Modification of central venous catheter polymers to prevent in vitro microbial colonisation

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...

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“…2c). In agreement with other investigations 15 , bacterial adherence was also reduced on commercial hydrophilic-coated catheters (Fig. 2c).…”

Section: New Technologysupporting

confidence: 93%

A new method for screening anti-infective biomaterials

Bechert

Steinrücke²,

Guggenbichler

2000

Nat Med

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“…The use of iodine-release from such coated catheters 70 can provoke allergic reactions, whereas use of glycopeptides 69 might be preserved for eradication of multiresistant staphylococci in the ICU. The coupling of antibiotics to quaternary ammonium (QA) catheters has been interpreted to be effective in vitro and in vivo 71,72 . A clinical study on tridodecylammoniumchloride (TDMAC)-antibiotic bonded arterial and central venous catheters has suggested significant infection reduction.…”

Section: Drugs Bonded On Device Surfacesmentioning

confidence: 99%

Novel Strategies to Prevent Catheter-Associated Infections in Oncology Patients

Schierholz¹,

Beuth²,

Rump³

et al. 2001

Journal of Chemotherapy

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Aggressive cytotoxic treatment of cancer contributes to the growing number of life-threatening infections. Vascular catheters create predominant risks for staphylococcal, enterococcal and candida blood stream infections. Although the contaminating microorganisms may be few in number, the altered host immune response in the presence of such implants as well as disease-associated immunosuppression implies that even small bacterial counts have to be regarded as highly virulent species. Diagnosis of catheter-related infection (CRI) remains difficult before withdrawal of the suspected catheter. Positive culture of catheter surface, lumen and hub and positive peripheral blood probes (paired quantitative blood culture) are predictive for catheter related bacteremia (CRB). Diligent catheter care and effective antimicrobial catheters may reduce prolonged hospital stay, increased morbidity or mortality and serious economical consequences. The most promising approach features the incorporation of antimicrobial drugs into the polymer matrices that entrap but do not bind the drugs, allowing for extended release. For the efficacious prevention of colonization in the microenvironment of the implantable device the concentration of the antimicrobial substances must exceed usual antibiotic concentrations by a thousand-fold. This is the desired effect--high concentration near the device surface and very low systemic concentration. Incorporation of antimicrobials in the bulk material that constitutes a device can be effective as shown in several in vitro and in vivo studies. In the future, modification of both short-term and long-term catheters by biofilm-active antimicrobials creating slow delivery systems may provide an effective method to protect patients from nosocomial infection in oncology.

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“…10 The silver ions are microdispersed in a proprietary polymer that may enhance antimicrobial activity by blocking bacterial adhesion to the endotracheal tube. [11][12][13][14] The North American Silver-Coated Endotracheal Tube (NASCENT) study 15 provided clinical evidence of efficacy in 2,003 patients expected to require mechanical ventilation for x24 hours. In this randomized, controlled, pivotal trial, the silver-coated endotracheal tube resulted in a 35.9% relative risk reduction of VAP ( ), P p .03 with a cumulative incidence of microbiologically confirmed VAP of 7.5% in patients managed with uncoated endotracheal tubes and 4.8% in patients managed with silver-coated endotracheal tubes.…”

mentioning

confidence: 99%