faecalis and Enterococcus faecium (four strains each). For each solution, we individually compared results obtained at each time point (months 3 and 6) with baseline (month 0). We also compared the median DH value of each variable at baseline and at months 3 and 6 of freezing with the values obtained for D alone. We used both statistical and clinical criteria when results were within 25% of the reference value. RESULTS: At the end of the experiment (month 6), neither a statistically nor a clinically significant reduction in the bioactivity of D solution was observed in terms of cfu count and metabolic activity against enterococcal biofilms. Regarding the DH solution, we found both statistical and clinical significance in the median percentage reduction in metabolic activity between months 0 and 6 in E. faecalis strains (51.8% vs. 77.8%, P = 0.007). Moreover, after freezing, the DH solution lost significant bioactivity compared with the D solution, especially in E. faecalis. CONCLUSION: A dalbavancin lock solution can be frozen for up to 6 months with no negative effect on its bioactivity against enterococcal biofilms. However, when combined with heparin, its efficacy was reduced. Therefore, we recommend that if lock therapy with frozen dalbavancin is used in the management of enterococcal C-RBSI, heparin should be added simultaneously at the time of catheter lock.

Antifungal lock therapy: an eternal promise or an effective alternative therapeutic approach?

Each year, millions of central venous catheter insertions are performed in intensive care units worldwide. The usage of these indwelling devices is associated with a high risk of bacterial and fungal colonization, leading to the development of microbial consortia, namely biofilms. These sessile structures provide fungal cells with resistance to the majority of antifungals, environmental stress and host immune responses. Based on different guidelines, colonized/infected catheters should be removed and changed immediately in the case of Candida-related central line infections. However, catheter replacement is not feasible for all patient populations. An alternative therapeutic approach may be antifungal lock therapy, which has received high interest, especially in the last decade. This review summarizes the published Candida-related in vitro, in vivo data and case studies in terms of antifungal lock therapy. The number of clinical studies remains limited and further studies are needed for safe implementation of the antifungal lock therapy into clinical practice.

Anticipated impact of recent ethanol lock shortage and price increase on practice among pediatric intestinal rehabilitation programs across the United States.

BACKGROUND: Ethanol lock use has been associated with significantly lower rates of central line-associated bloodstream infection (CLABSI) in children with intestinal failure. Concerns have been raised among intestinal rehabilitation program providers regarding the impact of recent changes in cost and availability of ethanol locks in the US. METHODS: We conducted a survey among the members of the North American Society For Pediatric Gastroenterology, Hepatology & Nutrition Intestinal Rehabilitation Special Interest Group (NASPGHAN IR-SIG) regarding practice changes among providers to tackle this issue and the anticipated effect on CLABSI rates. RESULTS: The results show that the vast majority of US participants use ethanol locks in their population with intestinal failure, with most anticipating or already experiencing reduction in access to ethanol locks. Most worrisome is that more than half of participating programs expect an increase in CLABSI rates in this vulnerable patient population as a consequence of limited access to ethanol locks. CONCLUSION: Further multicenter prospective studies to assess the efficacy of alternative locking agents, besides ethanol, are needed in order to have readily available and affordable options for CLABSI prevention in the future.

S-Nitroso-N-acetyl-l-cysteine Ethyl Ester (SNACET) Catheter Lock Solution to Reduce Catheter-Associated Infections.

Antimicrobial-lock therapy is an economically viable strategy to prevent/reduce the catheter-related bloodstream infections (CRBSI) that are associated with central venous catheters (CVCs). Herein, we report the synthesis and characterization of the S-nitroso-N-acetyl-l-cysteine ethyl ester (SNACET), a nitric oxide (NO)-releasing molecule, and for the first time its application as a catheter lock solution to combat issues of bacterial infection associated with indwelling catheters. Nitric oxide is an endogenous gasotransmitter that exhibits a wide range of biological properties, including broad-spectrum antimicrobial activity. The storage stability of the SNACET and the NO release behavior of the prepared lock solution were analyzed. SNACET lock solutions with varying concentrations exhibited tuneable NO release at physiological levels for >18 h, as measured using chemiluminescence. The SNACET lock solutions were examined for their efficacy in reducing microbial adhesion after 18 h of exposure toStaphylococcus aureus (Gram-positive bacteria) andEscherichia coli (Gram-negative bacteria). SNACET lock solutions with 50 and 75 mM concentrations were found to reduce >99% (ca. 3-log) of the adhered S. aureus and E. coli adhesion to the catheter surface after 18 h. The SNACET lock solutions were evaluated in a more challenging in vitro model to evaluate the efficacy against an established microbial infection on catheter surfaces using the same bacteria strains. A >90% reduction in viable bacteria on the catheter surfaces was observed after instilling the 75 mM SNACET lock solution within the lumen of the infected catheter for only 2 h. These findings propound that SNACET lock solution is a promising biocidal agent and demonstrate the initiation of a new platform technology for NO-releasing lock solution therapy for the inhibition and treatment of catheter-related infections.

Aspirin as an Antifungal-Lock Agent in Inhibition of Candidal Biofilm Formation in Surgical Catheters.

BACKGROUND: The antibiotic lock technique (ALT) has been recommended for the prevention and treatment of catheter-related candidaemia. Biofilms of Candida species are resistant to some of the antifungal agents currently used. Aspirin has been shown to have anti-fungal effect but its effect on candidal biofilm is poorly understood. PURPOSE: The aim of the current study was to evaluate the anti-biofilm effect of aspirin on Candida biofilms including C. albicans, C. glabrata, C. krusei and C. tropicalis formed on surgical catheters and the concentration and time required to eradicate the biofilms. METHODS: Biofilms of Candida species were grown on silicone catheters and incubated in aspirin at different concentrations for 2, 4 and 24 hours. The biofilms remaining were then determined quantitatively by colony-forming unit (CFU) counts and XTT assays. RESULTS: The results demonstrated that among the tested Candida species, C. albicans was the most sensitive species towards aspirin. Aspirin at a concentration of 40 mg/mL in 4 hours was effective in eradicating the biofilm. For all the other tested species, they were eradicated by aspirin at a concentration of 40 mg/mL in 24 hours. CONCLUSION: Our results showed that aspirin may be used as an anti-fungal agent in lock therapy in the treatment of catheter-related candidaemia.

Investigating the risk factors for antibiotic lock therapy failure in pediatric cancer: a single center retrospective analysis.

BACKGROUND: Catheter-related bloodstream infection (CRBSI) is one of the most common complications of central lines. Data concerning the effectiveness and safety of antibiotic lock therapy (ALT), especially in pediatric hematology and oncology patients, have not yet reached sufficient levels of evidence. We aimed to share our center`s experience on ALT in pediatric cancer and to investigate the causes of ALT failure. METHODS: All cases with CRBSI and treated with ALT administiration in children with cancer between January 2015 and May 2019 were reviewed. Patients characteristics, laboratory and clinical findings, treatments, outcome of ALT, recurrences and reinfections were recorded. Patients with successful and unsuccessful ALT outcomes were compared in order to identify the risk factors for ALT failure. RESULTS: Sixteen eligible CRBSI treated with adjunctive ALT were identified. The most common pathogens were coagulase negative staphylococci (8/16, 50%). Treatment failure was observed in 31.2% (5/16). Younger age alone was an independent risk factor for treatment failure (0.9 vs 6.8 years, p = 0.038). Recurrence and reinfection rates were 23.1% and 16.7%. Mild bleeding occured in two cases (12.5%) and occlusion causing catheter removal was seen in one (6.3%). CONCLUSIONS: ALT was found to be a safe modality with a success rate of 68.8% in children with cancer at our center and younger age was an independent risk factor for treatment failure. Future studies with larger sample sizes are needed to determine the factors affecting the ALT outcome, especially in childhood malignancies.