| 1. |
- Ahlstrand, Erik, 1974-, et al.
(författare)
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Alteration of the colonization pattern of coagulase-negative staphylococci in patients undergoing treatment for hematological malignancy
- 2012
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - New York, USA : Springer. - 0934-9723 .- 1435-4373. ; 31:7, s. 1679-1687
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Ahlstrand, Erik, 1974-
(författare)
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Coagulase-negative staphylococci in hematological malignancy
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bacterial infections are common in hematological malignancy. Coagulase-negative staphylococci (CoNS) are among the most prevalent causes of bacteremia in patients with hematological malignancies.In this thesis, different aspects of CoNS in hematological malignancy have been studied in four papers:In paper 1, CoNS blood culture isolates from patients with hematological malignancies treated at the University Hospital of Örebro from 1980 to 2009 were revaluated for the presence of reduced sensitivity to glycopeptides. A high incidence of heterogeneous-intermediate glycopeptide resistance was observed and there was a trend towards increasing incidence of this phenotype over time.In paper 2, the colonization pattern of CoNS among patients undergoing intensive chemotherapy for hematological malignancy was investigated. A successive homogenization and an accumulation of CoNS phenotypes mutually present in a majority of included patients were demonstrated.In paper 3, a PCR method to determine the clinical significance of positive blood cultures of the CoNS species Staphylococcus epidermidis was evaluated. The test failed to discriminate bloodstream infection from blood culture contamination.Finally, in paper 4, the long-term molecular epidemiology of S. epidermidis blood culture isolates from patients with hematological malignancies was studied with multilocus sequence typing. A predominance of sequence type 2 was demonstrated during the entire 30 year study period.In conclusion, the results are consistent with that CoNS have established as important pathogens by its capacity to colonize the human skin, its ability to reside and spread in the hospital environment and its rapid adaptation to stressors such as antimicrobials.
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| 3. |
- Ahlstrand, Erik, 1974-, et al.
(författare)
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Evaluation of a PCR method to determine the clinical significance of blood cultures with Staphylococcus epidermidis in patients with hematological malignancies
- 2014
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley-Blackwell. - 0903-4641 .- 1600-0463. ; 122:6, s. 539-544
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 4. |
- Ahlstrand, Erik, et al.
(författare)
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Glycopeptide resistance in coagulase-negative staphylococci isolated in blood cultures from patients with hematological malignancies during three decades
- 2011
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 30:11, s. 1349-1354
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Ahlstrand, Erik, 1974-, et al.
(författare)
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Long-term molecular epidemiology of staphylococcus epidermidis blood culture isolates from patients with hematological malignancies
- 2014
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Ingår i: PLOS ONE. - San Francisco, USA : Public Library Science. - 1932-6203. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Asfaw Idosa, Berhane, 1977-, et al.
(författare)
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C10X polymorphism in the CARD8 gene is associated with bacteraemia
- 2014
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Ingår i: Immunity, inflammation and disease. - West Sussex, UK : John Wiley & Sons. - 2050-4527. ; 2:1, s. 13-20
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Bang, Charlotte Sahlberg, 1967-, et al.
(författare)
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Multiresistant uropathogenic extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are susceptible to the carbon monoxide releasing molecule-2 (CORM-2).
- 2014
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Ingår i: Microbial Pathogenesis. - London : Elsevier. - 0882-4010 .- 1096-1208. ; 66, s. 29-35
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
- Bang, Charlotte Sahlberg, 1967-, et al.
(författare)
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The antibacterial effect of nitric oxide against ESBL-producing uropathogenic E-coli is improved by combination with miconazole and polymyxin B nonapeptide
- 2014
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Ingår i: BMC Microbiology. - London : BioMed Central. - 1471-2180. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- Bjørkeng, Eva, et al.
(författare)
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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 systems
- 2011
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley-Blackwell. - 0903-4641 .- 1600-0463. ; 119:4-5, s. 247-258
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 10. |
- Björkqvist, Maria, 1959-, et al.
(författare)
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Colonization pattern of coagulase-negative staphylococci in preterm neonates and the relation to bacteremia
- 2010
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer. - 0934-9723 .- 1435-4373. ; 29:9, s. 1085-1093
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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