Characteristics and Treatment of Medical Device Related Infections

Medical device related infections are becoming an increasing prevalent area of infectious disease. They can be attributed to a multitude of factors from an increasing elderly population with reduced immunological status to increasing microbial resistance and evolution. Of greatest significance is the failure of standard antimicrobial regimens to eradicate biomaterial-related infections due to the formation of microbial biofilms consisting of extracellular polymeric substances. Biofilms form and thrive at the abiotic device surface where nutrients are more concentrated and symbiotic colonies can be formed. The formation of a biofilm matrix occurs in a series of steps beginning with reversible attachment of bacteria to the surface of the substrate and terminating in dispersion of mature biofilm microcolonies that aim to colonise fresh surfaces high in nutrients. Mature biofilms can resist 10-1000 times the concentrations of standard antibiotic regimens that are required to kill genetically equivalent planktonic forms. The extent of the infection and the pathogen(s) present can be attributed to both the form and location of the device. It is important that preventative measures and treatment strategies relate to combating the causative microorganisms. Preventative measures include: the use of anti-infective biomaterials that can be coated or incorporated with standard or innovative antimicrobials; modified anti-adhesive medical devices; environmental sterilisation protocols and prophylactic drug therapy. Treatment of established infection may require removal of the device or if deemed possible the device may be salvageable through the initiation of antimicrobial therapy. The increasing spectre of antibiotic resistance and medical device related infections are a large and increasing burden on health care systems and the patient’s quality of life and long term prognosis. As an infectious disease it represents one of the most difficult challenges facing modern science and healthcare.

Sequential antimicrobial therapy: treatment of severe lower respiratory tract infections in children

Although there have been a number of studies in adults, to date there has been little research into sequential antimicrobial therapy (SAT) in paediatric populations. The present study evaluates the impact of a SAT protocol for the treatment of severe lower respiratory tract infection in paediatric patients. The study involved 89 paediatric patients (44 control and 45 SAT). The SAT patients had a shorter length of hospital stay (4.0 versus 8.3 days), shorter duration of inpatient antimicrobial therapy (4.0 versus 7.9 days) with the period of iv therapy being reduced from a mean of 5.6 to 1.7 days. The total healthcare costs were reduced by 52%. The resolution of severe lower respiratory tract infection with a short course of iv antimicrobials, followed by conversion to oral therapy yielded clinical outcomes comparable to those achieved using longer term iv therapy. SAT proved to be an important cost-minimizing tool for realizing substantial healthcare costs savings.

A role for the enteric nervous system in the response to helminth infections

The enteric nervous system (ENS) in the gut contains a particularly high concentration of nerve cells, and effectively functions as an independent 'minibrain'. Interactions between nerve, endocrine, immune and other cell types allow the sophisticated regulation of normal gut physiology. They can also bring about a co-ordinated response to parasitic infection, possibly leading to expulsion of the parasite. In this review, Derek McKay and Ian Fairweather will consider, in brief, data pertaining to changes in the ENS following intestinal helminth infections and speculate on the role that these alterations may have in the expulsion of the parasite burden and the putative ability of the parasite to modulate these events.

Antimicrobial peptide incorporated poly(2-hydroxyethyl methacrylate) hydrogels for the prevention of Staphylococcus epidermidis-associated biomaterial infections

The effectiveness of the antimicrobial peptide maximin-4, the ultrashort peptide H-Orn-Orn-Trp-Trp-NH(2) , and the lipopeptide C(12) -Orn-Orn-Trp-Trp-NH(2) in preventing adherence of pathogens to a candidate biomaterial were tested utilizing both matrix- and immersion-loaded poly(2-hydroxyethyl methacrylate) (poly(HEMA)) hydrogels. Antiadherent properties correlated to both the concentration released and the relative antimicrobial concentrations of each compound against Staphylococcus epidermidis ATCC 35984, at each time point. Immersion-loaded samples containing C(12) -Orn-Orn-Trp-Trp-NH(2) exhibited the lowest adherence profile for all peptides studied over 1, 4, and 24 h. The results outlined in this article show that antimicrobial peptides have the potential to serve as an important weapon against biomaterial associated infections. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.

Nasal immunization with Burkholderia multivorans outer membrane proteins and the mucosal adjuvant adamantylamide dipeptide confers efficient protection against experimental lung infections with B. multivorans and B. cenocepacia

Chronic lung infection by opportunistic pathogens, such as Pseudomonas aeruginosa and members of the Burkholderia cepacia complex, is a major cause of morbidity and mortality in patients with cystic fibrosis. Outer membrane proteins (OMPs) of gram-negative bacteria are promising vaccine antigen candidates. In this study, we evaluated the immunogenicity, protection, and cross-protection conferred by intranasal vaccination of mice with OMPs from B. multivorans plus the mucosal adjuvant adamantylamide dipeptide (AdDP). Robust mucosal and systemic immune responses were stimulated by vaccination of naive animals with OMPs from B. multivorans and B. cenocepacia plus AdDP. Using a mouse model of chronic pulmonary infection, we observed enhanced clearance of B. multivorans from the lungs of vaccinated animals, which correlated with OMP-specific secretory immunoglobulin A responses. Furthermore, OMP-immunized mice showed rapid resolution of the pulmonary infection with virtually no lung pathology after bacterial challenge with B. multivorans. In addition, we demonstrated that administration of B. multivorans OMP vaccine conferred protection against B. cenocepacia challenge in this mouse infection model, suggesting that OMPs provide cross-protection against the B. cepacia complex. Therefore, we concluded that mucosal immunity to B. multivorans elicited by intranasal vaccination with OMPs plus AdDP could prevent early steps of colonization and infection with B. multivorans and also ameliorate lung tissue damage, while eliciting cross-protection against B. cenocepacia. These results support the notion that therapies leading to increased mucosal immunity in the airways may help patients with cystic fibrosis.

Reconstitution of O-specific lipopolysaccharide expression in Burkholderia cenocepacia strain J2315, which is associated with transmissible infections in patients with cystic fibrosis

Burkholderia cenocepacia is an opportunistic bacterium that infects patients with cystic fibrosis. B. cenocepacia strains J2315, K56-2, C5424, and BC7 belong to the ET12 epidemic clone, which is transmissible among patients. We have previously shown that transposon mutants with insertions within the O antigen cluster of strain K56-2 are attenuated for survival in a rat model of lung infection. From the genomic DNA sequence of the O antigen-deficient strain J2315, we have identified an O antigen lipopolysaccharide (LPS) biosynthesis gene cluster that has an IS402 interrupting a predicted glycosyltransferase gene. A comparison with the other clonal isolates revealed that only strain K56-2, which produced O antigen and displayed serum resistance, lacked the insertion element inserted within the putative glycosyltransferase gene. We cloned the uninterrupted gene and additional flanking sequences from K56-2 and conjugated this plasmid into strains J2315, C5424, and BC7. All the exconjugants recovered the ability to form LPS O antigen. We also determined that the structure of the strain K56-2 O antigen repeat, which was absent from the LPS of strain J2315, consisted of a trisaccharide unit made of rhamnose and two N-acetylgalactosamine residues. The complexity of the gene organization of the K56-2 O antigen cluster was also investigated by reverse transcription-PCR, revealing several transcriptional units, one of which also contains genes involved in lipid A-core oligosaccharide biosynthesis.