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  • 51.
    Melhus, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Svernell, O.
    Polyarticular septic arthritis caused by non-encapsulated haemophilus influenzae biotype I in a rheumatic adult1998In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 30, no 6, p. 630-631Article in journal (Refereed)
    Abstract [en]

    Haemophilus influenzae causes less than 1% of all septic arthritis cases in adults. Most often serotype b is responsible. Here we describe a rare case of non-encapsulated H. influenzae-induced polyarticular septic arthritis in a rheumatic patient with no other infectious focus.

  • 52.
    Melhus, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Tjernberg, Ingela
    Blood culture bottles for transportation and recovery of anaerobic bacteria from non-blood samples2000In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 108, no 6, p. 453-458Article in journal (Refereed)
    Abstract [en]

    Using bacterial suspensions as simulated non-blood specimens, the capacity of three different BacT/ Alert blood culture bottles for the transportation and recovery of anaerobic bacteria with different sensitivity to air was evaluated. To better assess the performance of the BacT/Alert bottles, three other liquid media specially designed for anaerobes were included in the study. Attention was paid to recovery rates in relation to species, initial bacterial concentration, and time needed for detection. Of the BacT/Alert blood culture bottles, the anaerobic FAN bottle yielded the highest recovery rates, but its performance was limited compared with chopped meat broth in tubes. This broth allowed detection of all the tested species within 48 h. Since collection and transportation of anaerobic bacteria are of major importance for a reliable culture result, improvements are necessary.

  • 53.
    Melhus, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Tjernberg, Ingela
    First documented isolation of vancomycin-resistant Enterococcus faecium in Sweden1996In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 28, no 2, p. 191-193Article in journal (Refereed)
    Abstract [en]

    In recent years enterococci, and Enterococcus faecium in particular, have emerged as important nosocomial pathogens. Of major concern is the increasing antimicrobial resistance to traditionally used agents such as ampicillin, gentamicin and vancomycin. We present a patient with prosthetic heart valves colonized with vancomycin-resistant E. faecium. This is the first reported isolation of vancomycin-resistant E. faecium in Sweden.

  • 54. Nilsson, Anna C.
    et al.
    Alemo, Birgitta
    Björkman, Per
    Dillner, Lena
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nilsson, Berit
    Widell, Anders
    Around-the-clock, rapid diagnosis of influenza by means of membrane chromatography antigen testing confirmed by polymerase chain reaction2008In: Infection control and hospital epidemiology, ISSN 0899-823X, E-ISSN 1559-6834, Vol. 29, no 2, p. 177-9Article in journal (Refereed)
    Abstract [en]

    One rapid membrane chromatography test and 2 immunofluorescence tests were compared with polymerase chain reaction as tools for the diagnosis of influenza in 277 patients treated in an emergency department. The sensitivity on days 1-3 of symptoms was 71% for the rapid membrane chromatography test, 70% for the first immunofluorescence test, and 79% for the second immunofluorescence test. Rapid tests are useful for round-the-clock identification of influenza, with follow-up polymerase chain reaction used for confirmation.

  • 55. Orrling, A.
    et al.
    Karlsson, E.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stjernquist-Desatnik, A.
    Penicillin treatment failure in group A streptococcal tonsillopharyngitis: no genetic difference found between strains isolated from failures and nonfailures2001In: Annals of Otology, Rhinology and Laryngology, ISSN 0003-4894, E-ISSN 1943-572X, Vol. 110, no 7 Pt 1, p. 690-5Article in journal (Refereed)
    Abstract [en]

    Despite penicillin (pcV) treatment, tonsillopharyngitis caused by group A streptococci (GAS) is associated with bacterial failure rates as high as 25%. The reason for this rate of failure is not fully understood. One explanation might be that certain DNA profiles of GAS strains are responsible for treatment failures. Using arbitrarily primed polymerase chain reaction (AP-PCR), we compared the DNA profiles of GAS strains from 4 patients with several treatment failures following pcV treatment of tonsillopharyngitis with the profiles of strains of the same T type from patients who were clinically and bacteriologically cured after a single course of pcV. The isolates were obtained during the same time period and from the same geographic area. Thirty-seven strains of T types 4, 12, and R28 were investigated. Eleven different DNA profiles could be detected with the AP-PCR technique. Five DNA profiles were identified as T type 12, 3 as T type 4, and 3 as T type R28. The DNA profiles of the strains from the 4 patients with several treatment failures differed, but all isolates from each one of these patients exhibited the same or a very similar profile. The DNA profiles of the failure strains were also represented in nonfailure strains. Treatment failure in these 4 patients therefore seems to be due to insufficient eradication of GAS, rather than to reinfection with a new strain. The finding that the same DNA profile can be present in both failure and nonfailure strains suggests that the treatment failure may be to some extent host-related and not only due to bacterial factors.

  • 56. Palacios, Sean D.
    et al.
    Pak, Kwang
    Kayali, Ayse G.
    Rivkin, Alexander Z.
    Aletsee, Christoph
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Webster, Nicholas J. G.
    Ryan, Allen F.
    Participation of Ras and extracellular regulated kinase in the hyperplastic response of middle-ear mucosa during bacterial otitis media2002In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 186, no 12, p. 1761-9Article in journal (Refereed)
    Abstract [en]

    Hyperplasia of middle-ear mucosa (MEM) during otitis media (OM) is thought to be partially mediated by the actions of growth factors and their receptors. The intracellular pathway leading from the small G-protein Ras to the extracellular regulated kinases (Erks) often links growth factor stimulation to cellular proliferation. This study assessed whether this pathway is involved in MEM hyperplasia during bacterial OM via the activation of Erk1/Erk2 in MEM of an in vivo rat bacterial OM model. Activation was maximal at 1 and 6 h and at 1 week after introduction of bacteria into the middle ear. Additionally, an in vitro model of rat MEM in bacterial OM was treated with farnesyl transferase inhibitor 277 or the Mek inhibitor U0126. MEM explants treated with either inhibitor demonstrated significant suppression of bacterially induced growth. These data support a role for Ras and Erk signaling in MEM hyperplasia during bacterial OM.

  • 57. Palacios, Sean D.
    et al.
    Pak, Kwang
    Rivkin, Alexander Z.
    Kayali, Ayse G.
    Austen, Darrell
    Aletsee, Christoph
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Webster, Nicholas J. G.
    Ryan, Allen F.
    Role of p38 mitogen-activated protein kinase in middle ear mucosa hyperplasia during bacterial otitis media2004In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 72, no 8, p. 4662-7Article in journal (Refereed)
    Abstract [en]

    Hyperplasia of the middle ear mucosa contributes to the sequelae of acute otitis media. Understanding the signal transduction pathways that mediate hyperplasia could lead to the development of new therapeutic interventions for this disease and its sequelae. Endotoxin derived from bacteria involved in middle ear infection can contribute to the hyperplastic response. The p38 mitogen-activated protein kinase (MAPK) is known to be activated by endotoxin as well as cytokines and other inflammatory mediators that have been documented in otitis media. We assessed the activation of p38 in the middle ear mucosa of an in vivo rat bacterial otitis media model. Strong activity of p38 was observed 1 to 6 h after bacterial inoculation. Activity continued at a lower level for at least 7 days. The effects of p38 activation were assessed using an in vitro model of rat middle ear mucosal hyperplasia in which mucosal growth is stimulated by nontypeable Haemophilus influenzae during acute otitis media. Hyperplastic mucosal explants treated with the p38 alpha and p38 beta inhibitor SB203580 demonstrated significant inhibition of otitis media-stimulated mucosal growth. The results of this study suggest that intracellular signaling via p38 MAPK influences the hyperplastic response of the middle ear mucosa during bacterial otitis media.

  • 58. Prellner, Karin
    et al.
    Hermansson, Ann
    White, P.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Briles, D.
    Immunization and protection in pneumococcal otitis media studied in a rat model1999In: Microbial Drug Resistance, ISSN 1076-6294, E-ISSN 1931-8448, Vol. 5, no 1, p. 73-82Article in journal (Refereed)
    Abstract [en]

    The recent and growing problem of bacterial resistance to common antibiotics has generated great interest in different methods for prevention of infections. The treatment of the pathogens causing upper airway infections and especially acute otitis media (AOM) is especially interesting in this context because these infections are a common cause of prescription of antibiotics all over the world. Both in AOM and recurrent AOM, Streptococcus pneumoniae, the most frequently occurring bacterium is isolated in 30-50% of all AOM attacks. In the last decade, multiresistant S. pneumoniae have emerged as a major problem. Thus, it is important to explore possibilities that immunization may protect against pneumococcal OM. In a well-defined animal model using Sprague-Dawley rats, we have investigated the effects of different routes of immunization with different antigens and whole cells. Together with otomicroscopical evaluation of middle ear (ME) status, samples for bacterial cultivation as well as for studies of histopathological changes have been collected. Antibody titers have been followed during and after pneumococcal AOM by an enzyme-linked immunosorbent assay (ELISA) method.

  • 59.
    Rehberg, L.
    et al.
    Rhine Waal Univ Appl Sci, Marie Curie Str 1, D-47533 Kleve, Germany..
    Frontzek, A.
    Med Care Ctr Dr Stein Colleagues, Monchengladbach, Germany..
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Bockmuehl, D. P.
    Rhine Waal Univ Appl Sci, Marie Curie Str 1, D-47533 Kleve, Germany..
    Prevalence of beta-lactamase genes in domestic washing machines and dishwashers and the impact of laundering processes on antibiotic-resistant bacteria2017In: Journal of Applied Microbiology, ISSN 1364-5072, E-ISSN 1365-2672, Vol. 123, no 6, p. 1396-1406Article in journal (Refereed)
    Abstract [en]

    Aims: To investigate the prevalence of -lactamase genes in domestic washing machines and dishwashers, and the decontamination efficacy of laundering.

    Methods and Results: For the first investigation, swab samples from washing machines (n = 29) and dishwashers (n = 24) were analysed by real-time quantitative PCR to detect genes encoding beta-lactamases. To test the impact of laundering on resistant bacteria, cotton test swatches were artificially contaminated with susceptible and resistant strains of Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus within a second investigation. They were washed in a domestic washing machine with or without activated oxygen bleach (AOB)-containing detergent at 20-50 degrees C. beta-Lactamase genes (most commonly of the AmpC- and OXA-type) were detected in 79% of the washing machines and in 96% of the dishwashers and Pseudomonadaceae dominated the microbiota. The level of bacterial reduction after laundering was >= 80% for all Ps.aeruginosa and Kl.pneumoniae strains, while it was only 37-61% for the methicillin-resistant Staph.aureus outbreak strain. In general, the reduction was tendentially higher for susceptible bacteria than for the resistant outbreak strains, especially for Staph.aureus.

    Conclusions: beta-Lactamase genes seem to be frequently present in domestic appliances and may pose a potential risk for cross-contamination and horizontal transfer of genes encoding resistance against clinically important beta-lactams. In general, higher temperatures and the use of AOB can improve the reduction of antibiotic-resistant bacteria, including Staph.aureus which appears to be less susceptible to the decontamination effect of laundering.

    Significance and Impact of this Study: Data on the presence of antibiotic-resistant bacteria in the domestic environment are limited. This study suggests that -lactamase genes in washing machines and dishwashers are frequent, and that antibiotic-resistant strains are generally more resistant to the used washing conditions.

  • 60. Ryan, Allen F.
    et al.
    Ebmeyer, Jörg
    Furukawa, Masayuki
    Pak, Kwang
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wasserman, Stephen I.
    Chung, Won-Ho
    Mouse models of induced otitis media2006In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1091, no 1, p. 3-8Article in journal (Refereed)
    Abstract [en]

    The mouse has seen limited use as a model for experimental otitis media, due primarily to the small size of its middle ear. However, the genetic resources of this species offer substantial potential benefits. These include detailed genomic information, a wealth of genetic models, and gene arrays that represent virtually all mouse genes. This has led to the development of methods for inducing otitis in mice. These include surgical approaches to the middle ear, documentation of the murine middle ear response to various pathogens and inflammatory factors, as well as characterization of induced otitis media in several mouse strains. The results indicate that induced otitis media in the normal mouse is in most respects comparable to that observed in other animal models and in humans. They further suggest that the considerable genetic resources of this species can be harnessed to increase our understanding of this disease.

  • 61.
    Sandegren, Linus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Linkevicius, Marius
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Lytsy, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
    Åsa, Melhus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
    Andersson, Dan I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Transfer of an Escherichia coli ST131 multiresistance cassette has created a Klebsiella pneumoniae-specific plasmid associated with a major nosocomial outbreak2012In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 67, no 1, p. 74-83Article in journal (Refereed)
    Abstract [en]

    Objectives:

    To characterize the complete sequence, horizontal spread and stability of the CTX-M-15-encoding multiresistance plasmid of a Klebsiella pneumoniae strain involved in a large nosocomial outbreak.

    Methods:

    The 220 kbp plasmid pUUH239.2 was completely sequenced using 454 technology. The conjugational host range, conjugation frequencies, plasmid stability and fitness cost of plasmid carriage were studied in vitro. Conjugational spread during the outbreak was assessed retrospectively by multiplex PCR screening, restriction fragment length polymorphism and PFGE.

    Results:

    Plasmid pUUH239.2 encodes resistance to β-lactams (blaCTX-M-15, blaTEM-1 and blaOXA-1), aminoglycosides [aac-(6′)-1b-cr and aadA2], tetracyclines [tet(A) and tetR], trimethoprim (dhfrXII), sulphonamides (sul1) quaternary ammonium compounds (qacEΔ1), macrolides [mph(A)-mxr-mphR(A)] and heavy metal ions (silver, copper and arsenic). The plasmid consists of a backbone, highly similar to the K. pneumoniae plasmid pKPN3, and a 41 kbp resistance region, highly similar to the resistance regions of plasmids pEK499 and pC15-1a previously isolated from Escherichia coli strains belonging to the outbreak lineage ST131 (where ST stands for sequence type). The pUUH239.2 plasmid is stable in K. pneumoniae but unstable in E. coli and confers a fitness cost when introduced into a naive host cell. Transfer of pUUH239.2 from the outbreak K. pneumoniae clone to the E. coli of the patients’ intestinal floras has occurred on multiple occasions during the outbreak.

    Conclusions:

    The plasmid pUUH239.2 is a composite of the pKPN3 K. pneumoniae plasmid backbone and the blaCTX-M-15-encoding multiresistance cassette associated with the internationally recognized outbreak strain E. coli ST131. The resulting plasmid differs in stability between K. pneumoniae and E. coli, and this has probably limited the spread of this plasmid during the outbreak.

  • 62.
    Skog, Oskar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Korsgren, Stella
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Revisiting the notion of type 1 diabetes being a T-cell-mediated autoimmune disease2013In: Current Opinion In Endocrinology Diabetes And Obesity, ISSN 1752-296X, Vol. 20, no 2, p. 118-123Article, review/survey (Refereed)
    Abstract [en]

    Purpose of review Type 1 diabetes (T1D) research is at present in a critical period of development and during the past few years several large phase III studies targeting T-cell autoimmunity in recent-onset patients with T1D failed to reach the primary endpoint. Recent findings Cause and pathogenesis of T1D remain largely unknown. In humans, insulitis is discrete, affects few islets and is present only in about one-third of patients with recent-onset T1D. The rapid increase in incidence of T1D argues against a decisive role for genetic factors and instead for the hypothesis that infectious agents, possibly entering the pancreas via the ductal compartment, are involved in disease pathogenesis. Repeated episodes of bacteria or virus-induced innate inflammations affecting only certain lobes of the pancreas fit well with the reported heterogeneity of the disease within the pancreas as well as with the slow progression over many years. Summary In humans there is limited support for T1D being primarily an autoimmune disease; instead available findings support the view that T1D can be regarded as an innate inflammatory disease affecting the entire pancreas, but with its main clinical manifestations emanating from the loss of the insulin-producing cells.

  • 63.
    Sperber, Jesper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Centre for Clinical Research Sörmland, Department of Anesthesiology & Intensive Care Mälarsjukhuset, SE-631 88 Eskilstuna, Sweden.
    Nyberg, Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Centre for Clinical Research Sörmland, Department of Anesthesiology & Intensive Care Mälarsjukhuset, SE-631 88 Eskilstuna, Sweden.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Castegren, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Perioperative Medicine and Intensive Care, Karolinska University Hospital and CLINTEC, Karolinska Institute, Stockholm, Sweden.
    Protective ventilation reduces Pseudomonas aeruginosa growth in lung tissue in a porcine pneumonia model2017In: Intensive & Critical Care Nursing, ISSN 0964-3397, E-ISSN 1532-4036, Vol. 5, article id 40Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Mechanical ventilation with positive end expiratory pressure and low tidal volume, i.e. protective ventilation, is recommended in patients with acute respiratory distress syndrome. However, the effect of protective ventilation on bacterial growth during early pneumonia in non-injured lungs is not extensively studied. The main objectives were to compare two different ventilator settings on Pseudomonas aeruginosa growth in lung tissue and the development of lung injury.

    METHODS: A porcine model of severe pneumonia was used. The protective group (n = 10) had an end expiratory pressure of 10 cm H2O and a tidal volume of 6 ml x kg-1. The control group (n = 10) had an end expiratory pressure of 5 cm H2O and a tidal volume of 10 ml x kg-1. 1011 colony forming units of Pseudomonas aeruginosa were inoculated intra-tracheally at baseline, after which the experiment continued for 6 h. Two animals from each group received only saline, and served as sham animals. Lung tissue samples from each animal were used for bacterial cultures and wet-to-dry weight ratio measurements.

    RESULTS: The protective group displayed lower numbers of Pseudomonas aeruginosa (p < 0.05) in the lung tissue, and a lower wet-to-dry ratio (p < 0.01) than the control group. The control group deteriorated in arterial oxygen tension/inspired oxygen fraction, whereas the protective group was unchanged (p < 0.01).

    CONCLUSIONS: In early phase pneumonia, protective ventilation with lower tidal volume and higher end expiratory pressure has the potential to reduce the pulmonary bacterial burden and the development of lung injury.

  • 64.
    Starlander, Gustaf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Borjesson, Stefan
    Gronlund-Andersson, Ulrika
    Tellgren-Roth, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Melhusa, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Cluster of Infections Caused by Methicillin-Resistant Staphylococcus pseudintermedius in Humans in a Tertiary Hospital2014In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 52, no 8, p. 3118-3120Article in journal (Refereed)
    Abstract [en]

    The dog-associated Staphylococcus pseudintermedius is a rare pathogen in humans. Here we describe a cluster of infections caused by the methicillin-resistant S. pseudintermedius clone ST71-J-t02-II-III. It involved four elderly patients at a tertiary hospital. Three patients had wound infections, and the strain had a tendency to cause bullous skin lesions.

  • 65.
    Starlander, Gustaf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Fraenkel, Carl-Johan
    Tano, Eva
    Klintstedt, Markus
    Sütterlin, Susanne
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    The first Swedish outbreak with VIM-2-producing Pseudomonas aeruginosa was prolonged and probably due to contaminated hospital sinksManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa is an increasing clinical problem worldwide. VIM-2 is the predominant enzyme, and it has been linked to several outbreaks. During the spring of 2006, a cluster of patients were colonized or infected with multiresistant Pseudomonas aeruginosa at two neighbouring hospitals in southeast Sweden.

    Aim: To describe the first documented outbreak of a VIM-2-producing P. aeruginosa strain in Sweden.

    Methods: The isolates were characterized with PCR, pulse-field gel electrophoresis (PFGE), and whole genome sequencing. Patient charts, laboratory records and hygiene routines were reviewed, and patients, staff and the environment were screened.

    Findings: The investigation revealed that it was a clonal outbreak of a VIM-2-producing P. aeruginosa strain susceptible only to gentamicin and colistin. It belonged to the high-risk clonal complex 111. No direct contact between patients could be established, but most of them had stayed in the same room/wards with weeks to months apart. Environmental cultures from two sinks yielded growth of P. aeruginosa with the same PFGE-pattern as the patient isolates. The outbreak ended when control measures against the sinks were taken.

    Conclusions: Contaminated hospital sinks were the probable reservoir in the first nosocomial outbreak of MBL-producing P. aeruginosa in Sweden. When facing prolonged outbreaks with this bacterium, sinks and other water sources in the hospital environment should be considered. By implementing proactive control measures to limit the bacterial load in sinks and plumbing systems, the waterborne transmission of P. aeruginosa could probably be reduced.

  • 66.
    Starlander, Gustaf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Minor outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in an intensive care unit due to a contaminated sink2012In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 82, no 2, p. 122-124Article in journal (Refereed)
    Abstract [en]

    During a period of seven months four patients on the neurosurgical intensive care unit at a tertiary care hospital in Sweden became infected or colonized by an extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain. The investigation revealed that the source of the outbreak was a contaminated sink. By replacing the sink and its plumbing and improving routines regarding sink practices, the outbreak was successfully controlled.

  • 67.
    Starlander, Gustaf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Sütterlin, Susanne
    Tellgren-Roth, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    The Initial Epidemiology of a Major Clonal Outbreak Caused by VanB-Carrying Enterococcus faecium Clone ST192Manuscript (preprint) (Other academic)
  • 68.
    Starlander, Gustaf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Wirén, Marcus
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    First documented case of a Staphylococcus lugdunensis strain carrying the mecA gene in Northern Europe2011In: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 1, p. 8410-Article in journal (Refereed)
    Abstract [en]

    Staphylococcus lugdunensis is a clinically common wound pathogen belonging to coagulase-negative staphylococci. We herein report the first case of a S. lugdunensis isolate carrying the mecA gene in Northern Europe.

  • 69.
    Starlander, Gustaf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Yin, Hong
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Edquist, Petra
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Survival in the environment is a possible key factor for the expansion of Escherichia coli strains producing extended-spectrum beta-lactamases2014In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 122, no 1, p. 59-67Article in journal (Refereed)
    Abstract [en]

    Acquired resistance to cephalosporins in Enterobacteriaceae is a global problem. After an outbreak at Uppsala University Hospital of extended-spectrum -lactamase (ESBL)-positive Klebsiella pneumoniae producing CTX-M-15, there was a shift from AmpC to ESBL production among Escherichia coli isolates. To explore the basis for this epidemiological shift, 46 E. coli isolates (ESBLs, n=23; AmpC, n=23) were characterized with regard to genetic relatedness, -lactamase, replicon and integron types, antibiotic resistance profiles, and genes encoding virulence factors. In addition, the survival in the environment and on hospital-associated materials was analysed. CTX-M-15 was the most frequent ESBL (78%). Only three (13%) of the AmpC enzymes were harboured on plasmids (CMY-2, DHA-1). Independent of plasmid-mediated beta-lactamase, IncF plasmids predominated and only class I integrons were detected. The ESBL producers carried more virulence genes (p=0.04), exhibited a broader resistance phenotype (p=0.01) and survived significantly longer (p=0.03) on different materials than the AmpC-producing isolates. In conclusion, ESBL-producing isolates had properties which are likely to augment their competitiveness. Apart from antibiotic resistance and virulence factors, extended survival in the environment could be a selective trait for successful ESBL-producing E. coli strains.

  • 70. Söderblom, T.
    et al.
    Aspevall, O.
    Erntell, M.
    Hedin, G.
    Heimer, D.
    Hökeberg, I.
    Kidd-Ljunggren, K.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
    Olsson-Liljequist, B.
    Sjögren, I.
    Smedjegård, J.
    Struwe, J.
    Sylvan, Staffan
    Department of Communicable Disease Control, County of Uppsala, Sweden.
    Tegmark-Wisell, K.
    Thore, M.
    Alarming spread of vancomycin resistant enterococci in Sweden since 20072010In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 15, no 29, article id 19620Article in journal (Refereed)
    Abstract [en]

    The total number of persons infected or colonised with vancomycin-resistant enterococci mandatorily reported to the Swedish Institute for Infectious Disease Control increased dramatically during 2007 and 2008. During a period of twenty months from 1 July 2007 to 28 February 2009, a total of 760 cases were reported compared with 194 cases reported during the entire period from 2000 to 2006. This rise was mainly attributed to a wide dissemination of vancomycin resistant enterococci which started in a number of hospitals in Stockholm in the autumn of 2007 and was followed by dissemination in various healthcare facilities (hospitals and homes for the elderly) in a further two Swedish counties in 2008. The majority of the cases (97%) were acquired in Sweden and among these, healthcare-acquired E. faecium vanB dominated (n=634). The majority of these isolates had identical or closely related pulsed-field gel electrophoresis patterns indicating clonal dissemination in the affected counties. The median minimum inhibitory concentration of vancomycin was 32 mg/L (ranging from 4 to > 128 mg/L) and of teichoplanin 0.12 mg/L (ranging from 0.06 to 0.25 mg/L). Particular emphasis was placed on countermeasures such as screening, contact tracing, cleaning procedures, education in accurate use of infection control practices as well as increasing awareness of hygiene among patients and visitors. With these measures the dissemination rate decreased substantially, but new infections with the E. faecium vanB strain were still detected.

  • 71.
    Sütterlin, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Dahlö, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tellgren-Roth, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Schaal, Wesley
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    High frequency of silver resistance genes in invasive isolates of Enterobacter and Klebsiella species2017In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 96, no 3, p. 256-261Article in journal (Refereed)
    Abstract [en]

    Background: Silver-based products have been marketed as an alternative to antibiotics, and their consumption has increased. Bacteria may, however, develop resistance to silver.

    Aim: To study the presence of genes encoding silver resistance (silE, silP, silS) over time in three clinically important Enterobacteriaceae genera.

    Methods: Using polymerase chain reaction (PCR), 752 bloodstream isolates from the years 1990–2010 were investigated. Age, gender, and ward of patients were registered, and the susceptibility to antibiotics and silver nitrate was tested. Clonality and single nucleotide polymorphism were assessed with repetitive element sequence-based PCR, multi-locus sequence typing, and whole-genome sequencing.

    Findings: Genes encoding silver resistance were detected most frequently in Enterobacter spp. (48%), followed by Klebsiella spp. (41%) and Escherichia coli 4%. Phenotypical resistance to silver nitrate was found in Enterobacter (13%) and Klebsiella (3%) isolates. The lowest carriage rate of sil genes was observed in blood isolates from the neonatology ward (24%), and the highest in blood isolates from the oncology/haematology wards (66%). Presence of sil genes was observed in international high-risk clones. Sequences of the sil and pco clusters indicated that a single mutational event in the silS gene could have caused the phenotypic resistance.

    Conclusion: Despite a restricted consumption of silver-based products in Swedish health care, silver resistance genes are widely represented in clinical isolates of Enterobacter and Klebsiella species. To avoid further selection and spread of silver-resistant bacteria with a high potential for healthcare-associated infections, the use of silver-based products needs to be controlled and the silver resistance monitored.

  • 72.
    Sütterlin, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Edquist, Petra
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Sandegren, Linus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Adler, Marlen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Tängdén, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Drobni, Mirva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Silver resistance genes are overrepresented among Escherichia coli isolates with CTX-M production2014In: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336, Vol. 80, no 22, p. 6863-6869Article in journal (Refereed)
    Abstract [en]

    Members of the Enterobacteriaceae with extended-spectrum beta-lactamases (ESBLs) of the CTX-M type have disseminated rapidly in recent years and have become a threat to public health. In parallel with the CTX-M type expansion, the consumption and widespread use of silver-containing products has increased. To determine the carriage rates of silver resistance genes in different Escherichia coli populations, the presence of three silver resistance genes (silE, silP, and silS) and genes encoding CTX-M-, TEM-, and SHV-type enzymes were explored in E. coli isolates of human (n = 105) and avian (n = 111) origin. The antibiotic profiles were also determined. Isolates harboring CTX-M genes were further characterized, and phenotypic silver resistance was examined. The silE gene was present in 13 of the isolates. All of them were of human origin. Eleven of these isolates harbored ESBLs of the CTX-M type (P = 0.007), and eight of them were typed as CTX-M-15 and three as CTX-M-14. None of the silE-positive isolates was related to the O25b-ST131 clone, but 10 out of 13 belonged to the ST10 or ST58 complexes. Phenotypic silver resistance (silver nitrate MIC > 512 mg/liter) was observed after silver exposure in 12 of them, and a concomitant reduced susceptibility to piperacillin-tazobactam developed in three. In conclusion, 12% of the human E. coli isolates but none of the avian isolates harbored silver resistance genes. This indicates another route for or level of silver exposure for humans than that caused by common environmental contamination. Since silE-positive isolates were significantly more often found in CTX-M-positive isolates, it is possible that silver may exert a selective pressure on CTX-M-producing E. coli isolates.

  • 73.
    Sütterlin, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Hong, Yin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Zhang, Xiao-Jie
    Department of Paediatrics The Children's Hospital, Changchun City, China.
    Li, Li-Hong
    Department of Paediatrics The Children's Hospital, Changchun City, China.
    Sun, Li-Wei
    Department of Paediatrics The Children's Hospital, Changchun City, China.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    High carriage rate of CTX-M-producing Escherichia coli in Chinese preschool children2015Article in journal (Refereed)
  • 74.
    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.

  • 75.
    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.

  • 76.
    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.

  • 77.
    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.

  • 78.
    Tängdén, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Eriksson, Britt-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Cars, Otto
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Radical reduction of cephalosporin use at a tertiary hospital after educational antibiotic intervention during an outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae2011In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 66, no 5, p. 1161-1167Article in journal (Refereed)
    Abstract [en]

    Objectives: During an outbreak of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae at our hospital, we performed an educational antibiotic intervention aimed at reducing prescriptions of second- and third-generation cephalosporins and preventing increased use of fluoroquinolones and carbapenems. In this report, we describe the implementation strategy used and evaluate the intervention effect according to Cochrane recommendations. Methods: New recommendations for empirical intravenous antibiotic treatment were communicated to prescribers throughout the hospital by infectious diseases physicians working with Strama (the Swedish strategic programme against antibiotic resistance). No restrictive measures were used. The intervention effect was analysed with interrupted time series (ITS) regression analysis of local and national monthly antibiotic sales data. Results: A radical immediate and sustained reduction was demonstrated for the cephalosporins targeted in the intervention, whereas consumption of piperacillin/tazobactam and penicillin G increased substantially. Fluoroquinolone and carbapenem use was essentially unchanged. The ESBL outbreak subsided and no increased resistance to piperacillin/tazobactam was detected in K. pneumoniae, Escherichia coli or Pseudomonas aeruginosa blood isolates during the 2.5 year follow-up. Conclusions: Our study clearly demonstrates that an educational intervention can have an immediate and profound effect on antibiotic prescription patterns at a large tertiary hospital. ITS regression analysis of local and national antibiotic sales data was valuable to readily assess the immediate and sustained effects of the intervention.

  • 79. Westman, Eva
    et al.
    Lundin, Susanne
    Hermansson, Ann
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Beta-lactamase-producing nontypeable Haemophilus influenzae fails to protect Streptococcus pneumoniae from amoxicillin during experimental acute otitis media2004In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 48, no 9, p. 3536-42Article in journal (Other academic)
    Abstract [en]

    Acute otitis media (AOM) is the most common reason for outpatient antimicrobial therapy. Mixed infections pose a potential problem, since the first-line drug used for the treatment of AOM, amoxicillin, can be neutralized by beta-lactamase-producing pathogens of the upper respiratory tract. To study the effects of a 5-day course of amoxicillin on a mixed middle ear infection, rats were challenged with Streptococcus pneumoniae alone or in combination with beta-lactamase-producing nontypeable Haemophilus influenzae. Amoxicillin was introduced at the clinical peak of the infection. Local and systemic changes were monitored by otomicroscopy, bacterial culture, and analysis of histological changes and the expression of the transforming growth factor beta (TGF-beta) gene. beta-Lactamase-producing H. influenzae did not demonstrate an ability to protect S. pneumoniae. Amoxicillin eradicated the pneumococci in all treated animals but increased to some degree the ability of H. influenzae to persist at the site of infection. Thus, only an insignificant acceleration of the resolution of the AOM caused by a mixture of pathogens was observed during treatment. Moderate to major morphological changes could not be avoided by treatment of the mixed infections, but a slight downregulation of TGF-beta expression was observed. In contrast to infections caused by a single pathogen, the mixed infections induced white plaques in the tympanic membrane at a remarkably high frequency independent of treatment. These experimental findings constitute support for further studies of antimicrobial drugs and AOM caused by bacteria with and without mechanisms of antibiotic resistance.

  • 80. Westman, Eva
    et al.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    The treatment of Haemophilus influenzae acute otitis media with amoxicillin protects against reinfection but not against structural changes2002In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 49, no 1, p. 141-7Article in journal (Refereed)
    Abstract [en]

    Acute otitis media (AOM) is the most common reason for outpatient antimicrobial therapy today. With increasing problems with antibiotic resistance, a more restrictive use of antibiotics has been advocated for both single and recurrent episodes. The arguments advanced have been immunological as well as ecological. To study the effects of a 5 day course of amoxicillin on recurrent AOM caused by non-typeable Haemophilus influenzae, Sprague-Dawley rats were used. Amoxicillin was introduced at the clinical peak of the first infection. One month later the animals were rechallenged. Local and systemic changes were monitored by otomicroscopy, bacterial cultures, and analyses of systemic IgG responses and histological changes. Antibiotic treatment accelerated the resolution of the primary infection. After resolution, only minor morphological changes were observed. The protective rate at rechallenge was 100% in the treatment group, compared with 80% in the untreated control group. Although the production of serum IgG antibodies was initially slightly impeded by the treatment, it was significantly higher in treated animals after rechallenge. Major structural changes could not be avoided at the second infection, however, and a significantly higher frequency of myringosclerosis was observed in treated animals. These experimental findings constitute support for further studies of antimicrobial drugs and recurrent AOM.

  • 81. Westman, Eva
    et al.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hellström, S.
    Hermansson, A.
    Moraxella catarrhalis-induced purulent otitis media in the rat middle ear: Structure, protection, and serum antibodies1999In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 107, no 8, p. 737-46Article in journal (Refereed)
    Abstract [en]

    To study the effects of viable and heat-killed Moraxella catarrhalis bacteria on the middle ear mucosa and to evaluate the protection after whole-cell immunizations, Sprague-Dawley rats were challenged and rechallenged with four different M. catarrhalis strains. The animals were monitored by clinical observations, bacterial and histological samples from middle ears, and serum IgG levels. Only viable bacteria at a high concentration induced purulent otitis media, which was culture positive in 58% of the cases on day 4. The infection was characterized by a mild acute reaction lasting otomicroscopically about 8 days, together with quantitative and qualitative changes of the goblet cells. Structurally the mucosal effects of the heat-killed bacteria were less pronounced in the early phase compared to the viable bacteria, but similar at the end of the experiment at 6 months. The intrabullar and subcutaneous immunizations evoked an IgG antibody response in all animals, and the protection rate after immunization was 50% or more. The induced protection was not strain-specific. The study showed the rat to be a possible alternative for the study of different aspects of M. catarrhalis otitis media, an infection that is clinically and structurally different from that elicited by Streptococcus pneumoniae and Haemophilus influenzae in the rat.

  • 82. Wiström, Johan
    et al.
    Lindholm, Christina
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lundgren, Claes
    Hansson, Carita
    Infektioner och behandling vid kroniska bensår: Antibiotikaförbrukningen alltför hög, restriktivitet förordas1999In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 96, no 1-2, p. 42-46Article in journal (Refereed)
    Abstract [en]

    Chronic venous leg ulcers are contaminated or colonised with bacteria that seldom affects ulcer healing. Signs of clinical infection appear in only a minority of chronic ulcers. In spite of this, data show a high consumption of antibiotics in this group of patients. Treatment with antibiotics is indicated only when clinical signs of infection or obvious risk factors are present or when Streptococcus pyogenes is isolated from the ulcer. In these cases an oral antistaphylococcal agent (semisynthetic penicillinase-resistant penicillin or first generation oral cephalosporin) is recommended as the first choice. Enterococci, anaerobic bacteria and gram-negative bacteria including pseudomonas spp. often colonise chronic ulcers, but do not usually cause antibiotic requiring infection.

  • 83.
    Öhrmalm, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Eriksson, Ronnie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Jobs, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Simonson, Magnus
    Naitonal Food Agency, Uppsala.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Bondeson, Kåre
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Herrmann, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Variation-tolerant capture and multiplex detection of nucleic acids: application to detection of microbes2012In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 50, no 10, p. 3208-3215Article in journal (Refereed)
    Abstract [en]

    In contrast to ordinary PCRs, which have a limited multiplex capacity and often return false-negative results due to target variation or inhibition, our new detection strategy, VOCMA (variation-tolerant capture multiplex assay), allows variation-tolerant, target-specific capture and detection of many nucleic acids in one test. Here we demonstrate the use of a single-tube, dual-step amplification strategy that overcomes the usual limitations of PCR multiplexing, allowing at least a 22-plex format with retained sensitivity. Variation tolerance was achieved using long primers and probes designed to withstand variation at known sites and a judicious mix of degeneration and universal bases. We tested VOCMA in situations where enrichment from a large sample volume with high sensitivity and multiplexity is important (sepsis; streptococci, enterococci, and staphylococci, several enterobacteria, candida, and the most important antibiotic resistance genes) and where variation tolerance and high multiplexity is important (gastroenteritis; astrovirus, adenovirus, rotavirus, norovirus genogroups I and II, and sapovirus, as well as enteroviruses, which are not associated with gastroenteritis). Detection sensitivities of 10 to 1,000 copies per reaction were achieved for many targets. VOCMA is a highly multiplex, variation-tolerant, general purpose nucleic acid detection concept. It is a specific and sensitive method for simultaneous detection of nucleic acids from viruses, bacteria, fungi, and protozoa, as well as host nucleic acid, in the same test. It can be run on an ordinary PCR and a Luminex machine and is suitable for both clinical diagnoses and microbial surveillance.

12 51 - 83 of 83
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