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    ABSTRACT: New antifungal agents are required to compensate for the increase in resistance to standard antifungal agents of C. albicans, which is an important opportunistic fungal pathogen that causes minor infections in many individuals but very serious infections in those who are immune-compromised. In this study, combinations of the theaflavin and epicatechin are investigated as potential antifungal agents and also to establish whether antifungal synergy exists between these two readily accessible and cost-effective polyphenols isolated from black and green tea. The results of disc diffusion assays show stronger antibacterial activity of theaflavin:epicatechin combinations against C. albicans NCTC 3255 and NCTC 3179, than that of theaflavin alone. Minimum inhibitory concentrations (MICs) of theaflavin and the theaflavin:epicatechin combinations of 1024 ㎍/mL with theaflavin and 128-256 ㎍/mL with theaflavin:epicatechin combinations are found. FICIs were calculated and synergy between theaflavin and epicatechin against both isolates of C. albicans confirmed. Theaflavin:epicatechin combinations show real potential for future use as a treatment for infections caused by C. albicans.
    Journal of Microbiology and Biotechnology 09/2013; 23(9):1322-1326.
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    ABSTRACT: The problem of antimicrobial resistance is exemplified by multidrug-resistant (MDR) isolates of Gram-negative species. Of particular concern are expanded-spectrum cephalosporin-resistant isolates of Enterobacteriaceae, epidemic lineages of Acinetobacter baumannii producing OXA-type carbapenemases, and MDR Pseudomonas aeruginosa. In this study, the in vitro activity of the novel monosulfactam BAL30072 was investigated both alone and in combination with meropenem against a diverse collection of commonly encountered Gram-negative pathogens. Thirty-one isolates were studied, including type strains and clinical isolates with defined mechanisms conferring resistance to various antimicrobial agents including to carbapenems, colistin and tigecycline. BAL30072 minimum inhibitory concentrations (MICs) were determined in the presence and absence of meropenem (1:1, w/w) by agar dilution. Potential synergy or antagonism between BAL30072 and meropenem was investigated using standard chequerboard assays. Versus MDR A. baumannii strains producing class D oxacillinases, BAL30072 MICs were all ≤4mg/L with the exception of the isolate belonging to the UK 'Burn' lineage. BAL30072 exhibited MIC values of 0.5mg/L to >64mg/L towards the five P. aeruginosa strains. Against three meropenem-susceptible Escherichia coli, including the CTX-M-15 extended-spectrum β-lactamase-producer, BAL30072 exhibited MICs of 0.25-2mg/L; higher MICs were recorded against some of the Enterobacteriaceae isolates tested. The in vitro data suggest that BAL30072 has a potential role in the treatment of infections due to Gram-negative pathogens, including those with important resistances to other agents. In addition, BAL30072 shows powerful synergistic activity in combination with meropenem, potentially expanding its coverage for the treatment of infections caused by problematic species.
    International journal of antimicrobial agents 07/2013;
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    ABSTRACT: The activity of colistin in combination with daptomycin was assessed using 30 Gram-negative type strains and multidrug-resistant isolates with defined mechanisms of resistance. Daptomycin minimum inhibitory concentrations (MICs) were determined with and without sub-inhibitory concentrations of colistin. The activity of daptomycin was not affected with respect to Escherichia coli, Klebsiella pneumoniae or Pseudomonas aeruginosa. For colistin-susceptible Acinetobacter baumannii, sensitisation factors ranged from 8 to 128 (median 32), with the daptomycin MIC being reduced to the Clinical and Laboratory Standards Institute (CLSI) enterococci susceptibility breakpoint of 4 μg/ml for the ATCC 19606 type strain. A combination of daptomycin and colistin may be useful for the treatment of A. baumannii but not infections due to other Gram-negative species.
    European Journal of Clinical Microbiology 04/2013;
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    ABSTRACT: Treatment of Acinetobacter baumannii infections is challenging owing to widespread multidrug resistance and the lack of novel agents. There is now considerable interest in the potential of unorthodox combination therapies such as colistin and glycopeptides (e.g. vancomycin and teicoplanin), since potent synergy can be demonstrated in vitro. A simple invertebrate model (Galleria mellonella) has been developed to assess the in vivo activity of antimicrobial therapies and was used to investigate the efficacy of colistin combined with the lipoglycopeptide telavancin in the treatment of A. baumannii infection. Galleria mellonella larvae were inoculated with 10(5)CFU/larvae of A. baumannii type strain ATCC 19606 or the multidrug-resistant clinical isolate AB210. Infected caterpillars were treated with either telavancin (10mg/kg), colistin (2.5mg/kg) or a telavancin/colistin combination. Larvae were incubated at 37°C for up to 96h and were scored daily. Survival curves were plotted and analysed using the log-rank test. The telavancin/colistin combination was effective in the treatment of larvae infected with both strains but was superior to colistin monotherapy in the treatment of A. baumannii AB210 (P<0.001). The combination of telavancin and colistin was effective in a simple invertebrate model of A. baumannii infection. This is in agreement with a previous in vitro study and provides preliminary in vivo evidence that such a combination might be useful therapeutically.
    International journal of antimicrobial agents 01/2013;
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    ABSTRACT: Three selective chromogenic culture media (CHROMagars ESBL, CTX-M and KPC) were evaluated for their ability to support the growth of nine Klebsiella pneumoniae isolates producing OXA-48 carbapenemase in combination with other β-lactamases. CHROMagar ESBL and CHROMagar KPC were the most sensitive media, supporting growth of all isolates with a detection limit as low as < 100 CFU/ml. Five isolates failed to grow on CHROMagar CTX-M, and five were recovered on CHROMagar KPC only at counts > 10(6) CFU/ml. Both CHROMagar ESBL and CHROMagar KPC may be useful for enhanced isolation of K pneumoniae producing OXA-48-like carbapenemases.
    Journal of clinical pathology 01/2013;
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    ABSTRACT: Rates of sexually transmitted infections (STIs) in UK young people remain high in men and women. However, the National Chlamydia Screening Programme has had limited success in reaching men. The authors explored the acceptability of various medical, recreational and sports venues as settings to access self-collected testing kits for STIs and HIV among men in the general population and those who participate in sport. A stratified random probability survey of 411 (weighted n=632) men in Great Britain aged 18-35 years using computer-assisted personal and self-interviews. Young men engaged well with healthcare with 93.5% registered with, and 75.3% having seen, a general practitioner in the last year. 28.7% and 19.8% had previously screened for STIs and HIV, respectively. Willingness to access self-collected tests for STIs (85.1%) and HIV (86.9%) was high. The most acceptable pick-up points for testing kits were general practice 79.9%, GUM 66.8% and pharmacy 65.4%. There was a low acceptability of sport venues as pick-up points in men as a whole (11.7%), but this was greater among those who participated in sport (53.9%). Healthcare settings were the most acceptable places for accessing STI and HIV self-testing kits. Although young men frequently access general practice, currently little STI screening occurs in this setting. There is considerable potential to screen large numbers of men and find high rates of infection through screening in general practice. While non-clinical settings are acceptable to a minority of men, more research is needed to understand how these venues could be used most effectively.
    Sexually transmitted infections 04/2012; 88(6):427-32.
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    ABSTRACT: The treatment of Gram-negative infections is increasingly compromised by the spread of resistance. With few agents currently in development, clinicians are now considering the use of unorthodox combination therapies for multidrug-resistant strains. Here we assessed the in vitro activity of the novel lipoglycopeptide telavancin (TLV) when combined with colistin (COL) versus 13 Gram-negative type strains and 66 clinical isolates. Marked synergy was observed in either checkerboard (fractional inhibitory concentration index [FICI], <0.5; susceptibility breakpoint index [SBPI], >2) or time-kill assays (>2-log reduction in viable counts compared with starting inocula at 24 h) versus the majority of COL-susceptible enterobacteria, Stenotrophomonas maltophilia, and Acinetobacter baumannii isolates, but only limited effects were seen against Pseudomonas aeruginosa or strains with COL resistance. Using an Etest/agar dilution method, the activity of TLV was potentiated by relatively low concentrations of COL (0.25 to 0.75 μg/ml), reducing the MIC of TLV from >32 μg/ml to ≤ 1 μg/ml for 35% of the clinical isolates. This provides further evidence that glycopeptide-polymyxin combinations may be a useful therapeutic option in the treatment of Gram-negative infections.
    Antimicrobial Agents and Chemotherapy 04/2012; 56(6):3080-5.
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    ABSTRACT: Systemic lupus erythematosus (SLE) and Sjögren's syndrome are autoimmune disorders which are characterized by a disturbed B cell homeostasis which leads ultimately to dysfunction of various organs. One of the B cell subsets that appear in abnormal numbers is the population of transitional B cells, which is increased in the blood of patients with SLE and Sjögren's syndrome. Transitional B cells are newly formed B cells. In mice, transitional B cells undergo selection checks for unwanted specificity in the bone marrow and the spleen in order to eliminate autoreactive B cells from the circulating naive B cell population. In humans, the exact anatomical compartments and mechanisms of the specificity check-points for transitional B cells remain unclear, but appear to be defective in SLE and Sjögren's syndrome. This review aims to highlight the current understanding of transitional B cells and their defects in the two disorders before and after B cell-targeted therapies.
    Clinical & Experimental Immunology 01/2012; 167(1):7-14.
  • Journal of pediatric gastroenterology and nutrition 12/2011; 53(6):684-6.
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    ABSTRACT: The oral microbial community represents the best-characterized consortium associated with the human host. There are strong correlations between the qualitative composition of the oral microbiota and clinically healthy or diseased states. However, additional studies are needed to elucidate the mechanisms that define these microbial/host relationships.
    Cell host & microbe 10/2011; 10(4):302-6.
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