Medical Device Infections Research Articles

Complement C5a Generation by Staphylococcal Biofilms

Biofilms production is a central feature of nosocomial infection of catheters and other medical devices used in resuscitation and critical care. However, the very effective biofilm forming pathogen Staphylococcus epidermidis often produces a modest host inflammatory response and few of the signs and symptoms associated with more virulent pathogens. To examine the impact of bacterial biofilm formation on provocation of an innate immune response, we studied the elaboration of the major complement anaphylatoxin C5a by human serum upon contact with S. epidermidis biofilms. Wild-type S. epidermidis and mutants of sarA (a regulatory protein that promotes synthesis of the biofilm-forming polysaccharide intercellular adhesin [PIA]) and icaB (responsible for postexport processing of PIA) were studied. C5a release, as a function of exposed biofilm surface area, was on the order of 1 fmol · cm · s and was dependent on the presence of PIA. Experimental results were used to inform a physiologically based pharmacokinetic model of C5a release by an infected central venous catheter, one of S. epidermidis' primary means of causing human disease. These simulations revealed that the magnitude of C5a release on a superior vena cava catheter completely covered with S. epidermidis would be lower than necessary to alert circulating leukocytes. Combined, the experimental and computational results are highly consistent with clinical observations in which the clinical signs of central line-associated bloodstream infection are often muted in association with this important pathogen.

Relationship between surface properties and antibacterial behavior of wire arc spray copper coatings

There is a trend towards reducing bacterial harmfulness in recent years. Infection of medical devices and treatment rooms can result in significant morbidity and mortality. Having antibacterial surfaces such as silver and copper coatings the risk of bacteria growth has been decreased, noticeably. In the current study, wire arc spraying technique was employed to produce an ultra fine microstructure copper coating on stainless steel 316L substrates. This paper examined the microstructure and surface micromorphology of copper coatings by scanning electron microscope (SEM). The chemical composition was evaluated by X-ray diffraction (XRD). The roughness, surface free energy and wettability of the surfaces were characterized using surface roughness meter inception, dynamic contact angle meter (tensiometer). The antibacterial property of copper coatings was analyzed by ATCC 25922 Escherichia coli (gram negative) and bacteria ATCC 29213 Staphylococcus aureus (gram positive) and then was compared to stainless steel 316L and the commercially available copper sheet. The relationship between the contact angle and surface free energy (SFE) and antibacterial properties was studied. Results indicated that as-sprayed copper coatings showed the best bactericidal activities. The material surface characteristics including the high surface roughness, the high surface free energy, the low contact angle and other characteristics such as ultrafine grain structure and the chemical composition play key roles in increasing the antibacterial behavior of the surfaces.

Biocompatibility analysis of an electrically-activated silver-based antibacterial surface system for medical device applications

The costs associated with the treatment of medical device and surgical site infections are a major cause of concern in the global healthcare system. To prevent transmission of such infections, a prophylactic surface system that provides protracted release of antibacterial silver ions using low intensity direct electric current (LIDC; 28 μA system current at 6 V) activation has been recently developed. To ensure the safety for future in vivo studies and potential clinical applications, this study assessed the biocompatibility of the LIDC-activated interdigitated silver electrodes-based surface system; in vitro toxicity to human epidermal keratinocytes, human dermal fibroblasts, and normal human osteoblasts, and antibacterial efficacy against Staphylococcus aureus and Escherichia coli was evaluated. The study concluded that the technological applications of the surface system for medical devices and surgical tools, which contact human tissues for less than 1.5 h, are expected to be self-sterilizing without causing toxicity in vivo.

Molecular Characterization of Invasive Staphylococcus aureus Infection in Central New York Children: Importance of Two Clonal Groups and Inconsistent Presence of Selected Virulence Determinants.

The genetic makeup of circulating Staphylococcus aureus (SA) populations varies by region. The extent to which SA virulence determinants contribute to the severity of pediatric infections is poorly understood. The study objective was to describe the genetic population of invasive SA (ISA) isolates from children in the Central New York (CNY) area and the prevalence of selected virulence genes. Clinical and demographic information for hospitalized children <19 years of age with community-onset or community-associated ISA infections, determined from clinical microbiology records, was extracted from medical records from Upstate Golisano Children's Hospital in CNY. Antibiotic susceptibility was assessed, and available isolates were genotyped and tested for the presence of selected virulence determinants. Associations between clinical and laboratory findings were evaluated using standard statistical techniques. Ninety patients with ISA disease diagnosed between 2007 and 2010 were included in the study; 74% were due to methicillin-susceptible SA (MSSA). The most common clinical diagnosis was bacteremia. Fifty-seven of 90 isolates were available for further testing. The SA pulsed-field gel electrophoresis type, agr type, and clonal complexes most commonly isolated were USA300 (n = 25, 44%), agr1 (n = 30, 52%), and CC8 (n = 25, 44%), respectively. USA300 strains were more likely to be associated with deep abscesses (P = .007), whereas non-USA300 strains were associated with medical device infections (P = .018). Isolates from patients with deep abscesses and pneumonia were more likely to carry luk-PV genes (P = .023 and P = .051, respectively). MSSA remains an important problem of pediatric ISA infection in our region and results from genetically diverse SA populations.

Superparamagnetic Iron Oxide Nanoparticles (SPION) for the Treatment of Antibiotic‐Resistant Biofilms

Bacterial infections caused by antibiotic-resistant strains are of deep concern due to an increasing prevalence, and are a major cause of morbidity in the United States of America. In particular, medical device failures, and thus human lives, are greatly impacted by infections, where the treatments required are further complicated by the tendency of pathogenic bacteria, such as Staphylococcus aureus, to produce antibiotic resistant biofilms. In this study, a panel of relevant antibiotics used clinically including penicillin, oxacillin, gentamicin, streptomycin, and vancomycin are tested, and although antibiotics are effective against free-floating planktonic S. aureus, either no change in biofilm function is observed, or, more frequently, biofilm function is enhanced. As an alternative, superparamagnetic iron oxide nanoparticles (SPION) are synthesized through a two-step process with dimercaptosuccinic acid as a chelator, followed by the conjugation of metals including iron, zinc, and silver; thus, the antibacterial properties of the metals are coupled to the superparamagnetic properties of SPION. SPION might be the ideal antibacterial treatment, with a superior ability to decrease multiple bacterial functions, target infections in a magnetic field, and had activity better than antibiotics or metal salts alone, as is required for the treatment of medical device infections for which no treatment exists today.

Nanostructured selenium for preventing biofilm formation on polycarbonate medical devices

Biofilms are a common cause of persistent infections on medical devices as they are easy to form and hard to treat. The objective of this study was for the first time to coat selenium (a natural element in the body) nanoparticles on the surface of polycarbonate medical devices (such as those used for medical catheters) and to examine their effectiveness at preventing biofilm formation. The size and distribution of selenium coatings were characterized using scanning electron microscopy and atomic force microscopy. The strength of the selenium coating on polycarbonate was assessed by tape-adhesion tests followed by atomic absorption spectroscopy. Results showed that selenium nanoparticles had a diameter of 50-100 nm and were well distributed on the polycarbonate surface. In addition, more than 50% of the selenium coating survived the tape-adhesion test as larger nanoparticles had less adhesion strength to the underlying polycarbonate substrate than smaller selenium nanoparticles. Most significantly, the results of this in vitro study showed that the selenium coatings on polycarbonate significantly inhibited Staphylococcus aureus growth to 8.9% and 27% when compared with an uncoated polycarbonate surface after 24 and 72 h, respectively. Importantly, this was accomplished without using antibiotics but rather with an element (selenium) that is natural to the human body. Thus, this study suggests that coating polymers (particularly, polycarbonate) with nanostructured selenium is a fast and effective way to reduce bacteria functions that lead to medical device infections. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A: 3205-3210, 2012.

Combinatorial Approach for Fabrication of Coatings to Control Bacterial Adhesion

Due to the high importance of bacterial infections in medical devices there is an increasing interest in the design of anti-fouling coatings. The application of substrates with controlled chemical gradients to prevent microbial adhesion is presented. We describe here the co-polymerization of poly(ethylene glycol) dimethacrylate with a hyperbranched multimethacrylate (H30MA) using a chemical gradient generator; and the resulting films were characterized with respect to their ability to serve as coating for biomedical devices. The photo-polymerized materials present special surface properties due to the hyperbranched structure of H30MA and phase separation at specific concentrations in the PEGDM matrix. This approach affords the investigation of cell response to a large range of different chemistries on a single sample. Two bacterial strains commonly associated with surgical site infections, Escherichia coli and Pseudomonas aeruginosa, have been cultured on these substrates to study their attachment behaviour. These gradient-coated samples demonstrate less bacterial adhesion at higher concentrations of H30MA, and the adhesion is substantially affected by the extent of surface phase segregation.

Multilocus Sequence Typing and Phylogenetic Analysis of Propionibacterium acnes

ABSTRACTPropionibacterium acnesis a commensal of human skin but is also implicated in the pathogenesis of acne vulgaris, in biofilm-associated infections of medical devices and endophthalmitis, and in infections of bone and dental root canals. Recent studies associateP. acneswith prostate cancer. As the species includes evolutionary lineages with distinct association with health and disease, there is a need for a high-resolution typing scheme. Recently, two multilocus sequence typing (MLST) schemes were reported, one based on nine and one based on seven housekeeping genes. In the present study, the two schemes were compared with reference to a phylogenetic tree based on 78P. acnesgenomes and their gene contents. Further support for a basically clonal population structure ofP. acnesand a scenario of the global spread of epidemic clones ofP. acneswas obtained. Compared to the Belfast scheme, the Aarhus MLST scheme (http://pacnes.mlst.net/), which is based on nine genes, offers significantly enhanced resolution and phylogenetic inferences more concordant with analyses based on a comprehensive sampling of the entire genomes, their gene contents, and their putative pathogenic potential.

Nanostructured Selenium for Preventing Biofilm Formation on Medical Devices

ABSTRACTBiofilms are a common cause of persistent infections on medical devices as they are easy to form and hard to treat. Selenium and its compounds are considered to be a novel material for a wide range of applications including anticancer applications and antibacterial applications. The objective of this study was to coat selenium nanoparticles on the surface of polycarbonate medical devices and examine their effectiveness at preventing biofilm formation. The results of this in vitro study showed that the selenium coating significantly inhibited Staphylococcus aureus growth on the surface of polycarbonate after 24 hours. Thus, this study suggests that coating polymers with nanostructured selenium is a fast and effective way to reduce bacteria functions leading to medical device infections.

Incidence and clinical implication of nosocomial infections associated with implantable biomaterials - catheters, ventilator-associated pneumonia, urinary tract infections.

Health care associated infections, the fourth leading cause of disease in industrialised countries, are a major health issue. One part of this condition is based on the increasing insertion and implantation of prosthetic medical devices, since presence of a foreign body significantly reduces the number of bacteria required to produce infection. The most significant hospital-acquired infections, based on frequency and potential severity, are those related to procedures e.g. surgical site infections and medical devices, including urinary tract infection in catheterized patients, pneumonia in patients intubated on a ventilator and bacteraemia related to intravascular catheter use. At least half of all cases of nosocomial infections are associated with medical devices.Modern medical and surgical practices have increasingly utilized implantable medical devices of various kinds. Such devices may be utilized only short-time or intermittently, for months, years or permanently. They improve the therapeutic outcome, save human lives and greatly enhance the quality of life of these patients. However, plastic devices are easily colonized with bacteria and fungi, able to be colonized by microorganisms at a rate of up to 0.5 cm per hour. A thick biofilm is formed within 24 hours on the entire surface of these plastic devices once inoculated even with a small initial number of bacteria.The aim of the present work is to review the current literature on causes, frequency and preventive measures against infections associated with intravascular devices, catheter-related urinary tract infection, ventilator-associated infection, and infections of other implantable medical devices. Raising awareness for infection associated with implanted medical devices, teaching and training skills of staff, and establishment of surveillance systems monitoring device-related infection seem to be the principal strategies used to achieve reduction and prevention of such infections. The intelligent use of suitable antiseptics in combination with medical devices may further support reduction and prevention of such infections. In addition to reducing the adverse clinical outcomes related with these infections, such reduction may substantially decrease the economic burden caused by device-related infection for health care systems.

Combination therapy with daptomycin, linezolid, and rifampin as treatment option for MRSA meningitis and bacteremia

Methicillin-resistant Staphylococcus aureus (MRSA) meningitis is associated with a high mortality rate. Treatment is challenging in patients with allergy to vancomycin. Herein, we describe a case of MRSA bacteremia secondary to medical device infection with MRSA that was complicated by MRSA meningitis. This case provides evidence for a possible role of combination therapy of daptomycin, linezolid, and rifampin in cases of MRSA meningitis and bacteremia.

In vitro Activity of Daptomycin, Linezolid and Rifampicin on Staphylococcus epidermidis Biofilms

Owing to their massive use, Staphylococcus epidermidis has recently developed significant resistance to several antibiotics, and became one of the leading causes of hospital-acquired infections. Current antibiotics are typically ineffective in the eradication of bacteria in biofilm-associated persistent infections. Accordingly, the paucity of effective treatment against cells in this mode of growth is a key factor that potentiates the need for new agents active in the prevention or eradication of biofilms. Daptomycin and linezolid belong to the novel antibiotic therapies that are active against gram-positive cocci. On the other hand, rifampicin has been shown to be one of the most potent, prevalent antibiotics against S. epidermidis biofilms. Therefore, the main aim of this study was to study the susceptibility of S. epidermidis biofilm cells to the two newer antimicrobial agents previously mentioned, and compare the results obtained with the antimicrobial effect of rifampicin, widely used in the prevention/treatment of indwelling medical device infections. To this end the in vitro activities of daptomycin, linezolid, and rifampicin on S. epidermidis biofilms were accessed, using these antibiotics at MIC and peak serum concentrations. The results demonstrated that at MIC concentration, rifampicin was the most effective antibiotic tested. At peak serum concentration, both strains demonstrated similar susceptibility to rifampicin and daptomycin, with colony-forming units (CFUs) reductions of approximately 3-4 log(10), with a slightly lower response to linezolid, which was also more strain dependent. However, considering all the parameters studied, daptomycin was considered the most effective antibiotic tested, demonstrating an excellent in vitro activity against S. epidermidis biofilm cells. In conclusion, this antibiotic can be strongly considered as an acceptable therapeutic option for S. epidermidis biofilm-associated infections and can represent a potential alternative to rifampicin in serious infections where rifampicin resistance becomes prevalent.

Diameter of titanium nanotubes influences anti-bacterial efficacy

Bacterial infection of in-dwelling medical devices is a growing problem that cannot betreated by traditional antibiotics due to the increasing prevalence of antimicrobialresistance and biofilm formation. Here, due to changes in surface parameters, it isproposed that bacterial adhesion can be prevented through nanosurface modificationsof the medical device alone. Toward this goal, titanium was created to possessnanotubular surface topographies of highly controlled diameters of 20, 40, 60, or80 nm, sometimes followed by heat treatment to control chemistry and crystallinity,through a novel anodization process. For the first time it was found that throughthe control of Ti surface parameters including chemistry, crystallinity, nanotubesize, and hydrophilicity, significantly changed responses of both Staphylococcusepidermidis and Staphylococcus aureus (pathogens relevant for orthopaedic and othermedical device related infections) were measured. Specifically, heat treatment of80 nm diameter titanium tubes produced the most robust antimicrobial effectof all surface treatment parameters tested. This study provides the first steptoward understanding the surface properties of nano-structured titanium thatimprove tissue growth (as has been previously observed with nanotubular titanium),while simultaneously reducing infection without the use of pharmaceutical drugs.

The Use of Commercially Available Alpha-Amylase Compounds to Inhibit and Remove Staphylococcus aureus Biofilms

Staphylococcus aureus, a versatile human pathogen, is commonly associated with medical device infections. Its capacity to establish and maintain these infections is thought to be related to its ability to form adherent biofilms. In this study, commercially available α-amylase compounds from various biological sources were evaluated for their ability to reduce and prevent biofilm formation of several S. aureus isolates. Our data demonstrates that α-amylase compounds can rapidly detach biofilms of S. aureus, as well as inhibit biofilm formation. Our data also demonstrates that α-amylase compounds have an ability to reduce and disassociate S. aureus cell-aggregates grown in liquid suspension. These findings suggest that commercially available α-amylase compounds could be used in the future to control S. aureus biofilm-related infections.

Inhibition of Biofilm Formation in Staphylococcus aureus Isolates by Quercus cerris Extracts

Implanted medical device infections caused by Staphylococcus aureus make up a major subset of device complications and therefore place a substantial burden on the United States healthcare system [1]. Staphylococcal biofilms are intrinsically resistant to conventional antibiotic therapy, and biofilm inhibitors could be used to prevent device colonization or improve therapeutic efficacy of antibiotics in treating established infections. In this study, we investigated the effect of Quercus cerris L. extracts on the process of biofilm formation. Ethnobotanical reports in southern Italy indicate that this species is used for multiple traditional medicinal applications in humans, and it is also used to treat wounds in animals [2,3]. We have found that the ethyl acetate and aqueous fractions of Q. cerris reduce biofilm formation by clinically-relevant S. aureus isolates. In addition, these extracts do not affect the growth curves of S. aureus, suggesting that the mechanism of biofilm formation is not due to antimicrobial effects.

Vesicular Lipid Nanoparticles (Liposomes) for the Treatment of Medical Device Infections

AbstractLiposomes (a phospholipid bi-layer which can be formulated to contain drugs or other reagents) composed of endogenous phospholipid dipalmitoylphosphatidylcholine (DPPC) in combination with dioleoylphosphatidylethanolamine (DOPE), lauric acid, and silver sulfadiazine were made into vesicular nanoparticles in this study using an optimized extrusion technique. Liposomes were then tested for antibacterial activity against a range of bacteria species including Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and Bacillus subtilis (all are relevant human pathogens known to infect implants) and were also challenged to prevent the growth of adherent biofilms (a robust slimy extracellular matrix) through an in vitro assay relevant to device related infections. It was found that all liposomes reduced bacterial growth, and, most importantly, liposomes containing DPPC and DOPE reduced biofilm formation better than the commercially available antibiotic silver sulfadiazine. These results indicated for the first time that such liposomes might be a better approach to prevent device related infections.

Reducing infections through nanotechnology and nanoparticles.

The expansion of bacterial antibiotic resistance is a growing problem today. When medical devices are inserted into the body, it becomes especially difficult for the body to clear robustly adherent antibiotic-resistant biofilm infections. In addition, concerns about the spread of bacterial genetic tolerance to antibiotics, such as that found in multiple drug-resistant Staphylococcus aureus (MRSA), have significantly increased of late. As a growing direction in biomaterial design, nanomaterials (materials with at least one dimension less than 100 nm) may potentially prevent bacterial functions that lead to infections. As a first step in this direction, various nanoparticles have been explored for improving bacteria and biofilm penetration, generating reactive oxygen species, and killing bacteria, potentially providing a novel method for fighting infections that is nondrug related. This review article will first examine in detail the mechanisms and applications of some of these nanoparticles, then follow with some recent material designs utilizing nanotechnology that are centered on fighting medical device infections.

Surface immobilization of active vancomycin on calcium aluminum oxide

Implant and medical device infection is a significant and potentially deadly problem in biomaterials today. In order to mitigate this issue vancomycin was either adsorbed or covalently attached to the calcium aluminum oxide surface and tested for antibacterial activity. Covalent attachment was accomplished by a three-step solution immobilization method utilizing the hydroxyl groups on the calcium aluminum oxide surface. The three-step covalent antibiotic attachment method is applicable to any surface that contains hydroxyl and μ-oxo groups. Antibacterial activity of the immobilized antibiotics was evaluated by incubating the unmodified oxide and modified samples in a liquid Staphylococcus aureus bacterial solution. Growth of the bacteria was determined by optical density. Additionally, bacterial growth was evaluated in a zone inhibition assay. It was found that unmodified samples, vancomycin adsorbed, and vancomycin linked to the surface inhibited bacterial growth in liquid culture. Vancomycin linked or adsorbed to the surface produced zones of inhibition equal to that of the control antibiotic disk indicating it is as active on the surface as the native antibiotic. These samples can be autoclaved for sterilization and retain bioactivity. This is the first report of an attachment method for antibiotics on oxide surfaces that uses mild conditions.

Fungal Biofilms: Relevance in the Setting of Human Disease

The use of indwelling medical devices is rapidly growing and is often complicated by infections with biofilm-forming microbes that are resistant to antimicrobial agents and host defense mechanisms. Fungal biofilms have emerged as a clinical problem associated with these medical device infections, causing significant morbidity and mortality. This review discusses the recent advances in the understanding of fungal biofilms, including the role of fungal surface components in adherence, gene expression, and quorum sensing in biofilm formation. We propose novel strategies for the prevention or eradication of microbial colonization of medical prosthetic devices.

Vaccine development inStaphylococcus aureus: taking the biofilm phenotype into consideration

Vaccine development against pathogenic bacteria is an imperative initiative as bacteria are gaining resistance to current antimicrobial therapies and few novel antibiotics are being developed. Candidate antigens for vaccine development can be identified by a multitude of high-throughput technologies that were accelerated by access to complete genomes. While considerable success has been achieved in vaccine development against bacterial pathogens, many species with multiple virulence factors and modes of infection have provided reasonable challenges in identifying protective antigens. In particular, vaccine candidates should be evaluated in the context of the complex disease properties, whether planktonic (e.g. sepsis and pneumonia) and/or biofilm associated (e.g. indwelling medical device infections). Because of the phenotypic differences between these modes of growth, those vaccine candidates chosen only for their efficacy in one disease state may fail against other infections. This review will summarize the history and types of bacterial vaccines and adjuvants as well as present an overview of modern antigen discovery and complications brought about by polymicrobial infections. Finally, we will also use one of the better studied microbial species that uses differential, multifactorial protein profiles to mediate an array of diseases, Staphylococcus aureus, to outline some of the more recently identified problematic issues in vaccine development in this biofilm-forming species.