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  • 1.
    Baltekin, Özden
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Systems Biology.
    Boucharin, Alexis
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Systems Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Andersson, Dan I
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Elf, Johan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Systems Biology.
    Antibiotic susceptibility testing in less than 30 min using direct single-cell imaging2017In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 34, p. 9170-9175Article in journal (Refereed)
    Abstract [en]

    The emergence and spread of antibiotic-resistant bacteria are aggravated by incorrect prescription and use of antibiotics. A core problem is that there is no sufficiently fast diagnostic test to guide correct antibiotic prescription at the point of care. Here, we investigate if it is possible to develop a point-of-care susceptibility test for urinary tract infection, a disease that 100 million women suffer from annually and that exhibits widespread antibiotic resistance. We capture bacterial cells directly from samples with low bacterial counts (10(4) cfu/mL) using a custom-designed microfluidic chip and monitor their individual growth rates using microscopy. By averaging the growth rate response to an antibiotic over many individual cells, we can push the detection time to the biological response time of the bacteria. We find that it is possible to detect changes in growth rate in response to each of nine antibiotics that are used to treat urinary tract infections in minutes. In a test of 49 clinical uropathogenic Escherichia coli (UPEC) isolates, all were correctly classified as susceptible or resistant to ciprofloxacin in less than 10 min. The total time for antibiotic susceptibility testing, from loading of sample to diagnostic readout, is less than 30 min, which allows the development of a point-of-care test that can guide correct treatment of urinary tract infection.

  • 2.
    Carlsson, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Inflammatory and circulatory effects of the reduction of endotoxin concentration in established porcine endotoxemic shock: a model of endotoxin elimination2009In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 37, no 3, p. 1031-e4Article in journal (Refereed)
    Abstract [en]

    Objective:

    To study whether a reduction of the endotoxin load, once a generalized inflammatory state has been established, reduces the inflammatory response and endotoxin-induced effects on circulation, hypoperfusion, and organ dysfunction.

    Design:

    Prospective parallel-grouped placebo-controlled randomized interventional experimental study.

    Setting:

    University research unit.

    Subjects:

    Healthy pigs.

    Interventions:

    The animals were subjected to a continuous endotoxin infusion rate of either 4.0 or 0.063 µg endotoxin × kg-1 × h-1 for 1, 2, or 6 hours. The 1- and 2-hour infusion groups represented the applied therapy by a reduction of the endotoxin load of 5/6 and 2/3, respectively.

    Measurements and Main Results:

    During a 6-hour experiment, laboratory and physiologic parameters were recorded hourly in 26 anesthetized and mechanically ventilated pigs. Primary end point was to detect differences in tumor necrosis factor-[alpha] (TNF-[alpha]) concentration during the last 3 hours of the experiment. Despite the early reduction of the endotoxin load, no effect on TNF-[alpha] concentration was observed. Similarly, in circulatory parameters, such as mean arterial pressure and oxygen delivery, and in platelet count and renal function, no effects were noted. However, there was some improvement in pulmonary compliance and function as determined by Pao2, Paco2, and pH. These changes were associated with slight improvements in leukocyte response and capillary leakage.

    Conclusions:

    Termination of the endotoxin infusion represents an incontestable model of endotoxin concentration reduction. Endotoxin elimination strategies applied at the TNF-[alpha] peak or later will have very little or no effect on TNF-[alpha]–mediated toxicity. Nevertheless, there was an effect on the leukocyte response that was associated with an improvement in respiratory function and microcirculation, making it impossible to rule out fully the beneficial effect of this strategy. However, the effects were limited in relation to the magnitude of the endotoxin concentration reduction and the very early application of the antiendotoxin measure.

  • 3.
    Goscinski, Gunilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Löwdin, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Propensity to release endotoxin after two repeated doses of cefuroxime in an in vitro kinetic model: Higher release after the second dose2007In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 60, no 2, p. 328-333Article in journal (Refereed)
    Abstract [en]

    Objectives: To study endotoxin release from two strains of Escherichia coli after exposure to two repeated doses of cefuroxime in an in vitro kinetic model.

    Methods: Cefuroxime in concentrations simulating human pharmacokinetics was added to the bacterial solution with a repeated dose after 12 h. In another experiment, tobramycin was given concomitantly with the second dose of cefuroxime. Samples for viable counts and endotoxin analyses were drawn before the addition of antibiotics and at 2 and 4 h after each dose.

    Results: The propensity to release endotoxin, expressed as log10 endotoxin release (EU)/log10 killed bacteria, was higher after the second than after the first dose, 0.80 ± 0.04 and 0.65 ± 0.01, respectively, in the ATCC strain and 0.80 ± 0.04 and 0.65 ± 0.02, respectively, in the clinical strain (P < 0.001). Endotoxin was released earlier after the second dose (P < 0.001). Addition of tobramycin at the second dose reduced the endotoxin release in comparison with that of cefuroxime alone (P < 0.001).

    Conclusions: The propensity to liberate endotoxin is higher after the second dose of cefuroxime than after the first, resulting in a higher release of endotoxin than expected from bacterial count. The release after the second dose can be reduced by the addition of tobramycin.

  • 4.
    Goscinski, Gunilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Thulin, Pontus
    Norrby-Teglund, Anna
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Release of SpeA from Streptococcus pyogenes after exposure to penicillin: dependency on dose and inhibition by clindamycin2006In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 38, no 11-12, p. 983-987Article in journal (Refereed)
    Abstract [en]

    The amount and time course of SpeA release from group A streptococci (GAS) was studied at different starting inoculae after exposure to different doses of penicillin, clindamycin or a combination of the 2. The release was related to the bacterial concentration and killing rate. A clinical GAS strain was exposed to benzylpenicillin, 2 and 1000 × MIC, clindamycin, 2 and 32 × MIC, or combinations of the 2. Samples for viable counts and SpeA analyses were drawn before and after the addition of antibiotics and at 3, 6 and 24 h. The SpeA release was higher at low than at high concentrations of penicillin and the combination (both, p < 0.05). The addition of clindamycin to penicillin reduced SpeA production at both concentrations (p < 0.01). Most SpeA was released before 3 h, and for penicillin and the combination, the amount correlated to the number of killed bacteria during this period (r = 0.50; p < 0.05). A positive correlation was found between the inoculum size and the SpeA concentration at time zero (r = 0.54; p < 0.05). The SpeA concentration was dependent on the initial number of bacteria, the class of antibiotic, the dose of penicillin and the killing rate.

  • 5.
    Lytsy, Birgitta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sandegren, Linus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Torell, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Andersson, Dan I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    The first major extended-spectrum beta-lactamase outbreak in Scandinavia was caused by clonal spread of a multiresistant Klebsiella pneumoniae producing CTX-M-152008In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 116, no 4, p. 302-8Article in journal (Refereed)
    Abstract [en]

    Between May and December 2005, 64 multidrug-resistant isolates of Klebsiella pneumoniae were detected from patients admitted to Uppsala University Hospital. This represented a dramatic increase in ESBL-producing K. pneumoniae compared to previous years. To investigate the epidemiology and to characterize the resistance mechanisms of the isolates, a study was initiated. Antibiotic susceptibility was determined by means of the Etest and the disc diffusion method. Extended-spectrum beta-lactamase (ESBL) production was identified by clavulanic acid synergy test and confirmed with PCR amplification followed by DNA sequencing. DNA profiles of the isolates were examined with pulsed-field gel electrophoresis (PFGE). All isolates were resistant or exhibited reduced susceptibility to cefadroxil, cefuroxime, cefotaxime, ceftazidime, aztreonam, piperacillin/tazobactam, ciprofloxacin, tobramycin, and trimethoprim-sulfamethoxazole. They produced ESBL of the CTX-M-15 type, and the involvement of a single K. pneumoniae clone was shown. This is the first major clonal outbreak of multiresistant ESBL-producing K. pneumoniae in Scandinavia. The outbreak demonstrates the epidemic potential of enterobacteria containing ESBLs of the CTX-M type, even in a country with a relatively low selective pressure and a low prevalence of multiresistant bacteria.

  • 6.
    Melki, Vilyam
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Hakansson, Lena Douhan
    Tran, Phan-Kiet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Knutson, Folke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Malinski, Tadeusz
    Borowiec, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Effect of Glyceryl Trinitrate on Staphylococcus aureus Growth and Leukocyte Activation during Simulated Extracorporeal Circulation2014In: The thoracic and cardiovascular surgeon, ISSN 0171-6425, E-ISSN 1439-1902, Vol. 62, no 5, p. 402-408Article in journal (Refereed)
    Abstract [en]

    Background Previously, nitric oxide has been shown to possess antimicrobial effects. In this study, we aim to test the effect of glyceryl trinitrate (GTN) on Staphylococcus aureus growth during simulated extracorporeal circulation (SECC) and also to examine the effect of S. aureus, alone and in combination with GTN, on activation markers of the innate immune system during SECC. Methods In an in vitro system of SECC, we measured GTN-induced changes in markers of leukocyte activation in whole blood caused by S. aureus infestation, as well as the effect of GTN on S. aureus growth. Results GTN had no effect on S. aureus growth after 240 minutes SECC. Staphylococcus aureus reduced the expression of granulocyte Fc gamma-receptor CD32 but stimulated the expression of monocyte CD32. Staphylococcus aureus stimulated expression of some leukocyte adhesion key proteins, activation marker CD66b, lipopolysaccharide-receptor CD14, and C3b-receptor CD35. Staphylococcus aureus and GTN addition induced significant increases in monocyte CD63 (lysosomal granule protein) levels. Conclusion GTN does not affect S. aureus growth during SECC and has no effect on SECC-induced leukocyte activation.

  • 7.
    Melki, Vilyam
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Tran, P.K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Knutson, Folke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Borowiec, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Enhanced growth of Staphylococcus aureus after nitric oxide supplementation during simulated extracorporeal circulation2010In: The thoracic and cardiovascular surgeon, ISSN 0171-6425, E-ISSN 1439-1902, Vol. 58, no 2, p. 81-85Article in journal (Refereed)
    Abstract [en]

    Background: Several factors contribute to postoperative bacterial infections in cardiac surgery. Long operation times and the use of extracorporeal circulation increase the risk of infection. Nitric oxide has been shown to possess a broad spectrum antimicrobial effect. Methods: In this study, we investigated the effect of nitric oxide on S. aureus growth in whole blood during simulated extracorporeal circulation. Results: S. aureus growth increased 6.2-fold after 180 min SECC in the presence of nitric oxide. Leukocyte counts remained unchanged without any differences between the groups. We observed a steady increase in markers of oxidative stress and activity of the innate immune system. Myeloperoxidase levels increased 8-fold, and C3a and terminal complement complex by 2-fold after 180 min. Conclusion: S. aureus growth is not due to the effect of nitric oxide on the innate immune system but from its effect on the bacteria itself. It has been shown that nitric oxide stimulates the expression of inducible lactate dehydrogenase, specific to S. aureus, which improves its resistance to oxidative stress, and may give S. aureus a survival advantage resulting in increased growth.

  • 8.
    Osbjer, Kristina
    et al.
    Swedish Univ Agr Sci, Div Reprod, Dept Clin Sci, Box 7054, SE-75007 Uppsala, Sweden..
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Chhayheng, Leang
    Natl Inst Publ Hlth, Phnom Penh, Cambodia..
    Mac-Kwashie, Akofa Olivia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Fernstrom, Lise-Lotte
    Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Uppsala, Sweden..
    Ellström, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sokerya, Seng
    Ctr Livestock & Agr Dev, Phnom Penh, Cambodia..
    Sokheng, Choup
    Natl Inst Publ Hlth, Phnom Penh, Cambodia..
    Mom, Veng
    Natl Inst Publ Hlth, Phnom Penh, Cambodia..
    Chheng, Kannarath
    Natl Inst Publ Hlth, Phnom Penh, Cambodia..
    San, Sorn
    Natl Inst Vet Res, Phnom Penh, Cambodia..
    Davun, Holl
    Natl Inst Vet Res, Phnom Penh, Cambodia..
    Boqvist, Sofia
    Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Uppsala, Sweden..
    Rautelin, Hilpi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Magnusson, Ulf
    Swedish Univ Agr Sci, Div Reprod, Dept Clin Sci, Box 7054, SE-75007 Uppsala, Sweden..
    Detection of Campylobacter in human and animal field samples in Cambodia2016In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 124, no 6, p. 508-515Article in journal (Refereed)
    Abstract [en]

    Campylobacter are zoonotic bacteria and a leading cause of human gastroenteritis worldwide with Campylobacter jejuni and C. coli being the most commonly detected species. The aim of this study was to detect Campylobacter in humans and livestock (chickens, ducks, pigs, cattle, water buffalo, quail, pigeons and geese) in rural households by routine culturing and multiplex PCR in faecal samples frozen before analysis. Of 681 human samples, 82 (12%) tested positive by PCR (C. jejuni in 66 samples and C. coli in 16), but none by routine culture. Children were more commonly Campylobacter positive (19%) than adult males (8%) and females (7%). Of 853 livestock samples, 106 (12%) tested positive by routine culture and 352 (41%) by PCR. Campylobacter jejuni was more frequent in chickens and ducks and C. coli in pigs. In conclusion, Campylobacter proved to be highly prevalent by PCR in children (19%), ducks (24%), chickens (56%) and pigs (72%). Routine culturing was insufficiently sensitive in detecting Campylobacter in field samples frozen before analysis. These findings suggest that PCR should be the preferred diagnostic method for detection of Campylobacter in humans and livestock where timely culture is not feasible.

  • 9.
    Schönning, Caroline
    et al.
    Folkhälsomyndigheten.
    Jernberg, Cecilia
    Folkhälsomyndigheten.
    Klingenberg, D
    Folkhälsomyndigheten.
    Andersson, S
    Folkhälsomyndigheten.
    Pääjärvi, A
    Folkhälsomyndigheten.
    Alm, Erik
    Folkhälsomyndigheten.
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Lytsy, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Legionellosis acquired through a dental unit: a case study2017In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 96, no 1, p. 89-92Article in journal (Refereed)
    Abstract [en]

    In 2012, an elderly immunocompromised man died from legionellosis at a hospital in Uppsala, Sweden. The patient had visited a dental ward at the hospital during the incubation period. Legionella spp. at a concentration of 2000 colony-forming units/L were isolated from the cupfiller outlet providing water for oral rinsing. Isolates from the patient and the dental unit were Legionella pneumophila serogroup 1, subgroup Knoxville and ST9. Pulsed-field gel electrophoresis and whole-genome sequencing strongly suggested that the isolates were of common origin. This report presents one of few documented cases of legionellosis acquired through a dental unit.

  • 10.
    Skorup, Paul
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Maudsdotter, Lisa
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Castegren, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Dynamics of Endotoxin, Inflammatory Variables, and Organ Dysfunction After Treatment With Antibiotics in an Escherichia coli Porcine Intensive Care Sepsis Model.2018In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To investigate the dynamics of antibiotic-induced endotoxin liberation and inflammatory response in vivo in a clinically relevant large animal intensive care sepsis model and whether the addition of an aminoglycoside to a β-lactam antibiotic affects these responses.

    DESIGN: Prospective, placebo-controlled interventional experimental study.

    SETTING: University research unit.

    SUBJECTS: Thirty-six healthy pigs administered Escherichia coli as a 3-hour infusion.

    INTERVENTIONS: After 2 hours, during E. coli infusion, the animals were exposed to cefuroxime alone, the combination of cefuroxime and tobramycin, or saline.

    MEASUREMENTS AND MAIN RESULTS: Plasma endotoxin, interleukin-6, tumor necrosis factor-α, leucocytes, and organ dysfunction were recorded for 4 hours after antibiotic treatment, and differences to the values before treatment were calculated. In vitro experiments were performed to ascertain whether endotoxin is released during antibiotic-induced bacterial killing of this E. coli strain. Despite differences between the treatment arms in vitro, no differences in plasma endotoxin were observed in vivo. Antibiotic-treated animals demonstrated a higher interleukin-6 response (p < 0.001), greater leucocyte activation (p < 0.001), and more pronounced deterioration in pulmonary static compliance (p < 0.01) over time than controls. Animals treated with the combination showed a trend toward less inflammation.

    CONCLUSIONS: Treatment with antibiotics may elicit an increased inflammatory interleukin-6 response that is associated with leucocyte activation and pulmonary organ dysfunction. No observable differences were detected in plasma endotoxin concentrations. The reduction in cefuroxime-induced endotoxin release after the addition of an aminoglycoside in vitro could not be reproduced in this model.

  • 11. Smolle, C
    et al.
    Huss, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Lindblad, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Reischies, F
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Effectiveness of automated ultraviolet-C light for decontamination of textiles inoculated with Enterococcus faecium.2018In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 98, no 1, p. 102-104Article in journal (Refereed)
    Abstract [en]

    Healthcare textiles are increasingly recognized as potential vehicles for transmission of hospital-acquired infections. This study tested the ability of an automated ultraviolet-C (UV-C) room disinfection device (Tru-D Smart UV-C) to decontaminate textiles inoculated with Enterococcus faecium in a clinical setting. Contaminated polycotton (50/50 polyester/cotton) swatches were distributed to predefined locations in a ward room and exposed to UV-C light. UV-C decontamination reduced E. faecium counts by a mean log10 reduction factor of 1.37 (all P = 0.005, Wilcoxon signed rank test). UV-C decontamination may be a feasible adjunctive measure to conventional laundering to preserve the cleanliness of healthcare textiles in ward rooms.

  • 12.
    Sütterlin, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
    Bergsten, Agneta
    Tallberg, Anna-Brita
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
    Effects of Silver-based Wound Dressings on the Bacterial Flora in Chronic Leg Ulcers and Its Susceptibility In vitro to Silver2012In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 92, no 1, p. 34-39Article in journal (Refereed)
    Abstract [en]

    Silver-based dressings have been used extensively in wound management in recent years, but data on their antimicrobial activity in the clinical setting are limited. In order to explore their effects on chronic leg ulcer flora, 14 ulcers were cultured after at least 3 weeks treatment with Aquacel Ag (R) or Acticoat (R). Phenotypic and genetic silver resistance were investigated in a total of 56 isolates. Silver-based dressings had a limited effect on primary wound pathogens, which were present in 79% of the cultures before, and 71% after, treatment. One silver-resistant Enterobacter cloacae strain was identified (silver nitrate minimal inhibitory concentration (MIC)>512 mg/l, positive for silE, silS and silP). Further studies in vitro showed that inducible silver-resistance was more frequent in Enterobacteriaceae with cephalosporin-resistance and that silver nitrate had mainly a bacteriostatic effect on Staphylococcus aureus. Monitoring of silver resistance should be considered in areas where silver is used extensively.

  • 13.
    Tano, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Hylén, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Overrepresentation of the toxic shock syndrome toxin-1 gene among eldery men with bacteremic bone and joint infections caused by Staphylococcus aureusManuscript (preprint) (Other academic)
    Abstract [en]

    Staphylococcus aureus is a leading causative agent of Gram-positive septicemia. In recent years, there have been indications that both the severity and the number of staphylococcal infections have increased. In order to study the presence of genes encoding exfoliative toxins (eta/etb), Panton-Valentine leucocidin (lucS-PV-lucF-PV), and toxic shock syndrome toxin-1 (tst) in invasive isolates over time and space, 528 blood isolates of S. aureus collected during the years 2000-2012 from two Swedish university hospitals were investigated.  Age, gender and diagnosis of patients were registered, and the antibiotic susceptibility was tested. Toxin genes were detected with PCR, and the genetic relatedness was assessed with pulsed-field gel electrophoresis and whole genome sequencing. Blood cultures positive for S. aureus increased with 57.6% during the study period. Ninety-six of the isolates (18.2%) carried 97 toxin genes (one isolate carried both eta and etb). All isolates except one (PVL-producing and methicillin-resistant) were fully susceptible to the tested antibiotics. Most frequent was tst (79.4%), followed by eta (12.4%), lucS-PV-lucF-PV (7.2%), and etb (1.0%). The typical tst-positive patient was a male aged 55-74 years with a bone or joint infection. Tst-positive isolates exhibited a clear clonality, and that was independent of year and hospital. Most common was ST30-t012. To summarize, bacteremia caused by S. aureus increased during the study period, but the frequency of four important staphylococcal toxins and the antibiotic susceptibility remained low. To screen for these toxins is only cost-effective in Swedish patients with a typical clinical presentation.

  • 14.
    Tano, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
    Evaluation of three swab transport systems for the maintenance of clinically important bacteria in simulated mono- and polymicrobial samples2011In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 119, no 3, p. 198-203Article in journal (Refereed)
    Abstract [en]

    In this study, three swab transport systems were evaluated: M40 Transystem, Amies broth with a relatively new type of swab (both Copan Diagnostics, Corona, CA, USA), and SSI transportmedium (Statens Serum Institut, Copenhagen Denmark). The CLSI M40-A standard procedures and 11 culture collection strains were used. The transport systems were tested at room temperature for holding times of 0, 24, and 48 h, and both mono- and polymicrobial samples were included. After 24 h of simulated transportation, all systems were able to maintain the viability of all organisms tested. SSI transportmedium exhibited the lowest maintaining ability, whereas the two Copan systems were the most growth-promoting system. In polymicrobial samples, this latter feature was a problem. At 48 h, no transport system could maintain the viability of all strains, and the recovery rates differed depending on organism and device. The species most difficult to recover in all the three systems was Neisseria gonorrhoeae. When selecting a swab transport system, consideration must be given to the sample type, the conditions that prevail locally, and the performance in the clinical setting.

  • 15.
    Tano, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Level of decontamination after washing textiles at 60°C or 70°C followed by tumble drying2014In: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 4, article id 24314Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Several major outbreaks in healthcare facilities have occurred with the emergence of multi-resistant bacteria. A possible route for dissemination is the hospital textiles and inadequate laundering of them. The aim of this study was to develop an easy-to-use method for simulating the laundering process of hospital textiles, and thereafter apply the method when evaluating the decontaminating efficacy of two different washing temperatures.

    METHODS: The laundering process, including tumble drying, took place at two professional laundries. Enterococcus faecium was used as bioindicator.

    RESULTS: The results showed that a lowering of the washing temperature from 70°C to 60°C did not affect the decontamination efficacy; the washing cycle alone reduced the number of bacteria with 3-5 log10 CFU, whereas the following tumble drying reduced the bacterial numbers with another 3-4 log10 CFU, yielding the same final result independent of washing temperature. Without tumble drying, there was an obvious risk of adding non-fermenting gram-negative bacteria to the fabric. These bacteria originated from the washing cycle.

    CONCLUSION: A simple method to simulate hospital laundering was developed. To save energy, it is possible to use a washing temperature of 60°C, but the washing cycle should be followed by tumble drying, and the whole laundering process needs to be monitored to maintain sufficient textile hygiene.

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