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  • 1.
    Ahlstrand, Erik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medicine, Hematology, Örebro University Hospital,S-701 85 Örebro, Sweden.
    Bäckman, Anders
    Örebro University, School of Medical Sciences. Clinical Research Centre, Örebro University Hospital, S-701 85 Örebro, Sweden.
    Persson, Lennart
    Örebro University Hospital. Department of Infectious diseases, Örebro University Hospital, S-701 85 Örebro, Sweden.
    Mölling, Paula
    Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, S-701 85 Örebro, Sweden.
    Tidefelt, Ulf
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Infectious diseases & Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, S-701 85 Örebro, Sweden.
    Evaluation of a PCR method to determine the clinical significance of blood cultures with Staphylococcus epidermidis in patients with hematological malignancies2014In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 122, no 6, 539-544 p.Article in journal (Refereed)
    Abstract [en]

    The aim was to investigate whether the detection and quantification of Staphylococcus epidermidis DNA in blood could distinguish S. epidermidis blood stream infections (BSIs) from blood culture contaminations in patients with hematological malignancies. The hld gene was chosen to identify S. epidermidis DNA and DNA in blood samples was detected by real-time PCR. Blood samples were obtained simultaneously with blood cultures positive for S. epidermidis (n = 30), during blood culture-negative episodes (n = 10) and episodes of bacteremia with other bacteria than S. epidermidis (n = 4) and from healthy blood donors (n = 10). In addition, DNA from S. epidermidis and a selection of other bacterial species were analyzed. Three different sets of criteria were used to classify episodes with positive blood cultures with S. epidermidis as BSIs or contaminations. All DNA preparations from S. epidermidis (n = 48) were hld-positive, but other bacterial species (n = 13) were negative. Sixteen (53%) of 30 blood samples from patients with blood cultures positive for S. epidermidis were hld-positive, but none of the controls. There was no clear association between a positive hld PCR and episodes interpreted as BSIs. In conclusion, hld PCR failed to distinguish S. epidermidis BSIs from blood culture contaminations in patients with hematological malignancies.

  • 2.
    Ahlstrand, Erik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medicine, Division of Haematology, Örebro University Hospital, SE-701 85 Örebro, SWEDEN.
    Hellmark, Bengt
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, SE-701 85 Örebro, Sweden.
    Svensson, Karolina
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, SE-701 85 Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, SE-701 85 Örebro, Sweden.
    Long-term molecular epidemiology of Staphylococcus epidermidis blood culture isolates from patients with haematological malignanciesManuscript (preprint) (Other academic)
    Abstract [en]

    Staphylococcus epidermidis is an important cause of bloodstream infections in patients with haematological malignancies. Knowledge of the long-term epidemiology of these infections is limited. We surveyed all S. epidermidis blood culture isolates from patients treated for haematological malignancies at the University Hospital of Örebro, Sweden from 1980 to 2009. A total of 373 S. epidermidis isolates were identified and multilocus sequence typing and standard antibiotic susceptibility testing were employed to characterize these isolates. The majority of the isolates 361/373 (97%) belonged to clonal complex 2, and the 373 isolates were divided into 45 sequence types (STs); Simpson’s Diversity Index was 0.56. The most prevalent STs were ST2 (243/373, 65%) and ST215 (28/373, 8%). These two STs were isolated during the entire study period, and together caused temporal peaks in the incidence of positive blood cultures of S. epidermidis. Methicillin resistance was detected in 213/273 (78%) of all isolates. In the two predominating STs, ST2 and ST215, the proportion of methicillin resistance was 257/271 (95%); 234/271 (86%) displayed a multidrug-resistant phenotype. In conclusion, in this long-term study of patients with haematological malignancies, we demonstrate a predominance of methicillin-resistant ST2 among S. epidermidis blood culture isolates.

  • 3.
    Ahlstrand, Erik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Hematology.
    Hellmark, Bengt
    Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Svensson, Karolina
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Long-term molecular epidemiology of staphylococcus epidermidis blood culture isolates from patients with hematological malignancies2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 6, e99045Article in journal (Refereed)
    Abstract [en]

    Staphylococcus epidermidis is an important cause of bloodstream infections in patients with hematological malignancies. Knowledge of the long-term epidemiology of these infections is limited. We surveyed all S. epidermidis blood culture isolates from patients treated for hematological malignancies at the University Hospital of Orebro, Sweden from 1980 to 2009. A total of 373 S. epidermidis isolates were identified and multilocus sequence typing, staphylococcal chromosome cassette mec (SCCmec) typing and standard antibiotic susceptibility testing were employed to characterize these isolates. The majority of the isolates 361/373 (97%) belonged to clonal complex 2, and the 373 isolates were divided into 45 sequence types (STs); Simpson's Diversity Index was 0.56. The most prevalent STs were ST2 (243/373, 65%) and ST215 (28/373, 8%). Ninety three percent (226/243) of the ST2 isolates displayed either SCCmec type III or IV. ST2 and 215 were isolated during the entire study period, and together these STs caused temporal peaks in the number of positive blood cultures of S. epidermidis. Methicillin resistance was detected in 213/273 (78%) of all isolates. In the two predominating STs, ST2 and ST215, methicillin resistance was detected in 256/271 isolates (95%), compared with 34/100 (34%) in other STs (p<0.001). In conclusion, in this long-term study of patients with hematological malignancies, we demonstrate a predominance of methicillin-resistant ST2 among S. epidermidis blood culture isolates.

  • 4.
    Ahlstrand, Erik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Division of Hematology, Department of Medicine,Örebro University Hospital, Örebro, Sweden.
    Persson, Lennart
    Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Tidefelt, Ulf
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Clinical Microbiology, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Alteration of the colonization pattern of coagulase-negative staphylococci in patients undergoing treatment for hematological malignancy2012In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 31, no 7, 1679-1687 p.Article in journal (Refereed)
    Abstract [en]

    The aim was to prospectively describe the colonization pattern of coagulase-negative staphylococci (CoNS) and the relationship between colonizing and invasive CoNS isolates among patients undergoing treatment for hematological malignancy. Fourteen newly diagnosed patients were included with either multiple myeloma or acute leukemia. Patients were repeatedly sampled from nares, throat, axillae, and perineum, and the CoNS isolates obtained were phenotypically characterized together with blood isolates of CoNS using the PhenePlate system (PhP). During the treatment a gradual reduction in the heterogeneity of colonizing CoNS was observed as well as an inter-patient accumulation of phenotypically related and multi-drug-resistant CoNS. These clusters of CoNS persisted for 2–3 months after the end of therapy. Ten positive blood cultures of CoNS were obtained and in the majority of these cases CoNS of the same PhP type were found in superficial cultures collected prior to the blood culture sampling. In conclusion, the study shows that therapy for hematological malignancy is associated with a homogenization of colonizing CoNS isolates and that this acquired flora of CoNS is persistent several months after the end of therapy. Furthermore, the results suggest that the source of bloodstream infections of CoNS in hematological patients is colonizing CoNS of the skin and mucosa.

  • 5. Ahlstrand, Erik
    et al.
    Svensson, K.
    Persson, Lennart
    Tidefelt, Ulf
    Örebro University, School of Health and Medical Sciences.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    Glycopeptide resistance in coagulase-negative staphylococci isolated in blood cultures from patients with hematological malignancies during three decades2011In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 30, no 11, 1349-1354 p.Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to determine if there was a long-term increase in glycopeptide minimum inhibitory concentration (MIC) values, MIC creep, among bloodstream isolates of Staphylococcus epidermidis and S. haemolyticus isolated from patients with hematological malignancies. We conducted a retrospective single-center study where all positive blood cultures of S. epidermidis (n = 387) and S. haemolyticus (n = 19) isolated from patients with hematological malignancies during three decades, 1980 to 2009, were re-evaluated for the presence of reduced susceptibility to vancomycin and teicoplanin. Three different methods for the detection of reduced susceptibility to glycopeptides were used; standard Etest, macromethod Etest, and glycopeptide resistance detection (GRD) Etest. The median MIC value for vancomycin was 2 mg/L. MIC values for vancomycin and teicoplanin did not show any statistically significant increase during the study period. The presence of heterogeneously glycopeptide-intermediate staphylococci (hGIS) was analyzed among 405 coagulase-negative staphylococci (CoNS) isolates. hGIS were found in 31-45% of the CoNS isolates by the macromethod Etest and in 53-67% by the GRD Etest during the three decades. In conclusion, we did not observe any long-term glycopeptide MIC creep determined by the standard Etest, although a high and increasing proportion of heterogeneous vancomycin resistance was observed.

  • 6.
    Asfaw Idosa, Berhane
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Medicine.
    Sahdo, Berolla
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Medicine.
    Balcha, Ermias
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Medicine.
    Kelly, Anne
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Medicine.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Särndahl, Eva
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Medicine.
    C10X polymorphism in the CARD8 gene is associated with bacteraemia2014In: Immunity, inflammation and disease, E-ISSN 2050-4527, Vol. 2, no 1, 13-20 p.Article in journal (Refereed)
    Abstract [en]

    The NLRP3 inflammasome is an intracellular multi-protein complex that triggers caspase-1 mediated maturation of interleukin-1β (IL-1β); one of the most potent mediators of inflammation and a major cytokine produced during severe infections, like sepsis. However, the excessive cytokine levels seem to stage for tissue injury and organ failure, and high levels of IL-1β correlates with severity and mortality of sepsis. Instead, recent data suggest caspase-1 to function as a guardian against severe infections. CARD8 has been implied to regulate the synthesis of IL-1β via interaction to caspase-1. In recent years, polymorphism of CARD8 (C10X) per se or in combination with NLRP3 (Q705K) has been implicated with increased risk of inflammation. The aim was to investigate the correlation of these polymorphisms with severe blood stream infection. Human DNA was extracted from blood culture bottles that were found to be positive for microbial growth (i.e. patients with bacteraemia). Polymorphisms Q705K in the NLRP3 gene and C10X in the CARD8 gene were genotyped using TaqMan genotyping assay. The results were compared to healthy controls and to samples from patients with negative cultures. The polymorphism C10X was significantly over-represented among patients with bacteraemia as compared to healthy controls, whereas patients with negative blood culture were not associated with a higher prevalence. No association was observed with polymorphism Q705K of NLRP3 in either group of patients. Patients carrying polymorphism C10X in the CARD8 gene are at increased risk of developing bacteraemia and severe inflammation.

  • 7.
    Bang, Charlotte Sahlberg
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Kinnunen, Annica
    Univ Örebro, IRiSC, Fac Med & Hlth, Örebro, Sweden.
    Karlsson, Marie
    Univ Örebro, IRiSC, Fac Med & Hlth, Örebro, Sweden.
    Önnberg, Anna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro Univ Hosp, Dept Lab Med, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Dept Lab Med.
    Persson, Katarina
    Örebro University, School of Medicine, Örebro University, Sweden.
    The antibacterial effect of nitric oxide against ESBL-producing uropathogenic E-coli is improved by combination with miconazole and polymyxin B nonapeptide2014In: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 14, 65Article in journal (Refereed)
    Abstract [en]

    Background: Nitric oxide (NO) is produced as part of the host immune response to bacterial infections, including urinary tract infections. The enzyme flavohemoglobin, coded by the hmp gene, is involved in protecting bacterial cells from the toxic effects of NO and represents a potentially interesting target for development of novel treatment concepts against resistant uropathogenic bacteria. The aim of the present study was to investigate if the in vitro antibacterial effects of NO can be enhanced by pharmacological modulation of the enzyme flavohemoglobin.

    Results: Four clinical isolates of multidrug-resistant extended-spectrum beta-lactamase (ESBL)-producing uropathogenic E. coli were included in the study. It was shown that the NO-donor substance DETA/NO, but not inactivated DETA/NO, caused an initial growth inhibition with regrowth noted after 8 h of exposure. An hmp-deficient strain showed a prolonged growth inhibition in response to DETA/NO compared to the wild type. The imidazole antibiotic miconazole, that has been shown to inhibit bacterial flavohemoglobin activity, prolonged the DETA/NO-evoked growth inhibition. When miconazole was combined with polymyxin B nonapeptide (PMBN), in order to increase the bacterial wall permeability, DETA/NO caused a prolonged bacteriostatic response that lasted for up to 24 h.

    Conclusion: An NO-donor in combination with miconazole and PMBN showed enhanced antimicrobial effects and proved effective against multidrug-resistant ESBL-producing uropathogenic E. coli.

  • 8.
    Bang, Charlotte Sahlberg
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Kruse, Robert
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Demirel, Isak
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Önnberg, Anna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro Univ Hosp, Dept Lab Med, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Dept Lab Med.
    Persson, Katarina
    Örebro University, School of Medicine, Örebro University, Sweden.
    Multiresistant uropathogenic extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are susceptible to the carbon monoxide releasing molecule-2 (CORM-2).2014In: Microbial Pathogenesis, ISSN 0882-4010, E-ISSN 1096-1208, Vol. 66, 29-35 p.Article in journal (Refereed)
    Abstract [en]

    Carbon monoxide (CO) releasing molecules (CO-RMs) have been shown to inhibit growth of commensal Escherichia coli (E. coli). In the present study we examined the effect of CORM-2 on uropathogenic E. coli (UPEC) that produces extended-spectrum β-lactamase (ESBL). Viability experiments showed that CORM-2 inhibited the growth of several different ESBL-producing UPEC isolates and that 500 μM CORM-2 had a bactericidal effect within 4 h. The bactericidal effect of CORM-2 was significantly more pronounced than the effect of the antibiotic nitrofurantoin. CORM-2 demonstrated a low level of cytotoxicity in eukaryotic cells (human bladder epithelial cell line 5637) at the concentrations and time-points where the antibacterial effect was obtained. Real-time RT-PCR studies of different virulence genes showed that the expression of capsule group II kpsMT II and serum resistance traT was reduced and that some genes encoding iron acquisition systems were altered by CORM-2. Our results demonstrate that CORM-2 has a fast bactericidal effect against multiresistant ESBL-producing UPEC isolates, and also identify some putative UPEC virulence factors as targets for CORM-2. CO-RMs may be candidate drugs for further studies in the field of finding new therapeutic approaches for treatment of uropathogenic ESBLproducing E. coli.

  • 9.
    Berglund, Carolina
    et al.
    Örebro University, School of Health and Medical Sciences.
    Ito, Teruyo
    Ikeda, Megumi
    Ma, Xiao Xue
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    Hiramatsu, Keiichi
    Novel type of staphylococcal cassette chromosome mec in a methicillin-resistant Staphylococcus aureus strain isolated in Sweden2008In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 52, no 10, 3512-3516 p.Article in journal (Refereed)
    Abstract [en]

    We identified a novel type of staphylococcal cassette chromosome mec (SCCmec) element carried by methicillin-resistant Staphylococcus aureus (MRSA) strain JCSC6082 isolated in Sweden. The SCCmec element was demarcated by characteristic nucleotide sequences at both ends and was integrated at the 3' end of orfX. The element carried a novel combination of a type 5 ccr gene complex and class C1 mec gene complex. The J regions of the element were homologous to those of the SCCmercury element of S. aureus strain 85/2082, with nucleotide identity greater than 99%. However, the novel SCCmec element from JCSC6082 did not carry the mer operon nor Tn554, suggesting that evolution to SCCmec could have been from a common ancestor by acquisition of the class C1 mec gene complex. The novel SCCmec element from JCSC6082 was flanked by a novel SCC-like chromosome cassette (CC6082), which was demarcated by two direct repeats and could be excised from the chromosome independently of the SCCmec element. Our data suggest that novel SCCmec elements can be generated on the staphylococcal chromosome through the recombination between extant SCC elements and mec gene complexes.

  • 10.
    Berglund, Carolina
    et al.
    Örebro University, School of Health and Medical Sciences.
    Ito, Teruyo
    Ma, Xiao Xue
    Ikeda, Megumi
    Watanabe, Shinya
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    Hiramatsu, Keiichi
    Genetic diversity of methicillin-resistant Staphylococcus aureus carrying type IV SCCmec in Orebro County and the western region of Sweden2009In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 63, no 1, 32-41 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Recent studies have shown a predominance of type IV SCCmec among the methicillin-resistant Staphylococcus aureus (MRSA) isolated in the low endemic areas of Orebro County and the western region of Sweden. However, many of these isolates were not possible to classify as existing subtypes IVa, IVb, IVc or IVd. METHODS: We analysed 16 such MRSA isolates by multilocus sequence typing, spa typing, staphylocoagulase (SC) typing and detection of type IVg and IVh SCCmec. MRSA that remained as unknown type IV SCCmec were investigated by long-range PCR covering the J1 region; however, only two isolates were possible to amplify by PCR. The nucleotide sequences of the entire SCCmec of these two MRSA were determined. In addition, isolates that had unknown SC types were investigated by nucleotide sequencing of the coa genes. RESULTS: Five of 16 isolates were classified as type IVg SCCmec, and four isolates had type IVh SCCmec. Two subtypes of type IV SCCmec shared J1 regions previously identified in other types of SCCmec, types I.2 and II.2. The novel elements were designated as type IVi and IVj SCCmec. In addition, the genetic backgrounds of these Swedish MRSA were diverse and constituted at least nine sequence types and eight SC types, including four new types of SC. CONCLUSIONS: Type IV SCCmec is occurring in heterogeneous clones of MRSA in Sweden, and the majority of the type IV SCCmec were identified in community-acquired MRSA. We describe two novel subtypes of type IV SCCmec with common J1 regions shared by other types of SCCmec, which indicate that J1 regions occurred as primordial SCC.

  • 11.
    Berglund, Carolina
    et al.
    Örebro University, School of Health and Medical Sciences.
    Prévost, Gilles
    Laventie, Benoît-Joseph
    Keller, Daniel
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    The genes for Panton Valentine leukocidin (PVL) are conserved in diverse lines of methicillin-resistant and methicillin-susceptible Staphylococcus aureus2008In: Microbes and infection, ISSN 1286-4579, E-ISSN 1769-714X, Vol. 10, no 8, 878-884 p.Article in journal (Other academic)
    Abstract [en]

    Methicillin-resistant Staphylococcus aureus isolated in the community (CA-MRSA) have been reported to carry the loci for Panton Valentine leukocidin (PVL) in high frequency. CA-MRSA in Orebro County, Sweden, constitutes at least 50% of MRSA and the PVL locus is detected in as many as 66% of these CA-MRSA isolates. The aim of this study was to characterize PVL-positive methicillin-resistant and methicillin-susceptible Staphylococcus aureus by molecular methods, to determine the nucleotide sequence of lukS-PV and lukF-PV in S. aureus isolates of different origins, and to investigate the biological consequence of variations occurring in the genes. The PVL-positive MRSA investigated were composed of six different STs (ST8, 36, 80, 152, 154, and 256). Six additional STs (ST5, 22, 25, 30, 88, and 567) were detected when investigating PVL-positive methicillin-susceptible S. aureus with MLST. Despite the different genetic origins of the isolates analyzed, the PVL genes were well conserved and only one mutation was non-synonymous. Evaluation of the consequence of this mutation showed that the mutated toxin and wild-type toxin had comparable biological activity on human polymorphonuclear cells.

  • 12.
    Berglund, Carolina
    et al.
    Örebro University, School of Health and Medical Sciences.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    The origin of a methicillin-resistant Staphylococcus aureus isolate at a neonatal ward in Sweden: possible horizontal transfer of a staphylococcal cassette chromosome mec between methicillin-resistant Staphylococcus haemolyticus and Staphylococcus aureus2008In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 14, no 11, 1048-1056 p.Article in journal (Refereed)
    Abstract [en]

    The first methicillin-resistant Staphylococcus aureus (MRSA) strain originated when a staphylococcal cassette chromosome mec (SCCmec) with the gene mecA was integrated into the chromosome of a susceptible S. aureus cell. The SCCmec elements are common among the coagulase-negative staphylococci, e.g. Staphylococcus haemolyticus, and these are considered to be potential SCCmec donors when new clones of MRSA arise. An outbreak of MRSA occurred at a neonatal intensive-care unit, and the isolates were all of sequence type (ST) 45, as characterized by multilocus sequence typing, but were not typeable with respect to SCCmec types I, II, III or IV. During the same time period, methicillin-resistant S. haemolyticus (MRSH) isolates identified in blood cultures at the same ward were found to be genotypically homogenous by pulsed-field gel electrophoresis, and did not carry a type I, II, III or IV SCCmec either. Thus, the hypothesis was raised that an SCCmec of MRSH had been transferred to a methicillin-susceptible S. aureus strain and thereby created a new clone of MRSA that caused the outbreak. This study showed that MRSA from the outbreak carried a ccrC and a class C mec complex that was also found among MRSH isolates. Partial sequencing of the mec complexes showed more than 99% homology, indicative of a common type V SCCmec. This finding may provide evidence for a recent horizontal transfer of an SCCmec from MRSH to an identified potential recipient, an ST45 methicillin-susceptible S. aureus strain, thereby creating a new clone of MRSA that caused the outbreak.

  • 13.
    Björkqvist, Maria
    et al.
    Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Liljedahl, M.
    Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Zimmermann, J.
    Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Schollin, Jens
    Örebro University. Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences. Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Colonization pattern of coagulase-negative staphylococci in preterm neonates and the relation to bacteremia2010In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 29, no 9, 1085-1093 p.Article in journal (Refereed)
    Abstract [en]

    Coagulase-negative staphylococci (CoNS) are the major cause of sepsis in extreme preterm (EPT) newborns, but data on the CoNS colonization in EPT newborns prior to invasive infection are limited. Our aim was to describe the early establishment of the CoNS microflora in EPT newborns and to compare the colonization pattern in neonates with and without positive CoNS blood cultures. From a cohort of 46 EPT neonates, newborns with positive CoNS blood culture were identified (n = 10) and compared with matched controls. Samples for bacterial cultures were obtained repetitively from nares, perineum, and umbilicus. All CoNS isolates were characterized using the PhenePlate system for biochemical fingerprinting. Persistent CoNS strains were found on day 2-3 after delivery in 7/20 newborns, and there was a tendency for earlier colonization in nares than in the perineum or umbilicus. The CoNS blood strains were prevalent in superficial sites prior to positive blood culture (11/14 blood strains), but no single invasive pathway was identified. Most CoNS blood strains (9/14) persisted on superficial sites after antibiotic treatment. We hypothesize that the invasive pathways in neonatal CoNS sepsis are complex and that the colonization of mucosal membranes and umbilical catheters might be of equal importance.

  • 14. Bjørkeng, Eva
    et al.
    Rasmussen, Gunlög
    Sundsfjord, Arnfinn
    Sjöberg, Lennart
    Hegstad, Kristin
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    Clustering of polyclonal VanB-type vancomycin-resistant Enterococcus faecium in a low-endemic area was associated with CC17-genogroup strains harbouring transferable vanB2-Tn5382 and pRUM-like repA containing plasmids with axe-txe plasmid addiction systems2011In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 119, no 4-5, 247-258 p.Article in journal (Refereed)
    Abstract [en]

    VanB-type vancomycin-resistant Enterococcus faecium isolates (n = 17) from 15 patients at the Örebro University hospital in Sweden during a span of 18 months was characterized. All patients had underlying disorders and received broad-spectrum antimicrobial therapy. Pulsed-field gel electrophoresis (PFGE) grouped 14 isolates in three PFGE types and three isolates in unique PFGE patterns. All isolates had multi-locus sequence types [ST17 (n = 5); ST18 (n = 3); ST125 (n = 7); ST262 (n = 1); ST460 (n = 1)] belonging to the successful hospital-adapted clonal complex 17 (CC17), harboured CC17-associated virulence genes, were vanB2-positive and expressed diverse vancomycin minimum inhibitory concentration (MICs; 8 to > 256 mg/L). Isolate 1 had a unique PFGE type and a chromosomal transferable vanB2-Tn5382 element. Interestingly, the other five PFGE types had Tn5382 located on plasmids containing pRUM-like repA and a plasmid addiction system (axe-txe) shown by co-hybridization analysis of PFGE-separated S1-nuclease digested total DNA. The resistance plasmids were mainly of 120-kb and supported intraspecies vanB transfer. Two strains were isolated from patient 6 and we observed a possible transfer of the vanB2-resistance genes from PFGE type III ST460 to a more successful PFGE type I ST125. This latter PFGE type I ST125 became the predominant type afterwards. Our observations support the notion that vanB-type vancomycin-resistant Enterococcus faecium can persist in a low-endemic area through successful clones and plasmids with stability functions in hospital patients with known risk factors.

  • 15.
    Cajander, Sara
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Bäckman, Anders
    Örebro University, School of Medical Sciences. Clinical Research Centre, .
    Tina, Elisabet
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Clinical Research Centre.
    Strålin, Kristoffer
    Department of Infectious Diseases, Örebro University Hospital, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Huddinge, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Källman, Jan
    Örebro University Hospital. Örebro University, School of Medical Sciences. Department of Infectious Diseases.
    Preliminary results in quantitation of HLA-DRA by real-time PCR: a promising approach to identify immunosuppression in sepsis2013In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 17, no 5, R223Article in journal (Refereed)
    Abstract [en]

    Introduction: Reduced monocyte human leukocyte antigen (mHLA)-DR surface expression in the late phase of sepsis is postulated as a general biomarker of sepsis-induced immunosuppression and an independent predictor of nosocomial infections. However, traditional monitoring of mHLA-DR by flow cytometry has disadvantages due to specific laboratory requirements. An mRNA-based HLA-DR monitoring by polymerase chain reaction (PCR) would improve the clinical usage and facilitate conduction of large multicenter studies. In this study, we evaluated an mRNA-based HLA-DR monitoring by quantitative real-time PCR (qRT-PCR) as an alternative method to traditional flow cytometry.

    Methods: Fifty-nine patients with sepsis and blood culture growing pathogenic bacteria were studied. Blood samples were collected at day 1 or 2 after admission, for measurement of mHLA-DR by flow cytometry and mRNA expression of HLA-DRA and class II transactivator (CIITA) by qRT-PCR. Blood samples from blood donors were used as controls (n = 30).

    Results: A significant reduced expression of mHLA-DR, HLA-DRA, and CIITA was seen in septic patients compared with controls. HLA-DRA mRNA level in whole blood was highly correlated with surface expression of mHLA-DR.

    Conclusions: Patients with sepsis display a diminished expression of HLA-DR at the monocyte surface as well as in the gene expression at the mRNA level. The mRNA expression level of HLA-DRA monitored by qRT-PCR correlates highly with surface expression of HLA-DR and appears to be a possible future biomarker for evaluation of immunosuppression in sepsis.

  • 16.
    Cajander, Sara
    et al.
    Örebro University, School of Medical Sciences.
    Rasmussen, Gunlög
    Örebro University, School of Medical Sciences.
    Tina, Elisabet
    Örebro University, School of Medical Sciences.
    Magnuson, Anders
    Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medical Sciences.
    Källman, Jan
    Örebro University, School of Medical Sciences.
    Strålin, Kristoffer
    Karolinska University Hospital, Stockholm, Sweden; Karolinska Institute, Stockholm, Sweden .
    Monocytic HLA-DR expression differs between bacterial etiologies and is inversely related to C-reactive protein and neutrophil count during the course of bloodstream infectionManuscript (preprint) (Other academic)
  • 17.
    Cajander, Sara
    et al.
    Örebro University, School of Health Sciences. Department of Infectious Diseases.
    Tina, Elisabet
    Örebro University, School of Medical Sciences. Department of Clinical Research Laboratory.
    Bäckman, Anders
    Örebro University, School of Medical Sciences. Department of Clinical Research Laboratory.
    Magnuson, Anders
    Clinical Epidemiology and Biostatistics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Strålin, Kristoffer
    Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden .
    Söderquist, Bo
    Örebro University, School of Medical Sciences.
    Källman, Jan
    Örebro University, School of Medical Sciences. Department of Infectious Diseases.
    Quantitative Real-Time Polymerase Chain Reaction Measurement of HLA-DRA Gene Expression in Whole Blood Is Highly Reproducible and Shows Changes That Reflect Dynamic Shifts in Monocyte Surface HLA-DR Expression during the Course of Sepsis2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 5, e0154690Article in journal (Refereed)
    Abstract [en]

    Introduction: A decrease in the expression of monocyte surface protein HLA-DR (mHLA-DR), measured by flow cytometry (FCM), has been suggested as a marker of immunosuppression and negative outcome in severe sepsis. However, FCM is not always available due to sample preparation that limits its use to laboratory operational hours. In this prospective study we evaluated dynamic changes in mHLA-DR expression during sepsis in relation to changes in HLA-DRA gene expression and Class II transactivator (CIITA), measured by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR).

    Aims: The aims of this study were: 1. to validate the robustness of qRT-PCR measurement of HLA-DRA- and CIITA-mRNA expression, in terms of reproducibility; and 2. to see if changes in expression of these genes reflect changes in mHLA-DR expression during the course of severe and non-severe bacteraemic sepsis.

    Methods and Findings: Blood samples were collected from 60 patients with bacteraemic sepsis on up to five occasions during Days 1-28 after hospital admission. We found the reproducibility of the qRT-PCR method to be high by demonstrating low threshold variations (<0.11 standard deviation (SD)) of the qRT-PCR system, low intra-assay variation of Ct-values within triplicates (≤0.15 SD) and low inter-assay variations (12%) of the calculated target gene ratios. Our results also revealed dynamic HLA-DRA expression patterns during the course of sepsis that reflected those of mHLA-DR measured by FCM. Furthermore, HLA-DRA and mHLA-DR recovery slopes in patients with non-severe sepsis differed from those in patients with severe sepsis, shown by mixed model for repeated measurements (p<0.05). However, during the first seven days of sepsis, PCR-measurements showed a higher magnitude of difference between the two sepsis groups. Mean differences (95% CI) between severe sepsis (n = 20) and non-severe sepsis (n = 40) were; on day 1-2, HLA-DRA 0.40 (0.28-0.59) p<0.001, CIITA 0.48 (0.32-0.72) p = 0.005, mHLA-DR 0.63 (0.45-1.00) p = 0.04, day 7 HLA-DRA 0.59 (0.46-0.77) p<0.001, CIITA 0.56 (0.41-0.76) p<0.001, mHLA-DR 0.81 (0.66-1.00) p = 0.28.

    Conclusion: We conclude that qRT-PCR measurement of HLA-DRA expression is robust, and that this method appears to be preferable to FCM in identifying patients with severe sepsis that may benefit from immunostimulation.

  • 18.
    Davidsson, Sabina
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Mölling, Paula
    Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Gashi, Natyra
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Andrén, Ove
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Andersson, Swen-Olof
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Brzuszkiewicz, Elzbieta
    Department of Genomic and Applied Microbiology, Institute of Microbiology and Genetics, University of Göttingen, Göttingen, Germany.
    Poehlein, Anja
    Department of Genomic and Applied Microbiology, Institute of Microbiology and Genetics, University of Göttingen, Göttingen, Germany.
    Al-Zeer, Munir A.
    Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany.
    Brinkmann, Volker
    Microscopy Core Facility, Max Planck Institute for Infection Biology, Berlin, Germany.
    Scavenius, Carsten
    Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
    Nazipi, Seven
    Department of Biomedicine, Aarhus University, Aarhus, Denmark.
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Clinical Microbiology.
    Brüggemann, Holger
    Department of Biomedicine, Aarhus University, Aarhus, Denmark.
    Prevalence of Flp Pili-Encoding Plasmids in Cutibacterium acnes Isolates Obtained from Prostatic Tissue2017In: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 8, 2241Article in journal (Refereed)
    Abstract [en]

    Inflammation is one of the hallmarks of prostate cancer. The origin of inflammation is unknown, but microbial infections are suspected to play a role. In previous studies, the Gram-positive, low virulent bacterium Cutibacterium (formerly Propionibacterium) acnes was frequently isolated from prostatic tissue. It is unclear if the presence of the bacterium represents a true infection or a contamination. Here we investigated Cutibacterium acnes type II, also called subspecies defendens, which is the most prevalent type among prostatic C. acnes isolates. Genome sequencing of type II isolates identified large plasmids in several genomes. The plasmids are highly similar to previously identified linear plasmids of type I C. acnes strains associated with acne vulgaris. A PCR-based analysis revealed that 28.4% (21 out of 74) of all type II strains isolated from cancerous prostates carry a plasmid. The plasmid shows signatures for conjugative transfer. In addition, it contains a gene locus for tight adherence (tad) that is predicted to encode adhesive Flp (fimbrial low-molecular weight protein) pili. In subsequent experiments a tad locus-encoded putative pilin subunit was identified in the surface-exposed protein fraction of plasmid-positive C. acnes type II strains by mass spectrometry, indicating that the tad locus is functional. Additional plasmid-encoded proteins were detected in the secreted protein fraction, including two signal peptide-harboring proteins; the corresponding genes are specific for type II C. acnes, thus lacking from plasmid-positive type I C. acnes strains. Further support for the presence of Flp pili in C. acnes type II was provided by electron microscopy, revealing cell appendages in tad locus-positive strains. Our study provides new insight in the most prevalent prostatic subspecies of C. acnes, subsp. defendens, and indicates the existence of Flp pili in plasmid-positive strains. Such pili may support colonization and persistent infection of human prostates by C. acnes.

  • 19.
    Davidsson, Sabina
    et al.
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden; A Member of the Transdisciplinary Prostate Cancer Partnership (TopCaP), Örebro, Sweden .
    Mölling, Paula
    Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Rider, Jennifer R.
    Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA.
    Unemo, Magnus
    Örebro University, School of Health Sciences. Department of Laboratory Medicine, Clinical Microbiology.
    Karlsson, Mats G.
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Pathology, Örebro University Hospital, Örebro, Sweden.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Department of Urology; A Member of the Transdisciplinary Prostate Cancer Partnership (TopCaP), Örebro, Sweden.
    Andersson, Swen-Olof
    Örebro University, School of Health Sciences. Department of Urology; A Member of the Transdisciplinary Prostate Cancer Partnership (TopCaP), Örebro, Sweden.
    Elgh, Fredrik
    Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Söderquist, Bo
    Örebro University, School of Medical Sciences.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology; A Member of the Transdisciplinary Prostate Cancer Partnership (TopCaP), Örebro, Sweden.
    Erratum to: Frequency and typing of Propionibacterium acnes in prostate tissue obtained from men with and without prostate cancer2016In: Infectious Agents and Cancer, ISSN 1750-9378, E-ISSN 1750-9378, Vol. 11, 36Article in journal (Refereed)
  • 20.
    Davidsson, Sabina
    et al.
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden; A Member of the Transdisciplinary Prostate Cancer Partnership (TopCaP), Örebro, Sweden.
    Mölling, Paula
    Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Rider, Jennifer R.
    Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA; A Member of the Transdisciplinary Prostate Cancer Partnership (TopCaP), Örebro, Sweden.
    Unemo, Magnus
    Örebro University, School of Health Sciences. Department of Laboratory Medicine, Clinical Microbiology.
    Karlsson, Mats G.
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Pathology, Örebro University Hospital, Örebro, Sweden.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Department of Urology; A Member of the Transdisciplinary Prostate Cancer Partnership (TopCaP), Örebro, Sweden.
    Andersson, Swen-Olof
    Örebro University, School of Health Sciences. Department of Urology; A Member of the Transdisciplinary Prostate Cancer Partnership (TopCaP), Örebro, Sweden.
    Elgh, Fredrik
    Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Söderquist, Bo
    Örebro University, School of Medical Sciences.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology; A Member of the Transdisciplinary Prostate Cancer Partnership (TopCaP), Örebro, Sweden.
    Frequency and typing of Propionibacterium acnes in prostate tissue obtained from men with and without prostate cancer2016In: Infectious Agents and Cancer, ISSN 1750-9378, E-ISSN 1750-9378, Vol. 11, 26Article in journal (Refereed)
    Abstract [en]

    Background: Prostate cancer is the most common cancer among men in Western countries but the exact pathogenic mechanism of the disease is still largely unknown. An infectious etiology and infection-induced inflammation has been suggested to play a role in prostate carcinogenesis and Propionibacterium acnes has been reported as the most prevalent microorganism in prostatic tissue. We investigated the frequency and types of P. acnes isolated from prostate tissue samples from men with prostate cancer and from control patients without the disease.

    Methods: We included 100 cases and 50 controls in this study. Cases were men diagnosed with prostate cancer undergoing radical prostatectomy and controls were men undergoing surgery for bladder cancer without any histological findings of prostate cancer. Six biopsies taken from each patient's prostate gland at the time of surgery were used for cultivation and further characterization of P. acnes.

    Results: The results revealed that P. acnes was more common in men with prostate carcinoma than in controls, with the bacteria cultured in 60 % of the cases vs. 26 % of the controls (p = 0.001). In multivariable analyses, men with P. acnes had a 4-fold increase in odds of a prostate cancer diagnosis after adjustment for age, calendar year of surgery and smoking status (OR: 4.46; 95 % CI: 1.93-11.26). To further support the biologic plausibility for a P. acnes infection as a contributing factor in prostate cancer development, we subsequently conducted cell-based experiments. P. acnes- isolates were co-cultured with the prostate cell line PNT1A. An increased cell proliferation and cytokine/chemokine secretion in infected cells was observed.

    Conclusion: The present study provides further evidence for a role of P. acnes in prostate cancer development.

  • 21.
    Davidsson, Sabina
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Mölling, Paula
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Rider, Jennifer R.
    Karlsson, Mats G.
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Elgh, Fredrik
    Andrén, Ove
    Örebro University, School of Medicine, Örebro University, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden.
    Prevalence and typing of Propionibacterium acnes in prostate tissue obtained from men with prostate cancer and from health controlsManuscript (preprint) (Other academic)
  • 22.
    Davidsson, Sabina
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Elgh, Fredrik
    Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Olsson, Jan
    Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Andrén, Ove
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Multilocus sequence typing and repetitive-sequence-based PCR (DiversiLab) for molecular epidemiological characterization of Propionibacterium acnes isolates of heterogeneous origin2012In: Anaerobe, ISSN 1075-9964, E-ISSN 1095-8274, Vol. 18, no 4, 392-399 p.Article in journal (Refereed)
    Abstract [en]

    Propionibacterium acnes is a gram-positive bacillus predominantly found on the skin. Although it is considered an opportunistic pathogen it is also been associated with severe infections. Some specific P. acnes subtypes are hypothesized to be more prone to cause infection than others. Thus, the aim of the present study was to investigate the ability to discriminate between P. acnes isolates of a refined multilocus sequence typing (MLST) method and a genotyping method, DiversiLab, based on repetitive-sequence-PCR technology.

    The MLST and DiversiLab analysis were performed on 29 P. acnes isolates of diverse origins; orthopedic implant infections, deep infections following cardiothoracic surgery, skin, and isolates from perioperative tissue samples from prostate cancer. Subtyping was based on recA, tly, and Tc12S sequences.

    The MLST analysis identified 23 sequence types and displayed a superior ability to discriminate P. acnes isolates compared to DiversiLab and the subtyping. The highest discriminatory index was found when using seven genes. DiversiLab was better able to differentiate the isolates compared to the MLST clonal complexes of sequence types.

    Our results suggest that DiversiLab can be useful as a rapid typing tool for initial discrimination of P. acnes isolates. When better discrimination is required, such as for investigations of the heterogeneity of P. acnes isolates and its involvement in different pathogenic processes, the present MLST protocol is valuable.

  • 23.
    Demirel, Isak
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Kinnunen, Annica
    Örebro University, School of Science and Technology.
    Önnberg, Anna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Persson, Katarina
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Comparison of host response mechanisms evoked by extended spectrum beta lactamase (ESBL)- and non-ESBL-producing uropathogenic E. coli2013In: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 13, 181Article in journal (Refereed)
    Abstract [en]

    Background: Infections caused by extended spectrum beta-lactamases (ESBL)-producing bacteria have been emerging worldwide and the majority of ESBL-producing E. coli strains are isolated from patients with urinary tracts infections. The purpose of this study was to compare the host-response mechanisms in human polymorphonucleated leukocytes (PMN) and renal epithelial cells when stimulated by ESBL-or non-ESBL-producing uropathogenic E. coli (UPEC) isolates. The host-pathogen interaction of these ESBL-producing strains in the urinary tract is not well studied.

    Results: The ability of ESBL strains to evoke ROS-production from PMN cells was significantly higher than that of the non-ESBL strains. The growth of ESBL strains was slightly suppressed in the presence of PMN compared to non-ESBL strains after 30 min and 2 h, but the opposite was observed after 5 and 6 h. The number of migrating PMN was significantly higher in response to ESBL strains compared to non-ESBL strains. Stimulation of A498 cells with ESBL strains elicited lower production of IL-6 and IL-8 compared to non-ESBL strains.

    Conclusion: Significant differences in host-response mechanisms were identified when host cells were stimulated by ESBL-or non-ESBL producing strains. The obtained results on the early interactions of ESBL-producing strains with the host immune system may provide valuable information for management of these infections.

  • 24.
    Ehlersson, Gustaf
    et al.
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Hellmark, Bengt
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Svartström, Olov
    Department of Clinical Microbiology, Linköping University Hospital, Linköping, Sweden.
    Stenmark, Bianca
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Phenotypic characterisation of coagulase-negative staphylococci isolated from blood cultures in newborn infants, with a special focus on Staphylococcus capitis2017In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, no 10, 1576-1582 p.Article in journal (Refereed)
    Abstract [en]

    AIM: This Swedish study determined which species of coagulase-negative staphylococci (CoNS) were found in neonatal blood cultures and whether they included Staphylococcus capitis clones with decreased susceptibility to vancomycin.

    METHODS: CoNS isolates (n = 332) from neonatal blood cultures collected at Örebro University Hospital during 1987-2014 were identified to species level with matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). The antibiotic susceptibility pattern of S. capitis isolates was determined by the disc diffusion test and Etest, and the presence of heterogeneous glycopeptide-intermediate S. capitis (hGISC) was evaluated.

    RESULTS: Staphylococcus epidermidis (67.4%), Staphylococcus haemolyticus (10.5%) and S. capitis (9.6%) were the most common CoNS species. Of the S. capitis isolates, 75% were methicillin-resistant and 44% were multidrug-resistant. No isolate showed decreased susceptibility to vancomycin, but at least 59% displayed the hGISC phenotype. Staphylococcus capitis isolates related to the strain CR01 displaying pulsotype NRCS-A were found.

    CONCLUSION: Staphylococcus epidermidis, S. haemolyticus and S. capitis were the predominant species detected in neonatal blood cultures by MALDI-TOF MS. The number of episodes caused by S. capitis increased during the study period, but no isolates with decreased susceptibility to vancomycin were identified. However, S. capitis isolates related to the strain CR01 displaying pulsotype NRCS-A were found.

  • 25.
    Falk-Brynhildsen, Karin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Cardiothoracic Surgery and Anesthesiology, Örebro University Hospital, Örebro, Sweden; .
    Friberg, Örjan
    Örebro University Hospital. Department of Cardiothoracic Surgery and Anesthesiology.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Nilsson, Ulrica G.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Centre for Health Care Sciences; Department of Nursing, Umeå University, Umeå, Sweden.
    Bacterial colonization of the skin following aseptic preoperative preparation and impact of the use of plastic adhesive drapes2013In: Biological Research for Nursing, ISSN 1099-8004, E-ISSN 1552-4175, Vol. 15, no 2, 242-248 p.Article in journal (Refereed)
    Abstract [en]

    Surgical site contamination, for example, with coagulase-negative staphylococci, probably derives from both the patient’s own skin flora and those of the surgical team. Despite preoperative antiseptic preparation with chlorhexidine solution, complete sterilization of the skin is not possible and gradual recolonization will occur. Plastic adhesive drape is an established method used to prevent direct wound contamination from adjacent skin. In this study, the time to skin recolonization after antiseptic preparation was measured and the impact of using plastic adhesive drape on this recolonization was evaluated. Repeated bacterial sampling using three different methods over 6 hr was conducted after antiseptic preparation in 10 volunteers. Recolonization of skin was observed after 30 min with plastic drape and after 60 min without plastic drape; there were significantly more positive cultures with the plastic drape than without (31% vs. 7.5%, respectively, p < .001). Sampling with a rayon swab was the most sensitive sampling method. In conclusion, covering the skin with a plastic adhesive drape seems to hasten recolonization of the skin after antiseptic preparation. However, clinical trials to confirm this finding are warranted.

  • 26.
    Falk-Brynhildsen, Karin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Cardiothoracic and Vascular Surgery, Örebro University Hospital, Örebro.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Friberg, Örjan
    Örebro University Hospital. Department of Cardiothoracic and Vascular Surgery.
    Nilsson, Ulrica
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bacterial growth and wound infection following saphenous vein harvesting in cardiac surgery: a randomized controlled trial of the impact of microbial sealant2014In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 33, no 11, 1981-1987 p.Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to compare microbial skin sealant versus bare skin on the leg regarding intraoperative bacterial presence in the surgical wound and time to recolonization of the adjacent skin at the saphenous vein harvesting site. A second aim was to evaluate the incidence of leg wound infection 2 months after surgery. In this randomized controlled trial, 140 patients undergoing coronary artery bypass grafting (CABG) between May 2010 and October 2011 were enrolled. Bacterial samples were taken preoperatively and intraoperatively at multiple time points and locations. OF the patients, 125 (92.6 %) were followed up 2 months postoperatively regarding wound infection. Intraoperative bacterial growth did not differ between the bare skin (n = 68) and the microbial skin sealant group (n = 67) at any time point. At 2 months postoperatively, 7/61 patients (11.5 %) in the skin sealant versus 14/64 (21.9 %) in the bare skin group (p = 0.120) had been treated with antibiotics for a verified or suspected surgical site infection (SSI) at the harvest site. We found almost no intraoperative bacterial presence on the skin or in the subcutaneous tissue, irrespective of microbial skin sealant use. In contrast, we observed a relatively high incidence of late wound infection, indicating that wound contamination occurred postoperatively. Further research is necessary to determine whether the use of microbial skin sealant reduces the incidence of leg wound infection at the saphenous vein harvest site.

  • 27.
    Falk-Brynhildsen, Karin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Cardiothoracic and Vascular Surgery, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Friberg, Örjan
    Örebro University Hospital. Department of Cardiothoracic and Vascular Surgery.
    Nilsson, Ulrica
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Centre for Health Care Sciences.
    Bacterial recolonization of the skin and wound contamination during cardiac surgery: a randomized controlled trial of the use of plastic adhesive drape compared with bare skin2013In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 84, no 2, 151-158 p.Article in journal (Refereed)
    Abstract [en]

    Background: Sternal wound infection after cardiac surgery is a serious complication. Various perioperative strategies, including plastic adhesive drapes, are used to reduce bacterial contamination of surgical wounds.

    Aim: To compare plastic adhesive drape to bare skin regarding bacterial growth in wound and time to recolonization of the adjacent skin intraoperatively, in cardiac surgery patients.

    Methods: This single-blinded randomized controlled trial (May 2010 to May 2011) included 140 patients scheduled for cardiac surgery via median sternotomy. The patients were randomly allocated to the adhesive drape (chest covered with plastic adhesive drape) or bare skin group. Bacterial samples were taken preoperatively and intraoperatively every hour during surgery until skin closure.

    Results: Disinfection with 0.5% chlorhexidine solution in 70% alcohol decreased coagulase-negative staphylococci (CoNS), while the proportion colonized with Propionibacterium acnes was not significantly reduced and was still present in more than 50% of skin samples. P. acnes was significantly more common in men than in women. Progressive bacterial recolonization of the skin occurred within 2-3 h. At 120 min there were significantly more positive cultures in the adhesive drape group versus bare skin group for P. acnes (63% vs 44%; P = 0.034) and for CoNS (45% vs 24%; P = 0.013). The only statistically significant difference in bacterial growth in the surgical wound was higher proportion of CoNS at the end of surgery in the adhesive drape group (14.7% vs 4.4%; P = 0.044).

    Conclusion: Plastic adhesive drape does not reduce bacterial recolonization. P. acnes colonized men more frequently, and was not decreased by disinfection with chlorhexidine solution in alcohol.

  • 28.
    Falk-Brynhildsen, Karin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Cardiothoracic and Vascular Surgery, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Friberg, Örjan
    Örebro University Hospital. Department of Cardiothoracic and Vascular Surgery.
    Nilsson, Ulrica G.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Centre for Health Care Sciences.
    Response to MH Stevens and NM Klinger, re: Bacterial recolonization of the skin and wound contamination during cardiac surgery2013In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 85, no 4, 325-325 p.Article in journal (Refereed)
  • 29. Friberg, Ö.
    et al.
    Dahlin, L.-G.
    Söderquist, Bo
    Örebro University, Department of Clinical Medicine.
    Källman, J.
    Örebro University, Department of Clinical Medicine.
    Svedjeholm, R.
    Influence of more than six sternal fixation wires on the incidence of deep sternal wound infection2006In: The thoracic and cardiovascular surgeon, ISSN 0171-6425, E-ISSN 1439-1902, Vol. 54, no 7, 468-473 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim of the present study was to examine the influence of the number of sternal fixation wires used on deep sternal wound infection rate and to analyze any possible interaction between this and local collagen-gentamicin prophylaxis evaluated in a previous trial. METHODS: The number of sternal fixation wires in all patients from one of two participating centers was counted. The patients were categorized according to six or fewer (standard technique, ST group) vs. seven or more wires (extra wires, XW group). RESULTS: The incidence of deep sternal wound infection was 4.2 % in the ST group and 0.4 % in the XW group ( P = 0.001). An analysis of the effect of local gentamicin, excluding the ST group from the analysis, showed an approximately 70 % reduction in sternal wound infection for all depths. CONCLUSION: This study supports the theory that additional fixation wires at the lower sternum actually reduce the incidence of deep wound infections. We suggest that a rigid sternal fixation is required to achieve the full benefit of local collagen-gentamicin prophylaxis.

  • 30. Friberg, Örjan
    et al.
    Dahlin, Lars-Göran
    Källman, Jan
    Kihlström, Erik
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    Svedjeholm, Rolf
    Collagen-gentamicin implant for prevention of sternal wound infection: long-term follow-up of effectiveness2009In: Interactive Cardiovascular and Thoracic Surgery, ISSN 1569-9293, E-ISSN 1569-9285, Vol. 9, no 3, 454-458 p.Article in journal (Refereed)
    Abstract [en]

    In a previous randomized controlled trial (LOGIP trial) the addition of local collagen-gentamicin reduced the incidence of postoperative sternal wound infections (SWI) compared with intravenous prophylaxis only. Consequently, the technique with local gentamicin was introduced in clinical routine at the two participating centers. The aim of the present study was to re-evaluate the technique regarding the prophylactic effect against SWI and to detect potential shifts in causative microbiological agents over time. All patients in this prospective two-center study received prophylaxis with application of two collagen-gentamicin sponges between the sternal halves in addition to routine intravenous antibiotics. All patients were followed for 60 days postoperatively. From January 2007 to May 2008, 1359 patients were included. The 60-day incidences of any SWI was 3.7% and of deep SWI 1.5% (1.0% mediastinitis). Both superficial and deep SWI were significantly reduced compared with the previous control group (OR=0.34 for deep SWI, P<0.001). There was no increase in the absolute incidence of aminoglycoside resistant agents. The majority of SWI were caused by coagulase-negative staphylococci (CoNS). The incidence of deep SWI caused by Staphylococcus aureus was 0.07%. The results indicate a maintained effect of the prophylaxis over time without absolute increase in aminoglycoside resistance. (ClinicalTrials.gov NCT00484055).

  • 31. Friberg, Örjan
    et al.
    Källman, Jan
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    Olcén, P.
    Introduction: [to prevention of surgical site infections in cardiac surgery]2007In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 115, no 9, 987-988 p.Article in journal (Refereed)
  • 32. Friberg, Örjan
    et al.
    Svedjeholm, Rolf
    Källman, Jan
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    Incidence, microbiological findings, and clinical presentation of sternal wound infections after cardiac surgery with and without local gentamicin prophylaxis2007In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 26, no 2, 91-97 p.Article in journal (Refereed)
    Abstract [en]

    Sternal wound infection (SWI) is a serious complication after cardiac surgery. In a previous randomized controlled trial, the addition of local collagen-gentamicin in the sternal wound before wound closure was found to significantly reduce the incidence of postoperative wound infections compared with the routine intravenous prophylaxis of isoxazolyl-penicillin only. The aims of the present study were to analyse the microbiological findings of the SWIs from the previous trial as well as to correlate these findings with the clinical presentation of SWI. Differences in clinical presentation of SWIs, depending on the causative agent, could be identified. Most infections had a late, insidious onset, and the majority of these were caused by staphylococci, predominantly coagulase-negative staphylococci. The clinically most fulminant infections were caused by gram-negative bacteria and presented early after surgery. Local administration of gentamicin reduced the incidence of SWIs caused by all major, clinically important bacterial species. Propionibacterium acnes was identified as a possible cause of SWI and may be linked to instability in the sternal fixation. There was no indication of an increase in the occurrence of gentamicin-resistant bacterial isolates in the treatment group. Furthermore, the addition of local collagen-gentamicin reduced the incidence of SWIs caused by methicillin-resistant coagulase-negative staphylococci. This technique warrants further evaluation as an alternative to prophylactic vancomycin in settings with a high prevalence of methicillin-resistant Staphylococcus aureus.

  • 33. Friberg, Örjan
    et al.
    Svedjeholm, Rolf
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    Treating sternal wound infections after cardiac surgery with an implantable gentamicin-collagen sponge2010In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 304, no 19, 2123-2124 p.Article in journal (Refereed)
  • 34.
    Germel, C.
    et al.
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Haag, A.
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    In vitro activity of beta-lactam antibiotics to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)2012In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 31, no 4, 475-480 p.Article in journal (Refereed)
    Abstract [en]

    Community-associated (CA) MRSA often display low MIC values against oxacillin. The in vitro activity of various beta-lactam antibiotics against heterogeneous CA-MRSA (n = 98) isolated in a low endemic area was determined by Etest, and Mueller-Hinton agar (MUHAP) was compared with Mueller-Hinton agar supplemented with 2% NaCl (MUHSP). In general, the CA-MRSA isolates showed higher MIC values for the various beta-lactam antibiotics on MUHSP compared with MUHAP. MIC values for oxacillin ranged from 1 to >256 mg/L on MUHSP. Cephalothin, representing the first generation of cephalosporins, showed MICs from 0.75 to 96 mg/L and the MIC(50) and MIC(90) for cefuroxime, cefotaxime and cefepime, representing the second, third and fourth generations, respectively, were rather high. However, the MIC(50) and MIC(90) for ceftobiprole (fifth generation) were 1.5 and 2 mg/L, respectively, on MUHSP. The MIC(50) and MIC(90) for imipenem were 0.75 and 2 mg/L, respectively, on MUHSP. Only 3/98 (3%) CA-MRSA isolates showed a MIC >4 mg/L. Consequently, low MIC values for imipenem, lower than those of the newly developed fifth generation cephalosporins, were found among CA-MRSA. These findings may be considered for further studies including clinical trials in order to evaluate carbapenems as a potential treatment option for infections caused by CA-MRSA.

  • 35.
    Hamad, Tarza
    et al.
    Department of Laboratory Medicine, Clinical Microbiology, and Faculty of Medicine and Health, Örebro University, Örebro.
    Hellmark, Bengt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Clinical Microbiology.
    Nilsdotter-Augustinsson, Åsa
    Department of Infectious Diseases, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Laboratory Medicine, Clinical Microbiology.
    Antibiotic susceptibility among Staphylococcus epidermidis isolated from prosthetic joint infections, with focus on doxycycline2015In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 123, no 12, 1055-1060 p.Article in journal (Refereed)
    Abstract [en]

    In recent years, coagulase-negative staphylococci such as Staphylococcus epidermidis have gained importance as nosocomial pathogens, especially in immunocompromised patients and prosthetic joint infections (PJIs). These infections are often long lasting and difficult to treat due to the production of bacterial biofilm and the transformation of the bacteria into a stationary growth phase. Rifampicin is able to penetrate the biofilm, but to reduce the risk of development of rifampicin resistance it should be used in combination with an additional antibiotic. In this study we used Etest to investigate the antimicrobial susceptibility of 134 clinical isolates of S.epidermidis obtained from PJIs to six oral antibiotics: doxycycline, rifampicin, linezolid, fusidic acid, clindamycin, and ciprofloxacin. We also performed synergy testing on doxycycline in combination with each of the remaining antibiotics. Ninety-three (69%) of the 134 isolates were susceptible to doxycycline, 94/134 (70%) to rifampicin, 56/134 (42%) to clindamycin, 25/134 (19%) to ciprofloxacin, 81/134 (60%) to fusidic acid, and 100% to linezolid. Thirty-two (80%) of the 40 isolates not fully susceptible to rifampicin were susceptible to doxycycline. Doxycycline in combination with each of the other investigated antibiotics exerted an additive effect on nearly half of the isolates, with the exception of clindamycin, which displayed an even higher percentage of additive effect (69%). To conclude, as the majority of the S.epidermidis isolates were susceptible to doxycycline, this antimicrobial agent may provide a potential alternative for combination therapy together with rifampicin.

  • 36.
    Hedlund, Linda
    et al.
    Örebro University Hospital, Örebro, Sweden.
    Hellmark, Bengt
    Örebro University Hospital.
    Söderquist, Bo
    Örebro University Hospital.
    Presence of arginine catabolic mobile element among community-acquired meticillin-resistant staphylococcus aureus is linked to a specific genetic background2013In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 121, no 3, 221-225 p.Article in journal (Refereed)
    Abstract [en]

    The prevalence of arginine catabolic mobile element (ACME) among diverse and heterogeneous community-associated methicillin-resistant Staphylococcus aureus community-associated Methicillin-resistant S. aureus (CA-MRSA) (n = 114) in a low-endemic area, i.e. Sweden, was investigated. Among the CA-MRSA, represented by 47 different spa types, ACME was only found in 10 isolates with a common genetic background [t008, SCCmec type IV, Panton-Valentine leukocidin (PVL) positive, and indistinguishable or closely related pulsed-field gel electrophoresis (PFGE)-patterns] corresponding to USA300. This strain does not seem to be established in our area as most of the patients contracted the CA-MRSA abroad. Presence of ACME does not seem to be associated with colonization, long-term carriership, or intra-familiar transmission in a higher extent than CA-MRSA in general.

  • 37. Hellbacher, C
    et al.
    Törnqvist, E
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    Staphylococcus lugdunensis: clinical spectrum, antibiotic susceptibility, and phenotypic and genotypic patterns of 39 isolates2006In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 12, no 1, 43-49 p.Article in journal (Refereed)
    Abstract [en]

    Staphylococcus lugdunensis is a member of the coagulase-negative staphylococci with the potential to cause clinically significant infections. The spectrum of infections was investigated in 39 isolates of S. lugdunensis from 38 patients. Most (73%) infections were located below the waist, while those above the waist were mainly (5/7) breast abscesses. Most isolates were susceptible to the antibiotics tested, although 15.4% were beta-lactamase-positive and could be identified by the disk-diffusion method for penicillin G. There was very good concordance between the disk-diffusion method and the Etest method for oxacillin resistance. Pulsed-field gel electrophoresis (PFGE) showed that 56% of the isolates belonged to one SmaI pulsotype, while phenotypic analysis by the Phene Plate system identified three main phenotypic groups. Although the S. lugdunensis isolates analysed were obtained from different patients, treated in different wards and hospitals during a 4-year period, there was a low degree of diversity, both genotypically and phenotypically. For this reason, PFGE is not suitable for the analysis of an outbreak situation, and the homogeneity observed may indicate that S. lugdunensis is a genetically conserved species of coagulase-negative Staphylococcus.

  • 38.
    Hellmark, Bengt
    et al.
    Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Berglund, C.
    Department of Clinical Microbiology and Chemistry, Aleris MEDILAB, Täby, Sweden.
    Nilsdotter-Augustinsson, Å.
    Division of Infectious Diseases, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, University of Linköping, Linköping, Sweden.
    Unemo, Magnus
    Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Staphylococcal cassette chromosome mec (SCCmec) and arginine catabolic mobile element (ACME) in Staphylococcus epidermidis isolated from prosthetic joint infections2013In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 32, no 5, 691-697 p.Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to characterise the staphylococcal cassette chromosome mec (SCCmec) in Staphylococcus epidermidis isolated from prosthetic joint infections (PJIs) and, if possible, assign them to any of the presently known SCCmec types. In addition, the isolates were examined for the presence of the arginine catabolic mobile element (ACME). Sixty-one S. epidermidis isolates obtained from PJIs and 24 commensal S. epidermidis isolates were analysed. The mecA gene was detected in 49 of the 61 (80 %) PJI isolates and in four of the 24 (17 %) commensal isolates, and the composition of the SCCmec was further analysed. SCCmec types I and IV were the most common types among the PJI isolates. However, for over half (57 %) of the isolates, it was not possible to assign an SCCmec type. ACME was detected in eight (13 %) of the PJI isolates and in 14 (58 %) of the commensal isolates. The characterisation of the SCCmec elements revealed a large heterogeneity, with a high frequency of isolates carrying more than one type of the ccr gene complex. ACME was more common among the commensal isolates and may represent a survival benefit for S. epidermidis colonising healthy individuals in the community.

  • 39.
    Hellmark, Bengt
    et al.
    Örebro University, School of Health and Medical Sciences.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences.
    Simultaneous species identification and detection of rifampicin resistance in staphylococci by sequencing of the rpoB gene2008In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 28, no 2, 183-190 p.Article in journal (Refereed)
    Abstract [en]

    In recent years, coagulase-negative staphylococci (CoNS) have been increasingly recognised as causative agents of various infections, especially in immunocompromised patients and related to implanted foreign body materials. In this study, rpoB sequencing was used for simultaneous species identification and detection of rifampicin resistance in clinical staphylococci isolates. Forty-nine (96%) out of 51 isolates, representing 17 different Staphylococcus species according to the initial phenotypic species identification, were identified to the species level using rpoB sequencing. Furthermore, the two remaining isolates were Kocuria sp. and Corynebacterium sp. respectively, according to 16S rRNA sequencing. Comparison with the phenotypic diagnostics also revealed that 8 (16%) of the 49 isolates differed regarding identified species. Discrepant analysis confirmed the result of the rpoB sequencing for all except 2 of these isolates, which could not be distinguished as single species using 16S rRNA sequencing. Regarding detection of rifampicin resistance, isolates obtained pre- and post-treatment with rifampicin were examined. These isolates comprised S. aureus (7 patients) and S. lugdunensis (1 patient). Rifampicin resistance was mainly detected following short-term treatment with rifampicin in combination with isoxazolyl-penicillin, or long-term treatment with rifampicin and ciprofloxacin. Each rifampicin-resistant isolate displayed an identical rpoB sequence as their corresponding rifampicin-susceptible isolates except for one (n = 6) or two (n = 1) nonsynonymous single nucleotide polymorphisms, or insertion of one codon (n = 1). In conclusion, rpoB sequencing is a rapid, objective and accurate method of species identification and simultaneous detection of rifampicin resistance in staphylococci.

  • 40.
    Hellmark, Bengt
    et al.
    Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Unemo, Magnus
    Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Nilsdotter-Augustinsson, Åsa
    Division of Infectious Diseases, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, University of Linköping, Sweden.
    Comparison of Staphylococcus epidermidis isolated from prosthetic joint infections and commensal isolates in regard to antibiotic susceptibility, agr type, biofilm production, and epidemiology2013In: International Journal of Medical Microbiology, ISSN 1438-4221, E-ISSN 1618-0607, Vol. 303, no 1, 32-39 p.Article in journal (Refereed)
    Abstract [en]

    Staphylococcus epidermidis is the predominant bacterial species in the normal flora of the human skin and superficial mucosal membranes. However, it has also emerged as the most important pathogen in infections related to foreign-body materials, such as prosthetic joints and heart valves. The aims of this study were to characterise S. epidermidis isolated from prosthetic joint infections (PJI; n = 61) and commensal isolates from healthy individuals (n = 24) in regard to antimicrobial sensitivity, agr type, hid gene presence, biofllm production including presence of ica and aap genes involved in the biofilm formation process and epidemiology using both phenotypic (the PhenePlate-system) and genotypic [multilocus sequence typing (MLST)] methods. Among the PJI isolates, the majority (67%) were multidrug-resistant. Two major clusters of PJI isolates could be identified; 44% belonged to MLST sequence type (ST) 2, all but one were of agr type 1, and 31% were assigned ST215 and were of agr type 3. Of the commensal isolates, only one isolate was multidrug-resistant, and they were more molecular epidemiologically diverse with mainly MLST singletons and a maximum of 3 isolates assigned to the identical ST. Biofilm production was detected in 41% of the PJI isolates and 58% of the commensal isolates, with the aap gene (95%) more frequently detected than the ica genes (62%) in the biofilm-positive isolates. In conclusion, S. epidermidis isolated from PJIs and commensal isolates differed regarding antimicrobial sensitivity and molecular epidemiological typing using MLST, but not substantially in the distribution of agr types, biofilm production, or the presence of ica and aap genes.

  • 41.
    Hellmark, Bengt
    et al.
    Örebro University, School of Health and Medical Sciences.
    Unemo, Magnus
    Nilsdotter-Augustinsson, Å.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    Antibiotic susceptibility among Staphylococcus epidermidis isolated from prosthetic joint infections with special focus on rifampicin and variability of the rpoB gene2009In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 15, no 3, 238-244 p.Article in journal (Refereed)
    Abstract [en]

    Staphylococcus epidermidis is the most important pathogen in infections related to implanted foreign materials, especially prosthetic joint infections (PJIs). The aim of this study was to investigate the antimicrobial activities of 16 antibiotics against S. epidermidis isolated from PJIs, with special focus on rifampicin and rpoB variability. Ninety-one per cent of the isolates were multiresistant (i.e. resistant to members of more than three classes of antibiotics). Thirty-nine per cent were resistant to rifampicin, associated with one or two single-nucleotide polymorphisms (SNPs) in rpoB. Using IsoSensitest agar with supplements, 61% were resistant to oxacillin, and using Mueller-Hinton II agar with supplement, 84% were resistant. Using the Etest, 58% were resistant to cefoxitin, and using the disk diffusion test, 91% were resistant. The mecA gene was detected in 85% of the isolates. Regarding recently available antibiotics, all isolates were susceptible to tigecycline and linezolid, and 97% were susceptible to daptomycin. In addition, two novel antibiotics, dalbavancin and ceftobiprole, were tested, although not yet available for routine use. The MIC(50) and MIC(90) values of these novel antibiotics were 0.032 and 0.047 mg/L and 0.5 and 1.5 mg/L, respectively. Among the other antibiotics, the rates of resistance varied between 0% (vancomycin) and 82% (trimethoprim-sulphamethoxazole). S. epidermidis strains causing PJIs often show multiresistance, including resistance to rifampicin, which is mainly caused by one or two SNPs. Some of the newer antimicrobial agents may provide alternatives for monotherapy or combination therapy with rifampicin. Detection of mecA is necessary before initiating treatment of infections due to S. epidermidis when it displays intermediate susceptibility to cefoxitin.

  • 42.
    Hellmark, Bengt
    et al.
    Örebro University, School of Health and Medical Sciences.
    Unemo, Magnus
    Nilsdotter-Augustinsson, Åsa
    Söderquist, Bo
    In vitro antimicrobial synergy testing of coagulase-negative staphylococci isolated from prosthetic joint infections using Etest and with a focus on rifampicin and linezolid2010In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 29, no 5, 591-595 p.Article in journal (Refereed)
    Abstract [en]

    In recent years, coagulase-negative staphylococci (CoNS) have been increasingly recognised as causative agents of various infections, especially in immunocompromised patients and related to implanted foreign body materials. CoNS, and especially Staphylococcus epidermidis, transform into a stationary growth phase and produce biofilm when involved in a foreign body infection, making them difficult to eradicate with antimicrobials. Rifampicin has the ability to penetrate biofilm, but resistance may develop rapidly. To reduce the emergence of resistance, rifampicin should be combined with additional antimicrobials, of which several different ones have been proposed, including the relatively new class of antimicrobials, oxazolidinones, represented by linezolid. Thirty-seven CoNS isolates from patients with prosthetic joint infection were investigated by synergy testing using Etest. Nine antimicrobial combinations, based on either rifampicin or linezolid, were tested. For 16 (43%) of the isolates, a synergistic (n = 5), additive (n = 14) and/or antagonistic (n = 11) effect were identified. In conclusion, Etest is an objective and easily performed in vitro method for antimicrobial synergy testing. However, each isolate requires testing for the specific combination considered for treatment.

  • 43. Holmberg, A.
    et al.
    Lood, R.
    Mörgelin, M.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    Holst, E.
    Collin, M.
    Christensson, B.
    Rasmussen, M.
    Biofilm formation by Propionibacterium acnes is a characteristic of invasive isolates2009In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 15, no 8, 787-795 p.Article in journal (Refereed)
    Abstract [en]

    Propionibacterium acnes is a common and probably underestimated cause of delayed joint prosthesis infection. Bacterial biofilm formation is central in the pathogenesis of infections related to foreign material, and P. acnes has been shown to form biofilm both in vitro and in vivo. Here, biofilm formation by 93 P. acnes isolates, either from invasive infections (n = 45) or from the skin of healthy people (n = 48), was analysed. The majority of isolates from deep infections produced biofilm in a microtitre model of biofilm formation, whereas the skin isolates were poor biofilm producers (p <0.001 for a difference). This indicates a role for biofilm formation in P. acnes virulence. The type distribution, as determined by sequencing of recA, was similar among isolates isolated from skin and from deep infections, demonstrating that P. acnes isolates with different genetic backgrounds have pathogenic potential. The biofilm formed on plastic and on bone cement was analysed by scanning electron microscopy (EM) and by transmission EM. The biofilm was seen as a 10-mum-thick layer covering the bacteria and was composed of filamentous as well as more amorphous structures. Interestingly, the presence of human plasma in solution or at the plastic surface inhibits biofilm formation, which could explain why P. acnes primarily infect plasma-poor environments of, for example, joint prostheses and cerebrospinal shunts. This work underlines the importance of biofilm formation in P. acnes pathogenesis, and shows that biofilm formation should be considered in the diagnosis and treatment of invasive P. acnes infections.

  • 44.
    Idosa, Berhane Asfaw
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Sahdo, Berolla
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Balcha, Ermias
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Kelly, Anne
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, Sweden.
    Särndahl, Eva
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, Sweden.
    C10X polymorphism in the CARD8 gene is associated with bacteraemiaManuscript (preprint) (Other academic)
    Abstract [en]

    Introduction:: The NLRP3 inflammasome is an intracellular multi-protein complex that triggers caspase-1 mediated maturation of interleukin-1β (IL-1β); one of the most potent mediators of inflammation and a major cytokine produced during severe infections, like sepsis. However, the excessive cytokine levels seem to stage for tissue injury and organ failure, and high levels of IL-1β correlates with severity and mortality of sepsis. Instead, recent data suggest caspase- 1 to function as a guardian against severe infections. CARD8 has been implied to regulate the synthesis of IL-1β via interaction to caspase-1. In recent years, polymorphism of CARD8 (C10X) per se or in combination with NLRP3 (Q705K) has been implicated with increased risk of inflammation. The aim was to investigate the correlation of these polymorphisms with severe blood stream infection.

    Methods:: Human DNA was extracted from blood culture bottles that were found to be positive for microbial growth (i.e. patients with bacteraemia). Polymorphisms Q705K in the NLRP3 gene and C10X in the CARD8 gene were genotyped using TaqMan genotyping assay. The results were compared to healthy controls and to samples from patients with negative cultures.

    Results:: The polymorphism C10X was significantly over-represented among patients with bacteraemia as compared to healthy controls, whereas patients with negative blood culture were not associated with a higher prevalence. No association was observed with polymorphism Q705K of NLRP3 in eithergroup of patients.

    Conclusions:: Patients carrying polymorphism C10X in the CARD8 gene are at increased risk of developing bacteraemia and severe inflammation.

  • 45. International Working Group on the Classification of Staphylococcal Cassette Chromosome Elements, (IWG-SCC)
    et al.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    Classification of staphylococcal cassette chromosome mec (SCCmec): guidelines for reporting novel SCCmec elements.2009In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 53, no 12, 4961-4967 p.Article in journal (Refereed)
  • 46.
    Ito, Teruyo
    et al.
    Juntendo Univ, Dept Bacteriol, Tokyo, Japan .
    Hiramatsu, Keiichi
    Rockefeller Univ, New York, NY 10021 USA .
    Tomasz, Alexander
    Rockefeller Univ, New York, NY 10021 USA .
    de Lencastre, Herminia
    Rockefeller Univ, New York, NY 10021 USA;. Univ Nova Lisboa, Inst Tecnol Quim & Biol, Oeiras, Portugal.
    Perreten, Vincent
    Univ Bern, Inst Vet Bacteriol, Bern, Switzerland.
    Holden, Matthew T. G.
    Wellcome Trust Sanger Inst, Hinxton, Cambs, England.
    Coleman, David C.
    Univ Dublin, Dublin Dent Univ Hosp, Trinity Coll Dublin, Dublin, Ireland.
    Goering, Richard
    Creighton Univ, Med Ctr, Omaha, NE USA.
    Giffard, Philip M.
    Charles Darwin Univ, Menzies Sch Hlth Res, Darwin, NT 0909, Australia.
    Skov, Robert L.
    Statens Serum Inst, DK-2300 Copenhagen, Denmark .
    Zhang, Kunyan
    Univ Calgary, Calgary, AB, Canada.
    Westh, Henrik
    Univ Copenhagen, Fac Hlth, Copenhagen, Denmark; Univ Copenhagen, Hvidovre Hosp, Copenhagen, Denmark.
    O'Brien, Frances
    Curtin Univ Technol, Perth, WA, Australia.
    Tenover, Fred C.
    Cepheid, Sunnyvale, CA USA.
    Oliveira, Duarte C.
    Univ Nova Lisboa, Inst Tecnol Quim & Biol, Oeiras, Portugal; Univ Nova Lisboa, Fac Ciencias & Tecnol, Dept Life Sci, CREM, Caparica, Portugal .
    Boyle-Vavra, Susan
    Univ Nova Lisboa, Fac Ciencias & Tecnol, Dept Life Sci, CREM, Caparica, Portugal .
    Laurent, Frederic
    Hosp Civils Lyon, French Natl Reference Ctr Staphylococci, Lyon, France.
    Kearns, Angela M.
    Hlth Protect Agcy, Staphylococcus Reference Unit, London, England.
    Kreiswirth, Barry
    Publ Hlth Res Inst, New York, NY USA .
    Ko, Kwan Soo
    Sungkyunkwan Univ, Sch Med, Seoul, South Korea .
    Grundmann, Hajo
    Natl Inst Publ Hlth & Environm, Utrecht, Netherlands .
    Sollid, Johanna E.
    Univ Tromso, Tromso, Norway .
    John, Joseph F. Jr.
    Ralph H Johnson VA Med Ctr, Charleston, SC USA.
    Daum, Robert
    Univ Chicago, Chicago, IL 60637 USA.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden.
    Buist, Girbe
    Guidelines for Reporting Novel mecA Gene Homologues2012In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 56, no 10, 4997-4999 p.Article in journal (Other academic)
  • 47.
    Khassebaf, Jasmine
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro.
    Hellmark, Bengt
    Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Davidsson, Sabina
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Urology.
    Unemo, Magnus
    Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Nilsdotter-Augustinsson, Åsa
    Division of Infectious Diseases, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Infectious Diseases, County Council of Östergötland, Linköping, Sweden.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Antibiotic susceptibility of Propionibacterium acnes isolated from orthopaedic implant-associated infections2015In: Anaerobe, ISSN 1075-9964, E-ISSN 1095-8274, Vol. 32, 57-62 p.Article in journal (Refereed)
    Abstract [en]

    Introduction: Prosthetic joint infections (PJIs) caused by Propionibacterium acnes account for a larger proportion of the total number of PJIs than previously assumed and thus knowledge of the antimicrobial susceptibility patterns of P. acnes is of great value in everyday clinical practice.

    Materials and methods: Using Etest, the present study investigated the susceptibility of 55 clinical isolates of P. acnes, obtained from orthopaedic implant-associated infections of the knee joint (n = 5), hip joint (n = 17), and shoulder joint (n = 33), to eight antimicrobial agents: benzylpenicillin, clindamycin, metronidazole, fusidic acid, doxycycline, moxifloxacin, linezolid and rifampicin. Synergy testing was also conducted, in which rifampicin was combined with each of the remaining seven antibiotics.

    Results: All isolates (n = 55) were susceptible to most of the antibiotics tested, with the exception of 100% resistance to metronidazole, five (9.1%) isolates displaying decreased susceptibility to clindamycin, and one (1.8%) to moxifloxacin. None of the antimicrobial agents investigated were synergistic with each other when combined and nine isolates were antagonistic for various antimicrobial combinations. The majority of the antimicrobial combinations had an indifferent effect on the isolates of P. acnes. However, the combination of rifampicin and benzylpenicillin showed an additive effect on nearly half of the isolates.

    Conclusion: Almost all P. acnes, isolated from orthopaedic implant-associated infections, predominantly PJIs, were susceptible to the antibiotics tested, with the exception of complete resistance to metronidazole. Synergy test could not demonstrate any synergistic effect but additive effects were found when combining various antibiotics. Antagonistic effects were rare.

  • 48. Koskela, A.
    et al.
    Nilsdotter-Augustinsson, A.
    Persson, Lennart
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    Prevalence of the ica operon and insertion sequence IS256 among Staphylococcus epidermidis prosthetic joint infection isolates2009In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 28, no 6, 655-660 p.Article in journal (Refereed)
    Abstract [en]

    Joint replacement surgery has improved the quality of life for hundreds of thousands of patients. However, the infection of a joint implant is an important and serious complication, though the prevalence is low. Staphylococcus epidermidis is the most important pathogen involved in foreign-body infections. S. epidermidis is also a commensal that comprises a substantial part of the normal skin flora of humans. The possibility to demonstrate potential specific virulence markers may facilitate the interpretation of the bacteriological findings, as well as the clinical decision. The prevalence of the ica locus and insertion sequence IS256 by using polymerase chain reaction (PCR) among 32 clinical S. epidermidis isolates from prosthetic joint infections (PJIs) and 24 commensal isolates from nares and skin was investigated. Sixteen (50%) of the 32 PJI isolates harbored the ica operon compared with one-third of the commensal isolates obtained from the samples of the skin and nares of healthy individuals. The IS256 was demonstrated in 26 (81%) out of 32 PJI isolates. By contrast, IS256 was found in one of 24 commensal isolates. In conclusion, IS256 may be superior to the ica operon as a marker of the invasive capacity of S. epidermidis, since it was found in most of the PJI isolates, but rarely among commensals.

  • 49.
    Lindberg, Magnus
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Atopic dermatitis and gut microbiota2017In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 176, no 2, 297-298 p.Article in journal (Refereed)
  • 50.
    Littorin, C.
    et al.
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden .
    Hellmark, Bengt
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Nilsdotter-Augustinsson, Åsa
    Division of Infectious Diseases, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Infectious Diseases, County Council of Östergötland, Linköping, Sweden .
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Departments of Infectious Diseases and Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    In vitro activity of tedizolid and linezolid against Staphylococcus epidermidis isolated from prosthetic joint infections2017In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 36, no 9, 1549-1552 p.Article in journal (Refereed)
    Abstract [en]

    Prosthetic joint infections (PJIs) are rare but long-lasting and are serious complications without any spontaneous resolution, requiring additional surgery and long-term treatment with antibiotics. Staphylococci are the most important aetiological agents of PJIs, and among the coagulase-negative staphylococci Staphylococcus epidermidis is the most common. However, S. epidermidis often displays multidrug resistance (MDR), demanding additional treatment options. The objective was to examine the effectiveness of tedizolid and linezolid against S. epidermidis isolated from PJIs. The standard antibiotic susceptibility pattern of S. epidermidis (n = 183) obtained from PJIs was determined by disc diffusion test, and MIC was determined by Etest for tedizolid, linezolid, and vancomycin. Tedizolid displayed MIC values ranging from 0.094 to 0.5 mg/L (MIC50: 0.19 mg/L, MIC90: 0.38 mg/L), linezolid MIC values ranging from 0.25 to 2 mg/L (MIC50: 0.75 mg/L, MIC90: 1 mg/L), and vancomycin MIC values ranging from 0.5 to 3 mg/L (MIC50 and MIC90 both 2 mg/L). According to the disc diffusion test, 153/183 (84%) isolates were resistant to ≥3 antibiotic groups, indicating MDR. In conclusion, S. epidermidis isolates from PJIs were fully susceptible, and the MIC50 and MIC90 values for tedizolid were two- to four-fold dilution steps lower compared with linezolid. Tedizolid is not approved, and there are no reports of long-term treatment, but it may display better tolerability and fewer adverse effects than linezolid; it thus could be a possible treatment option for PJIs, alone or in combination with rifampicin.

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