Central venous catheters for chemotherapy of solid tumors--our results in the last 5 years

Central venous catheters provide an easy access for intravenous medications. Having a central line in place will relieve a child from the discomfort and danger of multiple regular intravenous lines for chemotherapy. The use of indwelling central venous catheters has become commonplace in the management of children undergoing oncological treatment. There are two types of central lines commonly used. There are Broviac catheters and Port-A-Cath (PAC) catheters. In the last 5 years we inserted 194 catheters in 175 children. We inserted 121 Broviac catheters and 73 PAC catheters. During the follow up of 39382 catheter days 44 complications were observed. In Broviac group the median follow up was 155 days and in PAC group was 230 days. We observed differences in the incidence between two devices. In Broviac group infections were more frequent and in PAC group other complications were more frequent than infections.     

Peripherally inserted central venous catheters. Low-risk alternatives for ongoing venous access.

We prospectively evaluated the use of peripherally inserted central venous catheters to provide ongoing venous access in general medical and surgical patients in a Department of Veterans Affairs medical center. Between 1985 and 1988 trained nurses successfully inserted 393 catheters in 460 suitable patients (an 85.4% success rate). Correct catheter tip placement in the superior vena cava was documented in 359 of the 393 (91.3%) catheter insertions, but an additional 30 catheters were in a position deemed adequate for the intended use. The mean duration of catheter use was 27.6 +/- 5.2 (1 standard deviation) days (median 20 days, range 1 to 370 days). A total of 65 patients left the hospital with catheters in place, with the mean length of catheter use at home being 36.2 +/- 6.0 days (range 2 to 266). In all, 79% of the catheters were in use until the successful completion of therapy or patient death; catheter-related complications led to premature catheter removal in the remaining 21%. Catheter-related complications included bland phlebitis (8.2%), occlusion (8.2%), local infection (3.6%), bacteremia or fungemia (2.1%), mechanical failure or rupture (2.6%), venous thrombosis (0.7%), and other (3.3%). One patient required vein excision for the management of suppurative phlebitis, but no deaths were attributed to catheter use. This study illustrates the use and safety of peripherally inserted central venous catheters to provide reliable vascular access over prolonged periods in an elderly veteran population. At our facility, percutaneous central venous catheters and surgically implanted (Hickman or Broviac) catheters are now reserved for use in patients in whom peripherally inserted catheters cannot be placed.     

Taurolidine Lock Is Superior to Heparin Lock in the Prevention of Catheter Related Bloodstream Infections and Occlusions

Background and Aims

Patients on home parenteral nutrition (HPN) are at risk for catheter-related complications; mainly infections and occlusions. We have previously shown in HPN patients presenting with catheter sepsis that catheter locking with taurolidine dramatically reduced re-infections when compared with heparin. Our HPN population therefore switched from heparin to taurolidine in 2008. The aim of the present study was to compare long-term effects of this catheter lock strategy on the occurrence of catheter-related bloodstream infections and occlusions in HPN patients.

Methods

Data of catheter-related complications were retrospectively collected from 212 patients who received HPN between January 2000 and November 2011, comprising 545 and 200 catheters during catheter lock therapy with heparin and taurolidine, respectively. We evaluated catheter-related bloodstream infection and occlusion incidence rates using Poisson-normal regression analysis. Incidence rate ratios were calculated by dividing incidence rates of heparin by those of taurolidine, adjusting for underlying disease, use of anticoagulants or immune suppressives, frequency of HPN/fluid administration, composition of infusion fluids, and duration of HPN/fluid use before catheter creation.

Results

Bloodstream infection incidence rates were 1.1/year for heparin and 0.2/year for taurolidine locked catheters. Occlusion incidence rates were 0.2/year for heparin and 0.1/year for taurolidine locked catheters. Adjusted incidence ratios of heparin compared to taurolidine were 5.9 (95% confidence interval, 3.9–8.7) for bloodstream infections and 1.9 (95% confidence interval, 1.1–3.1) for occlusions.

Conclusions

Given that no other procedural changes than the catheter lock strategy were implemented during the observation period, these data strongly suggest that taurolidine decreases catheter-related bloodstream infections and occlusions in HPN patients compared with heparin.     

Antimicrobial and antifouling efficacy of urinary catheters impregnated with a combination of macrolide and fluoroquinolone antibiotics against Pseudomonas aeruginosa

The incidence of catheter associated urinary tract infections (CAUTIs) is increasing worldwide. This study was designed to modify a biomaterial by impregnating a silicone urinary catheter with combination of a macrolide, azithromycin (AZM) and a fluoroquinolone, ciprofloxacin (CIP). Drug release profiles showed slow yet continuous release of antibiotics from catheters for one month. In vitro efficacy testing showed that group B catheters [3% (w v^?1) CIP + 6% (w v^?1) AZM] outperformed group A catheters [2% (w v^?1) CIP + 5% (w v^?1) AZM] by (1) showing larger zones of inhibition (>31 mm) compared to group A (<28 mm) for up to 30 days against Pseudomonas aeruginosa PAO1; (2) killing adhered bacteria in 24 h compared to 24–48 h in group A; (3) showing longer antimicrobial durability for four weeks; and (4) exhibiting a stable real-time shelf life of one year, suggesting that these catheters can be explored in clinical settings, especially in long-term CAUTI.     

Incidence of deep vein thrombosis related to peripherally inserted central catheters in children and adolescents

Background

Peripherally inserted central catheters (PICC) in children and adolescents are being used with increasing frequency. We sought to determine the incidence and characterize risk factors of deep vein thrombosis associated with peripherally inserted central catheters in a pediatric population.

Methods

We conducted a prospective study involving consecutive patients referred to the radiology department of a tertiary care university-affiliated hospital for insertion of a peripherally inserted central catheter. We included patients aged 18 years or less who weighed more than 2.5 kg and had a peripherally inserted central catheter successfully inserted in his or her arm between June 2004 and November 2005. The primary outcome was the occurrence of partial or complete deep vein thrombosis evaluated by clinical examination, ultrasonography and venous angiography.

Results

A total of 214 patients (101 girls, 113 boys) were included in the study. Partial or complete deep vein thrombosis occurred in 20 patients, for an incidence of 93.5 per 1000 patients and 3.85 per 1000 catheter-days. Only 1 of the cases was symptomatic. In the univariable analyses, the only variable significantly associated with deep vein thrombosis was the presence of factor II mutation G20210A (odds ratio 7.08, 95% confidence interval 1.11–45.15, p = 0.04), a genetic mutation that increases the risk of a blood clot and that was present in 5 (2.3%) of the 214 patients.

Interpretation

The incidence of deep vein thrombosis related to peripherally inserted central catheters in our study was lower than the incidence related to centrally inserted venous catheters described in the pediatric literature (11%–50%).Most data available in the adult and pediatric literature on the incidence of deep vein thrombosis concern centrally inserted venous catheters, which are inserted directly in a central vein (jugular, subclavian or femoral). Typical symptoms of deep vein thrombosis are frequently absent in children and adolescents. Although the diagnosis of deep vein thrombosis is more reliable when based on Doppler ultrasonography or venous angiography,^1–10 in most studies these diagnostic tests were performed only when patients presented clinical symptoms of deep vein thrombosis or catheter dysfunction. In studies focused on the pediatric population, the frequency of deep vein thrombosis related to centrally inserted venous catheters has varied from 11% to 50%.^1,5,6,8,11In the past 10 years, peripherally inserted central catheters (PICC) have been used with increasing frequency in children and adolescents. The catheter is inserted percutaneously via a peripheral vein, with its tip residing in the superior vena cava. The main indications for this type of catheter insertion are difficult venous access, home intravenous antibiotic therapy, administration of chemotherapy or other hyperosmolar solution and long-term parenteral nutrition. The risk of deep vein thrombosis related to peripherally inserted central catheters could be greater among children and adolescents than among adults, given the size of the veins. Several studies have published complications related to peripherally inserted central catheters,^12–20 but few focused on the pediatric population.^13–21 Furthermore, in all of these studies, screening for deep vein thrombosis was not systematic. The real incidence of deep vein thrombosis related to peripherally inserted central catheters and their complications in the pediatric population are therefore unknown. We conducted this study to determine the incidence and characterize the risk factors of deep vein thrombosis related to peripherally inserted central catheters in children and adolescents in our institution.     

Catheter related bloodstream infection (CR-BSI) in ICU patients: making the decision to remove or not to remove the central venous catheter

Background

Approximately 150 million central venous catheters (CVC) are used each year in the United States. Catheter-related bloodstream infections (CR-BSI) are one of the most important complications of the central venous catheters (CVCs). Our objective was to compare the in-hospital mortality when the catheter is removed or not removed in patients with CR-BSI.

Methods

We reviewed all episodes of CR-BSI that occurred in our intensive care unit (ICU) from January 2000 to December 2008. The standard method was defined as a patient with a CVC and at least one positive blood culture obtained from a peripheral vein and a positive semi quantitative (>15 CFU) culture of a catheter segment from where the same organism was isolated. The conservative method was defined as a patient with a CVC and at least one positive blood culture obtained from a peripheral vein and one of the following: (1) differential time period of CVC culture versus peripheral culture positivity of more than 2 hours, or (2) simultaneous quantitative blood culture with 5∶1 ratio (CVC versus peripheral).

Results

53 CR-BSI (37 diagnosed by the standard method and 16 by the conservative method) were diagnosed during the study period. There was a no statistically significant difference in the in-hospital mortality for the standard versus the conservative method (57% vs. 75%, p = 0.208) in ICU patients.

Conclusion

In our study there was a no statistically significant difference between the standard and conservative methods in-hospital mortality.     

Catheter-tract infections in rhesus macaques (Macaca mulatta) with indwelling intravenous catheters

Development of catheter-tract infections in experimental animals can have devastating consequences on animal health and the functional lifespan of surgical implants. To measure the incidence of catheter-tract infections in animals with exteriorized intravenous catheters in this facility and assess the effects of these infections on mean catheter lifespan, health records of 31 Macaca mulatta with catheters were reviewed. Records spanned the interval of January 1, 1996 through October 1, 1997. Catheter-tract infections in 16 of 53 (30.2%) monkeys with catheters were diagnosed based on a combination of clinical signs of infection and results of bacterial culture. Segmental catheter-tract infections reduced mean catheter lifespan to 147 days, compared with 354 days for uninfected catheters. Exit-wound, local tunnel, and surgical-site infections did not significantly reduce catheter lifespan. Bacterial culture reports documented 31 isolates; 41.9% (13 of 31) were coagulase-negative staphylococci, and 22.6% (7 of 31) were Staphylococcus aureus. Of 20 isolates tested, 15 (75%) were resistant to methicillin/oxacillin in vitro. Antimicrobial susceptibility testing of methicillin-resistant and methicillin-susceptible isolates indicated that, compared with methicillin-sensitive isolates, methicillin-resistant isolates had a pattern of multiple antibiotic resistance. Catheter-tract infections were common in this colony of rhesus macaques, and clinically severe infections caused a drastic reduction in catheter lifespan. Approximately half (48%) the bacterial isolates were methicillin-resistant gram-positive bacteria.     

Hospital-Wide Multidisciplinary,Multimodal Intervention Programme to Reduce Central Venous Catheter-Associated Bloodstream Infection

Central line-associated bloodstream infection (CLABSI) is the major complication of central venous catheters (CVC). The aim of the study was to test the effectiveness of a hospital-wide strategy on CLABSI reduction. Between 2008 and 2011, all CVCs were observed individually and hospital-wide at a large university-affiliated, tertiary care hospital. CVC insertion training started from the 3^rd quarter and a total of 146 physicians employed or newly entering the hospital were trained in simulator workshops. CVC care started from quarter 7 and a total of 1274 nurses were trained by their supervisors using a web-based, modular, e-learning programme. The study included 3952 patients with 6353 CVCs accumulating 61,366 catheter-days. Hospital-wide, 106 patients had 114 CLABSIs with a cumulative incidence of 1.79 infections per 100 catheters. We observed a significant quarterly reduction of the incidence density (incidence rate ratios [95% confidence interval]: 0.92 [0.88–0.96]; P<0.001) after adjusting for multiple confounders. The incidence densities (n/1000 catheter-days) in the first and last study year were 2.3/1000 and 0.7/1000 hospital-wide, 1.7/1000 and 0.4/1000 in the intensive care units, and 2.7/1000 and 0.9/1000 in non-intensive care settings, respectively. Median time-to-infection was 15 days (Interquartile range, 8-22). Our findings suggest that clinically relevant reduction of hospital-wide CLABSI was reached with a comprehensive, multidisciplinary and multimodal quality improvement programme including aspects of behavioural change and key principles of good implementation practice. This is one of the first multimodal, multidisciplinary, hospital-wide training strategies successfully reducing CLABSI.     

In Vitro Evaluation of the Efficacy of a Silver-Coated Catheter

Bacteria commonly associated with nosocomial urinary tract infections were examined in vitro for their relative adherence to latex, 100% silicone-, hydrogel-coated latex-, and hydrogel/silver-coated latex urinary catheters. Degrees of adherence within 2 h were determined with cells radiolabeled with leucine. Adherence was greatest and equivalent on silicone and latex catheters. Adherence of four strains of Escherichia coli to the hydrogel/silver-coated catheter was decreased by 50% to 99% in comparison with the other catheters. Repeat testing with strains of E. coli and Pseudomonas aeruginosa with over 50 catheters demonstrated a consistency in the inhibition. The hydrophilic coating of the catheter appeared to be primary in the decreased adherence phenomenon followed by a secondary biocidal effect of the silver ion. Received: 2 December 1995 / Accepted: 3 January 1996     

A Retrospective Study of Preferable Alternative Route to Right Internal Jugular Vein for Placing Tunneled Dialysis Catheters: Right External Jugular Vein versus Left Internal Jugular Vein

Background

Right internal jugular vein (IJV) is a preferred access route for tunneled (cuffed) dialysis catheters (TDCs), and both right external jugular vein (EJV) and left IJV are alternative routes for patients in case the right IJV isn’t available for TDC placement. This retrospective study aimed to determine if a disparity exists between the two alternative routes in hemodialysis patients in terms of outcomes of TDCs.

Methods

49 hemodialysis patients who required TDCs through right EJV (n = 21) or left IJV (n = 28) as long-term vascular access were included in this study. The primary end point was cumulative catheter patency. Secondary end points include primary catheter patency, proportion of patients that never required urokinase and incidence of catheter-related bloodstream infections (CRBSI).

Results

A total of 20,870 catheter-days were evaluated and the median was 384 (interquartile range, 262–605) catheter-days. Fewer catheters were removed in the right EJV group than in the left IJV group (P = 0.007). Mean cumulative catheter patency was higher in the right EJV group compared with the left IJV group (P = 0.031). There was no significant difference between the two groups in the incidence of CRBSI, primary catheter patency or proportion of patients that never required urokinase use. Total indwell time of antecedent catheters was identified as an independent risk factor for cumulative catheter patency by Cox regression hazards test with an HR of 2.212 (95% CI, 1.363–3.588; p = 0.001).

Conclusions

Right EJV might be superior to left IJV as an alternative insertion route for TDC placement in hemodialysis patients whose right IJVs are unavailable.     

Catheter-related thrombosis in hematologic patients

For many years central venous catheters (CVC) have been utilized to monitor hemodynamics and to deliver parenteral nutrition, blood products, pharmacological therapies or infusion fluids. Recently, CVC use has greatly increased with significant impact on the administration of chemotherapy, stem cell transplantation and other treatments to cancer patients. However, CVC use may be accompanied by a variety of side-effects, which increase with the duration of implantation. The most common catheter-related complications are thrombotic events and blood-stream infections. The true incidence of these complications is still uncertain and has changed over time due to CVC device improvement. More data are available in solid tumor than in oncohematologic patients. Recently, much attention has been paid to the issues of prevention and treatment of these complications. Some strategies have been proposed: fixed dose warfarin or low molecular weight heparins have been evaluated in some clinical trials of thromboprophylaxis in this condition. However, more studies are still needed to address this issue. This review will focus on CVC use and complications in oncohematologic patients.     

Clinical and Therapeutic Aspects of Candidemia: A Five Year Single Centre Study

BackgroundCandida is an important cause of bloodstream infections (BSI) in nosocomial settings causing significant mortality and morbidity. This study was performed to evaluate contemporary epidemiology, species distribution, antifungal susceptibility and outcome of candida BSI in an Italian hospital.MethodsAll consecutive patients who developed candidemia at Santa Maria della Misericordia University Hospital (Italy) between January 2009 and June 2014 were enrolled in the study.ResultsA total of 204 episodes of candidemia were identified during the study period with an incidence of 0.79 episodes/1000 admissions. C. albicans was isolated in 60.3% of cases, followed by C. parapsilosis (16.7%), C. glabrata (11.8%) and C. tropicalis (6.4%). Of all Candida BSI, 124 (60.8 %) occurred in patients admitted to IMW, 31/204 (15.2 %) in ICUs, 33/204 (16.2%) in surgical units and 16/204 (7.8%) in Hematology/Oncology wards. Overall, 47% of patients died within 30 days from the onset of candidemia. C. parapsilosis and C. glabrata candidemia were associated with the lowest mortality rate (36%), while patients with C. tropicalis BSI had the highest mortality rate (58.3%). Lower mortality rates were detected in patients receiving therapy within 48 hours from the time of execution of the blood cultures (57,1% vs 38,9%, P <0.05). At multivariate analysis, steroids treatment (OR= 0.27, p=0.005) and CVC removal (OR=3.77, p=0.014) were independently associated with lower and higher survival probability, respectively. Candidemia in patients with peripherally inserted central catheters (PICC) showed to be associated with higher mortality in comparison with central venous catheters (CVC, Short catheters and Portacath) and no CVC use. For each point increase of APACHE III score, survival probability decreased of 2%. Caspofungin (OR=3.45, p=0.015) and Amphothericin B lipid formulation (OR=15.26, p=0.033) were independently associated with higher survival probability compared with no treatment.     

腔静脉滤器植入联合导管溶栓术治疗下肢深静脉血栓的疗效分析

目的:探讨腔静脉滤器植入联合导管溶栓术治疗下肢深静脉血栓患者的临床疗效及安全性。方法:回顾性分析2012年10月~2014年10月来我院住院治疗的80例下肢深静脉血栓形成患者的临床资料,根据治疗方式及溶栓途径的差异分为两组,比较两组患者治疗前后下肢周径差变化、静脉通畅率、血栓后综合征情况及治疗后并发症的发生情况。结果:治疗后,两组患者下肢平均周径均有所减少,肿胀明显缓解,静脉通畅度评分显著降低,较治疗前差异有统计学意义(P0.05);其中,观察组患者下肢消肿率更为明显,静脉通畅度更好,较对照组差异有统计学意义(P0.05)。治疗后对照组患者PTS发生例数为9例(23.68%),观察组PTS发生率更低仅为1例(2.38%),差异有统计学意义(P0.05)。两组患者治疗后均出现并发症,但发生率比较无明显统计学意义(P0.05)。结论:采用腔静脉滤器植入联合导管溶栓术治疗下肢深静脉血栓可使静脉阻塞部位尽早恢复通畅,减少瓣膜功能损害,降低PTS等并发症的发生率。     

Mouse models of short- and long-term foreign body in the urinary bladder: analogies to the bladder segment of urinary catheters.

Catheter-associated bacteriuria is the most common infection occurring in hospitals, where urethral catheters are generally in place for a few days, and in nursing homes, where catheters may be in place for months or years. We developed murine models with intrabladder urinary catheters for studying complications of bacteriuria in short- and long-term catheterization. In the short-term model, a catheter segment was inserted transurethrally and lay free within the bladder lumen. Half of the animals expelled segments during a 2-to-7-day period, durations similar to catheterizations in hospitalized patients. For studies of long-term catheter use, the catheter segment was secured within the bladder by a single suture for up to 12 months. Antibiotics administered for 7 days after catheter placement and housing mice in cages with wire screen floors reduced spontaneous bacteriuria to an acceptably low incidence rate of only 7%. Proteus mirabilis bacteriuria of high concentration provoked the same complications that are common in patients with long-term catheters: acute pyelonephritis, chronic renal inflammation, and struvite stone formation. These models allow inoculation of the bacteria of interest and are suitable for studies of short- and long-term foreign body-associated bacteriuria and its complications.     

On-demand release of Candida albicans biofilms from urinary catheters by mechanical surface deformation

Abstract

Candida albicans is a leading cause of catheter-associated urinary tract infections and elimination of these biofilm-based infections without antifungal agents would constitute a significant medical advance. A novel urinary catheter prototype that utilizes on-demand surface deformation is effective at eliminating bacterial biofilms and here the broader applicability of this prototype to remove fungal biofilms has been demonstrated. C. albicans biofilms were debonded from prototypes by selectively inflating four additional intralumens surrounding the main lumen of the catheters to provide the necessary surface strain to remove the adhered biofilm. Deformable catheters eliminated significantly more biofilm than the controls (>90% eliminated vs 10% control; p < 0.001). Mechanical testing revealed that fungal biofilms have an elastic modulus of 45 ± 6.7 kPa with a fracture energy of 0.4–2 J m^?2. This study underscores the potential of mechanical disruption as a materials design strategy to combat fungal device-associated infections.     

High rate of Candida deep-seated infection in patients under chronic hemodialysis with extended central venous catheter use

BackgroundHemodialysis has been described as an important risk factor for the development of candidemia in patients suffering from chronic renal failure.AimsThe aim of this study was to evaluate the epidemiology of candidemia in outpatients with renal replacement therapy (RRT) by hemodialysis where the fungemia clearly represents a healthcare-associated infection.MethodsWe retrospectively collected clinical and laboratory data from patients undergoing at least 3 months of RRT by hemodialysis who developed candidemia within 48 h of hospital admission.ResultsWe identified 14 patients with candidemia with central venous catheters (CVC) in place for 11–277 days before developing fungemia. Deep-seated infection was documented in 6 out of 14 candidiasis cases (43%), including 5 cases of endocarditis (36%).ConclusionsCVC in patients under RRT should be promptly replaced by fistulas and grafts to avoid bloodstream infections. Facing a case of candidemia, adequate source control and prompt initiation of antifungal therapy are mandatory to avoid morbidity and mortality.     

The anti-biofilm and anti-virulence activities of trans-resveratrol and oxyresveratrol against uropathogenic Escherichia coli

Abstract

Uropathogenic Escherichia coli (UPEC) is the primary causative agent of urinary tract infections, which are one of the most common infectious disease types in humans. UPEC infections involve bacterial cell adhesion to bladder epithelial cells, and UPEC can also form biofilms on indwelling catheters that are often tolerant to common antibiotics. In this study, the anti-biofilm activities of t-stilbene, stilbestrol, t-resveratrol, oxyresveratrol, ε-viniferin, suffruticosol A, and vitisin A were investigated against UPEC. t-Resveratrol, oxyresveratrol, and ε-viniferin, suffruticosol A, and vitisin A significantly inhibited UPEC biofilm formation at subinhibitory concentrations (10–50?μg ml^?1). These findings were supported by observations that t-resveratrol and oxyresveratrol reduced fimbriae production and the swarming motility in UPEC. Furthermore, t-resveratrol and oxyresveratrol markedly diminished the hemagglutinating ability of UPEC, and enhanced UPEC killing by human whole blood. The findings show that t-resveratrol, oxyresveratrol, and resveratrol oligomers warrant further attention as antivirulence strategies against persistent UPEC infections.     

Use of Pistacia lentiscus mastic for sustained-release system of chlorocresol and benzoic acid for in vitro prevention of bacterial colonization of silicon urinary catheter

Urinary tract infections (UTI) are among the most common types of nosocomial infections. Patients with indwelling urinary catheters are at the highest risk of getting infections. A sustained-release method of chlorocresol and benzoic acid using a varnish of Pistacia lentiscus mastic was developed to prevent catheter colonization by Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Pseudomonas aeruginosa. Coatings of both antiseptics significantly reduced the number of colonizing bacteria on silicon urinary catheters for 72 h. Chlorocresol-coated catheters were significantly (P ≤ 0·05) more effective than benzoic acid. Except for the Pr. mirabilis, chlorocresol completely inhibited the colonization of catheters by the tested bacteria for 48 h. Nonetheless, the colonization of catheters by Pr. mirabilis was significantly reduced after 48 and 72 h by more than 3·5 logs. Although benzoic acid failed to completely inhibit bacterial growth, it significantly reduced the colonization of the catheters by all the tested bacteria by more than two logs for 72 h. The inhibition of colonization of catheters was confirmed by examining the tested catheters by scanning electron microscopy. The obtained results indicate the potential benefits of using mastic as a varnish for sustaining the release of chlorocresol and benzoic acid to prevent and reduce the colonization of urinary catheters by bacteria.     

Type 1 Fimbriae Contribute to Catheter-Associated Urinary Tract Infections Caused by Escherichia coli

Biofilm formation on catheters is thought to contribute to persistence of catheter-associated urinary tract infections (CAUTI), which represent the most frequent nosocomial infections. Knowledge of genetic factors for catheter colonization is limited, since their role has not been assessed using physicochemical conditions prevailing in a catheterized human bladder. The current study aimed to combine data from a dynamic catheterized bladder model in vitro with in vivo expression analysis for understanding molecular factors relevant for CAUTI caused by Escherichia coli. By application of the in vitro model that mirrors the physicochemical environment during human infection, we found that an E. coli K-12 mutant defective in type 1 fimbriae, but not isogenic mutants lacking flagella or antigen 43, was outcompeted by the wild-type strain during prolonged catheter colonization. The importance of type 1 fimbriae for catheter colonization was verified using a fimA mutant of uropathogenic E. coli strain CFT073 with human and artificial urine. Orientation of the invertible element (IE) controlling type 1 fimbrial expression in bacterial populations harvested from the colonized catheterized bladder in vitro suggested that the vast majority of catheter-colonizing cells (up to 88%) express type 1 fimbriae. Analysis of IE orientation in E. coli populations harvested from patient catheters revealed that a median level of ∼73% of cells from nine samples have switched on type 1 fimbrial expression. This study supports the utility of the dynamic catheterized bladder model for analyzing catheter colonization factors and highlights a role for type 1 fimbriae during CAUTI.