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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.

No abstract

Implantable medical devices such as catheters are indispensable in the management of critically and chronically ill patients for the administration of electrolytes, drugs, parenteral nutrients, blood components or drainage of secretions and pus. Artificial heart valves, prosthetics, ceramics, metals and bone cements are standard implants. All of these implants save human lives and enhance quality of life. At the same time they are the leading cause for millions of primary nosocomial bloodstream infections with substantial morbidity and mortality 1 . A property common to all these biomaterials is the ease by which they are colonized by pathogenic and nonpathogenic microorganisms, often requiring immediate removal.Several methods have been devised to decrease the risk of foreign body-associated infections. These include the use of meticulous hygienic precautions, the development of hydrophilic materials to minimize bacterial adhesion and impregnation with antiseptics and antibiotics. Silver, in particular free silver ions 2 , is well known for its powerful and broad-spectrum antimicrobial activity still allowing the independent use of therapeutic antibiotics. The investigation of the antimicrobial activity of implants containing silver as an antimicrobial agent is difficult because many silver compounds are poorly water soluble, resulting in low concentrations of silver ions released into the surrounding medium. Therefore, the antimicrobial efficacy of polymers impregnated with elementary silver cannot be tested by routine agar diffusion measurements 3 . Like other procedures 4,5 , the agar diffusion technique was also inappropriate for a simultaneous highthroughput screening of silver prototypes.Reliable in vitro methods for antimicrobial activity testing of surfaces are essential for the development of new anti-infective biomaterials. Cell proliferation is an important step in the course of infection 6 and must be included in any evaluation procedure. To date, assays 7-10 have focused on the monitoring of bacterial adherence but lack an analysis of the microbial proliferatory behavior. For a precise testing of antimicrobial efficacy three independent aspects must be considered: adhesion (the test must detect and quantify adherent microorganisms); proliferation (the test should assay the potential of adherent bacteria for proliferation); and detection of bactericidal and bacteriostatic activity.Here, we introduce a new technique for testing antimicrobial properties of biomaterials using a microplate system (Fig. 1). As a selected example, we show in vitro data for the antimicrobial activity of silver polymers, which correlate positively with multicenter clinical trials 11 . Implications of the approach.The number of new biomaterials in medicine is steadily growing. Highly efficient in vitro methods are required for quality control, screening and product improvement. Such comparative techniques should meet the following requirements: a quantification method to monitor microbial adherence; a sensitive and reproducib...

Azithromycin therapy appears to put selective pressure on the infective and native flora of children, promoting the carriage of macrolide-resistant strains.

No abstract

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.

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.