Beyond conventional antibiotics for the future treatment of methicillin-resistant Staphylococcus aureus infections: two novel alternatives.

The majority of antibiotics currently used to treat methicillin-resistant Staphylococus aureus (MRSA) infections target bacterial cell wall synthesis or protein synthesis. Only daptomycin has a novel mode of action. Reliance on limited targets for MRSA chemotherapy, has contributed to antimicrobial resistance. Two alternative approaches to the treatment of S. aureus infection, particularly those caused by MRSA, that have alternative mechanisms of action and that address the challenge of antimicrobial resistance are cationic host defence peptides and agents that target S. aureus virulence. Cationic host defence peptides have multiple mechanisms of action and are less likely than conventional agents to select resistant mutants. They are amenable to modifications that improve their stability, effectiveness and selectivity. Some cationic defence peptides such as bactenecin, mucroporin and imcroporin have potent in vitro bactericidal activity against MRSA. Antipathogenic agents also have potential to limit the pathogenesis of S aureus. These are generally small molecules that inhibit virulence targets in S. aureus without killing the bacterium and therefore have limited capacity to promote resistance development. Potential antipathogenic targets include the sortase enzyme system, the accessory gene regulator (agr) and the carotenoid biosynthetic pathway. Inhibitors of these targets have been identified and these may have potential for further development

The revolving door between hospital and community: extended-spectrum beta-lactamase-producing Escherichia coli in Dublin.

BACKGROUND: Escherichia coli that produce extended-spectrum beta-lactamases (ESBLs) are an increasing cause of healthcare-associated infection, and community healthcare facilities may be a reservoir for important epidemic clones. AIM: To characterize retrospectively and investigate the epidemiology of ESBL-producing E. coli collected in a Dublin hospital, during 2009 and 2010, and to investigate the dissemination of specific clones within hospital and community healthcare facilities. METHODS: Pulsed-field gel electrophoresis (PFGE) was used to determine the genetic relatedness of 100 ESBL-producing E. coli isolates. Phylogenetic groups were determined and the O25b-ST131 clone identified in the collection. The genetic data were correlated with antimicrobial susceptibility, clinical and demographic data to explore the epidemiology of specific clones. FINDINGS: Phylogenetic groups B2 (62%) and D (18%) were the most common and were associated with non-urinary isolates (P CONCLUSIONS: E. coli O25b-ST131 is largely responsible for ESBL-producing E. coli in LTCFs in Dublin. The distribution of ESBL-producing E. coli in our hospital and community highlights a \u27revolving door\u27 through which these resistant bacteria spread and disseminate

Diagnosis and treatment of chlamydia and gonorrhoea in general practice in England 2000–2011: a population-based study using data from the UK Clinical Practice Research Datalink

Objectives: To determine the relative contribution of general practices (GPs) to the diagnosis of chlamydia and gonorrhoea in England and whether treatment complied with national guidelines. Design: Analysis of longitudinal electronic health records in the Clinical Practice Research Datalink (CPRD) and national sexually transmitted infection (STI) surveillance databases, England, 2000–2011. Setting: GPs, and community and specialist STI services. Participants: Patients diagnosed with chlamydia (n=1 386 169) and gonorrhoea (n=232 720) at CPRD GPs, and community and specialist STI Services from 2000–2011. Main outcome measures: Numbers and rates of chlamydia and gonorrhoea diagnoses; percentages of patients diagnosed by GPs relative to other services; percentage of GP patients treated and antimicrobials used; percentage of GP patients referred. Results: The diagnosis rate (95% CI) per 100 000 population of chlamydia in GP increased from 22.8 (22.4–23.2) in 2000 to 29.3 (28.8–29.7) in 2011 (p<0.001), while the proportion treated increased from 59.5% to 78.4% (p=0.001). Over 90% were prescribed a recommended antimicrobial. Over the same period, the diagnosis rate (95% CI) per 100 000 population of gonorrhoea in GP ranged between 3.2 (3–3.3) and 2.4 (2.2–2.5; p=0.607), and the proportion treated ranged between 32.7% and 53.6% (p=0.262). Despite being discontinued as a recommended therapy for gonorrhoea in 2005, ciprofloxacin accounted for 42% of prescriptions in 2007 and 20% in 2011. Over the study period, GPs diagnosed between 9% and 16% of chlamydia cases and between 6% and 9% of gonorrhoea cases in England. Conclusions: GP makes an important contribution to the diagnosis and treatment of bacterial STIs in England. While most patients diagnosed with chlamydia were managed appropriately, many of those treated for gonorrhoea received antimicrobials no longer recommended for use. Given the global threat of antimicrobial resistance, GPs should remain abreast of national treatment guidelines and alert to treatment failure in their patients

Novel class of Bi(iii) hydroxamato complexes: synthesis, urease inhibitory activity and activity against H. pylori.

Reaction of Bi(NO3)3 with benzohydroxamic acid (Bha) and salicylhydroxamic acid (Sha) gives the novel Bi(iii) complexes [Bi2(Bha-1H)2(μ-Bha-1H)2(η(2)-NO3)2] () and [Bi6(CH3OH)2(η(1)-NO3)2(η(2)-NO3)(OH2)2(Sha-1H)12](NO3)2 (). X-ray crystal structure of reveals two hydroxamato coordination modes; bidentate bridging (O, O\u27) and bidentate non-bridging (O, O\u27) and of reveals one coordination mode; bidentate bridging (O, O\u27). , specifically designed to and demonstrated to inhibit the activity of urease, exhibits excellent antibacterial activity against three strains of Helicobacter pylori with MIC ≥ 16 μg mL(-1)

A Resolved Millimeter Emission Belt in the AU Mic Debris Disk

We present imaging observations at 1.3 millimeters of the debris disk surrounding the nearby M-type flare star AU Mic with beam size 3 arcsec (30 AU) from the Submillimeter Array. These data reveal a belt of thermal dust emission surrounding the star with the same edge-on geometry as the more extended scattered light disk detected at optical wavelengths. Simple modeling indicates a central radius of ~35 AU for the emission belt. This location is consistent with the reservoir of planetesimals previously invoked to explain the shape of the scattered light surface brightness profile through size-dependent dust dynamics. The identification of this belt further strengthens the kinship between the debris disks around AU Mic and its more massive sister star beta Pic, members of the same ~10 Myr-old moving group.Comment: 10 pages, 2 figures. Accepted for publication in ApJ Letter

DNA Microarray Genotyping and Virulence and Antimicrobial Resistance Gene Profiling of Methicillin-Resistant Staphylococcus aureus Bloodstream Isolates from Renal Patients.

Thirty-six methicillin-resistant Staphylococcus aureus (MRSA) bloodstream isolates from renal patients were genetically characterized by DNA microarray analysis and spa typing. The isolates were highly clonal, belonging mainly to ST22-MRSA-IV. The immune evasion and enterotoxin gene clusters were found in 29/36 (80%) and 33/36 (92%) of isolates, respectively

Search and you will find: detecting extended-spectrum β-lactamase-producing Klebsiella pneumoniae from a patient\u27s immediate environment.

Contamination of inanimate surfaces contribute to the transmission of healthcare-associated infection which is well documented for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci VRE (3, 5, 10). The high rate of skin colonisation with these bacteria among healthcare workers increases the risk of cross-contamination of high-touch surfaces (6). Since Gram-negative bacteria survive poorly on surfaces, their role in transmission of infection has not been as widely investigated. Extended spectrum beta-lactamase-producing enterobacteriaciae (ESBL-PE) are now widespread and endemic in nosocomial settings (2, 4) and given the increasing prevalence of infections involving ESBL-PE, the role of the environment in ESBL-PE transmission should be explored. This study reports the evaluation of two ESBL-PE recovery methods from typical hospital surface materials and their application for recovery of ESBL-PE adjacent to an ESBL-positive patient

Directional eddy current probe configuration for in-line detection of out-of-plane wrinkles

Real-time monitoring of carbon fibre composites during Automated Fibre Placement (AFP) manufacturing remains a challenge for non-destructive evaluation (NDE) techniques. An directional eddy-current (EC) probe with asymmetric transmit and differential receive (Tx-dRx) coils is designed, constructed and characterized to evaluate the detectability of out-of-plane wrinkles. Initial studies were conducted to determine suitable excitation frequencies and to analyse the impact of relative orientations of driver and pickup coils on wrinkle detectability. The probe configurations are evaluated experimentally and employ a new finite element modelling approach to better understand the relationship between eddy-current density and defect detection. The findings indicate that a probe configuration with an asymmetric driver coil normal to the material surface and aligned with the fibre directions, and with differential pickup coils 90 degrees to the scanning direction, shows the best capability for out-of-plane wrinkle detection, with SNR >20 for wrinkles over 1.3 mm in amplitude