Cellulose acetate-based composites with antimicrobial properties from embedded molybdenum trioxide particles.

The objective of this research was to develop novel cellulose acetate (biopolymer) composite materials with an excellent antimicrobial activity by embedding molybdenum trioxide particles with unique high specific surface area. High surface area molybdenum trioxide particles were prepared from freshly precipitated molybdenum trioxide dihydrate (MoO3 ·2H2 O) and subsequent calcination at 340°C under H2 /N2 gas. Microbiological evaluation against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were performed applying a roll-on test and excellent antimicrobial activities were determined for composites with embedded anhydrous molybdenum trioxide with a high specific surface area. Cellulose acetate composites comprising MoO3 particles can eliminate three harmful bacteria as a result of the release of protons from the material and surface enlargement of the molybdenum trioxide particles. The findings support a proposed antimicrobial mechanism based on local acidity increase due to large specific surface areas. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, development of a novel thermoplastic bio-based composite with excellent antimicrobial surface properties is investigated. To the best of our knowledge, this is the first report to evaluate the antimicrobial properties of molybdenum trioxide embedded into a cellulose acetate as biopolymer matrix. The developed composites might step up to innovative applications used in modern medical and public environments.

Prevention of catheter-related infections: the potential of a new nano-silver impregnated catheter.

Contaminated or infected catheters are a major source of nosocomial infections responsible for >40% of all episodes of nosocomial sepsis in acute-care hospitals. Antibiotics as well as surface modifications with, for example, hydrogels proved to be of little value in preventing the contamination of indwelling catheters. The even distribution of 10(12-13) activated silver nanoparticles per gram in various polymers, e.g. polyurethane and silicone, results in an excellent antimicrobial activity against a broad spectrum of organisms in vitro. Substantial reduction of incrustation of these catheters was also observed. These preliminary experimental data warrant clinical studies.

[Acid oligosaccharides as the active principle of aqueous carrot extracts for prevention and therapy of gastrointestinal infections]. / Saure Oligosaccharide als Wirkprinzip von wässrigen Zubereitungen aus der Karotte in der Prophylaxe und Therapie von gastrointestinalen Infektionen.

Adherence of microorganisms to the intestinal mucosa is an important and initial step in the pathogenesis of gastrointestinal infections and mediated by carbohydrate structures on the cell surface. Adherence can be blocked by carbohydrate receptor analogues. Aqueous extracts from carrots (carrot soup) contain acidic oligosaccharides, which are able to block adherence of various enteropathogenic microorganisms to HEp-2 cells and human intestinal mucosa in vitro. Dependent on the grade of polymerisation the most potent blocking ability was seen for trigalacturonic acid. Clinical studies revealed, that aqueous carrot extracts are significantly superior to the basic glucose-electrolyt-solution for oral rehydration in acute gastrointestional infections of children.

Contamination of central venous catheters in immunocompromised patients: a comparison between two different types of central venous catheters.

Catheters impregnated with silver have been proposed as a means of reducing catheter-related infection. We therefore performed a prospective randomized study to compare a new silver-impregnated central venous catheter (CVC) with a commercially available CVC in a cohort of immunocompromised patients. We studied 157 patients of whom 97 could be analysed. The median indwelling time in the study group (SC) was 10.5 days and 11 days in the control group (CC). The incidence of contamination in the SC group was 15.6 vs 24.6 in the CC group referring to 1000 catheter days. In both groups, we found 6% of catheter-related infections according to the definitions of a published scoring system. The differences between the two groups were not significant. We conclude that the SC decrease the incidence of catheter contamination and may have a positive effect on the reduction of CVC-related infections.

Influence of macrolide antibiotics on promotion of resistance in the oral flora of children.

BACKGROUND: The long elimination half-life of azithromycin allows subinhibitory serum and epithelial lining fluid (ELF) concentrations over a period of several weeks post treatment, which may have an impact on the emergence of macrolide resistance. In this prospective, open-label, randomized study, four macrolides and the azalide azithromycin were studied for their likelihood to promote resistance in the oral flora of children with respiratory tract infections. PATIENTS AND METHODS: Children were randomly assigned to receive azithromycin, clarithromycin, erythromycin, roxithromycin and josamycin. Throat swabs were obtained prior to treatment and weekly for 6 weeks. Minimum inhibitory concentrations (MICs) for resistant strains were assessed by E-test and National Committee for Clinical laboratory Standards (NCClS) broth microdilution. RESULTS: One week post treatment, up to 90% of children harbored macrolide-resistant strains in their oral flora. Except for azithromycin, the percentage of patients colonized by resistant organisms decreased to a rate of 17% for clarithromycin (10/60), erythromycin (2/12) and josamycin (2/12) and 33% for roxithromycin (4/12) after 6 weeks. In the azithromycin group, 85% (51/60) of patients were colonized by macrolide-resistant organisms after 6 weeks, 11.6% (7/60) of children suffered from reinfection. CONCLUSION: Azithromycin therapy appears to put selective pressure on the infective and native flora of children, promoting the carriage of macrolide-resistant strains.

[Papilledema and acute bilateral amaurosis accompanying acute sinusitis]. / Papillenödem und akute bilaterale Amaurose bei akuter Sinusitis.

BACKGROUND: Acute sinusitis can lead to severe complications. This includes involvement of the optical nerve with visual loss and brain abscess as a life-threatening complication. PATIENTS: Empyema of the chiasma opticum region with neuritis nervi optici and bilateral acute amaurosis was observed in a 13 year old boy with sinusitis sphenoidalis and ethmoidalis. In a 11 year old girl, pronounced papilledema was found to be closely associated with sinusitis sphenoidalis. While she recovered completely on appropriate antibiotic therapy, visual loss in the boy was irreversible despite surgical intervention. CONCLUSIONS: Sinusitis should always be considered in patients with impaired vision, neuritis nervi optici or unexplained papilledema, especially if occurring in association with an upper respiratory infection. In addition to physical examination, cranial computer tomography or magnetic resonance imaging of the brain including sinuses and chiasma opticum should be applied early. If empyema is found, immediate surgical intervention is of prognostic importance.

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

Metal 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.

Thrombogenicity testing of central venous catheters in vitro.

To 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 flow in vitro was therefore developed. For this test, fresh blood was drawn from healthy human donors and anti-coagulated 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 (thrombin-antithrombin 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.

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

The 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 of Staphylococcus 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.

Biocompatibility testing of a new silver-impregnated catheter in vivo.

The purpose of this investigation was to compare the local effects of polyurethane (Tecothane) and silicone tubes with or without silver impregnation in rats. Bacterial colonization or infection of the exit site and/or tunnel were documented and interpreted. All tubes were placed subcutaneously or percutaneously in the neck of 41 Sprague-Dawley rats and guided beneath the dorsal muscles into the peritoneal cavity. The incidence of bacterial abscesses along the implanted tubes was evaluated daily. After 90 days, or earlier if sepsis developed, the animals were killed painlessly and various organs and tissues from the entry site and the catheter tunnel examined histologically. In the group where polyurethane tubes were placed percutaneously, there was no difference in the frequency of abscesses between silver-impregnated and non-impregnated tubes (5/6 with and 5/7 without silver). The only difference noted was in the group with percutaneously placed silicone tubes between those with and without silver. Abscesses only occurred in 2/4 animals in the silver group and in 5/5 animals in the control group. Histological examination showed no difference in either group between infectious and foreign body reactions. Silver particles in subcutaneous, muscle and peritoneal tissue could not be demonstrated.

Analysis of the acute cytotoxicity of the Erlanger silver catheter.

The 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 phytohemagglutinin (PHA)-stimulated human lymphocytes. The addition of silver powder of up to 2% by weight to the basic catheter polyurethane Tecothane led to no increase in acute cytotoxicity in comparison with untreated Tecothane. The Erlanger silver catheter is a new intravenous catheter with good biocompatibility.

A new scoring system for the clinical diagnosis of catheter-related infections.

It is difficult to make the clinical diagnosis of catheter-related infections using the available and established definitions of the HICPAC (Hospital Infection Control Practices Advisory Committee) of the CDC (Centers for Disease Control, definitions of nosocomial infections). The scoring system shown here is a modification of these definitions and has enabled the causal relationship between the catheter and clinical episodes of systemic infections to be quantitatively graded. The scoring system included the following criteria: height and rate of rise of body temperature, attendant shivering, identification of pathogens in blood and/or catheter tip cultures, improvement in the clinical course after catheter removal, signs of catheter exit site inflammation and results of diagnostic tests for other possible sources of infection. These criteria were graded using points and weighted according to their specificity. The comparative evaluation of 65 episodes of systemic infections using the scoring system and the diagnostic criteria of HICPAC showed agreement in 85%. No case was graded "false-negative." In nine of ten false-positive cases additional findings supported the presence of a catheter-associated infection. This scoring system appears, therefore, to be more sensitive than existing diagnostic criteria, without loss of specificity.

Silver catheter study: methods and results of microbiological investigations.

Within 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 statistically significant (chi-square test: P = 0.04).

Clinical study of the Erlanger silver catheter--data management and biometry.

The 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.

Reduced rates of catheter-associated infection by use of a new silver-impregnated central venous catheter.

A central venous catheter with a new form of silver impregnation of the internal and external surfaces was investigated for antimicrobial activity and tolerance in patients in a controlled comparative, prospective and randomized clinical study. Commercially available catheters with no antimicrobial activity were used as controls. One hundred sixty-five catheters were included in the final evaluation. All catheters were percutaneously inserted for the first time with a duration of > or = 5 days and a microbiological examination of the catheter tip. Catheter location (> 90% internal jugular vein), mean duration of catheterization (8-9 days), patients' age and diagnosis were comparable in both groups. Silver-impregnated catheter tips showed an incidence of colonization in 14.2/1000 catheter days and control catheters in 22.8/1000 catheter days. This represents a reduction of 37.7%. Catheter-associated infections were diagnosed in the silver group in 5.26/1000 catheter days and 18.34/1000 catheter days in the control group, indicating a reduction rate of 71.3% (P < 0.05, chi 2-test). No complications or side effects were documented in either group.

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

Central 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 demonstrable Pseudomonas 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.

Pharmacokinetic and clinical evaluation of serious infections in premature and newborn infants under therapy with imipenem/cilastatin.

Efficacy and pharmacokinetic parameters of imipenem/cilastatin (I/C) were investigated in a retrospective evaluation in 104 premature and newborn infants. Patients enrolled in this investigation constituted a particularly high risk group with extreme prematurity, perinatal asphyxia and amnion infection as well as various malformations. In 15 of the 104 infants serum concentrations were measured for drug monitoring and determination of optimal total daily dosage. A total daily dose of 50 mg/kg birth weight for premature and newborn infants divided into two doses led to imipenem peak concentrations of 17.7 mg/l +/- 9.2 mg/l (range: 1.95-38.05) and trough levels were 2.35 mg/l +/-1.02 (range 2.34-10.88) in premature infants. Imipenem peak concentrations of 20.6 +/- 10.8 (range 3.94-32.3) and trough levels of 0.43 +/- 0.17 (range 0.16-0.94) were measured in newborns. The half-life of elimination was 3.3 h and 1.86 h, respectively. Six of the 104 treated patients died, five of them of causes unrelated to infection. Seizures occurred in 8.9% of patients during therapy with I/C compared with 5.8% of a large survey of premature and newborn infants in our intensive care unit (ICU). However, the severity of illness of these two groups cannot be compared. I/C can be expected to constitute effective therapy in premature and newborn infants with serious nosocomial infections even after failure of other broad spectrum antibiotics.