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  • 1. Brazier, J
    et al.
    Chmelar, D
    Dubreuil, L
    Feierl, G
    Hedberg, Maria
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Kalenic, S
    Könönen, E
    Lundgren, B
    Malamou-Ladas, H
    Nagy, E
    Sullivan, Å
    Nord, CE
    European surveillance study on antimicrobial susceptibility of Gram-positive anaerobic cocci2008In: International Journal of Antimicrobial Agents, ISSN 0924-8579, E-ISSN 1872-7913, Vol. 31, no 4, p. 316-320Article in journal (Refereed)
    Abstract [en]

    Gram-positive anaerobic cocci (GPAC) are a heterogeneous group of microorganisms frequently isolated from local and systemic infections. In this study, the antimicrobial susceptibilities of clinical strains isolated in 10 European countries were investigated. After identification of 299 GPAC to species level, the minimum inhibitory concentrations of penicillin, imipenem, clindamycin, metronidazole, vancomycin and linezolid were determined by the agar dilution method according to the Clinical and Laboratory Standards Institute. The majority of isolates were identified as Finegoldia magna and Parvimonas micra (formerly Peptostreptococcus micros), isolated from skin and soft tissue infections. All isolates were susceptible to imipenem, metronidazole, vancomycin and linezolid. Twenty-one isolates (7%) were resistant to penicillin (n=13) and/or to clindamycin (n=12). Four isolates were resistant to both agents. The majority of resistant isolates were identified as F. magna and originated from blood, abscesses and soft tissue infections.

  • 2. Chu, Hencelyn
    et al.
    Slepenkin, Anatoly
    Elofsson, Mikael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Keyser, Pia
    de la Maza, Luis M
    Peterson, Ellena M
    Candidate vaginal microbicides with activity against Chlamydia trachomatis and Neisseria gonorrhoeae2010In: International Journal of Antimicrobial Agents, ISSN 0924-8579, E-ISSN 1872-7913, Vol. 36, no 2, p. 145-150Article in journal (Refereed)
    Abstract [en]

    Vaginal microbicides with activity towards organisms that cause sexually transmitted infections have been proposed as a strategy to reduce transmission. Small-molecule inhibitors of Chlamydia trachomatis serovar D belonging to the class of salicylidene acylhydrazides (INPs) have been shown to work through a mechanism that involves iron restriction. Expanding on this work, ten INPs were tested against a lymphogranuloma venereum strain of C. trachomatis (serovar L2), Neisseria gonorrhoeae, and hydrogen peroxide-producing Lactobacillus crispatus and Lactobacillus jensenii. Seven INPs had minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations of <50 microM towards C. trachomatis L2. Three INPs had a MIC <12.5 microM against N. gonorrhoeae. Inhibition was reversed by iron, holo-transferrin and holo-lactoferrin but not by the iron-poor forms of these compounds. The compounds exhibited no bactericidal activity toward Lactobacillus. The INPs were not cytotoxic to HeLa 229 cells. When INP 0341 was tested in a mouse model of a Chlamydia vaginal infection there was a significant reduction in the number of mice shedding C. trachomatis up to 4 days after infection (P<0.01). In summary, select INPs are promising vaginal microbicide candidates as they inhibit the growth of two common sexually transmitted organisms in vitro, are active in a mouse model against C. trachomatis, are not cytotoxic and do not inhibit organisms that compose the normal vaginal flora.

  • 3. Forthal, Donald N
    et al.
    Phan, Tran B
    Slepenkin, Anatoly V
    Landucci, Gary
    Chu, Hencelyn
    Elofsson, Mikael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Peterson, Ellena
    In vitro anti-HIV-1 activity of salicylidene acylhydrazide compounds2012In: International Journal of Antimicrobial Agents, ISSN 0924-8579, E-ISSN 1872-7913, Vol. 40, no 4, p. 354-360Article in journal (Refereed)
    Abstract [en]

    Salicylidene acylhydrazide compounds have been shown to inhibit bacterial pathogens, including Chlamydia and Neisseria gonorrhoeae. If such compounds could also target HIV-1, their potential use as topical microbicides to prevent sexually transmitted infections would be considerable. In this study, the in vitro anti-HIV-1 activity, cytotoxicity and mechanism of action of several salicylidene acylhydrazides were determined. Inhibitory activity was assessed using TZM-bl cells and primary peripheral blood mononuclear cells (PBMCs) as targets for HIV-1 infection. Antiviral activity was measured against cell-free and cell-associated virus and in vaginal fluid and semen simulants. Since the antibacterial activity of salicylidene acylhydrazides is reversible by Fe(2+), the ability of Fe(2+) and other cations to reverse the anti-HIV-1 activity of the compounds was determined. Real-time PCR was also employed to determine the stage affected in the HIV-1 replication cycle. Four compounds with 50% inhibitory concentrations against HIV-1 of 1-7μM were identified. In vitro toxicity varied but was generally limited. Activity was similar against three R5 clade B primary isolates and whether the target for virus replication was TZM-bl cells or PBMCs. Compounds inhibited cell-free and cell-associated virus and were active in vaginal fluid and semen simulants. Fe(2+), but not other cations, reversed the anti-HIV-1 effect. Finally, the inhibitory effect of the compounds occurred at a post-integration step. In conclusion, salicylidene acylhydrazides were identified with in vitro anti-HIV-1 activity in the micromolar range. The activity of these compounds against other sexually transmitted pathogens makes them potential candidates to formulate for use as a broad-spectrum topical genital microbicide.

  • 4.
    Sóki, J.
    et al.
    University of Szeged.
    Edwards, R.
    Hedberg, Maria
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Fang, H.
    Nagy, E.
    Nord, C. E.
    Examination of cfiA-mediated carbapenem resistance in Bacteroides fragilis strains from a European antibiotic susceptibility survey2006In: International Journal of Antimicrobial Agents, ISSN 0924-8579, E-ISSN 1872-7913, Vol. 28, no 6, p. 497-502Article in journal (Refereed)
    Abstract [en]

    Of 1284 Bacteroides strains collected in Europe in 2000 for antibiotic susceptibility surveillance, 65 isolates displayed imipenem minimum inhibitory concentrations (MICs) > or =1 mg/L and were chosen for a thorough analysis of their resistance mechanism. Twenty-five of the isolates were positive for the cfiA carbapenem resistance gene. The resistance rates were 0.8% and 1.3% for imipenem and meropenem, respectively. In six of the strains, insertion sequence (IS) elements (IS613, IS614B, IS1186 and IS1187) activated the cfiA gene. However, other strains displayed at least elevated carbapenem MICs or were carbapenem resistant and produced measurable carbapenemase activities but did not harbour IS elements in the region upstream of the cfiA gene. The major determinant of carbapenem resistance in Bacteroides fragilis is production of CfiA metallo-beta-lactamase via activation of the cfiA gene by IS elements (higher level resistance) or by activation of its putative own promoter.

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