Abstract: Biofilm formation in wounds is a serious problem which inhibits proper wound healing. One possible contributor to biofilm formation in a wound is the bacteria growing within the overlying bandage. To test this mechanism, we used bandages that contained a coating of organo-selenium that was covalently attached to the bandage. We tested the ability of this coating to kill bacteria on the bandage and in the underlying tissue. The bandage material was tested with both lab strains and clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa and Staphylococcus epidermidis. It was found thatthe organo-selenium coated bandage showed inhibition, of biofilm formation on the bandage in vitro (7–8 logs), with all the different bacteria tested, at selenium concentrations in the coating of less than 1.0%. These coatings were found to remain stable for over one month in aqueous solution, 15 min in boiling water, and over 6 years at room temperature. The bandages were also tested on a mouse wound model where the bacteria were injected between the bandage and the wound. Not only did the selenium bandage inhibit biofilm formation in the bandage, but it also inhibited biofilm formation in the wound tissue. Since selenium does not leave the bandage, this would appear to support the idea that a major player in wound biofilm formation is bacteria which grows in the overlying bandage.
Abstract: The Class D β-lactamases have emerged as a prominent resistance mechanism against β-lactam antibiotics that previously had efficacy against infections caused by pathogenic bacteria, especially by Acinetobacter baumannii and the Enterobacteriaceae. The phenotypic and structural characteristics of these enzymes correlate to activities that are classified either as a narrow spectrum, an extended spectrum, or a carbapenemase spectrum. We focus on Class D β-lactamases that are carried on plasmids and, thus, present particular clinical concern. Following a historical perspective, the susceptibility and kinetics patterns of the important plasmid-encoded Class D β-lactamases and the mechanisms for mobilization of the chromosomal Class D β-lactamases are discussed.
Abstract: The number of implanted medical devices is steadily increasing and has become an effective intervention improving life quality, but still carries the risk of infection. These infections are mainly caused by biofilm-forming staphylococci that are difficult to treat due to the decreased susceptibility to both antibiotics and host defense mechanisms. To understand the particular pathogenesis and treatment tolerance of implant-associated infection (IAI) animal models that closely resemble human disease are needed. Applications of the tissue cage and catheter abscess foreign body infection models in the mouse will be discussed herein. Both models allow the investigation of biofilm and virulence of various bacterial species and a comprehensive insight into the host response at the same time. They have also been proven to serve as very suitable tools to study the anti-adhesive and anti-infective efficacy of different biomaterial coatings. The tissue cage model can additionally be used to determine pharmacokinetics, efficacy and cytotoxicity of antimicrobial compounds as the tissue cage fluid can be aspirated repeatedly without the need to sacrifice the animal. Moreover, with the advance in innovative imaging systems in rodents, these models may offer new diagnostic measures of infection. In summary, animal foreign body infection models are important tools in the development of new antimicrobials against IAI and can help to elucidate the complex interactions between bacteria, the host immune system, and prosthetic materials.
Abstract: Urinary tract infections (UTI) are among the most frequently acquired infections in the community, but also in hospitals and other health care institutions, causing a huge amount of antibiotic consumption. During the last decade we have seen significant changes in the field of urinary tract infections regarding causative pathogens and antibiotic treatment calling for an update of current trends. The worldwide increase of uropathogens resistant to former first line antibiotics, such as cotrimoxazole, fluoroquinolones and cephalosporins, has had detrimental consequences not only for treatment but also for prophylaxis of infectious complications after urological interventions. A paradigm shift concerning asymptomatic bacteriuria has had a great impact on the definition and management of UTIs today [1–4]. [...]
Abstract: Antibiotics exert several effects on host cells including regulation of immune components. Antimicrobial peptides (AMPs), e.g., cathelicidins and defensins display multiple functions in innate immunity. In colonic mucosa, cathelicidins are induced by butyrate, a bacterial fermentation product. Here, we investigated the effect of antibiotics on butyrate-induced expression of cathelicidins and beta-defensins in colon epithelial cells. Real-time PCR analysis revealed that ciprofloxacin and clindamycin reduce butyrate-induced transcription of the human cathelicidin LL-37 in the colonic epithelial cell line HT-29. Suppression of LL-37 peptide/protein by ciprofloxacin was confirmed by Western blot analysis. Immunohistochemical analysis demonstrated that ciprofloxacin suppresses the rabbit cathelicidin CAP-18 in rectal epithelia of healthy and butyrate-treated Shigella-infected rabbits. Ciprofloxacin also down-regulated butyrate-induced transcription of the human beta-defensin-3 in HT-29 cells. Microarray analysis of HT-29 cells revealed upregulation by butyrate with subsequent down-regulation by ciprofloxacin of additional genes encoding immune factors. Dephosphorylation of histone H3, an epigenetic event provided a possible mechanism of the suppressive effect of ciprofloxacin. Furthermore, LL-37 peptide inhibited Clostridium difficile growth in vitro. In conclusion, ciprofloxacin and clindamycin exert immunomodulatory function by down-regulating AMPs and other immune components in colonic epithelial cells. Suppression of AMPs may contribute to the overgrowth of C. difficile, causing antibiotic-associated diarrhea.
Abstract: Uncomplicated urinary tract infections are typically monobacterial and are predominantly caused by Escherichia coli. Although several effective treatment options are available, the rates of antibiotic resistance in urinary isolates of E. coli have increased during the last decade. Knowledge of the actual local rates of antibiotic resistant pathogens as well as the underlying mechanisms are important factors in addition to the geographical location and the health state of the patient for choosing the most effective antibiotic treatment. Recommended treatment options include trimethoprim alone or in combination with sulfamethoxazol, fluoroquinolones, β-lactams, fosfomycin-trometamol, and nitrofurantoin. Three basic mechanisms of resistance to all antibiotics are known, i.e., target alteration, reduced drug concentration and inactivation of the drug. These mechanisms—alone or in combination—contribute to resistance against the different antibiotic classes. With increasing prevalence, combinations of resistance mechanisms leading to multiple drug resistant (mdr) pathogens are being detected and have been associated with reduced fitness under in vitro situations. However, mdr clones among clinical isolates such as E. coli sequence type 131 (ST131) have successfully adapted in fitness and growth rate and are rapidly spreading as a worldwide predominating clone of extraintestinal pathogenic E. coli.