The resistance of polyvinylpyrrolidone–Iodine–poly(e-caprolactone) blends to adherence of Escherichia coli

In this study, the resistance of biodegradable biomaterials, composed of blends of poly(e-caprolactone) (PCL) and the polymeric antimicrobial complex, polyvinylpyrrolidone–iodine (PVP-I) to the adherence of a clinical isolate of Escherichia coli is described. Blends of PCL composed of a range of high (50,000 g mol1) to low (5000 g mol1) molecular weight ratios of polymer and either
devoid of or containing PVP-I (1% w/w) were prepared by solvent evaporation. Following incubation (4 h), there was no relationship between m. wt. ratio of PCL in ?lms devoid of PVP-I and adherence ofE. coli. Conversely, microbial adherence to PCL containing PVP-I decreased as the ratio of high:low m. wt. polymer was decreased and was approximately 1000 fold lower than that to comparator ?lms devoid of PVP-I. Following periods of immersion of PVP-I containing PCL ?lms under sink conditions in phosphate buffered saline, subsequent adherence of E. coli was substantially reduced for 2 days (40:60 m. wt. ratio) and 6 days (100:0 m. wt. ratio). Concurrent exposure of PCL and E. coli to sub-minimum inhibitory concentrations (sub-MIC) of PVP-I signi?cantly reduced microbial adherence to the biomaterial; however, the molecular weight ratio of PCL did not affect this outcome. Pretreatment of PCL with similar sub-MIC of PVP-I prior to inclusion within the microbial adherence assay signi?cantly decreased the subsequent adherence of E. coli. Greatest reduction in adherence was observed following treatment of PCL (40:60 m. wt. ratio) with 0.0156% w/w PVP-I. In conclusion, this study has illustrated the utility of PVP-I as a suitable therapeutic agent for incorporation within PCL as a novel biomaterial. Due to the combined antimicrobial and biodegradable properties, these biomaterials offer a promising strategy for the reduction in medical device related infection. © 2004 Elsevier Ltd. All rights reserved.

The use of lytic bacteriophages in the prevention and eradication of biofilms of Proteus mirabilis and Escherichia coli.

Antibiotics have been the cornerstone of the clinical management of bacterial infections since their discovery in the early part of the last century. Eight decades later, their widespread, often indiscriminate use, has resulted in an overall reduction in their effectiveness, with reports of multidrug-resistant bacteria now commonplace. Increasing reliance on indwelling medical devices, which are inherently susceptible to biofilm-mediated infections, has contributed to unacceptably high rates of nosocomial infections, placing a strain on healthcare budgets. This study investigates the use of lytic bacteriophages in the treatment and prevention of biofilms of bacterial species commonly associated with infections of indwelling urological devices and catheter-associated urinary tract infections. The use of lytic bacteriophages against established biofilms of Proteus mirabilis and Escherichia coli is described, whereby biofilm populations have been reduced successfully by three to four log cycles (99.9-99.99% removal). The prevention of biofilm formation on Foley catheter biomaterials following impregnation of hydrogel-coated catheter sections with a lytic bacteriophage has also been investigated. This has revealed an approximate 90% reduction in both P. mirabilis and E. coli biofilm formation on bacteriophage-treated catheters when compared with untreated controls.

CD18-dependent activation of the neutrophil NADPH oxidase during phagocytosis of Escherichia coli or Staphylococcus aureus is regulated by class III but not class I or II PI3Ks

Phagocytosis and activation of the NADPH oxidase are important mechanisms by which neutrophils and macrophages engulf and kill microbial pathogens. We investigated the role of PI3K signaling pathways in the regulation of the oxidase during phagocytosis of Staphylococcus aureus and Escherichia coli by mouse and human neutrophils, a mouse macrophage-like cell line and a human myeloid-like cell line. Phagocytosis of these bacteria was promoted by serum, independent of serum-derived antibodies, and effectively abolished in mouse neutrophils lacking the beta(2)-integrin common chain, CD18. A combination of PI3K isoform-selective inhibitors, mouse knock-outs, and RNA-interference indicated CD18-dependent activation of the oxidase was independent of class I and II PI3Ks, but substantially dependent on the single class III isoform (Vps34). Class III PI3K was responsible for the synthesis of PtdIns( 3) P on phagosomes containing either bacteria. The use of mouse neutrophils carrying an appropriate knock-in mutation indicated that PtdIns(3) P binding to the PX domain of their p40(phox) oxidase subunit is important for oxidase activation in response to both S aureus and E coli. This interaction does not, however, account for all the PI3K sensitivity of these responses, particularly the oxidase response to E coli, suggesting that additional mechanisms for PtdIns( 3) P-regulation of the oxidase must exist. ( Blood. 2008; 112: 5202-5211)