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

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)

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

A novel dual-functioning ruthenium(II)–arene complex of an anti-microbial ciprofloxacin derivative — anti-proliferative and anti-microbial activity

7-(4-(Decanoyl)piperazin-1-yl)-ciprofloxacin, CipA, (1) which is an analogue of the antibiotic ciprofloxacin, and its ruthenium(II) complex [Ru(η6-p-cymene)(CipA-H)Cl], (2) have been synthesised and the x-ray crystal structures of 1·1.3H2O·0.6CH3OH and 2·CH3OH·0.5H2O determined. The complex adopts a typical pseudo-octahedral ‘piano-stool’ geometry, with Ru(II) π-bonded to the p-cymene ring and σ-bonded to a chloride and two oxygen atoms of the chelated fluoroquinolone ligand. The complex is highly cytotoxic in the low μM range and is as potent as the clinical drug cisplatin against the human cancer cell lines A2780, A549, HCT116, and PC3. It is also highly cytotoxic against cisplatin- and oxaliplatin-resistant cell lines suggesting a different mechanism of action. The complex also retained low μM cytotoxicity against the human colon cancer cell line HCT116p53 in which the tumour suppressor p53 had been knocked out, suggesting that the potent anti-proliferative properties associated with this complex are independent of the status of p53 (in contrast to cisplatin). The complex also retained moderate anti-bacterial activity in two Escherichia coli, a laboratory strain and a clinical isolate resistant to first, second and third generation β-lactam antibiotics

Cytokine responses to Staphylococcus aureus bloodstream infection differ between patient cohorts that have different clinical courses of infection.

BackgroundThe clinical course of Staphylococcus aureus bloodstream infection is unpredictable and bacterial virulence, host immune response and patient characteristics are among the factors that contribute to the clinical course of infection. To investigate the relationship between cytokine response and clinical outcome, circulating cytokine levels were investigated in response to S. aureus bloodstream infection in patient with different clinical courses of infection.MethodsA prospective study was carried out in 61 patients with S. aureus bloodstream infection and circulating levels of IL-6, GRO-¿, RANTES and leptin were assessed over the course of the infection. Levels were compared in patients with complicated courses of infection (e.g. infective endocarditis) versus uncomplicated courses of S. aureus bloodstream infection and methicillin-resistant S. aureus Vs methicillin-susceptible S. aureus infection.ResultsSignificantly lower leptin levels (p

When are the hands of healthcare workers positive for methicillin-resistant Staphylococcus aureus?

Hand hygiene is a key component in reducing infection. There are few reports on the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) on healthcare workers\u27 (HCWs\u27) hands. The aim of this study was to establish whether HCWs\u27 fingertips were contaminated with MRSA in a clinical hospital setting. The study was conducted in an acute tertiary referral hospital on four MRSA wards that were part of a larger research study on MRSA epidemiology and four other wards not included in the study. The fingertips from all categories of 523 HCWs were sampled on 822 occasions by the imprinting of fingertips on MRSA chromogenic agar plates. The type of hand hygiene agent used, if any, and the immediate prior activity of the HCW were recorded. Overall, 38/822 (5%) fingertips from 523 HCWs were MRSA-positive; 12/194 (6%) after clinical contact, 10/138 (10%) after contact with the patient\u27s environment and 15/346 (4%) after no specific contact. MRSA was recovered on 2/61 (3%) occasions after use of alcohol hand rub, 2/35 (6%) after 4% chlorhexidine detergent, 7/210 (3%) hand washing with soap and water, and 27/493 (5%) when no hand hygiene had been performed. MRSA was recovered from HCWs on seven of the eight wards. MRSA was more frequently present on fingertips on the four non-study wards vs the four MRSA study wards [18/250 (7%), 3/201 (1%), respectively; P\u3c=0.004]. The isolation of MRSA from HCWs\u27 fingertips, including after hand hygiene, indicates that more educational programmes are necessary to improve the quality of hand hygiene to prevent transmission of MRSA

Eradication of Staphylococcus aureus Biofilm Infections Using Synthetic Antimicrobial Peptides

Here, we demonstrate that antimicrobial peptides (AMPs) are an effective antibiofilm treatment when applied as catheter lock solutions (CLSs) against S. aureus biofilm infections. The activity of synthetic AMPs (Bac8c, HB43, P18, Omiganan, WMR, Ranalexin, and Polyphemusin) was measured against early and mature biofilms produced by methicillin-resistant S. aureus and methicillin-susceptible S. aureus isolates from patients with device-related infections grown under in vivo-relevant biofilm conditions. The cytotoxic and hemolytic activities of the AMPs against human cells and their immunomodulatory potential in human blood were also characterized. The D-Bac8c2,5Leu variant emerged as the most effective AMP during in vitro studies and was also highly effective in eradicating S. aureus biofilm infection when used in a CLS rat central venous catheter infection model. These data support the potential use of D-Bac8c2,5Leu, alone or in combination with other AMPs, in the treatment of S. aureus intravenous catheter infections