S. Lugauer

A new technology of microdispersed silver in polyurethane induces antimicrobial activity in central venous catheters

SummaryMetal ions or metal ions in complexes or compounds have been used for centuries to disinfect fluids, solids and tissues. The biocidal effect of silver, with its broad spectrum of activity including bacterial, fungal and viral agents, is particularly well known and the term “oligodynamic activity” was coined for this phenomenon. Silver ions have an affinity to sulfhydryl groups in enzyme systems of the cell wall, through which they interfere with the transmembranous energy transfer and electron transport of bacterial microorganisms. Silver ions also block the respiratory chain of microorganisms reversibly in low concentrations and irreversibly in higher concentrations. Binding to the DNA of bacteria and fungi increases the stability of the bacterial double helix and thus inhibits proliferation. There is no cross resistance with antibiotics and also no induction of antimicrobial resistance by silver ions. The concentrations required for bactericidal activity are in the range 10−9 mol/l. These concentrations can be achieved in solution by the interaction of metallic silver with electrolytes only if there is a large enough surface of silver. By a novel technology, metallic silver is distributed in submicron particles in polyurethane and results in a concentration of 0.8% in an active surface of 450 cm2/g polyurethane. Polyurethane is hygroscopic and rapidly attracts water; the interaction of electrolyte solutions with the extremely finely distributed silver throughout the polyurethane releases bactericidal concentrations of silver ions over a period of years to the surface of the material. The electronegatively charged surface of bacteria attracts the positively charged silver ions. The concentrations released from the polyurethane are far below the toxic concentrations for humans.

The Erlanger silver catheter: in vitro results for antimicrobial activity.

SummaryThe antimicrobial activity of a silver-impregnated polymer catheter (the Erlanger silver catheter) was demonstrated by determining the microbial adhesion to the surface of the catheter and by measuring the rate of proliferation (viability) of microorganisms at this site. On the surface of a catheter impregnated with silver, according to previously described methods, the bacterial adhesion ofStaphylococcus epidermidis is reduced by 28–40%. Bacterial proliferation on the surface of the catheter and biofilm production are also substantially reduced by the elution of free silver ions from the catheter matrix. Bacteriostatic and bactericidal activities can be determined. The antimicrobial efficacy of the silver catheter is not reduced by blood components. There is no loss in antimicrobial activity for weeks after preincubation in water or phosphate buffered saline. The antimicrobial activity depends on the extent of the active silver surface.

Reducing catheter-associated infections with silver-impregnated catheters in long-term therapy of children

SummaryCentral venous long-term catheters offer reliable, large-lumen vascular access with high flow rates for delivery of nutrition or for cell-containing infusions and perfusions. Catheter-associated infections (CAI) pose the greatest threat to such vascular access, despite existing preventive measures. In this article one prospective and one retrospective study of CAI in pediatric therapy are presented. Study I: A retrospective investigation from 1990 through 1995 of 60 conventional long-term catheters in 50 patients. The total number of days in which the catheters were in place was 11,818. The calculated CAI incidence was 1 per 1,000 days of catheter insertion. Bacteriologically demonstrated CAI (identical isolate on the catheter tip and in a blood culture) occurred in three instances (5%). Five cases (8.3%) were diagnosed with a therapy-resistant, septic clinical picture. Study II: A prospective, randomized comparison of long-term silver-impregnated (Erlanger silver catheters) and control catheters (Quinton® Instrument Co.) was made with 41 patients (20 with a silver catheter, 21 with a Quinton® catheter). To date, the silver catheters have been distinguished by sterile bacteriological findings, whereas three cases of CAI have been demonstrated with the comparative catheters. One patient recently underwent intensive care after becoming unstable with signs of septic shock and demonstrablePseudomonas aeruginosa, and two other patients manifested coagulase-negative staphylococci on the catheter tips. In three of nine control catheters an incidence of 1.18 per 1,000 days of indwelling catheters was found, whereas no CAI has occurred with the eight microbiologically tested silver catheters.

Analysis of the acute cytotoxicity of the erlanger silver catheter

SummaryThe Erlanger silver catheter consists of a new form of polyurethane, which contains finely dispersed metallic silver. The aim of this study was to establish the biocompatibility of this intravenous catheter by investigating the acute cytotoxicity of extracts from the Erlanger silver catheter on human fibroblasts and lymphocytes. Extracts of the Erlanger silver catheter were not cytotoxic for MRC-5 human fibroblasts nor for sensitized phytohem-agglutinin (PHA)-stimulated human lymphocytes. The addition of silver powder of up to 2% by weight to the basic catheter polyurethane TecothaneTM led to no increase in acute cytotoxicity in comparison with untreated TecothaneTM. The Erlanger silver catheter is a new intravenous catheter with good biocompatibility.

Catheter-associated infections in urology: possible use of silver-impregnated catheters and the Erlanger silver catheter.

SummaryIndwelling urinary catheters play a very important part in urology. However, their use is accompanied by a considerable increase in the risk of nosocomial urinary tract infections. The pathophysiological cause is ascribed to pathogens that adhere to the catheter surface, proliferate and produce a biofilm. In addition to aseptic techniques, modification of the catheter material to confer antimicrobial activity plays an essential part in the prevention of catheter-related urinary tract infections. The antimicrobial efficacy of silver against gram-positive and gram-negative bacteria is well known and amply shownin vitro. The efficacy of silver-impregnated catheters is critically dependent on both the chemical structure of the incorporated silver and the way the silver has been combined with the basic catheter material. Hence, clinical studies on silver-modified catheters have so far given inconsistent results. The new technology of the Erlanger silver catheter offers the opportunity of an effective reduction in catheter-related infections.

Thrombogenicity testing of central venous cathetersin vitro

SummaryTo date there have been no standard methods for assessing the thrombogenicity of central venous catheters. A procedure for testing the thrombogenicity of intravenous lines such as the silver-impregnated catheter by continuous blood flowin vitro was therefore developed. For this test, fresh blood was drawn from healthy human donors and anticoagulated with sodium citrate (1∶9). All material tested (catheter tubes with and without silver manufactured in the same way, polyethylene tubes and tubes with potentially thrombogenic material) were perfused through their lumen with anticoagulated blood for up to 31 hours. Blood samples were collected at different times from the test system at sites before and after the perfusion of the test catheters. The hemoglobin concentration, erythrocyte, leukocyte and thrombocyte counts and markers for thrombin activation (thrombinantithrombin III-complex, F1+2-prothrombin fragments) and for hyperfibrinolysis (d-dimers) were determined. No thrombin activation or signs of hyperfibrinolysis were detected in any material tested. Polyethylene tubes were found to cause hemolysis, as shown by a decrease in hemoglobin content from 15 g% to 4.5 g%. Tecothane® tubes with and without silver did not induce hemolysis.

Silver catheter study: Methods and results of microbiological investigations

SummaryWithin the framework of the clinical study of the Erlangen silver catheter 104 silver catheters and 105 control catheters were tested by microbiological culture. This was done by rolling the catheter on a blood agar plate, washing the lumen through with tryptic soy broth (TSB) and, after ultrasound treatment, incubating the catheter tip in TSB as an enrichment culture for detecting very low bacterial counts. There was good agreement in the numbers of colony-forming units (CFU) detected by the roll plate and luminal washout cultures in 92% of the silver and 89% of the control catheters tested. Seventy-six (73%) of the 104 silver catheters showed no bacterial growth and 16 (15%) showed very low bacteria counts (<15 CFU), or growth only after enrichment, which were attributed in both instances to catheter contamination. Twelve catheter tips (12%) showed significant bacterial counts greater than 15 CFU which were indicative of colonization or catheter-related infection. Corresponding results in the control catheters were 59 (56%), 28 (27%) and 18 (17%), respectively, a higher rate of infection or contamination which was stastistically significant (chi-square test: P=0.04).

Optimal Tobramycin Dosage in Patients with Cystic Fibrosis - Evidence for Predictability Based on Previous Drug Monitoring

SummaryA retrospective analysis of files of patients with cystic fibrosis and pulmonary exacerbations was performed to investigate whether an individual dosage of tobramycin once established by serum level determination allows a reliable prediction of the adequate dosage in a consecutive exacerbation. All patients hospitalized ≥ 2 times between May 1997 and September 1998 with pulmonary exacerbation due to Pseudomonas aeruginosa infection susceptible to tobramycin were included. The initial dosage to tobramycin was 5 mg/kg body weight every 12 h followed by drug level determinations to establish the optimal dose. In a consecutive exacerbation the same dosage per kg body weight was used again and drug level determinations were repeated. Sixteen patients (six female = 38%) with a mean age of 24 years (median: 26) years, range: 9–,33) were hospitalized for 49 pulmonary exacerbations (2–6 per patient, mean: 3, median: 2.5). During the first episode of tobramycin treatment in the study period all trough levels were < 2 μg/ml (median: 0.6) and the peak levels were 7.1–16.9 μg/ml (median: 11.9). In four patients the peak level was > 12 μg/ml. In 28 consecutive episodes the dosage of tobramycin was chosen based on optimal results of previous drug level monitoring and in 27 instances (96%) the previously established optimal dose was confirmed. In five consecutive episodes the tobramycin dosage had been increased erroneously and this resulted in abnormally high peak levels in three cases. These findings suggest that a safe and therapeutic tobramycin dosage in an individual patient with cystic fibrosis is predictable based on a previously established optimal dosage.

Clinical study of the erlanger silver catheter—Data management and biometry

SummaryThe clinical evaluation of venous catheters for catheter-induced infections must conform to a strict biometric methodology. The statistical planning of the study (target population, design, degree of blinding), data management (database design, definition of variables, coding), quality assurance (data inspection at several levels) and the biometric evaluation of the Erlanger silver catheter project are described. The three-step data flow included: 1) primary data from the hospital, 2) relational database, 3) files accessible for statistical evaluation. Two different statistical models were compared: analyzing the first catheter only of a patient in the analysis (independent data) and analyzing several catheters from the same patient (dependent data) by means of the generalized estimating equations (GEE) method. The main result of the study was based on the comparison of both statistical models.