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  • 1.
    Ahlstrom, Christina A.
    et al.
    US Geol Survey, AK 99508 USA.
    Ramey, Andrew M.
    US Geol Survey, AK 99508 USA.
    Woksepp, Hanna
    Dept Dev and Publ and Hlth, Sweden.
    Bonnedahl, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Dept Infect Dis, Sweden.
    Repeated Detection of Carbapenemase-Producing Escherichia coil in Gulls Inhabiting Alaska2019In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 63, no 8, article id e00758-19Article in journal (Refereed)
    Abstract [en]

    Here, we report the first detection of carbapenemase-producing Escherichia coli in Alaska and in wildlife in the United States. Wild bird (gull) feces sampled at three locations in Southcentral Alaska yielded isolates that harbored plasmidencoded bla(kpc-2), or chromosomally encoded bla(OXA-48) and genes associated with antimicrobial resistance to up to eight antibiotic classes.

  • 2.
    Ajileye, Adebisi
    et al.
    Birmingham Heartlands Hospital, England.
    Alvarez, Nataly
    Corp Invest Biol, Colombia; University of Pontificia Bolivariana, Colombia.
    Merker, Matthias
    Research Centre Borstel, Germany; German Centre Infect Research, Germany.
    Walker, Timothy M.
    University of Oxford, England.
    Akter, Suriya
    Institute Trop Med, Belgium.
    Brown, Kerstin
    Birmingham Heartlands Hospital, England.
    Moradigaravand, Danesh
    Wellcome Trust Sanger Institute, England.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar County Hospital, Sweden.
    Andres, Soenke
    Research Centre Borstel, Germany.
    Schleusener, Viola
    Research Centre Borstel, Germany.
    Omar, Shaheed V.
    Centre TB, South Africa.
    Coll, Francesc
    London School Hyg and Trop Med, England.
    Huang, Hairong
    Capital Medical University, Peoples R China.
    Diel, Roland
    University Hospital, Germany.
    Ismail, Nazir
    Centre TB, South Africa.
    Parkhill, Julian
    Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
    de Jong, Bouke C.
    Institute Trop Med, Belgium.
    Peto, Tim E. A.
    University of Oxford, England.
    Crook, Derrick W.
    University of Oxford, England; Public Health England Microbiol Serv, England.
    Niemann, Stefan
    Research Centre Borstel, Germany; German Centre Infect Research, Germany.
    Robledo, Jaime
    Corp Invest Biol, Colombia; University of Pontificia Bolivariana, Colombia.
    Grace Smith, E.
    Birmingham Heartlands Hospital, England.
    Peacock, Sharon J.
    Wellcome Trust Sanger Institute, England; London School Hyg and Trop Med, England; University of Cambridge, England.
    Koeser, Claudio U.
    University of Cambridge, England.
    Some Synonymous and Nonsynonymous gyrA Mutations in Mycobacterium tuberculosis Lead to Systematic False-Positive Fluoroquinolone Resistance Results with the Hain GenoType MTBDRsl Assays2017In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 61, no 4, article id e02169-16Article in journal (Refereed)
    Abstract [en]

    In this study, using the Hain GenoType MTBDRsl assays (versions 1 and 2), we found that some nonsynonymous and synonymous mutations in gyrA in Mycobacterium tuberculosis result in systematic false-resistance results to fluoroquinolones by preventing the binding of wild-type probes. Moreover, such mutations can prevent the binding of mutant probes designed for the identification of specific resistance mutations. Although these mutations are likely rare globally, they occur in approximately 7% of multidrug-resistant tuberculosis strains in some settings.

  • 3.
    Berglund, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Claesson, Carina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Letter: High Prevalence of Heterogeneously Glycopeptide-Intermediate Coagulase-Negative Staphylococci in Sternal Wounds in ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol 60, issue 8, pp 5097-50982016In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 60, no 8, p. 5097-5098Article in journal (Other academic)
    Abstract [en]

    n/a

  • 4.
    Bäckman, Anders
    et al.
    Department of Clinical Microbiology and Immunology, Örebro Medical Center Hospital, Örebro.
    Orvelid, Paula
    Department of Clinical Microbiology and Immunology, Örebro Medical Center Hospital, Örebro.
    Vazquez, Julio A.
    Servicio de Bacteriologı́ca, Centro Nacional de Microbiologı́ca, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
    Sköld, Ola
    Department of Pharmaceutical Bioscience, Biomedical Centre, Uppsala University, Uppsala.
    Olcén, Per
    Department of Clinical Microbiology and Immunology, Örebro Medical Center Hospital, Örebro.
    Complete Sequence of a β-Lactamase-Encoding Plasmid in Neisseria meningitidis2000In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 44, no 1, p. 210-212Article in journal (Refereed)
    Abstract [en]

    Identical β-lactamase-encoding (TEM-1) plasmids were found in two different clinical Neisseria meningitidis strains. They were completely sequenced (5,597 bp) and designated pAB6. The plasmid is almost identical to Neisseria gonorrhoeae plasmid pJD5 (5,599 kb) and may have been picked up from a gonococcus in vivo.

  • 5.
    Davies Forsman, L.
    et al.
    Karolinska Institute, Sweden; Karolinska University Hospital Solna, Sweden.
    Giske, C. G.
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Bruchfeld, J.
    Karolinska Institute, Sweden; Karolinska University Hospital Solna, Sweden.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar County Hospital, Sweden.
    Jureen, P.
    Public Health Agency Sweden, Sweden.
    Angeby, K.
    Karolinska University Hospital, Sweden; University of W Indies, Jamaica.
    Meropenem-Clavulanic Acid Has High In Vitro Activity against Multidrug-Resistant Mycobacterium tuberculosis2015In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 59, no 6, p. 3630-3632Article in journal (Refereed)
    Abstract [en]

    We investigated the activity of meropenem-clavulanic acid (MEM-CLA) against 68 Mycobacterium tuberculosis isolates. We included predominantly multi- and extensively drug-resistant tuberculosis (MDR/XDR-TB) isolates, since the activity of MEM-CLA for resistant isolates has previously not been studied extensively. Using Middlebrook 7H10 medium, all but four isolates showed an MIC distribution of 0.125 to 2 mg/liter for MEM-CLA, below the non-species-related breakpoint for MEM of 2 mg/liter defined by EUCAST. MEM-CLA is a potential treatment option for MDR/XDR-TB.

  • 6.
    Davies Forsman, L.
    et al.
    Karolinska Institute, Sweden; Karolinska University, Sweden.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences. Linnaeus University, Sweden.
    Simonsson, U. S. H.
    Uppsala University, Sweden.
    Bruchfeld, J.
    Karolinska Institute, Sweden; Karolinska University, Sweden.
    Larsson, Marie C
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Jureen, P.
    Public Health Agency Sweden, Sweden.
    Sturegard, E.
    Regional and University of Labs, Sweden.
    Giske, C. G.
    Karolinska University Hospital, Sweden.
    Angeby, K.
    Karolinska University Hospital, Sweden; University of W Indies, Jamaica.
    Intra- and Extracellular Activities of Trimethoprim-Sulfamethoxazole against Susceptible and Multidrug-Resistant Mycobacterium tuberculosis2014In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 58, no 12, p. 7557-7559Article in journal (Refereed)
    Abstract [en]

    We investigated the activity of trimethoprim-sulfamethoxazole (SXT) against Mycobacterium tuberculosis, the pathogen that causes tuberculosis (TB). The MIC distribution of SXT was 0.125/2.4 to 2/38 mg/liter for the 100 isolates tested, including multi- and extensively drug-resistant isolates (MDR/XDR-TB), whereas the intracellular MIC90 of sulfamethoxazole (SMX) for the pansusceptible strain H37Rv was 76 mg/liter. In an exploratory analysis using a ratio of the unbound area under the concentration-time curve from 0 to 24 h over MIC (fAUC(0-24)/MIC) using greater than= 25 as a potential target, the cumulative fraction response was greater than= 90% at doses of greater than= 2,400 mg of SMX. SXT is a potential treatment option for MDR/XDR-TB.

  • 7.
    Hanberger, Håkan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Maller, Rolf
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Isaksson, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Pharmacodynamics of daptomycin and vancomycin on Enterococcus faecalis and Staphylococcus aureus demonstrated by studies of initial killing and postantibiotic effect and influence of Ca2+ and albumin on these drugs.1991In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 35, no 9, p. 1710-1716Article in journal (Refereed)
    Abstract [en]

    The pharmacodynamics of daptomycin and vancomycin on Enterococcus faecalis ATCC 29212 and Staphylococcus aureus ATCC 25923 were investigated by studying the postantibiotic effect (PAE) and initial killing. The influence of Ca2+ and albumin on these drugs was also evaluated. The PAE was studied by use of bioluminescence assay of bacterial ATP. Daptomycin at clinically achievable concentrations produced a dose-dependent PAE on E. faecalis (0.6 to 6.7 h) and S. aureus (1.0 to 6.3 h). The long PAE of daptomycin was seen simultaneously with a potent dose-dependent initial killing assayed by viable count determination. The initial change in bacterial ATP was not as extensive as the decrease in viability. Vancomycin at corresponding concentrations produced shorter PAEs on E. faecalis (0.5 to 1.0 h) and S. aureus (1.3 to 1.8 h). This coincides with a weak non-dose-dependent initial change in viability and intracellular ATP. The MICs of vancomycin were not influenced by different Ca2+ concentrations or by the addition of albumin to the broth. The MICs of daptomycin for both strains were lowered, and the PAEs were prolonged with increasing concentrations of Ca2+ in the broth. The PAE of daptomycin was Ca2+ dependent to the same extent as the MIC was. In the presence of physiological concentrations of albumin and free Ca2+, the PAEs of daptomycin on both strains were reduced and the MICs were increased in comparison with the results obtained in pure Mueller-Hinton broth with approximately the same free Ca2+ concentration. This decrease in daptomycin activity was considered to be due to the albumin binding of daptomycin. Despite the albumin binding of daptomycin, the PAE produced on E. faecalis and S. aureus in the presence of a physiological free Ca2+ concentration was still over 6 h at clinically achievable concentrations.

  • 8.
    Haversen, L.
    et al.
    Univ Gothenburg, Dept Infect Med Clin Bacteriol, S-41346 Gothenburg, Sweden.
    Kondori, N.
    Univ Gothenburg, Dept Infect Med Clin Bacteriol, S-41346 Gothenburg, Sweden.
    Baltzer, Lars
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    A Hanson, L A
    Univ Gothenburg, Dept Clin Immunol, S-41346 Gothenburg, Sweden.
    Dolphin, Gunnar
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Duner, K.
    Univ Gothenburg, Dept Infect Med Clin Bacteriol, S-41346 Gothenburg, Sweden.
    Mattsby-Baltzer, I.
    Univ Gothenburg, Dept Infect Med Clin Bacteriol, S-41346 Gothenburg, Sweden.
    Structure-Microbicidal Activity Relationship of Synthetic Fragments Derived from the Antibacterial alpha-Helix of Human Lactoferrin2010In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 54, no 1, p. 418-425Article in journal (Refereed)
    Abstract [en]

    There is a need for new microbicidal agents with therapeutic potential due to antibiotic resistance in bacteria and fungi. In this study, the structure-microbicidal activity relationship of amino acid residues 14 to 31 (sequence 14-31) from the N-terminal end, corresponding to the antibacterial alpha-helix of human lactoferrin (LF), was investigated by downsizing, alanine scanning, and substitution of amino acids. Microbicidal analysis (99% killing) was performed by a microplate assay using Escherichia coli, Staphylococcus aureus, and Candida albicans as test organisms. Starting from the N-terminal end, downsizing of peptide sequence 14-31 showed that the peptide sequence 19-31 (KCFQWQRNMRKVR, HL9) was the optimal length for antimicrobial activity. Furthermore, HL9 bound to lipid A/lipopolysaccharide, as shown by neutralizing endotoxic activity in a Limulus assay. Alanine scanning of peptide sequence 20-31 showed that Cys20, Trp23, Arg28, Lys29, or Arg31 was important for expressing full killing activity, particularly against C. albicans. Substituting the neutral hydrophilic amino acids Gln24 and Asn26 for Lys and Ala (HLopt2), respectively, enhanced microbicidal activity significantly against all test organisms compared to the amino acids natural counterpart, also, in comparison with HL9, HLopt2 had more than 10-fold-stronger fungicidal activity. Furthermore, HLopt2 was less affected by metallic salts than HL9. The microbicidal activity of HLopt2 was slightly reduced only at pH 7.0, as tested in the pH range of 4.5 to 7.5. The results showed that the microbicidal activity of synthetic peptide sequences, based on the antimicrobial alpha-helix region of LF, can be significantly enhanced by optimizing the length and substitution of neutral amino acids at specific positions, thus suggesting a sequence lead with therapeutic potential.

  • 9.
    Heyckendorf, Jan
    et al.
    Res Ctr Borstel, Germany; German Ctr Infect Res DZIF, Germany; Univ Lubeck, Germany.
    Andres, Soenke
    Res Ctr Borstel, Germany.
    Koser, Claudio U.
    Univ Cambridge, England.
    Olaru, Ioana D.
    Res Ctr Borstel, Germany; German Ctr Infect Res DZIF, Germany.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar Cty Hosp, Sweden.
    Sturegard, Erik
    Lund Univ, Sweden.
    Beckert, Patrick
    German Ctr Infect Res DZIF, Germany; Karolinska Inst, Sweden.
    Schleusener, Viola
    Karolinska Inst, Sweden.
    Kohl, Thomas A.
    German Ctr Infect Res DZIF, Germany; Karolinska Inst, Sweden.
    Hillemann, Doris
    Res Ctr Borstel, Germany.
    Moradigaravand, Danesh
    Wellcome Trust Sanger Inst, England.
    Parkhill, Julian
    Wellcome Trust Sanger Inst, England.
    Peacock, Sharon J.
    Wellcome Trust Sanger Inst, England; London Sch Hyg and Trop Med, England.
    Niemann, Stefan
    German Ctr Infect Res DZIF, Germany; Univ Cambridge, England; Res Ctr Borstel, Germany.
    Lange, Christoph
    Res Ctr Borstel, Germany; German Ctr Infect Res DZIF, Germany; Univ Lubeck, Germany; Karolinska Inst, Sweden; Univ Namibia, Namibia.
    Merker, Matthias
    German Ctr Infect Res DZIF, Germany; Res Ctr Borstel, Germany.
    What Is Resistance? Impact of Phenotypic versus Molecular Drug Resistance Testing on Therapy for Multi-and Extensively Drug-Resistant Tuberculosis2018In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 62, no 2, article id e01550-17Article in journal (Refereed)
    Abstract [en]

    Rapid and accurate drug susceptibility testing (DST) is essential for the treatment of multi-and extensively drug-resistant tuberculosis (M/XDR-TB). We compared the utility of genotypic DST assays with phenotypic DST (pDST) using Bactec 960 MGIT or Lowenstein-Jensen to construct M/XDR-TB treatment regimens for a cohort of 25 consecutive M/XDR-TB patients and 15 possible anti-TB drugs. Genotypic DST results from Cepheid GeneXpert MTB/RIF (Xpert) and line probe assays (LPAs; Hain GenoType MTBDRplus 2.0 and MTBDRsl 2.0) and whole-genome sequencing (WGS) were translated into individual algorithmderived treatment regimens for each patient. We further analyzed if discrepancies between the various methods were due to flaws in the genotypic or phenotypic test using MIC results. Compared with pDST, the average agreement in the number of drugs prescribed in genotypic regimens ranged from just 49% (95% confidence interval [ CI], 39 to 59%) for Xpert and 63% (95% CI, 56 to 70%) for LPAs to 93% (95% CI, 88 to 98%) for WGS. Only the WGS regimens did not contain any drugs to which pDST showed resistance. Importantly, MIC testing revealed that pDST likely underestimated the true rate of resistance for key drugs (rifampin, levofloxacin, moxifloxacin, and kanamycin) because critical concentrations (CCs) were too high. WGS can be used to rule in resistance even in M/XDR strains with complex resistance patterns, but pDST for some drugs is still needed to confirm susceptibility and construct the final regimens. Some CCs for pDST need to be reexamined to avoid systematic false-susceptible results in low-level resistant isolates.

  • 10.
    Koeser, Claudio U.
    et al.
    Univ Cambridge, England; Res Ctr Borstel, Germany.
    Heyckendorf, Jan
    Res Ctr Borstel, Germany; German Ctr Infect Res DZIF, Germany; Univ Lubeck, Germany.
    Andres, Sonke
    Res Ctr Borstel, Germany.
    Olaru, Ioana D.
    Res Ctr Borstel, Germany; German Ctr Infect Res DZIF, Germany.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar Cty Hosp, Sweden.
    Sturegard, Erik
    Lund Univ, Sweden.
    Beckert, Patrick
    Res Ctr Borstel, Germany; German Ctr Infect Res DZIF, Germany.
    Schleusener, Viola
    Res Ctr Borstel, Germany.
    Kohl, Thomas A.
    Res Ctr Borstel, Germany; German Ctr Infect Res DZIF, Germany.
    Hillemann, Doris
    Res Ctr Borstel, Germany.
    Moradigaravand, Danesh
    Wellcome Trust Sanger Inst, England.
    Parkhill, Julian
    Wellcome Trust Sanger Inst, England.
    Peacock, Sharon J.
    Univ Cambridge, England; Wellcome Trust Sanger Inst, England; London Sch Hyg and Trop Med, England.
    Niemann, Stefan
    Res Ctr Borstel, Germany; German Ctr Infect Res DZIF, Germany.
    Lange, Christoph
    Res Ctr Borstel, Germany; German Ctr Infect Res DZIF, Germany; Univ Lubeck, Germany; Karolinska Inst, Sweden.
    Merker, Matthias
    Res Ctr Borstel, Germany; German Ctr Infect Res DZIF, Germany.
    Reply to Dookie et al., "Whole-Genome Sequencing To Guide the Selection of Treatment for Drug-Resistant Tuberculosis"2018In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 62, no 8, article id e00616-18Article in journal (Other academic)
    Abstract [en]

    n/a

  • 11.
    Nakatani, Yoshio
    et al.
    University of Otago, New Zealand; University of Auckland, New Zealand; University of Otago, New Zealand.
    Opel-Reading, Helen K.
    University of Otago, New Zealand.
    Merker, Matthias
    Research Centre Borstel, Germany; German Centre Infect Research, Germany.
    Machado, Diana
    University of Nova Lisboa, Portugal.
    Andres, Sonke
    National TB Reference Lab, Germany.
    Siva Kumar, S.
    National Institute Research TB, India.
    Moradigaravand, Danesh
    Wellcome Trust Sanger Institute, England.
    Coll, Francesc
    London School Hyg and Trop Med, England.
    Perdigao, Joao
    University of Lisbon, Portugal.
    Portugal, Isabel
    University of Lisbon, Portugal.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar County Hospital, Sweden.
    Nair, Dina
    National Institute Research TB, India.
    Uma Devi, K. R.
    National Institute Research TB, India.
    Kohl, Thomas A.
    Research Centre Borstel, Germany.
    Beckert, Patrick
    Research Centre Borstel, Germany; German Centre Infect Research, Germany.
    Clark, Taane G.
    London School Hyg and Trop Med, England.
    Maphalala, Gugu
    Minist Heatlh, Swaziland.
    Khumalo, Derrick
    Minist Heatlh, Swaziland.
    Diel, Roland
    University Hospital Schleswig Holstein, Germany.
    Klaos, Kadri
    Tartu University Hospital, Estonia.
    Lin Aung, Htin
    University of Otago, New Zealand; University of Auckland, New Zealand.
    Cook, Gregory M.
    University of Otago, New Zealand; University of Auckland, New Zealand.
    Parkhill, Julian
    Wellcome Trust Sanger Institute, England.
    Peacock, Sharon J.
    Wellcome Trust Sanger Institute, England; London School Hyg and Trop Med, England; University of Cambridge, England.
    Swaminathan, Soumya
    Indian Council Medical Research, India.
    Viveiros, Miguel
    University of Nova Lisboa, Portugal.
    Niemann, Stefan
    Research Centre Borstel, Germany; German Centre Infect Research, Germany.
    Krause, Kurt L.
    University of Auckland, New Zealand; University of Otago, New Zealand.
    Koser, Claudio U.
    University of Cambridge, England.
    Role of Alanine Racemase Mutations in Mycobacterium tuberculosis D-Cycloserine Resistance2017In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 61, no 12, article id e01575-17Article in journal (Refereed)
    Abstract [en]

    A screening of more than 1,500 drug-resistant strains of Mycobacterium tuberculosis revealed evolutionary patterns characteristic of positive selection for three alanine racemase (Alr) mutations. We investigated these mutations using molecular modeling, in vitro MIC testing, as well as direct measurements of enzymatic activity, which demonstrated that these mutations likely confer resistance to D-cycloserine.

  • 12.
    Niward, Katarina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Ek Blom, Linnea
    Karolinska Inst, Sweden.
    Davies Forsman, Lina
    Karolinska Inst, Sweden.
    Bruchfeld, Judith
    Karolinska Inst, Sweden; Karolinska Univ Hosp Solna, Sweden.
    Eliasson, Erik
    Karolinska Univ Hosp Huddinge, Sweden.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Chryssanthou, Erja
    Karolinska Inst, Sweden; Karolinska Univ Hosp Solna, Sweden.
    Paues, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Plasma Levels of Rifampin Correlate with the Tuberculosis Drug Activity Assay2018In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 62, no 5, article id e00218-18Article in journal (Refereed)
    Abstract [en]

    The plasma tuberculosis drug activity (TDA) assay may be an alternative tool for therapeutic drug monitoring in resource-limited settings. In tuberculosis (TB) patients (n = 30), TDA and plasma levels of first-line drugs were analyzed 2 h post-dose, 2 weeks after treatment initiation. Patients with plasma levels of rifampin lower than 8 mg/liter had a significantly lower median TDA (1.40 versus 1.68, P = 0.0013). TDA may be used to identify TB patients with suboptimal rifampin levels during TB treatment.

  • 13.
    Schaufler, Katharina
    et al.
    Ernst Moritz Arndt Univ Greifswald, Germany; Free Univ Berlin, Germany.
    Semmler, Torsten
    Robert Koch Inst, Germany.
    Wieler, Lothar H.
    Robert Koch Inst, Germany.
    Trott, Darren J.
    Univ Adelaide, Australia.
    Pitout, Johann
    Calgary Lab Serv, Canada; Univ Calgary, Canada.
    Peirano, Gisele
    Calgary Lab Serv, Canada; Univ Calgary, Canada.
    Bonnedahl, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Kalmar Cty Council, Sweden.
    Dolejska, Monika
    Univ Vet and Pharmaceut Sci Brno, Czech Republic; Univ Vet and Pharmaceut Sci Brno, Czech Republic.
    Literak, Ivan
    Univ Vet and Pharmaceut Sci Brno, Czech Republic; Univ Vet and Pharmaceut Sci Brno, Czech Republic.
    Fuchs, Stephan
    Robert Koch Inst, Germany.
    Ahmed, Niyaz
    Int Ctr Diarrheal Dis Res Bangladesh, Bangladesh.
    Grobbel, Mirjam
    German Fed Inst Risk Assessment, Germany.
    Torres, Carmen
    Univ La Rioja, Spain.
    McNally, Alan
    Univ Birmingham, England.
    Pickard, Derek
    Wellcome Trust Sanger Inst, England.
    Ewers, Christa
    Justus Liebig Univ Giessen, Germany.
    Croucher, Nicholas J.
    Imperial Coll, England.
    Corander, Jukka
    Wellcome Trust Sanger Inst, England; Univ Helsinki, Finland; Univ Oslo, Norway.
    Guenther, Sebastian
    Free Univ Berlin, Germany; Ernst Moritz Arndt Univ Greifswald, Germany.
    Genomic and Functional Analysis of Emerging Virulent and Multidrug-Resistant Escherichia coli Lineage Sequence Type 6482019In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 63, no 6, article id e00243-19Article in journal (Refereed)
    Abstract [en]

    The pathogenic extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli lineage ST648 is increasingly reported from multiple origins. Our study of a large and global ST648 collection from various hosts (87 whole-genome sequences) combining core and accessory genomics with functional analyses and in vivo experiments suggests that ST648 is a nascent and generalist lineage, lacking clear phylogeographic and host association signals. By including large numbers of ST131 (n = 107) and ST10 (n = 96) strains for comparative genomics and phenotypic analysis, we demonstrate that the combination of multidrug resistance and high-level virulence are the hallmarks of ST648, similar to international high-risk clonal lineage ST131. Specifically, our in silico, in vitro, and in vivo results demonstrate that ST648 is well equipped with biofilm-associated features, while ST131 shows sophisticated signatures indicative of adaption to urinary tract infection, potentially conveying individual ecological niche adaptation. In addition, we used a recently developed NFDS (negative frequency-dependent selection) population model suggesting that ST648 will increase significantly in frequency as a cause of bacteremia within the next few years. Also, ESBL plasmids impacting biofilm formation aided in shaping and maintaining ST648 strains to successfully emerge worldwide across different ecologies. Our study contributes to understanding what factors drive the evolution and spread of emerging international high-risk clonal lineages.

  • 14.
    Sun, Pan
    et al.
    Shandong University, Peoples R China.
    Bi, Zhenwang
    Shandong Centre Disease Control and Prevent, Peoples R China.
    Nilsson, Maud
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Zheng, Beiwen
    Zhejiang University, Peoples R China.
    Berglund, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Stalsby Lundborg, Cecilia
    Karolinska Institute, Sweden.
    Borjesson, Stefan
    National Vet Institute, Sweden.
    Li, Xuewen
    Shandong University, Peoples R China.
    Chen, Baoli
    Shandong Centre Disease Control and Prevent, Peoples R China.
    Yin, Hong
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Occurrence of bla(KPC-2), bla(CTX-M), and mcr-1 in Enterobacteriaceae from Well Water in Rural China2017In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 61, no 4, article id e02569Article in journal (Refereed)
    Abstract [en]

    We report on the coexistence of mcr-1 and blaCTX-M in multidrugresistant, extended-spectrum beta-lactamase-producing Escherichia coli belonging to the sequence type 10 complex isolated from well water in rural China. Raoultella ornithinolytica with bla(KPC-2) was also detected in well water from the same area. This study shows that genes coding for resistance to last-resort antibiotics are present in wells in rural China, indicating a potential source of antibiotic resistance.

  • 15.
    Svensson, M
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine.
    Ström, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, EMK-magtarm.
    Nilsson, Maud
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine.
    Sörberg, M
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine.
    Pharmacodynamic effects of nitroimidazoles alone and in combination with clarithromycin on Helicobacter pylori2002In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 46, no 7, p. 2244-2248Article in journal (Refereed)
    Abstract [en]

    Pharmacodynamic studies of Helicobacter pylori exposed to metronidazole and tinidazole alone and in combination with clarithromycin were performed by bioluminescence assay of intracellular ATP. The pharmacodynamic parameter control-related effective regrowth time (CERT) was used. CERT is defined as the time required for the resumption of logarithmic growth and a return of the level of growth to the preexposure inoculum in the test culture minus the corresponding time in the control culture. CERT measures the combined effects of the initial level of killing and postantibiotic effect. The incubation times and drug concentrations were chosen according to their half-lives and their clinically achievable concentrations. The study shows that the parameter CERT is useful for the testing of antibiotic combinations. The CERTs induced by clarithromycin, metronidazole, and tinidazole alone and in the combinations tested were concentration dependent, with no maximum response, indicating that the use of high doses may be preferable. The combinations with the highest concentrations induced synergistic effects and prevented regrowth. The use of tinidazole in combination with clarithromycin proved to give the longest CERTs, indicating that this is the most effective combination.

  • 16.
    Svensson, Margareta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Ström, Magnus
    Divisions of Clinical Microbiology.
    Nilsson, Maud
    Divisions of Clinical Microbiology.
    Sörberg, Mikael
    Infectious Diseases Unit, Department of Medicine, Karolinska Hospital, Stockholm, Sweden .
    Erratum: Pharmacodynamic effects of nitroimidazoles alone and in combination with clarithromycin on Helicobacter pylori (Antimicrobial Agents and Chemotherapy (2002) 462002In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 46, no 11, p. 3693article id 3693Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 17.
    Thulin, Sara
    et al.
    Örebro University Hospital.
    Olcén, Per
    Örebro University Hospital.
    Fredlund, Hans
    Örebro University Hospital.
    Unemo, Magnus
    Örebro University Hospital.
    Total variation in the penA gene of Neisseria meningitides: Correlation between susceptibility to beta-lactam antibiotics and penA gene heterogeneity.2006In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 50, no 10, p. 3317-3324Article in journal (Refereed)
    Abstract [en]

    In recent decades, the prevalence of Neisseria meningitidis isolates with reduced susceptibility to penicillins has increased. The intermediate resistance to penicillin (Peni) for most strains is due mainly to mosaic structures in the penA gene, encoding penicillin-binding protein 2. In this study, susceptibility to ß-lactam antibiotics was determined for 60 Swedish clinical N. meningitidis isolates and 19 reference strains. The penA gene was sequenced and compared to 237 penA sequences from GenBank in order to explore the total identified variation of penA. The divergent mosaic alleles differed by 3% to 24% compared to those of the designated wild-type penA gene. By studying the final 1,143 to 1,149 bp of penA in a sequence alignment, 130 sequence variants were identified. In a 402-bp alignment of the most variable regions, 84 variants were recognized. Good correlation between elevated MICs and the presence of penA mosaic structures was found especially for penicillin G and ampicillin. The Peni isolates comprised an MIC of >0.094 µg/ml for penicillin G and an MIC of >0.064 µg/ml for ampicillin. Ampicillin was the best antibiotic for precise categorization as Pens or Peni. In comparison with the wild-type penA sequence, two specific Peni sites were altered in all except two mosaic penA sequences, which were published in GenBank and no MICs of the corresponding isolates were described. In conclusion, monitoring the relationship between penA sequences and MICs to penicillins is crucial for developing fast and objective methods for susceptibility determination. By studying the penA gene, genotypical determination of susceptibility in culture-negative cases can also be accomplished.

  • 18. Vásquez, Julio A
    et al.
    Arreaza, Luisa
    Block, Colin
    Ehrhard, Ingrid
    Gray, Stephen J
    Heuberger, Sigrid
    Hoffmann, Steen
    Kriz, Paula
    Nicolas, Pierre
    Olcén, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine.
    Skoczynska, Anna
    Spanjaard, Lodewijk
    Stefanelli, Paola
    Taha, Muhamed-Kheir
    Tzanakaki, Georgina
    Interlaboratory comparison of agar dilution and etest methods for determining the MICs of antibiotics used in management of Neisseria meningitidis infections.2003In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 47, p. 3430-3434Article in journal (Refereed)
  • 19.
    Yu, Xia
    et al.
    Capital Medical University, Peoples R China.
    Wang, Guirong
    Capital Medical University, Peoples R China.
    Chen, Suting
    Capital Medical University, Peoples R China.
    Wei, Guomei
    Capital Medical University, Peoples R China.
    Shang, Yuanyuan
    Capital Medical University, Peoples R China.
    Dong, Lingling
    Capital Medical University, Peoples R China.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar County Hospital, Sweden.
    Moradigaravand, Danesh
    Wellcome Trust Sanger Institute, England.
    Parkhill, Julian
    Wellcome Trust Sanger Institute, England.
    Peacock, Sharon J.
    Wellcome Trust Sanger Institute, England; University of Cambridge, England; London School Hyg and Trop Med, England.
    Koser, Claudio U.
    University of Cambridge, England.
    Huang, Hairong
    Capital Medical University, Peoples R China.
    Wild-Type and Non-Wild-Type Mycobacterium tuberculosis MIC Distributions for the Novel Fluoroquinolone Antofloxacin Compared with Those for Ofloxacin, Levofloxacin, and Moxifloxacin2016In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 60, no 9, p. 5232-5237Article in journal (Refereed)
    Abstract [en]

    Antofloxacin (AFX) is a novel fluoroquinolone that has been approved in China for the treatment of infections caused by a variety of bacterial species. We investigated whether it could be repurposed for the treatment of tuberculosis by studying its in vitro activity. We determined the wild-type and non-wild-type MIC ranges for AFX as well as ofloxacin (OFX), levofloxacin (LFX), and moxifloxacin (MFX), using the microplate alamarBlue assay, of 126 clinical Mycobacterium tuberculosis strains from Beijing, China, of which 48 were OFX resistant on the basis of drug susceptibility testing on Lowenstein-Jensen medium. The MIC distributions were correlated with mutations in the quinolone resistance-determining regions of gyrA (Rv0006) and gyrB (Rv0005). Pharmacokinetic/pharmacodynamic (PK/PD) data for AFX were retrieved from the literature. AFX showed lower MIC levels than OFX but higher MIC levels than LFX and MFX on the basis of the tentative epidemiological cutoff values (ECOFFs) determined in this study. All strains with non-wild-type MICs for AFX harbored known resistance mutations that also resulted in non-wild-type MICs for LFX and MFX. Moreover, our data suggested that the current critical concentration of OFX for Lowenstein-Jensen medium that was recently revised by the World Health Organization might be too high, resulting in the misclassification of phenotypically non-wildtype strains with known resistance mutations as wild type. On the basis of our exploratory PK/PD calculations, the current dose of AFX is unlikely to be optimal for the treatment of tuberculosis, but higher doses could be effective.

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