| 1. |
- Baltekin, Özden, et al.
(författare)
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Antibiotic susceptibility testing in less than 30 min using direct single-cell imaging
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 114:34, s. 9170-9175
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Tidskriftsartikel (refereegranskat)abstract
- The emergence and spread of antibiotic-resistant bacteria are aggravated by incorrect prescription and use of antibiotics. A core problem is that there is no sufficiently fast diagnostic test to guide correct antibiotic prescription at the point of care. Here, we investigate if it is possible to develop a point-of-care susceptibility test for urinary tract infection, a disease that 100 million women suffer from annually and that exhibits widespread antibiotic resistance. We capture bacterial cells directly from samples with low bacterial counts (10(4) cfu/mL) using a custom-designed microfluidic chip and monitor their individual growth rates using microscopy. By averaging the growth rate response to an antibiotic over many individual cells, we can push the detection time to the biological response time of the bacteria. We find that it is possible to detect changes in growth rate in response to each of nine antibiotics that are used to treat urinary tract infections in minutes. In a test of 49 clinical uropathogenic Escherichia coli (UPEC) isolates, all were correctly classified as susceptible or resistant to ciprofloxacin in less than 10 min. The total time for antibiotic susceptibility testing, from loading of sample to diagnostic readout, is less than 30 min, which allows the development of a point-of-care test that can guide correct treatment of urinary tract infection.
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| 2. |
- Carlsson, Markus, et al.
(författare)
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Inflammatory and circulatory effects of the reduction of endotoxin concentration in established porcine endotoxemic shock : a model of endotoxin elimination
- 2009
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 37:3, s. 1031-e4
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To study whether a reduction of the endotoxin load, once a generalized inflammatory state has been established, reduces the inflammatory response and endotoxin-induced effects on circulation, hypoperfusion, and organ dysfunction.Design:Prospective parallel-grouped placebo-controlled randomized interventional experimental study.Setting:University research unit.Subjects: Healthy pigs.Interventions:The animals were subjected to a continuous endotoxin infusion rate of either 4.0 or 0.063 µg endotoxin × kg-1 × h-1 for 1, 2, or 6 hours. The 1- and 2-hour infusion groups represented the applied therapy by a reduction of the endotoxin load of 5/6 and 2/3, respectively.Measurements and Main Results:During a 6-hour experiment, laboratory and physiologic parameters were recorded hourly in 26 anesthetized and mechanically ventilated pigs. Primary end point was to detect differences in tumor necrosis factor-[alpha] (TNF-[alpha]) concentration during the last 3 hours of the experiment. Despite the early reduction of the endotoxin load, no effect on TNF-[alpha] concentration was observed. Similarly, in circulatory parameters, such as mean arterial pressure and oxygen delivery, and in platelet count and renal function, no effects were noted. However, there was some improvement in pulmonary compliance and function as determined by Pao2, Paco2, and pH. These changes were associated with slight improvements in leukocyte response and capillary leakage.Conclusions:Termination of the endotoxin infusion represents an incontestable model of endotoxin concentration reduction. Endotoxin elimination strategies applied at the TNF-[alpha] peak or later will have very little or no effect on TNF-[alpha]–mediated toxicity. Nevertheless, there was an effect on the leukocyte response that was associated with an improvement in respiratory function and microcirculation, making it impossible to rule out fully the beneficial effect of this strategy. However, the effects were limited in relation to the magnitude of the endotoxin concentration reduction and the very early application of the antiendotoxin measure.
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| 3. |
- Fraenkel, Carl-Johan, et al.
(författare)
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The First Swedish Outbreak with VIM-2-Producing Pseudomonas aeruginosa, Occurring between 2006 and 2007, Was Probably Due to Contaminated Hospital Sinks
- 2023
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Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- Multidrug-resistant Pseudomonas aeruginosa is an increasing clinical problem worldwide. The aim of this study was to describe the first outbreak of a Verona integron-borne metallo-ss-lactamase (VIM)-2-producing P. aeruginosa strain in Sweden and its expansion in the region. A cluster of multidrug-resistant P. aeruginosa appeared at two neighbouring hospitals in 2006. The isolates were characterized by PCR, pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing. Patient charts, laboratory records, and hygiene routines were reviewed, and patients, staff, and the environment were screened. The investigation revealed a clonal outbreak of a VIM-2-producing P. aeruginosa strain belonging to the high-risk clonal complex 111, susceptible only to gentamicin and colistin. No direct contact between patients could be established, but most of them had stayed in certain rooms/wards weeks to months apart. Cultures from two sinks yielded growth of the same strain. The outbreak ended when control measures against the sinks were taken, but new cases occurred in a tertiary care hospital in the region. In conclusion, when facing prolonged outbreaks with this bacterium, sinks and other water sources in the hospital environment should be considered. By implementing proactive control measures to limit the bacterial load in sinks, the waterborne transmission of P. aeruginosa may be reduced.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Goscinski, Gunilla, et al.
(författare)
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Propensity to release endotoxin after two repeated doses of cefuroxime in an in vitro kinetic model : Higher release after the second dose
- 2007
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 60:2, s. 328-333
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To study endotoxin release from two strains of Escherichia coli after exposure to two repeated doses of cefuroxime in an in vitro kinetic model. Methods: Cefuroxime in concentrations simulating human pharmacokinetics was added to the bacterial solution with a repeated dose after 12 h. In another experiment, tobramycin was given concomitantly with the second dose of cefuroxime. Samples for viable counts and endotoxin analyses were drawn before the addition of antibiotics and at 2 and 4 h after each dose. Results: The propensity to release endotoxin, expressed as log10 endotoxin release (EU)/log10 killed bacteria, was higher after the second than after the first dose, 0.80 ± 0.04 and 0.65 ± 0.01, respectively, in the ATCC strain and 0.80 ± 0.04 and 0.65 ± 0.02, respectively, in the clinical strain (P < 0.001). Endotoxin was released earlier after the second dose (P < 0.001). Addition of tobramycin at the second dose reduced the endotoxin release in comparison with that of cefuroxime alone (P < 0.001). Conclusions: The propensity to liberate endotoxin is higher after the second dose of cefuroxime than after the first, resulting in a higher release of endotoxin than expected from bacterial count. The release after the second dose can be reduced by the addition of tobramycin.
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| 8. |
- Goscinski, Gunilla, et al.
(författare)
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Release of SpeA from Streptococcus pyogenes after exposure to penicillin : dependency on dose and inhibition by clindamycin
- 2006
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 38:11-12, s. 983-987
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Tidskriftsartikel (refereegranskat)abstract
- The amount and time course of SpeA release from group A streptococci (GAS) was studied at different starting inoculae after exposure to different doses of penicillin, clindamycin or a combination of the 2. The release was related to the bacterial concentration and killing rate. A clinical GAS strain was exposed to benzylpenicillin, 2 and 1000 × MIC, clindamycin, 2 and 32 × MIC, or combinations of the 2. Samples for viable counts and SpeA analyses were drawn before and after the addition of antibiotics and at 3, 6 and 24 h. The SpeA release was higher at low than at high concentrations of penicillin and the combination (both, p < 0.05). The addition of clindamycin to penicillin reduced SpeA production at both concentrations (p < 0.01). Most SpeA was released before 3 h, and for penicillin and the combination, the amount correlated to the number of killed bacteria during this period (r = 0.50; p < 0.05). A positive correlation was found between the inoculum size and the SpeA concentration at time zero (r = 0.54; p < 0.05). The SpeA concentration was dependent on the initial number of bacteria, the class of antibiotic, the dose of penicillin and the killing rate.
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| 9. |
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| 10. |
- Granström, Brith, et al.
(författare)
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Return to work after oropharyngeal cancer treatment-Highlighting a growing working-age population
- 2020
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Ingår i: Head and Neck-Journal for the Sciences and Specialties of the Head and Neck. - : Wiley. - 1043-3074 .- 1097-0347. ; 42:8, s. 1893-1901
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Tidskriftsartikel (refereegranskat)abstract
- Background To describe the frequency of patients returning to work after treatment for oropharyngeal cancer and to identify predictors and physical barriers that might interfere with the return to work process. Methods Cross-sectional study including 295 patients. Data were collected regarding work/sick leave situation at 1 month before diagnosis and 15 months after diagnosis. The situation before diagnosis was retrospectively recalled by the patients. Two subscales and two single items from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-H&N35 were used. Data were analyzed with multivariate logistic regression. Results Fifteen months after diagnosis, 212 patients (72%) were working. To be working 15 months after diagnosis was associated with working before diagnosis. Swallowing difficulties, problems talking on the telephone, and physical appearance were negatively associated with returning to work. Conclusions The large number of individuals returning to work is encouraging for patients diagnosed with oropharyngeal cancer.
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| 11. |
- Hanslin, Katja, et al.
(författare)
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The impact of the systemic inflammatory response on hepatic bacterial elimination in experimental abdominal sepsis
- 2019
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Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bacterial translocation from the gut has been suggested to induce a systemic inflammatory response syndrome (SIRS) and organ dysfunction. The liver has a pivotal role in eliminating circulating bacteria entering from the gut. We investigated whether pre-existing inflammation affects hepatic bacterial elimination.METHODS: Fifteen anaesthetised piglets were infused with E. coli in the portal vein for 3 h. The naive group (n = 6) received the bacterial infusion without endotoxin exposure. SIRS (SIRS group, n = 6) was induced by endotoxin infusion 24 h before the bacterial infusion. For effects of anaesthesia, controls (n = 3) received saline instead of endotoxin for 24 h. Bacterial counts and endotoxin levels in the portal and hepatic veins were analysed during bacterial infusion.RESULTS: The bacterial killing rate was higher in the naive group compared with the SIRS group (p = 0.001). The ratio of hepatic to portal venous bacterial counts, i.e. the median bacterial influx from the splanchnic circulation, was 0.06 (IQR 0.01-0.11) in the naive group and 0.71 (0.03-1.77) in the SIRS group at 3 h, and a magnitude lower in the naive group during bacteraemia (p = 0.03). Similar results were seen for hepatic endotoxin elimination. Peak log tumour necrosis factor alpha was higher in the naive 4.84 (4.77-4.89) vs. the SIRS group 3.27 (3.26-3.32) mg/L (p < 0.001).CONCLUSIONS: Our results suggest that hepatic bacterial and endotoxin elimination is impaired in pigs with pre-existing SIRS while the inflammatory response to bacterial infusion is diminished. If similar mechanisms operate in human critical illness, the hepatic elimination of bacteria from the gut could be impaired by SIRS.
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| 12. |
- Heydecke, Anna, et al.
(författare)
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Limitations in predicting reduced susceptibility to third generation cephalosporins in Escherichia coli based on whole genome sequence data
- 2023
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:11, s. e0295233-e0295233
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Tidskriftsartikel (refereegranskat)abstract
- Prediction of antibiotic resistance from whole genome sequence (WGS) data has been proposed. However, the performance of WGS data analysis for this matter may be influenced by the resistance mechanism’s biology. This study compared traditional antimicrobial susceptibility testing with whole genome sequencing for identification of extended-spectrum beta-lactamases (ESBL) in a collection of 419 Escherichia coli isolates. BLASTn-based prediction and read mapping with srst2 gave matching results, and in 381/419 (91%) isolates WGS was congruent with phenotypic testing. Incongruent results were grouped by potential explanations into biological-related and sequence analysis-related results. Biological-related explanations included weak ESBL-enzyme activity (n = 4), inconclusive phenotypic ESBL-testing (n = 4), potential loss of plasmid during subculturing (n = 7), and other resistance mechanisms than ESBL-enzymes (n = 2). Sequence analysis-related explanations were cut-off dependency for read depth (n = 5), too stringent (n = 3) and too loose cut-off for nucleotide identity and coverage (n = 13), respectively. The results reveal limitations of both traditional antibiotic susceptibility testing and sequence-based resistance prediction and highlight the need for evidence-based standards in sequence analysis.
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| 13. |
- Karlsson, Philip A., et al.
(författare)
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Molecular Characterization of Multidrug-Resistant Yersinia enterocolitica From Foodborne Outbreaks in Sweden
- 2021
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Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The foodborne pathogen Yersinia enterocolitica causes gastrointestinal infections worldwide. In the spring of 2019, the Swedish Public Health Agency and Statens Serum Institut in Denmark independently identified an outbreak caused by Yersinia enterocolitica 4/O:3 that after sequence comparison turned out to be a cross-border outbreak. A trace-back investigation suggested shipments of fresh prewashed spinach from Italy as a common source for the outbreak. Here, we determined the genome sequences of five Y. enterocolitica clinical isolates during the Swedish outbreak using a combination of Illumina HiSeq short-read and Nanopore Technologies’ MinION long-read whole-genome sequencing. WGS results showed that all clinical strains have a fully assembled chromosome of approximately 4.6 Mbp in size and a 72-kbp virulence plasmid; one of the strains was carrying an additional 5.7-kbp plasmid, pYE-tet. All strains showed a high pathogen probability score (87.5%) with associated genes for virulence, all of which are closely related to an earlier clinical strain Y11 from Germany. In addition, we identified a chromosomally encoded multidrug-resistance cassette carrying resistance genes against chloramphenicol (catA1), streptomycin (aadA1), sulfonamides (sul1), and a mercury resistance module. This chromosomally encoded Tn2670 transposon has previously been reported associated with IncFII plasmids in Enterobacteriaceae: a Shigella flexneri clinical isolate from Japan in 1950s, a Klebsiella pneumoniae outbreak from Australia in 1997, and Salmonella enterica serovar Typhimurium. Interestingly, we identified an additional 5.7-kbp plasmid with tetB (encoding an ABC transporter), Rep, and its own ORI and ORIt sites, sharing high homology with small tetB-Rep plasmids from Pasteurellaceae. This is the first time that Tn2670 and Pasteurellaceae plasmids have been reported in Y. enterocolitica. Taken together, our study showed that the Swedish Y. enterocolitica outbreak strains acquired multi-antibiotic and metal-resistance genes through horizontal gene transfer, suggesting a potential reservoir of intraspecies dissemination of multidrug-resistance genes among foodborne pathogens. This study also highlights the concern of food-chain contamination of prewashed vegetables as a perpetual hazard against public health.
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| 14. |
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| 15. |
- Lindblad, Marie, et al.
(författare)
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Infection control measures to stop the spread of sequence type 15 OXA-23-producing Acinetobacter baumannii in a Swedish Burn Center
- 2022
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Ingår i: Burns. - : Elsevier. - 0305-4179 .- 1879-1409. ; 48:8, s. 1940-1949
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To describe the course of the outbreak and infection control measures to stop the spread of sequence type 15 OXA-23-producing Acinetobacter baumannii in the Burn Center of Uppsala University Hospital, between November 2014 and the end of April 2015.METHODS: Compliance with hand hygiene, dress code, and cleaning routines were reviewed, the ward's environment was systematically investigated to identify potential environmental sources. Sampling routines for A. baumannii, from patients and environment, were established, and the epidemiological relationship was analysed for all carbapenem-resistant A. baumannii isolates using arbitrarily primed polymerase chain reaction (AP-PCR) and pulsed-field gel electrophoresis (PFGE).RESULTS: A total of 54 patients were treated at the burn intensive care unit during the studied, approximately five months period, and an OXA-23-producing A. baumannii was isolated from nine patients (9/54, 17%), whereof two died (2/9, 22.2%). All isolates shared identical PFGE-genotype patterns and belonged to sequence type 15; AP-PCR was eligible for prompt epidemiological investigations.CONCLUSIONS: Higher awareness and increased compliance with hand hygiene and dress code as well as intensified cleaning protocols of the environment and equipment were successfully established and likely to have led to stop the spread of sequence type 15 OXA-23-producing Acinetobacter baumannii.
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| 16. |
- Lindblad, Marie, et al.
(författare)
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Ultraviolet-C decontamination of a hospital room : Amount of UV light needed
- 2020
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Ingår i: Burns. - : ELSEVIER SCI LTD. - 0305-4179 .- 1879-1409. ; 46:4, s. 842-849
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Our primary aim was to investigate, using a commercial radiometer, the ultraviolet C (UVC) dose received in different areas in a burn ICU ward room after an automated UVC decontamination. The secondary aim was to validate a disposable UVC-dose indicator with the radiometer readings. Methods: Disposable indicators and an electronic radiometer were positioned in ten different positions in a burn ICU room. The room was decontaminated using the Tru-D (TM)-UVC device. Colour changes of the disposable indicators and radiometer readings were noted and compared. Experiment was repeated 10 times. Findings: The UVC radiation received in different areas varied between 15.9 mJ/cm(2) and 1068 mJ/cm(2) (median 266 mJ/cm(2)). Surfaces, at shorter distances and in the direct line of sight of the UVC device showed statistically significant higher UVC doses than surfaces in the shadow of equipment (p=0.019). The UVC-dose indicator's colour change corresponded with the commercially radiometer readings. Conclusions: The amount of UVC radiation that is received in surfaces depends on their locations in the room (ie distance from the UVC emitter) and whether any objects shadow the light. In this study we suggest that quality controls should be used to assure that enough UVC radiation reaches all surfaces. (C) 2019 The Authors. Published by Elsevier Ltd.
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| 17. |
- Lytsy, Birgitta, et al.
(författare)
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The first major extended-spectrum beta-lactamase outbreak in Scandinavia was caused by clonal spread of a multiresistant Klebsiella pneumoniae producing CTX-M-15
- 2008
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 116:4, s. 302-8
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Tidskriftsartikel (refereegranskat)abstract
- Between May and December 2005, 64 multidrug-resistant isolates of Klebsiella pneumoniae were detected from patients admitted to Uppsala University Hospital. This represented a dramatic increase in ESBL-producing K. pneumoniae compared to previous years. To investigate the epidemiology and to characterize the resistance mechanisms of the isolates, a study was initiated. Antibiotic susceptibility was determined by means of the Etest and the disc diffusion method. Extended-spectrum beta-lactamase (ESBL) production was identified by clavulanic acid synergy test and confirmed with PCR amplification followed by DNA sequencing. DNA profiles of the isolates were examined with pulsed-field gel electrophoresis (PFGE). All isolates were resistant or exhibited reduced susceptibility to cefadroxil, cefuroxime, cefotaxime, ceftazidime, aztreonam, piperacillin/tazobactam, ciprofloxacin, tobramycin, and trimethoprim-sulfamethoxazole. They produced ESBL of the CTX-M-15 type, and the involvement of a single K. pneumoniae clone was shown. This is the first major clonal outbreak of multiresistant ESBL-producing K. pneumoniae in Scandinavia. The outbreak demonstrates the epidemic potential of enterobacteria containing ESBLs of the CTX-M type, even in a country with a relatively low selective pressure and a low prevalence of multiresistant bacteria.
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| 18. |
- Melki, Vilyam, et al.
(författare)
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Effect of Glyceryl Trinitrate on Staphylococcus aureus Growth and Leukocyte Activation during Simulated Extracorporeal Circulation
- 2014
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Ingår i: The thoracic and cardiovascular surgeon. - : Georg Thieme Verlag KG. - 0171-6425 .- 1439-1902. ; 62:5, s. 402-408
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Tidskriftsartikel (refereegranskat)abstract
- Background Previously, nitric oxide has been shown to possess antimicrobial effects. In this study, we aim to test the effect of glyceryl trinitrate (GTN) on Staphylococcus aureus growth during simulated extracorporeal circulation (SECC) and also to examine the effect of S. aureus, alone and in combination with GTN, on activation markers of the innate immune system during SECC. Methods In an in vitro system of SECC, we measured GTN-induced changes in markers of leukocyte activation in whole blood caused by S. aureus infestation, as well as the effect of GTN on S. aureus growth. Results GTN had no effect on S. aureus growth after 240 minutes SECC. Staphylococcus aureus reduced the expression of granulocyte Fc gamma-receptor CD32 but stimulated the expression of monocyte CD32. Staphylococcus aureus stimulated expression of some leukocyte adhesion key proteins, activation marker CD66b, lipopolysaccharide-receptor CD14, and C3b-receptor CD35. Staphylococcus aureus and GTN addition induced significant increases in monocyte CD63 (lysosomal granule protein) levels. Conclusion GTN does not affect S. aureus growth during SECC and has no effect on SECC-induced leukocyte activation.
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| 19. |
- Melki, Vilyam, 1972-, et al.
(författare)
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Enhanced growth of Staphylococcus aureus after nitric oxide supplementation during simulated extracorporeal circulation
- 2010
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Ingår i: The thoracic and cardiovascular surgeon. - : Georg Thieme Verlag KG. - 0171-6425 .- 1439-1902. ; 58:2, s. 81-85
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several factors contribute to postoperative bacterial infections in cardiac surgery. Long operation times and the use of extracorporeal circulation increase the risk of infection. Nitric oxide has been shown to possess a broad spectrum antimicrobial effect. Methods: In this study, we investigated the effect of nitric oxide on S. aureus growth in whole blood during simulated extracorporeal circulation. Results: S. aureus growth increased 6.2-fold after 180 min SECC in the presence of nitric oxide. Leukocyte counts remained unchanged without any differences between the groups. We observed a steady increase in markers of oxidative stress and activity of the innate immune system. Myeloperoxidase levels increased 8-fold, and C3a and terminal complement complex by 2-fold after 180 min. Conclusion: S. aureus growth is not due to the effect of nitric oxide on the innate immune system but from its effect on the bacteria itself. It has been shown that nitric oxide stimulates the expression of inducible lactate dehydrogenase, specific to S. aureus, which improves its resistance to oxidative stress, and may give S. aureus a survival advantage resulting in increased growth.
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| 20. |
- Mezger, Anja, et al.
(författare)
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A General Method for Rapid Determination of Antibiotic Susceptibility and Species in Bacterial Infections
- 2015
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Ingår i: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 53:2, s. 425-432
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Tidskriftsartikel (refereegranskat)abstract
- To ensure correct antibiotic treatment and reduce the unnecessary use of antibiotics, there is an urgent need for new rapid methods for species identification and determination of antibiotic susceptibility in infectious pathogenic bacteria. We have developed a general method for the rapid identification of the bacterial species causing an infection and the determination of their antibiotic susceptibility profiles. An initial short cultivation step in the absence and presence of different antibiotics was combined with sensitive species-specific padlock probe detection of the bacterial target DNA to allow a determination of growth (i.e., resistance) and no growth (i.e., susceptibility). A proof-of-concept was established for urinary tract infections in which we applied the method to determine the antibiotic susceptibility profiles of Escherichia coli for two drugs with 100% accuracy in 3.5 h. The short assay time from sample to readout enables fast appropriate treatment with effective drugs and minimizes the need to prescribe broad-spectrum antibiotics due to unknown resistance profiles of the treated infection.
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| 21. |
- Nilsson, Kenneth, Docent, 1953-, et al.
(författare)
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Impact of prolonged storage of clinical samples at 4 degrees C on the recovery of dermatophytes by culture or PCR analysis
- 2019
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Ingår i: Journal de Mycologie Médicale. - : MASSON EDITEUR. - 1156-5233 .- 1773-0449. ; 29:1, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Dermatophytes are common pathogens in superficial mycoses that are routinely identified by culture or PCR analysis of freshly collected skin, nail or hair specimens. Although clinical samples are normally processed without delay, practical or research issues may necessitate sample storage until later analysis. However, the influence of extended sample storage on the ability to recover fungi by culture vs. PCR analysis has not been specifically studied. Here, a total of 172 dermatological samples collected from 2013-2015 were examined before and after refrigerated storage at 4 degrees C for 10.2-32.3 (mean 25.6) months. By culture, 35% of the dermatophyte-containing fresh samples remained positive at reexamination. At species level, only 19% of initially Trichophyton rubrum-positive samples yielded a positive result after refrigeration, whereas few samples containing Trichophyton violaceum, Microsporum canis or Microsporum audouinii remained culture-positive. Using PCR, 76% of dermatophyte DNA-positive fresh samples were still positive at re-analysis. Notably, 92% of the samples targeted by the T. rubrum DNA primer remained positive after storage. Hence, PCR analysis is more favourable than cultivation with regard to the detectability of dermatophytes in long-term refrigerated clinical samples.
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| 22. |
- Osbjer, Kristina, et al.
(författare)
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Detection of Campylobacter in human and animal field samples in Cambodia
- 2016
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 124:6, s. 508-515
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Tidskriftsartikel (refereegranskat)abstract
- Campylobacter are zoonotic bacteria and a leading cause of human gastroenteritis worldwide with Campylobacter jejuni and C. coli being the most commonly detected species. The aim of this study was to detect Campylobacter in humans and livestock (chickens, ducks, pigs, cattle, water buffalo, quail, pigeons and geese) in rural households by routine culturing and multiplex PCR in faecal samples frozen before analysis. Of 681 human samples, 82 (12%) tested positive by PCR (C. jejuni in 66 samples and C. coli in 16), but none by routine culture. Children were more commonly Campylobacter positive (19%) than adult males (8%) and females (7%). Of 853 livestock samples, 106 (12%) tested positive by routine culture and 352 (41%) by PCR. Campylobacter jejuni was more frequent in chickens and ducks and C. coli in pigs. In conclusion, Campylobacter proved to be highly prevalent by PCR in children (19%), ducks (24%), chickens (56%) and pigs (72%). Routine culturing was insufficiently sensitive in detecting Campylobacter in field samples frozen before analysis. These findings suggest that PCR should be the preferred diagnostic method for detection of Campylobacter in humans and livestock where timely culture is not feasible.
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| 23. |
- Schönning, Caroline, et al.
(författare)
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Legionellosis acquired through a dental unit : a case study
- 2017
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Ingår i: Journal of Hospital Infection. - : Elsevier BV. - 0195-6701 .- 1532-2939. ; 96:1, s. 89-92
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Tidskriftsartikel (refereegranskat)abstract
- In 2012, an elderly immunocompromised man died from legionellosis at a hospital in Uppsala, Sweden. The patient had visited a dental ward at the hospital during the incubation period. Legionella spp. at a concentration of 2000 colony-forming units/L were isolated from the cupfiller outlet providing water for oral rinsing. Isolates from the patient and the dental unit were Legionella pneumophila serogroup 1, subgroup Knoxville and ST9. Pulsed-field gel electrophoresis and whole-genome sequencing strongly suggested that the isolates were of common origin. This report presents one of few documented cases of legionellosis acquired through a dental unit.
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| 24. |
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| 25. |
- Sjölund, Maria, et al.
(författare)
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Persistence of resistant Staphylococcus epidermidis after single course of clarithromycin
- 2005
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Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 11:9, s. 1389-1393
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Tidskriftsartikel (refereegranskat)abstract
- We examined how a common therapy that includes clarithromycin affects normally colonizing Staphylococcus epidermidis. Samples from the nostrils of 5 patients receiving therapy were collected before, immediately after, 1 year after, and 4 years after treatment. From each patient and sample, S. epidermidis strains were isolated and analyzed for clarithromycin susceptibility and presence of the erm(C) gene. We show that macrolide-resistant strains of S. epidermidis were selected during therapy and that the same resistant strain may persist for 4 years, in the absence of further antimicrobial treatment.
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| 26. |
- Skorup, Paul, et al.
(författare)
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Dynamics of Endotoxin, Inflammatory Variables, and Organ Dysfunction After Treatment With Antibiotics in an Escherichia coli Porcine Intensive Care Sepsis Model
- 2018
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 46:7, s. e634-e641
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the dynamics of antibiotic-induced endotoxin liberation and inflammatory response in vivo in a clinically relevant large animal intensive care sepsis model and whether the addition of an aminoglycoside to beta-lactam antibiotic affects these responses.Design: Prospective, placebo-controlled interventional experimental study.Setting: University research unit.Subjects: Thirty-six healthy pigs administered Escherichia coli as a 3-hour infusion.Interventions: After 2 hours, during E. coli infusion, the animals were exposed to cefuroxime alone, the combination of cefuroxime and tobramycin, or saline.Measurements and Main Results: Plasma endotoxin, interleukin-6, tumor necrosis factor-alpha, leucocytes, and organ dysfunction were recorded for 4 hours after antibiotic treatment, and differences to the values before treatment were calculated. In vitro experiments were performed to ascertain whether endotoxin is released during antibiotic-induced bacterial killing of this E. coli strain. Despite differences between the treatment arms in vitro, no differences in plasma endotoxin were observed in vivo. Antibiotic-treated animals demonstrated a higher interleukin-6 response (p < 0.001), greater leucocyte activation (p < 0.001), and more pronounced deterioration in pulmonary static compliance (p < 0.01) over time than controls. Animals treated with the combination showed a trend toward less inflammation.Conclusions: Treatment with antibiotics may elicit an increased inflammatory interleukin-6 response that is associated with leucocyte activation and pulmonary organ dysfunction. No observable differences were detected in plasma endotoxin concentrations. The reduction in cefuroxime-induced endotoxin release after the addition of an aminoglycoside in vitro could not be reproduced in this model.
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| 27. |
- Smolle, C, et al.
(författare)
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Effectiveness of automated ultraviolet-C light for decontamination of textiles inoculated with Enterococcus faecium.
- 2018
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Ingår i: Journal of Hospital Infection. - : Elsevier BV. - 0195-6701 .- 1532-2939. ; 98:1, s. 102-104
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Tidskriftsartikel (refereegranskat)abstract
- Healthcare textiles are increasingly recognized as potential vehicles for transmission of hospital-acquired infections. This study tested the ability of an automated ultraviolet-C (UV-C) room disinfection device (Tru-D Smart UV-C) to decontaminate textiles inoculated with Enterococcus faecium in a clinical setting. Contaminated polycotton (50/50 polyester/cotton) swatches were distributed to predefined locations in a ward room and exposed to UV-C light. UV-C decontamination reduced E. faecium counts by a mean log10 reduction factor of 1.37 (all P = 0.005, Wilcoxon signed rank test). UV-C decontamination may be a feasible adjunctive measure to conventional laundering to preserve the cleanliness of healthcare textiles in ward rooms.
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| 28. |
- Starlander, Gustaf, et al.
(författare)
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The first Swedish outbreak with VIM-2-producing Pseudomonas aeruginosa was prolonged and probably due to contaminated hospital sinks
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa is an increasing clinical problem worldwide. VIM-2 is the predominant enzyme, and it has been linked to several outbreaks. During the spring of 2006, a cluster of patients were colonized or infected with multiresistant Pseudomonas aeruginosa at two neighbouring hospitals in southeast Sweden.Aim: To describe the first documented outbreak of a VIM-2-producing P. aeruginosa strain in Sweden.Methods: The isolates were characterized with PCR, pulse-field gel electrophoresis (PFGE), and whole genome sequencing. Patient charts, laboratory records and hygiene routines were reviewed, and patients, staff and the environment were screened.Findings: The investigation revealed that it was a clonal outbreak of a VIM-2-producing P. aeruginosa strain susceptible only to gentamicin and colistin. It belonged to the high-risk clonal complex 111. No direct contact between patients could be established, but most of them had stayed in the same room/wards with weeks to months apart. Environmental cultures from two sinks yielded growth of P. aeruginosa with the same PFGE-pattern as the patient isolates. The outbreak ended when control measures against the sinks were taken.Conclusions: Contaminated hospital sinks were the probable reservoir in the first nosocomial outbreak of MBL-producing P. aeruginosa in Sweden. When facing prolonged outbreaks with this bacterium, sinks and other water sources in the hospital environment should be considered. By implementing proactive control measures to limit the bacterial load in sinks and plumbing systems, the waterborne transmission of P. aeruginosa could probably be reduced.
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| 29. |
- Sütterlin, Susanne, et al.
(författare)
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Coresistance to quaternary ammonium compounds in extended-spectrum beta-lactamase-producing Escherichia coli
- 2020
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Ingår i: International Journal of One Health. - India. - 2455-8931. ; 6:2, s. 134-142
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aim: Extended-spectrum β-lactamases (ESBL) in Escherichia coli constitutes one of the major threats to modern medicine, and the increasing pollution with quaternary ammonium compounds (QACs) has been suspected to contribute to the spread of ESBL-producing bacteria. The aim of the study was to investigate ESBLA and ESBLM-C-producing E. coli isolates for their coresistance to QACs and their phylogeny isolated from a Swedish University Hospital.Materials and Methods: Coresistance in E. coli with production of ESBL enzymes of the type blaCTX-M (n=23) was compared to E. coli producing AmpC type ESBL enzymes blaCMY and blaDHA (n=27). All isolates were tested for susceptibility to antibiotics and QACs, and high-quality whole-genome sequences were analyzed for resistance determinants.Results: The plasmid-borne small multidrug resistance (SMR) efflux pump sugE(p) was solely present in blaCMY-producing E. coli (n=9), within the same genetic environment blaCMY–blc–sugE(p). Other small multidrug efflux pumps were found without association for ESBL-types: emrE (n=5) and the truncated qacEΔ1 (n=18).Conclusion: Coresistance of ESBL enzymes and SMR efflux pumps in E. coli was common and might indicate that other substances than antibiotics contribute to the spread and emergence of antibiotic resistance.
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| 30. |
- Sütterlin, Susanne, et al.
(författare)
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Distribution of class 1 integrons in historic and contemporary collections of human pathogenic Escherichia coli
- 2020
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:6
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Tidskriftsartikel (refereegranskat)abstract
- Integrons play a major role in the evolution and spread of antimicrobial resistance in human pathogens, including Escherichia coli. This study describes the occurrence of class 1 integrons in human pathogenic E. coli, in three isolate collections involving three periods from the last 100 years (i) the Murray collection (n = 58 bacteria isolated from the 1910s to 1940s); (ii) the E. coli reference (ECOR) collection (n = 37 isolates mainly from the 1980s); and (iii) a recently assembled collection (n = 88 isolates obtained in 2016). High-quality whole genome sequences (WGSs) were available for all isolates. Integrons were detected in the WGSs with the program IntegronFinder and the results compared with three established methods: (i) polymerase chain reaction detection of the integrase gene; (ii) BLAST searching using draft genomes; and (iii) mapping of short reads. No integrons were found in any of the Murray Collection isolates; however, integrons were present in 3% of the isolates from ECOR collection, assembled in the 1980s, and 26% of the isolates from the 2010s. Similarly, antimicrobial resistance determinants were not present in the Murray Collection isolates, whereas they were present in 19% of the ECOR Collection isolates and in 55% of the isolates obtained in during the 2010s.
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| 31. |
- Sütterlin, Susanne, et al.
(författare)
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Effects of Silver-based Wound Dressings on the Bacterial Flora in Chronic Leg Ulcers and Its Susceptibility In vitro to Silver
- 2012
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 92:1, s. 34-39
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Tidskriftsartikel (refereegranskat)abstract
- Silver-based dressings have been used extensively in wound management in recent years, but data on their antimicrobial activity in the clinical setting are limited. In order to explore their effects on chronic leg ulcer flora, 14 ulcers were cultured after at least 3 weeks treatment with Aquacel Ag (R) or Acticoat (R). Phenotypic and genetic silver resistance were investigated in a total of 56 isolates. Silver-based dressings had a limited effect on primary wound pathogens, which were present in 79% of the cultures before, and 71% after, treatment. One silver-resistant Enterobacter cloacae strain was identified (silver nitrate minimal inhibitory concentration (MIC)>512 mg/l, positive for silE, silS and silP). Further studies in vitro showed that inducible silver-resistance was more frequent in Enterobacteriaceae with cephalosporin-resistance and that silver nitrate had mainly a bacteriostatic effect on Staphylococcus aureus. Monitoring of silver resistance should be considered in areas where silver is used extensively.
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| 32. |
- Tano, Eva, et al.
(författare)
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Evaluation of three swab transport systems for the maintenance of clinically important bacteria in simulated mono- and polymicrobial samples
- 2011
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 119:3, s. 198-203
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Tidskriftsartikel (refereegranskat)abstract
- In this study, three swab transport systems were evaluated: M40 Transystem, Amies broth with a relatively new type of swab (both Copan Diagnostics, Corona, CA, USA), and SSI transportmedium (Statens Serum Institut, Copenhagen Denmark). The CLSI M40-A standard procedures and 11 culture collection strains were used. The transport systems were tested at room temperature for holding times of 0, 24, and 48 h, and both mono- and polymicrobial samples were included. After 24 h of simulated transportation, all systems were able to maintain the viability of all organisms tested. SSI transportmedium exhibited the lowest maintaining ability, whereas the two Copan systems were the most growth-promoting system. In polymicrobial samples, this latter feature was a problem. At 48 h, no transport system could maintain the viability of all strains, and the recovery rates differed depending on organism and device. The species most difficult to recover in all the three systems was Neisseria gonorrhoeae. When selecting a swab transport system, consideration must be given to the sample type, the conditions that prevail locally, and the performance in the clinical setting.
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| 33. |
- Tano, Eva, et al.
(författare)
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Level of decontamination after washing textiles at 60°C or 70°C followed by tumble drying
- 2014
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Ingår i: Infection Ecology & Epidemiology. - : Informa UK Limited. - 2000-8686. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Several major outbreaks in healthcare facilities have occurred with the emergence of multi-resistant bacteria. A possible route for dissemination is the hospital textiles and inadequate laundering of them. The aim of this study was to develop an easy-to-use method for simulating the laundering process of hospital textiles, and thereafter apply the method when evaluating the decontaminating efficacy of two different washing temperatures.METHODS: The laundering process, including tumble drying, took place at two professional laundries. Enterococcus faecium was used as bioindicator.RESULTS: The results showed that a lowering of the washing temperature from 70°C to 60°C did not affect the decontamination efficacy; the washing cycle alone reduced the number of bacteria with 3-5 log10 CFU, whereas the following tumble drying reduced the bacterial numbers with another 3-4 log10 CFU, yielding the same final result independent of washing temperature. Without tumble drying, there was an obvious risk of adding non-fermenting gram-negative bacteria to the fabric. These bacteria originated from the washing cycle.CONCLUSION: A simple method to simulate hospital laundering was developed. To save energy, it is possible to use a washing temperature of 60°C, but the washing cycle should be followed by tumble drying, and the whole laundering process needs to be monitored to maintain sufficient textile hygiene.
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| 34. |
- Tano, Eva, 1957-, et al.
(författare)
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Overrepresentation of the toxic shock syndrome toxin-1 gene among eldery men with bacteremic bone and joint infections caused by Staphylococcus aureus
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Staphylococcus aureus is a leading causative agent of Gram-positive septicemia. In recent years, there have been indications that both the severity and the number of staphylococcal infections have increased. In order to study the presence of genes encoding exfoliative toxins (eta/etb), Panton-Valentine leucocidin (lucS-PV-lucF-PV), and toxic shock syndrome toxin-1 (tst) in invasive isolates over time and space, 528 blood isolates of S. aureus collected during the years 2000-2012 from two Swedish university hospitals were investigated. Age, gender and diagnosis of patients were registered, and the antibiotic susceptibility was tested. Toxin genes were detected with PCR, and the genetic relatedness was assessed with pulsed-field gel electrophoresis and whole genome sequencing. Blood cultures positive for S. aureus increased with 57.6% during the study period. Ninety-six of the isolates (18.2%) carried 97 toxin genes (one isolate carried both eta and etb). All isolates except one (PVL-producing and methicillin-resistant) were fully susceptible to the tested antibiotics. Most frequent was tst (79.4%), followed by eta (12.4%), lucS-PV-lucF-PV (7.2%), and etb (1.0%). The typical tst-positive patient was a male aged 55-74 years with a bone or joint infection. Tst-positive isolates exhibited a clear clonality, and that was independent of year and hospital. Most common was ST30-t012. To summarize, bacteremia caused by S. aureus increased during the study period, but the frequency of four important staphylococcal toxins and the antibiotic susceptibility remained low. To screen for these toxins is only cost-effective in Swedish patients with a typical clinical presentation.
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| 35. |
- Tano, Eva, 1957-
(författare)
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Survival of infectious agents and detection of their resistance and virulence factors
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the first study, three different transport systems for bacteria were evaluated. The CLSI M40-A guideline was used to monitor the maintenance of both mono- and polymicrobial samples during a simulated transportation at room temperature that lasted 0-48 h. All systems were able to maintain the viability of all organisms for 24 h, but none of them could support all tested species after 48 h. The most difficult species to recover was Neisseria gonorrhoeae, and in polymicrobial samples overgrowth was an observed problem. The aim of the second study was to study the presence of TSST-1 and three other important toxin genes in invasive isolates of Staphylococcus aureus collected during the years 2000-2012 at two tertiary hospitals. The genes encoding the staphylococcal toxins were detected by PCR, and whole-genome sequencing was used for analyzing the genetic relatedness between isolates. The results showed that the most common toxin was TSST-1, and isolates positive for this toxin exhibited a clear clonality independent of year and hospital. The typical patient was a male aged 55-74 years and with a bone or a joint infection. The third study was a clinical study of the effect of silver-based wound dressings on the bacterial flora in chronic leg ulcers. Phenotypic and genetic silver-resistance were investigated before and after topical silver treatment, by determining the silver nitrate MICs and by detecting sil genes with PCR. The silver-based dressings had a limited effect on primary wound pathogens, and the activity of silver nitrate on S. aureus was mainly bacteriostatic. A silver-resistant Enterobacter cloacae strain was identified after only three weeks of treatment, and cephalosporin-resistant members of the Enterobacteriaceae family were relatively prone to developed silver-resistance after silver exposure in vitro. The last study was undertaken in order to develop an easy-to-use method for simulating the laundering process of hospital textiles, and apply the method when evaluating the decontaminating efficacy of two different washing temperatures. The laundering process took place at professional laundries, and Enterococcus faecium was used as a bioindicator. The results showed that a lowering of the washing temperature from 70°C to 60°C did not affect the decontamination efficacy; the washing cycle alone reduced the number of bacteria with 3-5 log10 CFU, whereas the following tumble drying reduced the bacterial numbers with another 3-4 log10 CFU, yielding the same final result independent of the washing temperature. To ensure that sufficient textile hygiene is maintained, the whole laundering process needs to be monitored. The general conclusion is that all developmental work in the bacterial field requires time and a large strain collection.
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| 36. |
- Tano, Kent, et al.
(författare)
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Comparison of control strategies for a hematite processing plant
- 1999
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Ingår i: Powder Technology. - 0032-5910 .- 1873-328X. ; 105:1-3, s. 443-450
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Tidskriftsartikel (refereegranskat)abstract
- A model-assisted method is used for designing the control strategy for the new LKAB hematite plant in Malmberget (Sweden). Steady-state and dynamic process simulations successively help to select strategic controlled and manipulated variables, and specify the corresponding instrumentation. The control system implemented in the plant reflects the conclusions of the study. It includes an optimizing control system based on specified software, with a fuzzy logic expert system, a dynamic model of the process and an optimizer.
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| 37. |
- Thorsted, Anders, et al.
(författare)
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A non-linear mixed effect model for innate immune response : In vivo kinetics of endotoxin and its induction of the cytokines tumor necrosis factor alpha and interleukin-6
- 2019
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:2
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Tidskriftsartikel (refereegranskat)abstract
- Endotoxin, a component of the outer membrane of Gram-negative bacteria, has been extensively studied as a stimulator of the innate immune response. However, the temporal aspects and exposure-response relationship of endotoxin and resulting cytokine induction and tolerance development is less well defined. The aim of this work was to establish an in silico model that simultaneously captures and connects the in vivo time-courses of endotoxin, tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and associated tolerance development. Data from six studies of porcine endotoxemia in anesthetized piglets (n = 116) were combined and used in the analysis, with purified endotoxin (Escherichia coli O111: B4) being infused intravenously for 1-30 h in rates of 0.063-16.0 mu g/kg/h across studies. All data were modelled simultaneously by means of importance sampling in the non-linear mixed effects modelling software NONMEM. The infused endotoxin followed one-compartment disposition and non-linear elimination, and stimulated the production of TNF-alpha to describe the rapid increase in plasma concentration. Tolerance development, observed as declining TNF-alpha concentration with continued infusion of endotoxin, was also driven by endotoxin as a concentration-dependent increase in the potency parameter related to TNF-alpha production (EC50). Production of IL-6 was stimulated by both endotoxin and TNF-a, and four consecutive transit compartments described delayed increase in plasma IL-6. A model which simultaneously account for the time-courses of endotoxin and two immune response markers, the cytokines TNF-alpha and IL-6, as well as the development of endotoxin tolerance, was successfully established. This model-based approach is unique in its description of the time-courses and their interrelation and may be applied within research on immune response to bacterial endotoxin, or in pre-clinical pharmaceutical research when dealing with study design or translational aspects.
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| 38. |
- Thorsted, Anders, et al.
(författare)
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Extension of Pharmacokinetic/Pharmacodynamic Time-Kill Studies To Include Lipopolysaccharide/Endotoxin Release from Escherichia coli Exposed to Cefuroxime.
- 2020
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Ingår i: Antimicrobial Agents and Chemotherapy. - asm.aac.org. - 0066-4804 .- 1098-6596. ; 64:4
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Tidskriftsartikel (refereegranskat)abstract
- The release of inflammatory bacterial products, such as lipopolysaccharide (LPS)/endotoxin, may be increased upon the administration of antibiotics. An improved quantitative understanding of endotoxin release and its relation to antibiotic exposure and bacterial growth/killing may be gained by an integrated analysis of these processes. The aim of this work was to establish a mathematical model that relates Escherichia coli growth/killing dynamics at various cefuroxime concentrations to endotoxin release in vitro Fifty-two time-kill experiments informed bacterial and endotoxin time courses and included both static (0×, 0.5×, 1×, 2×, 10×, and 50× MIC) and dynamic (0×, 15×, and 30× MIC) cefuroxime concentrations. A model for the antibiotic-bacterium interaction was established, and antibiotic-induced bacterial killing followed a sigmoidal Emax relation to the cefuroxime concentration (MIC-specific 50% effective concentration [EC50], maximum antibiotic-induced killing rate [E max] = 3.26 h-1 and γ = 3.37). Endotoxin release was assessed in relation to the bacterial processes of growth, antibiotic-induced bacterial killing, and natural bacterial death and found to be quantitatively related to bacterial growth (0.000292 endotoxin units [EU]/CFU) and antibiotic-induced bacterial killing (0.00636 EU/CFU). Increased release following the administration of a second cefuroxime dose was described by the formation and subsequent antibiotic-induced killing of filaments (0.295 EU/CFU). Release due to growth was instantaneous, while release due to antibiotic-induced killing was delayed (mean transit time of 7.63 h). To conclude, the in vitro release of endotoxin is related to bacterial growth and antibiotic-induced killing, with higher rates of release upon the killing of formed filaments. Endotoxin release over 24 h is lowest when antibiotic exposure rapidly eradicates bacteria, while increased release is predicted to occur when growth and antibiotic-induced killing occur simultaneously.
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| 39. |
- Thorsted, Anders, et al.
(författare)
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Toxicokinetics of Endotoxin and its relation to Pro-Inflammatory Cytokines Tumor Necrosis Factor α (TNF-α) and Interleukin-6 (IL-6) in a Pig sepsis model
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background and purpose: Infection with Gram-negative bacteria and the immune system’s subsequent recognition of the potent membrane-bound activator endotoxin (ETX), can lead to persistent immune activation. The purpose of the current work was to develop a model-based description of the time-course of ETX concentrations and its effect on the release of the pro-inflammatory, cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6).Methods: Non-linear mixed effects models were developed based on data from experimental studies in a porcine model of sepsis. Intravenous infusions of E. coli ETX were administered to the piglets at different doses and durations of infusion. ETX, TNF-α and IL-6 plasma levels were measured throughout the infusion time.Results: The concentration-time profile of ETX was well described with a one-compartment model with non-linear elimination. Observation of contamination in early ETX measurements was handled by initializing the central compartment to an estimated parameter. The concentration of ETX over time was used as the driver of the inflammatory response. An indirect response model with ETX stimulated production (Emax model), delayed through a transit chain (three compartments) was used to describe the observed cytokine concentration-time profiles. To describe tolerance to ETX exposure, an exponential time-dependent increase was added to the parameter describing the potency of ETX to stimulate cytokine release (EC50).Conclusions: A mathematical model was developed to depict the time-course of ETX in plasma and its induction of the two immune response markers TNF-α and IL-6. This model-based approach is unique in its description of the three time-courses, and may later be expanded to better understand immune cell release in bacterial infections and sepsis-type pathophysiological changes
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| 40. |
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| 41. |
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