Microbiological analysis of tunneled hemodialysis catheters isolated from patients receiving hemodialysis in Saskatchewan.

Aim: To compare the microbial communities inside hemodialysis catheters from symptomatic and asymptomatic patients to determine their differences.Materials & methods: Catheters (n = 41) were removed from patients in the Saskatchewan Health Authority over an 18-month period. The catheter section inside the body was flushed and the contents were evaluated using culture-dependent and culture-independent analysis.Results: All catheters were colonized by bacteria, with considerable overlap between groups based on microbial communities and the individual species detected. More Gram-negative species were detected by sequencing, whereas predominantly Gram-positive strains were cultured. Antibiotic resistance and biofilm formation was widespread and not correlated with either catheter group.Conclusion: Common pathogens were detected in each set of catheters, therefore predicting infections based on the microbiology is difficult.

Many patients use catheters to help clean their blood, a process called hemodialysis. The use of catheters is also associated with complications, such as blood infections. We looked at the types of bacteria associated with catheters from patients who had infections (n = 21) and compared them to catheters from patients who had no signs of infection (n = 20). Once removed from the patient, we flushed out each catheter and tried to grow bacteria in different conditions. We also looked at DNA from within the catheter to identify bacterial species that were present. All 41 catheters had bacteria and there were many common species detected. We detected species known to cause illness such as Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Pseudomonas, Enterobacter, Morganella and Stenotrophomonas species. S. aureus was only grown from patients that had infections. Resistance to antibiotics was found to be common in bacteria grown from catheters. This did not seem to be influenced by whether patients were infected or not. Finally, we identified several catheters where two species, S. epidermidis and P. aeruginosa, were detected together. Our main conclusion was that bacteria are commonly present inside catheters that are used for hemodialysis, regardless of whether patients are infected or not.

The bacterial displacement test: an in vitro microbiological test for the evaluation of intermittent catheters and urinary tract infection.

AIMS: Intermittent catheters (ICs) are commonly used in bladder management, but catheter-associated urinary tract infections (CAUTIs) remain challenging. Insertion tips may reduce the risk of CAUTIs by minimizing bacterial transfer along the urinary tract. However, there are few laboratory tests to evaluate such technologies. We describe the use of an adapted in vitro urethra agar model to assess bacterial displacement by ICs. METHODS AND RESULTS: Simulated urethra agar channels (UACs) were prepared with catheter-specific sized channels in selective media specific to the challenge organisms. UACs were inoculated with Escherichia coli and Enterococcus faecalis before insertion of ICs, and enumeration of UAC sections was performed following insertion. Four ICs were evaluated: Cure Catheter® Closed System (CCS), VaPro Plus Pocket™, Bard® Touchless® Plus, and SpeediCath® Flex Set. CCS demonstrated significantly reduced bacterial displacement along the UACs compared to the other ICs and was also the only IC with undetectable levels of bacteria toward the end of the UAC (representing the proximal urethra). CONCLUSION: The bacterial displacement test demonstrated significant differences in bacterial transfer between the test ICs with insertion tips, which may reflect their different designs. This method is useful for evaluating CAUTI prevention technology and may help guide future technology innovations.

An in-vitro model for bacteria-related catheter encrustations.

PURPOSE: About 50% of individuals with long-term indwelling catheters are affected by catheter encrustations and bladder stone formation. Therefore, prophylaxis of catheter encrustations is important. Currently, however, neither an established prophylaxis nor a standardized in-vitro model to test different measures exist. We have therefore developed and qualitatively evaluated an in-vitro model of catheter encrustation. METHODS: Size 14 French suprapubic catheters were incubated under sterile conditions at 37 degrees Celsius in five different media: (1) sterile artificial urine (n = 16), (2) artificial urine with E. coli (n = 8), (3) with Pseudomonas aeruginosa (n = 8), (4) with Proteus mirabilis (n = 8), and (5) with a mix of these three strains (n = 8). Catheter balloons were inflated either a glycerine or a bactericidal solution. After 6 weeks, the catheters were removed from the solution, dried, and weighed, and a photometric determination of the retrieved encrustations was performed. RESULTS: Most frequently and pronounced encrustations were detected in the Pseudomonas group. The median weight of these encrustations (50% struvite and brushite) was 84.4 mg (47.7 mg / 127.3 mg). Even on catheters stored in sterile urine, encrustations (69.2% struvite) were found. Bacterial growth was not affected by the medium used for catheter blockage. CONCLUSION: Although in-vitro models appear to be limited because they lack "the human factor", they are valuable for systematically assessing physico-chemical factors affecting encrustations. Therefore, our model, being reliable and cost-effective, may foster further research despite its limitations.

Infective endocarditis secondary to a hemodialysis catheter revealed by subarachnoid hemorrhage: Case report.

INTRODUCTION: Endocarditis associated with medical care is a rare and serious entity. The risk of occurrence is increased in hemodialysis patients due to the immunosuppression and the multiplicity of vascular accesses of different kinds. The mode of revelation can be variable given the diversity of symptoms it causes. Herein, we describe the case of endocarditis associated with medical care in a patient with renal failure who presents with neurological symptoms. OBSERVATION: A 38-year-old patient with a history of kidney disease in the hemodialysis stage presented to the emergency room with altered neurological status in the context of fever. The patient's condition requires airway control, sedation, and vasopressor medication. Brain imaging revealed Fisher 4 subarachnoid hemorrhage with brain turgor. Transthoracic and transesophageal cardiac ultrasound exploration revealed infective mitro-aortic endocarditis with trigonal abscess fistulized in the left ventricle and destruction of the aortic valve with massive regurgitation. The additional imaging in a second step did not highlight any images of mycotic aneurysm. The indication for early surgery was not approved given the hemodynamic instability and the poor intracerebral hemodynamics demonstrated by transcranial doppler ultrasound. The initial outcome under antibiotic treatment and renal replacement was favorable. But the subsequent course was fatal due to septic shock with multiple organ failure. CONCLUSION: The diagnosis of infective endocarditis should always be considered in hemodialysis patients presenting in a septic state with signs of systemic involvement. It is a source of mortality in these debilitated patients.

Bacteriemia asociada a catéteres venosos centrales no tunelizados en niños en hemodiálisis crónica / Bacteremia associated with non-tunneled central venous catheters in children undergoing chronic hemodialysis

Introducción. La infección asociada a catéter venoso central (CVC) es la principal complicación que presentan los pacientes en hemodiálisis en los que se usa este tipo de acceso. Objetivo. Estimar la incidencia de bacteriemia asociada a CVC no tunelizado, analizar la frecuencia de agentes causales y explorar factores de riesgo asociados en niños en hemodiálisis. Población y métodos. Estudio retrospectivo realizado en niños en hemodiálisis por CVC no tunelizado entre el 1 junio de 2015 y el 30 de junio de 2019. Para evaluar factores de riesgo predictores de bacteriemia asociada a CVC, se realizó regresión logística. Los factores de riesgo independiente se expresaron con odds ratio con sus respectivos intervalos de confianza del 95 %. Se consideró estadísticamente significativo un valor de p <0,05. Resultados. En este estudio se incluyeron 121 CVC no tunelizados. La incidencia de bacteriemia fue de 3,15 por 1000 días de catéter. El microorganismo aislado con mayor frecuencia fue Staphylococcus epidermidis (16 casos, 51,5 %). La infección previa del catéter fue el único factor de riesgo independiente encontrado para el desarrollo de bacteriemia asociada a CVC no tunelizado (OR: 2,84; IC95%: 1,017,96; p = 0,04). Conclusiones. El uso prolongado de los CVC no tunelizados para hemodiálisis crónica se asoció con una incidencia baja de bacteriemia. Los gérmenes grampositivos predominaron como agentes causales. La presencia de infección previa del CVC aumentó en casi 3 veces el riesgo de bacteriemia asociada a CVC en nuestra población pediátrica en hemodiálisis.

Introduction. Central venous catheter (CVC)-related infection is the main complication observed in patients undergoing hemodialysis with this type of venous access. Objective. To estimate the incidence of non-tunneled CVC-related bacteremia, analyze the frequency ofcausative agents, and explore associated risk factors in children undergoing hemodialysis. Population and methods. Retrospective study in children receiving hemodialysis via a non-tunneled CVC between June 1 st, 2015 and June 30 th, 2019. A logistic regression was carried out to assess risk factors that were predictors of CVC-related bacteremia. Independent risk factors were described as odds ratios with their corresponding 95% confidence interval (CI). A value of p < 0.05 was considered statistically significant. Results. A total of 121 non-tunneled CVCs were included in this study. The incidence of bacteremia was 3.15 per 1000 catheter-days. The most commonly isolated microorganism was Staphylococcus epidermidis(16 cases, 51.5%). Prior catheter infection was the only independent risk factor for the development of bacteremia associated with non-tunneled CVC (OR: 2.84, 95% CI: 1.01­7.96, p = 0.04). Conclusions. Prolonged use of non-tunneled CVCs for chronic hemodialysis was associated with a low incidence of bacteremia. Gram-positive microorganisms prevailed among causative agents. A prior CVC infection almost trebled the risk for CVC-related bacteremia in our pediatric population receiving hemodialysis.

Bundle care approach to reduce device associated infections in post-living-donor-liver transplantation in a tertiary care hospital, Egypt.

BACKGROUND: Device-associated infections (DAIs) are a significant cause of morbidity following living donor liver transplantation (LDLT). We aimed to assess the impact of bundled care on reducing rates of device-associated infections. METHODS: We performed a before-and-after comparative study at a liver transplantation facility over a three-year period, spanning from January 2016 to December 2018. The study included a total of 57 patients who underwent LDLT. We investigated the implementation of a care bundle, which consists of multiple evidence-based procedures that are consistently performed as a unified unit. We divided our study into three phases and implemented a bundled care approach in the second phase. Rates of pneumonia related to ventilators [VAP], bloodstream infections associated with central line [CLABSI], and urinary tract infections associated with catheters [CAUTI] were assessed throughout the study period. Bacterial identification and antibiotic susceptibility testing were performed using the automated Vitek-2 system. The comparison between different phases was assessed using the chi-square test or the Fisher exact test for qualitative values and the Kruskal-Wallis H test for quantitative values with non-normal distribution. RESULTS: In the baseline phase, the VAP rates were 73.5, the CAUTI rates were 47.2, and the CLABSI rates were 7.4 per one thousand device days (PDD). During the bundle care phase, the rates decreased to 33.3, 18.18, and 4.78. In the follow-up phase, the rates further decreased to 35.7%, 16.8%, and 2.7% PDD. The prevalence of Klebsiella pneumonia (37.5%) and Methicillin resistance Staph aureus (37.5%) in VAP were noted. The primary causative agent of CAUTI was Candida albicans, accounting for 33.3% of cases, whereas Coagulase-negative Staph was the predominant organism responsible for CLABSI, with a prevalence of 40%. CONCLUSION: This study demonstrates the effectiveness of utilizing the care bundle approach to reduce DAI in LDLT, especially in low socioeconomic countries with limited resources. By implementing a comprehensive set of evidence-based interventions, healthcare systems can effectively reduce the burden of DAI, enhance infection prevention strategies and improve patient outcomes in resource-constrained settings.

Peritoneal dialysis-related peritonitis caused by Stephanoascus ciferrii: A Case Report.

Stephanoascus ciferrii, a conditional pathogenic fungus prevalent in nature, is more frequently encountered in patients with compromised immunity. However, the literature rarely reports infections caused by Stephanoascus ciferrii in peritoneal dialysis patients. Here, we detail the case of a 66-year-old female suffering from renal failure who experienced catheter-related infection during peritoneal dialysis. Dialysate turbidity prompted the detection of Stephanoascus ciferrii in both peritoneal dialysate and tubes through microbiological cultures. Subsequent treatment involved antifungal drugs and a transition to hemodialysis, resulting in the disappearance of peritonitis symptoms and the patient's discharge. In recent years, fungal infections, particularly dialysis-related infections, are on the rise. This marks the first reported case of catheter-related peritonitis infection caused by Stephanoascus ciferrii. Compared to bacterial infections, fungal infections pose challenges due to limited drug options, significant side effects, and prolonged treatment durations. Hence, prompt pathogen diagnosis and drug sensitivity testing are crucial for effective clinical treatment. In essence, this scientific case report underscores the uncommon occurrence of catheter-related peritonitis attributed to Stephanoascus ciferrii in a peritoneal dialysis patient with renal failure, emphasizing the distinctive management challenges and underscoring the critical significance of prompt diagnosis and suitable intervention in such instances.

Six-year evaluation of device-associated nosocomial infections in intensive care units.

INTRODUCTION: Invasive device-associated nosocomial infections commonly occur in intensive care units (ICUs). These infections include intravascular catheter-related bloodstream infection (CRBSI), ventilator-associated pneumonia (VAP), and catheter-associated urinary tract infection (CAUTI). This study aimed to evaluate the factors associated with invasive device-associated nosocomial infections based on the underlying diseases of the patients and antibiotic resistance profiles of the pathogens causing the infections detected in the ICU in our hospital over a five-year period. METHODOLOGY: Invasive device-associated infections (CRBSI, VAP, and CAUTI) were detected retrospectively by the laboratory- and clinic-based active surveillance system according to the criteria of the US Centers for Disease Control and Prevention (CDC) in patients hospitalized in the ICU of the tertiary hospital between 1 January 2018 and 30 June 2023. RESULTS: A total of 425 invasive device-associated nosocomial infections and 441 culture results were detected (179 CRBSI, 176 VAP, 70 CAUTI). Out of them, 57 (13.4%) patients had hematological malignancy, 145 (34.1%) had solid organ malignancy, and 223 (52.5%) had no histopathologic diagnosis of any malignancy. An increase in extended-spectrum beta lactamase (ESBL) and carbapenem resistance in pathogens was detected during the study period. CONCLUSIONS: Antibiotic resistance of the Gram-negative bacteria associated with invasive device-associated infections increased during the study period. Antimicrobial stewardship will reduce rates of nosocomial infections, reduce mortality, and shorten hospital stay. Long-term catheterization and unnecessary antibiotic use should be avoided.

The role of N-acetylcysteine on adhesion and biofilm formation of Candida parapsilosis isolated from catheter-related candidemia.

Objectives. Anti-fungal agents are increasingly becoming less effective due to the development of resistance. In addition, it is difficult to treat Candida organisms that form biofilms due to a lack of ability of drugs to penetrate the biofilms. We are attempting to assess the effect of a new therapeutic agent, N-acetylcysteine (NAC), on adhesion and biofilm formation in Candida parapsilosis clinical strains. Meanwhile, to detect the transcription level changes of adhesion and biofilm formation-associated genes (CpALS6, CpALS7, CpEFG1 and CpBCR1) when administrated with NAC in C. parapsilosis strains, furthermore, to explore the mechanism of drug interference on biofilms.Hypothesis/Gap statement. N-acetylcysteine (NAC) exhibits certain inhibitory effects on adhesion and biofilm formation in C. parapsilosis clinical strains from CRBSIs through: (1) down-regulating the expression of the CpEFG1 gene, making it a highly potential candidate for the treatment of C. parapsilosis catheter-related bloodstream infections (CRBSIs), (2) regulating the metabolism and biofilm -forming factors of cell structure.Methods. To determine whether non-antifungal agents can exhibit inhibitory effects on adhesion, amounts of total biofilm formation and metabolic activities of C. parapsilosis isolates from candidemia patients, NAC was added to the yeast suspensions at different concentrations, respectively. Reverse transcription was used to detect the transcriptional levels of adhesion-related genes (CpALS6 and CpALS7) and biofilm formation-related factors (CpEFG1 and CpBCR1) in the BCR1 knockout strain, CP7 and CP5 clinical strains in the presence of NAC. To further explore the mechanism of NAC on the biofilms of C. parapsilosis, RNA sequencing was used to calculate gene expression, comparing the differences among samples. Gene Ontology (GO) enrichment analysis helps to illustrate the difference between two particular samples on functional levels.Results. A high concentration of NAC reduces the total amount of biofilm formation in C. parapsilosis. Following co-incubation with NAC, the expression of CpEFG1 in both CP7 and CP5 clinical strains decreased, while there were no significant changes in the transcriptional levels of CpBCR1 compared with the untreated strain. GO enrichment analysis showed that the metabolism and biofilm-forming factors of cell structure were all regulated after NAC intervention.Conclusions. The non-antifungal agent NAC exhibits certain inhibitory effects on clinical isolate biofilm formation by down-regulating the expression of the CpEFG1 gene, making it a highly potential candidate for the treatment of C. parapsilosis catheter-related bloodstream infections.

Off-label use of dalbavancin in children: a case series.

INTRODUCTION: Dalbavancin is an antibiotic active against most Gram-positive bacteria approved for acute bacterial skin and skin structure infections (ABSSSI). Owing to its long half-life, it is being increasingly used for other indications. PATIENTS AND METHODS: We present a case series of children and adolescents treated with dalbavancin for osteoarticular, catheter-related and other non-ABSSSI infections. RESULTS: Dalbavancin was prescribed to 15 patients. Six (40%) were female and median age at prescription was 11.9 (IQR 1.3-18.0) years. Most of them (12/15) had significant comorbidities. Patients presented mainly with deep surgical site infections, osteoarticular infections and central-line-associated bloodstream infections. The most common isolate was Staphylococcus aureus followed by Staphylococcus epidermidis. Major reasons to prescribe dalbavancin were to ensure compliance and patients' convenience. Two patients discontinued the drug due to adverse events possibly related to it. The rest of the patients completed the treatment with dalbavancin, with a median duration of 56 days (IQR 17.5, 115.5). All achieved complete resolution and present no relapse after a median follow-up of 9.9 months (IQR 4.8, 16.6). CONCLUSIONS: Dalbavancin was a safe, effective and convenient alternative in selected paediatric patients with complicated non-ABSSSI infections caused by Gram-positive bacteria.

Identification of mechanisms modulating chlorhexidine and octenidine susceptibility in Proteus mirabilis.

AIMS: We aimed to identify mechanisms underlying the tolerance of Proteus mirabilis-a common cause of catheter associated urinary tract infection-to the clinically used biocides chlorhexidine (CHD) and octenidine (OCT). METHODS AND RESULTS: We adapted three clinical isolates to grow at concentrations of 512 µg ml-1 CHD and 128 µg ml-1 OCT. Genetic characterization and complementation studies revealed mutations inactivating the smvR repressor and increasing smvA efflux expression were associated with adaptation to both biocides. Mutations in mipA (encoding the MltA interacting protein) were less prevalent than smvR mutations and only identified in CHD adapted populations. Mutations in the rppA response regulator were exclusive to one adapted isolate and were linked with reduced polymyxin B susceptibility and a predicted gain of function after biocide adaptation. Biocide adaptation had no impact on crystalline biofilm formation. CONCLUSIONS: SmvR inactivation is a key mechanism in both CHD and OCT tolerance. MipA inactivation alone confers moderate protection against CHD, and rppA showed no direct role in either CHD or OCT susceptibility.

Assessment of Biofilm Forming Capability and Antibiotic Resistance in Proteus mirabilis Colonizing Indwelling Catheter.

<b>Background and Objective:</b> Urinary tract infections from the use of an indwelling urinary catheter are one of the most common infections caused by <i>Proteus mirabilis</i>. Due to their biofilm-producing capacity and the increasing antimicrobial resistance in this microorganism, this study aimed to determine the prevalence, biofilm-producing capacity, antimicrobial resistance patterns, multidrug resistance and plasmid mediated resistance of the recovered isolates. <b>Materials and Methods:</b> A total of 50 urinary samples were collected from May to August, 2018 from patients on indwelling urinary catheters. Using routine microbiological and biochemical methods, 37 <i>P. mirabilis</i> were isolated. Biofilm forming capability was determined among the isolates using the tube method while antimicrobial susceptibility and plasmid curing were also performed. <b>Results:</b> All isolates were biofilm producers with 17(46%) being moderate producers while 20(54%) were strong biofilm formers. The study isolates exhibited a high resistance rate to empiric antibiotics, including ceftazidime (75.8%), cefuroxime (54.5%), ampicillin (69.7%) and amoxicillin-clavulanic acid (51.5%). Low resistance was seen in the fluoroquinolones, gentamicin and nitrofurantoin. Plasmid curing experiment revealed that most isolates lost their resistance indicating that resistance was borne on plasmids. Plasmid carriage is likely the reason for the high MDR rate of 56.8% observed. <b>Conclusion:</b> These findings necessitate the provision of infection control programs which will guide and implement policies.

Dysbiosis and Staphylococcus species over representation in the exit site skin microbiota of hemodialysis patients carrying tunneled cuffed central venous catheter.

OBJECTIVES: Hemodialysis patients with end-stage renal disease (ESRD) are susceptible to infections and dysbiosis. Catheter-related infections are typically caused by opportunistic skin pathogens. This study aims to compare the skin microbiota changes around the exit site of tunneled cuffed catheters (peri-catheter group) and the contralateral site (control group). METHODS: ESRD patients on hemodialysis were recruited. The skin microbiota were collected with moist skin swabs and analyzed using high-throughput sequencing of the 16S rDNA V3-V4 region. After denoising, de-replication, and removal of chimeras, the reads were assigned to zero-radius operational taxonomic units (ZOTU). RESULTS: We found significantly reduced alpha diversity in the peri-catheter group compared to the control group, as indicated by the Shannon, Jost, and equitability indexes, but not by the Chao1 or richness indexes. Beta diversity analysis revealed significant deviation of the peri-catheter microbiota from its corresponding control group. There was an overrepresentation of Firmicutes and an underrepresentation of Actinobacteria, Proteobacteria, and Acidobacteria at the phylum level in the peri-catheter group. The most abundant ZOTU (Staphylococcus spp.) drastically increased, while Cutibacterium, a commensal bacterium, decreased in the peri-catheter group. Network analysis revealed that the skin microbiota demonstrated covariance with both local and biochemical factors. CONCLUSIONS: In conclusion, there was significant skin microbiota dysbiosis at the exit sites compared to the control sites in ESRD dialysis patients. Managing skin dysbiosis represents a promising target in the prevention of catheter-related bacterial infections.

Regulation of candidalysin underlies Candida albicans persistence in intravascular catheters by modulating NETosis.

Candida albicans is a leading cause of intravascular catheter-related infections. The capacity for biofilm formation has been proposed to contribute to the persistence of this fungal pathogen on catheter surfaces. While efforts have been devoted to identifying microbial factors that modulate C. albicans biofilm formation in vitro, our understanding of the host factors that may shape C. albicans persistence in intravascular catheters is lacking. Here, we used multiphoton microscopy to characterize biofilms in intravascular catheters removed from candidiasis patients. We demonstrated that, NETosis, a type of neutrophil cell death with antimicrobial activity, was implicated in the interaction of immune cells with C. albicans in the catheters. The catheter isolates exhibited reduced filamentation and candidalysin gene expression, specifically in the total parenteral nutrition culture environment. Furthermore, we showed that the ablation of candidalysin expression in C. albicans reduced NETosis and conferred resistance to neutrophil-mediated fungal biofilm elimination. Our findings illustrate the role of neutrophil NETosis in modulating C. albicans biofilm persistence in an intravascular catheter, highlighting that C. albicans can benefit from reduced virulence expression to promote its persistence in an intravascular catheter.

In vitro activity of taurolidine against clinical Candida auris isolates: relevance to catheter-related bloodstream infections.

Candida auris is an evolving and concerning global threat. Of particular concern are bloodstream infections related to central venous catheters. We evaluated the activity of taurolidine, a broad-spectrum antimicrobial in catheter lock solutions, against 106 C. auris isolates. Taurolidine was highly active with a MIC50/MIC90 of 512/512 mg/L, over 20-fold lower than lock solution concentrations of ≥13,500 mg/L. Our data demonstrate a theoretical basis for taurolidine-based lock solutions for prevention of C. auris catheter-associated infections.

Pantoea dispersa peritoneal dialysis catheter-related infection.

Enteric gram-negative bacteria-associated peritoneal dialysis (PD) peritonitis is common. These organisms are such as Escherichia coli, Klebsiella and Enterobacter species. Pantoea dispersa belongs to the order Enterobacterales, it has known benefits and a role in agricultural and environmental biotechnology. Pantoea dispersa, although still relatively rare, is being increasingly recognised to cause human infections. We are reporting a case of PD peritonitis caused by Pantoea dispersa in a kidney failure patient on continuous ambulatory peritoneal dialysis (CAPD). His peritonitis was treated well with intraperitoneal antibiotics and the patient can resume his CAPD therapy. The increasing reports of Pantoea dispersa-related human infections warrant concerns, both in immunocompromised and immunocompetent patients.

C1q is elevated during chronic Staphylococcus epidermidis central nervous system catheter infection.

Introduction: Significant neurologic morbidity is caused by pediatric cerebrospinal fluid (CSF) shunt infections. The underlying mechanisms leading to impaired school performance and increased risk of seizures are unknown, however, a better understanding of these mechanisms may allow us to temper their consequences. Recent evidence has demonstrated important roles for complement proteins in neurodevelopment and neuroinflammation. Methods: We examined complement activation throughout Staphylococcus epidermidis (S. epidermidis) central nervous system (CNS) catheter infection. In addition, based on accumulating evidence that C3 plays a role in synaptic pruning in other neuroinflammatory states we determined if C3 and downstream C5 led to alterations in synaptic protein levels. Using our murine model of S. epidermidis catheter infection we quantified levels of the complement components C1q, Factor B, MASP2, C3, and C5 over the course of infection along with bacterial burdens. Results: We found that MASP2 predominated early in catheter infection, but that Factor B was elevated at intermediate time points. Unexpectedly C1q was elevated at late timepoints when bacterial burdens were low or undetectable. Based on these findings and the wealth of information regarding the emerging roles of C1q in the CNS, this suggests functions beyond pathogen elimination during S. epidermidis CNS catheter infection. To identify if C3 impacted synaptic protein levels we performed synaptosome isolation and quantified levels of VGLUT1 and PSD95 as well as pre-, post- and total synaptic puncta in cortical layer V of C3 knockout (KO) and wild type mice. We also used C5 KO and wild type mice to determine if there was any difference in pre-, post- and total synaptic puncta. Discussion: Neither C3 nor C5 impacted synaptic protein abundance. These findings suggest that chronic elevations in C1q in the brain that persist once CNS catheter infection has resolved may be modulating disease sequalae.

Salvage strategy for long-term central venous catheter-associated Staphylococcus aureus infections in children: a multi-centre retrospective study in France.

OBJECTIVES: Catheter removal is recommended in adults with Staphylococcus aureus central-line-associated bloodstream infection (CLABSI) but is controversial in children with long-term central venous catheters (LTCVC). We evaluated the occurrence of catheter salvage strategy (CSS) in children with S. aureus LTCVC-associated CLABSI and assessed determinants of CSS failure. METHODS: We retrospectively included children (<18 years) with an LTCVC and hospitalized with S. aureus CLABSI in eight French tertiary-care hospitals (2010-2018). CSS was defined as an LTCVC left in place ≥72 h after initiating empiric antibiotic treatment for suspected bacteraemia. Characteristics of patients were reviewed, and multi-variable logistic regression was performed to identify factors associated with CSS failure (i.e., persistence, recurrence or complications of bacteraemia). RESULTS: We included 273 episodes of S. aureus LTCVC-associated CLABSI. CSS was chosen in 194 out of 273 (71%) cases and failed in 74 of them (38%). The main type of CSS failure was the persistence of bacteraemia (39 of 74 cases, 53%). Factors independently associated with CSS failure were: history of catheter infection (adjusted odds ratio (aOR) 3.18, 95% confidence interval (CI) 1.38-7.36), CLABSI occurring on an implantable venous access device (aOR 7.61, 95% CI 1.98-29.20) when compared with tunnelled-cuffed CVC, polymicrobial CLABSI (aOR 3.45, 95% CI 1.25-9.50), and severe sepsis at the initial stage of infection (aOR 4.46, 95% CI 1.18-16.82). CONCLUSIONS: CSS was frequently chosen in children with S. aureus LTCVC-associated CLABSI, and failure occurred in one-third of cases. The identified risk factors may help clinicians identify children at risk for CSS failure.

Treatment of positive catheter tip culture without bloodstream infections in critically ill patients. A case-cohort study from the OUTCOMEREA network.

PURPOSE: This study aimed to evaluate the impact on subsequent infections and mortality of an adequate antimicrobial therapy within 48 h after catheter removal in intensive care unit (ICU) patients with positive catheter tip culture. METHODS: We performed a retrospective analysis of prospectively collected data from 29 centers of the OUTCOMEREA network. We developed a propensity score (PS) for adequate antimicrobial treatment, based on expert opinion of 45 attending physicians. We conducted a 1:1 case-cohort study matched on the PS score of being adequately treated. A PS-matched subdistribution hazard model was used for detecting subsequent infections and a PS-matched Cox model was used to evaluate the impact of antibiotic therapy on mortality. RESULTS: We included 427 patients with a catheter tip culture positive with potentially pathogenic microorganisms. We matched 150 patients with an adequate antimicrobial therapy with 150 controls. In the matched population, 30 (10%) subsequent infections were observed and 62 patients died within 30 days. Using subdistribution hazard models, the daily risk to develop subsequent infection up to Day-30 was similar between treated and non-treated groups (subdistribution hazard ratio [sHR] 1.08, 95% confidence interval [CI] 0.62-1.89, p = 0.78). Using Cox proportional hazard models, the 30-day mortality risk was similar between treated and non-treated groups (HR 0.89, 95% CI 0.45-1.74, p = 0.73). CONCLUSIONS: Antimicrobial therapy was not associated with decreased risk of subsequent infection or death in short-term catheter tip colonization in critically ill patients. Antibiotics may be unnecessary for positive catheter tip cultures.