Cause Of Catheter-related Bloodstream Infections Research Articles

A new dynamic in vitro model for evaluating antimicrobial activity against bacterial biofilms on central venous catheters.

Central venous catheters (CVCs) are widely used for intravenous medication administration. However, biofilm formation along the catheter surface is the main most important cause of catheter-related bloodstream infections. Nowadays, several antimicrobial-coated catheters are available to prevent biofilm development. In this study, we introduced a new dynamic in vitro model to evaluate the antimicrobial activity against bacterial biofilms on CVCs. Rifampicin-minocycline-coated catheters and control catheters without antimicrobial component were assembled into the model to test the antimicrobial activity on external surface and internal surface. After 1 h irrigation of Staphylococcus epidermidis or Staphylococcus aureus preculture and 23 h irrigation of Trypticase Soy Broth, the viable adherent organism was collected and counted. The enumeration results showed that the number of bacteria attached to antibacterial catheter was significantly less than that of the control catheter, both on external surface (P < 0.05) and internal surface (P < 0.05). The results were further confirmed by the scanning electron microscopy. In conclusion, the dynamic in vitro model can be applied to evaluate the antimicrobial activity against bacterial biofilms grown on the external and internal surfaces of CVCs used in clinical practice.IMPORTANCEFor the first time, a new dynamic in vitro model was constructed to evaluate the antimicrobial activity against bacterial biofilms on central venous catheters (CVCs) on both external surface and internal surface. This model could be applied to evaluate the antimicrobial activity against bacterial biofilms not only on CVCs but also other types of catheters.

Epidemiology and Clinical Insights of Catheter-Related Candidemia in Non-ICU Patients with Vascular Access Devices.

Vascular access devices (VADs), namely peripheral VADs (PVADs) and central venous VADs (CVADs), are crucial in both intensive care unit (ICU) and non-ICU settings. However, VAD placement carries risks, notably catheter-related bloodstream infections (CRBSIs). Candida spp. is a common pathogen in CRBSIs, yet its clinical and microbiological characteristics, especially in non-ICU settings, are underexplored. We conducted a monocentric, retrospective observational study at Luigi Sacco Hospital from 1 May 2021 to 1 September 2023. We reviewed medical records of non-ICU adult patients with CVADs and PVADs. Data on demographics, clinical and laboratory results, VAD placement, and CRBSI occurrences were collected. Statistical analysis compared Candida spp. CRBSI and bacterial CRBSI groups. Out of 1802 VAD placements in 1518 patients, 54 cases of CRBSI were identified, and Candida spp. was isolated in 30.9% of episodes. The prevalence of CRBSI was 3.05%, with Candida spp. accounting for 0.94%. Incidence rates were 2.35 per 1000 catheter days for CRBSI, with Candida albicans and Candida non-albicans at 0.47 and 0.26 per 1000 catheter days, respectively-patients with Candida spp. CRBSI had more frequent SARS-CoV-2 infection, COVID-19 pneumonia, and hypoalbuminemia. During the COVID-19 pandemic, Candida spp. was a notable cause of CRBSIs in our center, underscoring the importance of considering Candida spp. in suspected CRBSI cases, including those in non-ICU settings and in those with PVADs.

Increasing Gram-Negative Catheter-Related Bloodstream Infection in Cancer Patients.

Background: We aimed to assess the incidence, etiology and outcomes of catheter-related bloodstream infection (CRBSI) in onco-hematological patients, to assess the differences between patients with hematological malignancies (HMs) and solid tumors (STs) and to identify the risk factors for Gram-negative (GN) CRBSI. Methods: All consecutive episodes of BSI in adult cancer patients were prospectively collected (2006-2020). The etiology of CRBSI was analyzed in three different 5-year periods. Risk factors for GN CRBSI were assessed in the whole cohort and separately in patients with HMs and STs. Results: Among 467 episodes of monomicrobial CRBSI, 407 were Gram-positive (GP) (87.1%), 49 GN (10.5%) and 11 fungal (2.4%). Hematological patients (369 episodes) were more frequently neutropenic and were more likely to carry central venous catheters and develop GP CRBSI. Patients with STs (98 episodes) had more comorbidities, more frequently carried port reservoirs and commonly presented more GN CRBSI. GN CRBSI significantly increased over the study period, from 5.2% to 23% (p < 0.001), whereas GP CRBSI decreased from 93.4% to 73.3% (p < 0.001). CRBSI episodes involving port reservoirs and peripherally-inserted central catheters were significantly increased (p < 0.001). The most frequent GPs were coagulase-negative staphylococci (CoNS) (57.8%) and Pseudomonas aeruginosa was the most common GN (3%). Multidrug-resistant (MDR) GN represented 32.7% of all GN CRBSIs and increased over time (p = 0.008). The independent risk factors for GN CRBSI in the whole cohort were solid tumor, chronic kidney disease and carrying a port reservoir. Carrying a port reservoir was also a risk factor in patients with STs. Health-care acquisition was identified as a risk factor for GN CRBSI in the whole cohort, as well as in patients with STs and HMs. Inadequate empirical antibiotic treatment (IEAT) occurred regardless of the etiology: 49% for GNs and 48.6% for GPs (p = 0.96). In GP CRBSI, IEAT was mainly due to inadequate coverage against CoNS (87%), whereas in GN CRBSI, IEAT was associated with multidrug resistance (54.2%). Early (48 h and 7-day) and 30-day case-fatality rates were similar when analyzed according to the type of underlying disease and etiology, except for the 30-day case-fatality rate, which was higher in the group of patients with STs compared to those with HMs (21.5% vs. 12.5%, p = 0.027). The 48 h case-fatality rate was significantly higher in patients in whom the catheter had not been removed (5.6% vs. 1%; p = 0.011), and it remained significant for GP CRBSI (6% vs. 1.3%, p = 0.023). Conclusions: GNs are an increasing cause of CRBSI in cancer patients, particularly in solid tumor patients carrying port reservoirs. Multidrug resistance among GNs is also increasing and is associated with higher rates of IEAT. Decreased 48 h survival was associated with the non-removal of the catheter. These findings should be considered when deciding on early therapeutic management for cancer patients with suspected CRBSI.

1777. Shorter Versus Longer Antibiotic Durations for Coagulase-Negative Staphylococcus Catheter-Related Bloodstream Infections and Potential Impact on Antimicrobial Stewardship in a County Hospital

Abstract Background Coagulase negative Staphylococcus (CoNS) is a common cause of catheter-related bloodstream infection (CRBSI). Current guidelines are to provide 10-14 days (d) of antibiotics (abx) plus lock abx in the absence of catheter removal, and if the catheter has been removed, 5-7 d after removal. Olive View UCLA-Medical Center (Sylmar, CA) is an academic county hospital, serving the medical needs of the underserved community. The purpose of this study was to evaluate differences in treatment (tx) durations for CoNS CRBSI on clinical outcomes and evaluate the potential impact on antimicrobial stewardship. Methods Single center retrospective chart review from January 2018 to December 2021 on all central line-obtained blood cultures (Bcx) positive for CoNS. Exclusion criteria included suspected contamination or no abx tx, invasive CoNS infection, and concomitant infection treated with abx that have activity against CoNS. Duration of abx tx was divided into two groups: &amp;gt;10 d vs ≤10 d with or without catheter removal and &amp;gt;7 d vs ≤7 d post catheter removal. Primary outcomes assessed were recurrence of CoNS CRBSI within 90 d and 30 d hospital readmission. Secondary outcomes included hospital length of stay (LOS), 30 d all-cause mortality, and days of Bcx positivity. Groups were compared using Wilcoxon rank-sum for continuous variables and Fisher’s exact for categorical variables using Stata (Version 15). Results 153 positive CoNS central line Bcx were screened, 40 met study inclusion. 37 received vancomycin as initial abx with a median total tx duration of 13.5 d [IQR 8-14] and 9 d [IQR 6-13.5] after line removal. 22 (55%) received total abx duration of &amp;gt;10 d and 18 (45%) received total abx duration of ≤10 d. Baseline characteristics were similar between &amp;gt;10 d and ≤10 d (table 1). There was no significant difference in primary and secondary outcomes, respectively, between &amp;gt;10 d and ≤10 d (table 2). After catheter removal, there were no significant differences in outcomes whether antibiotics were continued for &amp;gt;7 d (n=18) vs ≤7 d (n=15) (table 3). Table 1:Baseline CharacteristicsTable 2:Outcomes according to days of therapyTable 3:Outcomes post catheter removal days of therapy Conclusion Abx tx duration of ≤10 d compared with &amp;gt;10 d for CoNS CRBSI did not result in differences in 90 d recurrence and 30 d readmission. Shorter courses of tx for CoNS CRBSI should be considered as a target for antimicrobial stewardship to minimize antibiotic exposure. Disclosures All Authors: No reported disclosures.

Infections and colonisation of central venous catheters in patients admitted to intensive care units at two tertiary care hospitals

Introduction: Central venous catheters (CVC) are frequently used in modern health care systems. However, CVCs are likely to get colonised with microorganisms, resulting in catheter-related blood stream infections (CRBSI). This study investigated microorganisms causing CRBSI and CVC colonisation, their antibiotic resistance, and factors associated with CRBSI in patients in the intensive care units (ICU) at the Colombo North Teaching Hospital (CNTH) and Apeksha hospital, Sri Lanka. Methods: The study included 300 adult patients in ICUs with a CVC in-situ for &gt;48 hours. Blood taken through the CVC, peripheral blood and CVC tips were cultured. Microorganisms were identified and tested for antibiotic susceptibility. Demographic factors were recorded. Results: Seventeen patients (13.1%) developed CRBSI. The CRBSI rate was 13.3 per 1,000 catheter days in CNTH while it was 10 (5.9%) cases and 5.2 per 1,000 catheter days in Apeksha hospital. In CNTH, CVC colonisation was detected in 35 (26.9%). Coagulase negative staphylococci (CoNS) were the leading cause of both CRBSI (41%) and colonisation (58%). In Apeksha hospital, Klebsiella sp. (5/10) were the predominant pathogens that caused CRBSI. Eighty-nine CVCs (52.3%) were colonised by CoNS (58%). In CNTH, CRBSI was detected more in males (14/17) (p&lt;0.05). The majority of microorganisms that caused CRBSI and CVC colonisation in both hospitals showed resistance to commonly used antibiotics. Conclusion: The CRBSI rates and the incidences were higher in CNTH. CoNS was the most common cause of CRBSI in CNTH and Gram negative bacteria in Apeksha hospital. CVC colonisation with CoNS was common in both hospitals. Antibiotic resistance was high among bacteria causing CRBSI and colonisation.

A short course of antibiotic treatment is safe after catheter withdrawal in catheter-related bloodstream infections due to coagulase-negative staphylococci.

CoNS is the main cause of catheter-related bloodstream infections (CRBSI). Current guidelines recommend catheter withdrawal followed by antibiotics for at least 5days. We aimed to assess the efficacy and safety of a shorter course of antibiotherapy in patients with CoNS CRBSI. All proven cases of CoNS CRBSI at our institution (Jan 12/Dec 17) were retrospectively analysed. Comparison of clinical characteristics and outcomes between patients receiving a short (SC ≤ 3days) versus long antibiotic course (LC > 3days) was performed. Cox regression models predicting the risk for complications (including propensity score [PS] for treatment assignment as covariate) were designed to adjust baseline differences among both treatment groups. A total of 79 cases were included. Most patients (75.9%) showed clinical response at day 7 after catheter removal. Complications occurred in 3.8% (three cases of septic thrombophlebitis) with no cases of endocarditis. Microbiological relapse (MR) occurred in 13 patients (16.5%). SC and LC were administered to 25 (31.6%) and 54 (68.4%) patients, respectively, with no significant differences in MR-free survival between SC and LC groups (87.8 vs 86.3%; P = 0.6). In PS-adjusted Cox regression analyses, a tunnelled catheter as the source of CRBSI was the only independent risk factor for MR (hazard ratio, 5.71; 95% confidence interval, 1.6-21) whereas the duration of therapy had no apparent impact. Shortening antibiotic therapy to ≤ 3days is not associated with a poorer outcome or a greater risk of MR in patients with CoNS CRBI with catheter withdrawal.

Clinical impact of delayed catheter removal for patients with central-venous-catheter-related Gram-negative bacteraemia

Gram-negative bacteria are increasingly the cause of catheter-related bloodstream infection (CRBSI), and the prevalence of multi-drug-resistant strains is rising rapidly. This study evaluated the impact of delayed central venous catheter (CVC) removal on clinical outcomes in patients with Gram-negative CRBSI. Between January 2007 and December 2016, patients with Gram-negative bacteraemia and CVC placement, from two tertiary care hospitals, were included retrospectively. Cases with CVC removal more than three days after onset of bacteraemia or without CVC removal were classified as having delayed CVC removal. In total, 112 patients were included. Of these, 78 had CRBSI (43 definite and 35 probable) and 34 had Gram-negative bacteraemia from another source (non-CRBSI). Enterobacteriaceae were less common pathogens in patients with CRBSI than in patients with non-CRBSI (11.5% vs 41.3%; P<0.001). Delayed CVC removal was associated with increased 30-day mortality (40.5% vs 11.8%; P=0.01) in patients with Gram-negative CRBSI; this was not seen in patients with non-CRBSI (25.0% vs 14.3%; P>0.99). Delayed CVC removal [odds ratio (OR) 6.8], multi-drug-resistant (MDR) Gram-negative bacteraemia (OR 6.3) and chronic renal failure (OR 11.1) were associated with 30-day mortality in patients with CRBSI. The protective effect of early CVC removal on mortality was evident in the MDR group (48.3% vs 18.2%; P=0.03), but not in the non-MDR group (11.1% vs 0%; P=0.43). CVCs should be removed early to improve clinical outcomes in patients with Gram-negative CRBSI, especially in settings where MDR isolates are prevalent.

Assessing the impact of quality improvement measures on catheter related blood stream infections and catheter salvage: Experience from a national intestinal failure unit

Prevention of catheter related blood stream infections (CRBSI) and salvage of infected central venous catheters (CVC) are vital to maintaining long term venous access in patients needing home parenteral nutrition (HPN). It remains unclear as to whether patients are best trained for catheter care at home or in hospital or whether CRBSIs are lower if the patient self-cares for the CVC. Furthermore, there is minimal data on the longer term outcome following salvage of infected catheter and limited consensus on agreed protocols for catheter salvage. We conducted a retrospective 5-year evaluation of CRBSI occurrence and CVC salvage outcomes in adult patients requiring HPN managed at a national UK Intestinal Failure Unit from 2012 to 2016. Prior to 2012, patients were primarily trained to administer PN in hospital; thereafter, patients underwent training at home. A total of 134 CRBSI were recorded in 92 patients (62 patients with a single CRBSI and 30 patients with more than 1 CRBSI) in a cohort of 559 HPN patients, with a total of 1163 HPN years. The overall CRBSI rate was 0.31 per 1000 catheter days. CNS were the most common isolates (41/134 (30.5%)), followed by polymicrobial infections (14/134 (10.4%)), Klebsiella spp. (16/134 (11.9%)) and methicillin - sensitive Staphylococcus aureus (MSSA) 5/134 ((3.7%)). Salvage was not attempted in 34 cases due to methicillin - resistant (MRSA) infection (1/34), fungal infection (13/34) or clinical instability due to sepsis (20/34). Of the 100 cases where salvage was attempted, 67% were successful. 82.8% of CNS salvage attempts were successful; there was no difference in salvage rates between CNS CRBSIs salvaged with a 10-day (22/26) or 14-day protocol (7/9) (p=0.4). CRBSI rate, in those cared for by trained home care nurses was the lowest at 0.270 (self care: 0.342 and non-medical carer (e.g. family member): 0.320) (p=0.03). We previously reported a sustained very low CRBSI rate in a large cohort of HPN patients in a national unit; we now further report that this is not influenced by training patients at home rather than in hospital but is influenced by the individual managing the catheter at home. CNS remains the primary cause of CRBSIs and can be successfully salvaged with a reduced duration of antibiotic therapy compared to our previous experience.

Heparin Mimics Extracellular DNA in Binding to Cell Surface-Localized Proteins and Promoting Staphylococcus aureus Biofilm Formation.

Staphylococcus aureus is a leading cause of catheter-related bloodstream infections. Biofilms form on these implants and are held together by a matrix composed of proteins, polysaccharides, and extracellular DNA (eDNA). Heparin is a sulfated glycosaminoglycan that is routinely used in central venous catheters to prevent thrombosis, but it has been shown to stimulate S.aureus biofilm formation through an unknown mechanism. Data presented here reveal that heparin enhances biofilm capacity in many S.aureus and coagulase-negative staphylococcal strains, and it is incorporated into the USA300 methicillin-resistant S.aureus (MRSA) biofilm matrix. The S. aureus USA300 biofilms containing heparin are sensitive to proteinase K treatment, which suggests that proteins have an important structural role during heparin incorporation. Multiple heparin-binding proteins were identified by proteomics of the secreted and cell wall fractions. Proteins known to contribute to biofilm were identified, and some proteins were reported to have the ability to bind eDNA, such as the major autolysin (Atl) and the immunodominant surface protein B (IsaB). Mutants defective in IsaB showed a moderate decrease in biofilm capacity in the presence of heparin. Our findings suggested that heparin is substituting for eDNA during S.aureus biofilm development. To test this model, eDNA content was increased in biofilms through inactivation of nuclease activity, and the heparin enhancement effect was attenuated. Collectively, these data support the hypothesis that S.aureus can incorporate heparin into the matrix and enhance biofilm capacity by taking advantage of existing eDNA-binding proteins. IMPORTANCEStaphylococcusaureus and coagulase-negative staphylococci (CoNS) are the leading causes of catheter implant infections. Identifying the factors that stimulate catheter infection and the mechanism involved is important for preventing such infections. Heparin, the main component of catheter lock solutions, has been shown previously to stimulate S.aureus biofilm formation through an unknown pathway. This work identifies multiple heparin-binding proteins in S.aureus, and it reveals a potential mechanism through which heparin enhances biofilm capacity. Understanding the details of the heparin enhancement effect could guide future use of appropriate lock solutions for catheter implants.

Slicing silicone neonatal vascular catheter tips improves colonization detection by the roll-plate technique

ObjectiveSilicone neonatal peripherally inserted central catheters (SN-PICCs) are a common cause of catheter-related bloodstream infection (C-RBSI) in neonates. Our objective was to compare the yield of traditional roll-plate technique (TRP), roll-plate after slicing (RPS), and sonication after slicing (SS) for the detection of colonization and C-RBSI in SN-PICCs. MethodsWe prospectively cultured tips from SN-PICCs withdrawn from paediatric patients admitted to our institution with suspicion of infection. We first cultured the catheter tip using TRP and then divided the catheter into two segments. RPS was performed by longitudinally slicing one segment and the fragments were cultured. SS was performed by transversally slicing the other segment followed by culture after sonication. We calculated the validity values of each technique individually by comparing them with the diagnostic standard of colonization and C-RBSI. ResultsWe included 162 SN-PICCs, 46 of which were colonized. Sensitivity rates for colonization and C-RBSI with TRP, RPS and SS were, respectively, 71.7%, 80.4% and 67.4%; and 74.2%, 90.3% and 77.4%. ConclusionCatheter slicing should be performed before the roll-plate technique to ensure optimal diagnosis on SN-PICCs.

Risk factors for persistent bacteremia in infants with catheter-related bloodstream infection due to coagulase-negative Staphylococcus in the neonatal intensive care unit.

Coagulase-negative Staphylococcus (CoNS) is the predominant cause of catheter-related bloodstream infections (CRBSI). Infants in neonatal intensive care units (NICU) often suffer from CoNS CRBSI, which are often refractory to treatment. We sought to evaluate risk factors for developing persistent bacteremia due to CoNS CRBSI in infants, in order to identify those who require early aggressive management. We conducted a retrospective case-control study of infants in the NICU who developed CRBSI due to CoNS. Patient demographics, condition and management of CRBSI were compared between those with persistent and non-persistent bacteremia. Furthermore, prognosis of infants in the NICU after CoNS CRBSI was evaluated. Seventy six episodes of CRBSI, including 17 persistent bacteremia and 59 non-persistent bacteremia, were analyzed. In univariate analyses, persistent bacteremia was significantly associated with corrected age equivalent to gestational age of 22-28weeksat onset of CRBSI [Odds ratio (OR)=4.33; P=0.04], platelet count <100,000/μL (OR=11.5; P<0.001), use of vasopressor (OR=5.38; P=0.003), and delayed CVC removal (OR=6.25; P=0.003). In multivariate analysis, persistent bacteremia was significantly associated with platelet count <100,000/μL (OR=7.80; P=0.007), and delayed CVC removal (OR=5.07; P=0.03). Infants with persistent bacteremia tended to have a lower survival rate after CoNS CRBSI, however this was not statistically significant (P=0.21). Early CVC removal should be considered for the treatment of CRBSI due to CoNS in infants with platelet counts of less than 100,000/μL.

An Optimized Lock Solution Containing Micafungin, Ethanol and Doxycycline Inhibits Candida albicans and Mixed C. albicans - Staphyloccoccus aureus Biofilms.

Candida albicans is a major cause of catheter-related bloodstream infections and is associated with high morbidity and mortality. Due to the propensity of C. albicans to form drug-resistant biofilms, the current standard of care includes catheter removal; however, reinsertion may be technically challenging or risky. Prolonged exposure of an antifungal lock solution within the catheter in conjunction with systemic therapy has been experimentally attempted for catheter salvage. Previously, we demonstrated excellent in vitro activity of micafungin, ethanol, and high-dose doxycycline as single agents for prevention and treatment of C. albicans biofilms. Thus, we sought to investigate optimal combinations of micafungin, ethanol, and/or doxycycline as a lock solution. We performed two- and three-drug checkerboard assays to determine the in vitro activity of pairwise or three agents in combination for prevention or treatment of C. albicans biofilms. Optimal lock solutions were tested for activity against C. albicans clinical isolates, reference strains and polymicrobial C. albicans-S. aureus biofilms. A solution containing 20% (v/v) ethanol, 0.01565 μg/mL micafungin, and 800 μg/mL doxycycline demonstrated a reduction of 98% metabolic activity and no fungal regrowth when used to prevent fungal biofilm formation; however there was no advantage over 20% ethanol alone. This solution was also successful in inhibiting the regrowth of C. albicans from mature polymicrobial biofilms, although it was not fully bactericidal. Solutions containing 5% ethanol with low concentrations of micafungin and doxycycline demonstrated synergistic activity when used to prevent monomicrobial C. albicans biofilm formation. A combined solution of micafungin, ethanol and doxycycline is highly effective for the prevention of C. albicans biofilm formation but did not demonstrate an advantage over 20% ethanol alone in these studies.

Central venous catheter related blood stream infections in an intensive care unit from a tertiary care teaching hospital

Introduction – Central venous catheters (CVC) have become essential in the management of critically ill patients and patient who requires long-term medical care. CRBSI (Catheter Related Blood Stream Infection) is one of the most frequent and lethal complication of catheter use. The objective of this study was to determine incidence of CRBSIs and antibiotic susceptibility pattern of isolated bacteria in an ICU set up. Methods – This study was carried out in patients admitted at ICU during a 3 year period (January 2012 to December 2014). A total of 434 samples were received in the laboratory with clinical diagnosis of septicemia after central venous catheterization. Semi quantitative method (roll-plate) was used for catheter tip culture. Peripheral blood cultures were obtained and were processed by standard methods. Results – Out of 434 catheters a total of 256 (59%) catheter tips were colonized. Staphylococcus aureus (42%) were most common colonizers followed by Enterobacteriaceae family, gram negative non-fermenters and Candida albicans. Incidence of CRBSI was 7.8% (33/434) or 9.5 per 1000 catheter days. Staphylococcus aureus was the major (63%) cause of CRBSI followed by Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli. MRSA rate was 76%. All the Acinetobacter baumannii and 33% Pseudomonas aeruginosa were MDR. All the Escherichia coli and Klebsiella pneumoniae were ESBL producers with 33% Klebsiella pneumoniae being MDR. Discussion - Since CVCs are increasingly being used in the critical care and have direct bearing on the mortality and morbidity, regular microbiological surveillance need to be undertaken to prevent complication.

Synergy of ambroxol with vancomycin in elimination of catheter-related Staphylococcus epidermidis biofilm in vitro and in vivo

Central venous catheters are widely used in neonatal intensive care units (NICUs) nowadays. The commonest cause of catheter-related bloodstream infections (CRBSIs) is coagulase-negative staphylococci (CoNS). Ambroxol, an active metabolite of bromhexine, exhibits antimicrobial activity against strains producing biofilm and enhances the bactericidal effect of some antibiotic by breaking the structure of biofilm. In this study, we aimed to determine the effect of ambroxol with vancomycin on the biofilm of Staphylococcus epidermidis (S. epidermidis) in vitro and in vivo. In the in vitro study, the biofilm of S. epidermidis was assessed by XTT reduction assay and analysed by confocal laser scanning microscopy (CLSM). In the in vivo study, a rabbit model of CRBSIs was created by intravenous intubation with a tube covered with S. epidermidis biofilm. The rabbits received one of the following four treatments by means of antibiotic lock therapy: normal heparin, ambroxol, vancomycin, or vancomycin plus ambroxol each for 3 days. The microstructure of the biofilm was assessed by scanning electron microscopy (SEM). The number of bacterial colonies in the organs (liver, heart, and kidney) and on the intravenous tubes was measured on agar plates. Pathological changes in the organs (liver, heart, and kidney) were observed with Hematoxylin-Eosin staining. The ambroxol exhibits significant efficacy to potentiate the bactericidal effect of vancomycin on S. epidermidis biofilm both in vitro and in vivo. The antibiotic lock therapy using a combination of ambroxol and vancomycin reveals a high ability to eradicate S. epidermidis biofilms in vivo. These results provide the basis of a useful anti-infection strategy for the treatment of CRBSIs.

The Role of Antifungals against Candida Biofilm in Catheter-Related Candidemia.

Catheter-related bloodstream infection (C-RBSI) is one of the most frequent nosocomial infections. It is associated with high rates of morbidity and mortality. Candida spp. is the third most common cause of C-RBSI after coagulase-negative staphylococci and Staphylococcus aureus and is responsible for approximately 8% of episodes. The main cause of catheter-related candidemia is the ability of some Candida strains—mainly C. albicans and C. parapsilosis—to produce biofilms. Many in vitro and in vivo models have been designed to assess the activity of antifungal drugs against Candida biofilms. Echinocandins have proven to be the most active antifungal drugs. Potential options in situations where the catheter cannot be removed include the combination of systemic and lock antifungal therapy. However, well-designed and -executed clinical trials must be performed before firm recommendations can be issued.

Quinacrine inhibits Candida albicans growth and filamentation at neutral pH.

Candida albicans is a common cause of catheter-related bloodstream infections (CR-BSI), in part due to its strong propensity to form biofilms. Drug repurposing is an approach that might identify agents that are able to overcome antifungal drug resistance within biofilms. Quinacrine (QNC) is clinically active against the eukaryotic protozoan parasites Plasmodium and Giardia. We sought to investigate the antifungal activity of QNC against C. albicans biofilms. C. albicans biofilms were incubated with QNC at serially increasing concentrations (4 to 2,048 μg/ml) and assessed using a 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay in a static microplate model. Combinations of QNC and standard antifungals were assayed using biofilm checkerboard analyses. To define a mechanism of action, QNC was assessed for the inhibition of filamentation, effects on endocytosis, and pH-dependent activity. High-dose QNC was effective for the prevention and treatment of C. albicans biofilms in vitro. QNC with fluconazole had no interaction, while the combination of QNC and either caspofungin or amphotericin B demonstrated synergy. QNC was most active against planktonic growth at alkaline pH. QNC dramatically inhibited filamentation. QNC accumulated within vacuoles as expected and caused defects in endocytosis. A tetracycline-regulated VMA3 mutant lacking vacuolar ATPase (V-ATPase) function demonstrated increased susceptibility to QNC. These experiments indicate that QNC is active against C. albicans growth in a pH-dependent manner. Although QNC activity is not biofilm specific, QNC is effective in the prevention and treatment of biofilms. QNC antibiofilm activity likely occurs via several independent mechanisms: vacuolar alkalinization, inhibition of endocytosis, and impaired filamentation. Further investigation of QNC for the treatment and prevention of biofilm-related Candida CR-BSI is warranted.

Arterial Catheters as a Source of Bloodstream Infection

Catheter-related bloodstream infections are associated with significant costs and adverse consequences. Arterial catheters are commonly used in the critical care setting and are among the most heavily manipulated vascular access devices. We sought to evaluate the prevalence of arterial catheter-related bloodstream infection. PubMed, CinAHL, EMBASE, and Web of Science. Included studies reported prevalence rate of catheter-related bloodstream infection for arterial catheters used for critical illness or postoperative monitoring. For the purposes of this study, catheter-related bloodstream infection was defined as positive blood culture collected from an arterial catheter and from the periphery with the same organism in a patient demonstrating systemic signs of sepsis. The study population, site of insertion, antiseptic preparation, catheter days, and prevalence of catheter-related bloodstream infection were abstracted. When data were not available, authors were contacted for further information. Forty-nine studies met criteria including 222 cases of arterial catheter-related bloodstream infection in 30,841 catheters. Pooled incidence was 3.40/1,000 catheters or 0.96/1,000 catheter days. Prevalence was considerably higher in the subgroup of studies that cultured all catheters (1.26/1,000 catheter days) compared with those studies that cultured only when the arterial catheter was suspected as the source for the catheter-related bloodstream infection (0.70/1,000 catheter days). Pooled data also found a significantly increased risk of infection for femoral site of insertion compared with radial artery for arterial catheter placement (relative risk, 1.93; 95% CI, 1.32-2.84; p = 0.001) CONCLUSIONS: Arterial catheters are an underrecognized cause of catheter-related bloodstream infection. Pooled incidence when catheters were systematically cultured and correlated to blood culture results indicated a substantial burden of arterial catheter-related bloodstream infection. Selection of a radial site over a femoral site will help reduce the risk of arterial catheter-related bloodstream infection. Future studies should evaluate technologies applied to preventing central venous catheter-related bloodstream infection to arterial catheters as well.

Catheter-related bloodstream infection caused by Enterococcus spp.

The role of Enterococcus spp. as a cause of catheter-related bloodstream infections (CR-BSI) is almost unexplored. We assessed the incidence and clinical characteristics of enterococcal CR-BSI (ECR-BSI) over an 8-year period in our hospital. We performed a retrospective study (January 2003 to December 2010) in a large teaching institution. We recorded the incidence, and the microbiological and clinical data from patients with ECR-BSI. The incidence per 10 000 admissions for enterococcal BSI and ECR-BSI was 25 and 1.7, respectively. ECR-BSI was the fourth leading cause of CR-BSI in our institution (6%). A total of 75 episodes of ECR-BSI were detected in 73 patients (6% of all enterococcal BSI). The incidence of ECR-BSI increased by 17% annually (95% CI 19.0–21.0%) during the study period. Nineteen percent of ECR-BSI episodes were polymicrobial. Overall mortality was 33%. ECR-BSI is an emerging and increasingly common entity with a high mortality. This finding should be taken into account when selecting empirical treatment for presumptive CR-BSI.

Comparative Epidemiology of Staphylococcus epidermidis Isolates from Patients with Catheter-Related Bacteremia and from Healthy Volunteers

Staphylococcus epidermidis is a major cause of catheter-related bloodstream infections (CRBSIs). Recent studies suggested the existence of well-adapted, highly resistant, hospital-associated S. epidermidis clones. The molecular epidemiology of S. epidermidis in Belgian hospitals and the Belgian community has not been explored yet. We compared a set of 33 S. epidermidis isolates causing CRBSI in hospitalized patients with a set of 33 commensal S. epidermidis isolates. The factors analyzed included resistance to antibiotics and genetic diversity as determined by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and SCCmec typing. Additionally, the presence of virulence-associated mobile genetic elements, the ica operon and the arginine catabolic mobile element (ACME), was assessed and compared against clinical data. CRBSI S. epidermidis isolates were significantly resistant to more antibiotics than commensal S. epidermidis isolates. The two populations studied were very diverse and genetically distinct as only 23% of the 37 PFGE types observed were harbored by both CRBSI and commensal isolates. ACME was found in 76% of S. epidermidis strains, regardless of their origin, while the ica operon was significantly more prevalent in CRBSI isolates than in commensal isolates (P < 0.05). Nine patients presented a clinically severe CRBSI, eight cases of which were due to an ica-positive multiresistant isolate belonging to sequence type 2 (ST2) or ST54. S. epidermidis isolates causing CRBSI were more resistant and more often ica positive than commensal S. epidermidis isolates, which were genetically heterogeneous and susceptible to the majority of antibiotics tested. Clinically severe CRBSIs were due to isolates belonging to two closely related MLST types, ST2 and ST54.

Fluid Flow Induces Biofilm Formation in Staphylococcus epidermidis Polysaccharide Intracellular Adhesin-Positive Clinical Isolates

Staphylococcus epidermidis is a common cause of catheter-related bloodstream infections, resulting in significant morbidity and mortality and increased hospital costs. The ability to form biofilms plays a crucial role in pathogenesis; however, not all clinical isolates form biofilms under normal in vitro conditions. Strains containing the ica operon can display significant phenotypic variation with respect to polysaccharide intracellular adhesin (PIA)-based biofilm formation, including the induction of biofilms upon environmental stress. Using a parallel microfluidic approach to investigate flow as an environmental signal for S. epidermidis biofilm formation, we demonstrate that fluid shear alone induces PIA-positive biofilms of certain clinical isolates and influences biofilm structure. These findings suggest an important role of the catheter microenvironment, particularly fluid flow, in the establishment of S. epidermidis infections by PIA-dependent biofilm formation.