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ABSTRACT: In recent years the employment of implantable medical devices has increased remarkably, notwithstanding that microbial infections are a frequent complication associated with their use. Different strategies have been attempted to overcome this problem, including the incorporation of antimicrobial agents into the device itself. In this study a new approach to obtain intrinsically antimicrobial materials was developed. Polymer anionomers containing Ag(I), Cu(II), Zn(II), Al(III) and Fe(III) were prepared by neutralization of a carboxylated polyurethane. In the case of the PEUA-Ag, PEUA-Fe and PEUA-Cu ionomers the ion aggregates behaved as reinforcing filler particles, increasing the mechanical properties of the systems in terms of hardness and strength at break over the pristine carboxylated polymer. With the exception of the Al-containing polymer, all the other experimented ionomers showed satisfactory antimicrobial properties. The best antibacterial effect was obtained with the silver ion-containing polymer, which inhibited Staphylococcus epidermidis growth for up to 16days. Ciprofloxacin was also adsorbed onto the above mentioned ionomers. A synergistic effect of the antibiotic and silver ions on bacterial growth inhibition was observed for at least 25days.
Acta biomaterialia 04/2010; 6(9):3482-90. · 3.98 Impact Factor
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ABSTRACT: Antibiotic therapies to eradicate medical device-associated infections often fail because of the ability of sessile bacteria, encased in their exopolysaccharide matrix, to be more drug resistant than planktonic organisms. In the last two decades, several strategies to prevent microbial adhesion and biofilm formation on the surfaces of medical devices, based mainly on the use of antiadhesive, antiseptic, and antibiotic coatings on polymer surfaces, have been developed. More recent alternative approaches are based on molecules able to interfere with quorum-sensing phenomena or to dissolve biofilms. Interestingly, a newly purified beta-N-acetylglucosaminidase, dispersin B, produced by the gram-negative periodontal pathogen Actinobacillus actinomycetemcomitans, is able to dissolve mature biofilms produced by Staphylococcus epidermidis as well as some other bacterial species. Therefore, in this study, we developed new polymeric matrices able to bind dispersin B either alone or in combination with an antibiotic molecule, cefamandole nafate (CEF). We showed that our functionalized polyurethanes could adsorb a significant amount of dispersin B, which was able to exert its hydrolytic activity against the exopolysaccharide matrix produced by staphylococcal strains. When microbial biofilms were exposed to both dispersin B and CEF, a synergistic action became evident, thus characterizing these polymer-dispersin B-antibiotic systems as promising, highly effective tools for preventing bacterial colonization of medical devices.
Antimicrobial Agents and Chemotherapy 09/2007; 51(8):2733-40. · 4.84 Impact Factor
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ABSTRACT: VanA-type human (n=69), animal (n=49), and food (n=36) glycopeptide-resistant enterococci (GRE) from different geographic areas were investigated to study their possible reservoirs and transmission routes. Pulsed-field gel electrophoresis (PFGE) revealed two small genetically related clusters, M39 (n=4) and M49 (n=13), representing Enterococcus faecium isolates from animal and human feces and from clinical and fecal human samples. Multilocus sequence typing showed that both belonged to the epidemic lineage of CC17. purK allele analysis of 28 selected isolates revealed that type 1 was prevalent in human strains (8/11) and types 6 and 3 (14/15) were prevalent in poultry (animals and meat). One hundred and five of the 154 VanA GRE isolates, encompassing different species, origins, and PFGE types, were examined for Tn1546 type and location (plasmid or chromosome) and the incidence of virulence determinants. Hybridization of S1- and I-CeuI-digested total DNA revealed a plasmid location in 98% of the isolates. Human intestinal and animal E. faecium isolates bore large (>150 kb) vanA plasmids. Results of PCR-restriction fragment length polymorphism and sequencing showed the presence of prototype Tn1546 in 80% of strains and the G-to-T mutation at position 8234 in three human intestinal and two pork E. faecium isolates. There were no significant associations (P>0.5) between Tn1546 type and GRE source or enterococcal species. Virulence determinants were detected in all reservoirs but were significantly more frequent (P<0.02) among clinical strains. Multiple determinants were found in clinical and meat Enterococcus faecalis isolates. The presence of indistinguishable vanA elements (mostly plasmid borne) and virulence determinants in different species and PFGE-diverse populations in the presence of host-specific purK housekeeping genes suggested that all GRE might be potential reservoirs of resistance determinants and virulence traits transferable to human-adapted clusters.
Applied and Environmental Microbiology 05/2007; 73(10):3307-19. · 3.83 Impact Factor
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ABSTRACT: As a preventive strategy to inhibit fungal biofilm formation on medical devices, we planned experiments based on polyurethane loading with fluconazole plus pore-former agents in order to obtain a promoted release of the antifungal drug.
Different functional groups including carboxyl, hydroxyl, primary and tertiary amino groups, were introduced in polyurethanes. Fluconazole was adsorbed in higher amounts by the most hydrophilic polymers and its release was influenced by the degree of polymer swelling in water. The entrapping in the polymer of polyethylenglycol as a pore former significantly improved the fluconazole release while the entrapping of the higher molecular weight porogen albumin resulted in a controlled drug release and in an improved antifungal activity over time.
Among the tested in vitro models, best results were achieved with an hydrophobic polymer impregnated with 25% (w/w) albumin and fluconazole which inhibited Candida albicans growth and biofilm formation on polymeric surfaces up to 8 days.
The combined entrapping in polymers of pore formers and an antifungal drug and the consequent controlled release over time is a novel, promising approach in the development of medical devices refractory to fungal colonization.
Journal of Applied Microbiology 04/2006; 100(3):615-22. · 2.34 Impact Factor
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ABSTRACT: Enterococci are gram-positive bacteria that are part of the normal human intestinal flora and can colonize the upper respiratory tract, biliary tract and vagina of otherwise healthy people. Although their virulence is relatively low, recently enterococci have emerged as significant nosocomial pathogens and are currently the 4th leading cause of hospital-acquired infections, including those associated with intravascular catheter and biliary stent implants. The frequent use of these medical devices is often associated with severe complications, including catheter-related bloodstream infections (CRBSIs) and biliary stent occlusions, because of microbial biofilm formation on the device surface. Furthermore, other than a high level of resistance to penicillin, ampicillin and aminoglycosides, a dramatic increase in vancomycin resistance of enterococci has been recently observed in most clinical settings. Clinical strains exhibiting novel mechanisms of acquired resistance to antimicrobials are frequently isolated. In addition, enterococci have a great ability to transmit these resistance traits to other species and even to other genera. Due to their associated morbidity and mortality, enterococcal infections related to medical devices currently represent a major challenge for clinicians, especially for the management of critically ill patients, resulting in prolonged hospitalization and additional health costs.
The journal of vascular access 5(1):3-9. · 1.09 Impact Factor
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ABSTRACT: In recent years the employment of implantable medical devices has increased remarkably, notwithstanding that microbial infections are a frequent complication associated with their use. Different strategies have been attempted to overcome this problem, including the incorporation of antimicrobial agents into the device itself. In this study a new approach to obtain intrinsically antimicrobial materials was developed. Polymer anionomers containing Ag(I), Cu(II), Zn(II), Al(III) and Fe(III) were prepared by neutralization of a carboxylated polyurethane. In the case of the PEUA-Ag, PEUA-Fe and PEUA-Cu ionomers the ion aggregates behaved as reinforcing filler particles, increasing the mechanical properties of the systems in terms of hardness and strength at break over the pristine carboxylated polymer. With the exception of the Al-containing polymer, all the other experimented ionomers showed satisfactory antimicrobial properties. The best antibacterial effect was obtained with the silver ion-containing polymer, which inhibited Staphylococcus epidermidis growth for up to 16 days. Ciprofloxacin was also adsorbed onto the above mentioned ionomers. A synergistic effect of the antibiotic and silver ions on bacterial growth inhibition was observed for at least 25 days.
Acta Biomaterialia.
