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- Ekwall-Larson, Anna, et al.
(författare)
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Analytical Performance and Potential Clinical Utility of EUCAST Rapid Antimicrobial Susceptibility Testing in Blood Cultures after Four Hours of Incubation
- 2023
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Ingår i: Microbiology Spectrum. - : AMER SOC MICROBIOLOGY. - 2165-0497. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- EUCAST rapid antimicrobial susceptibility testing (RAST) provides antibiotic susceptibility results after 4 to 8 h of incubation. This study assessed the diagnostic performance and clinical usefulness of EUCAST RAST after 4 h. This was a retrospective clinical study performed on blood cultures with Escherichia coli and Klebsiella pneumoniae complex (K. pneumoniae and Klebsiella variicola) at Karolinska University Laboratory (Stockholm, Sweden). The rate of categorized RAST results and the categorical agreement (CA) of RAST with the standard EUCAST 16-to-20-h disk diffusion (DD) method for piperacillin-tazobactam, cefotaxime, ceftazidime, meropenem, and ciprofloxacin were analyzed, as well as the utility of RAST for adjusting the empirical antibiotic therapy (EAT) and the combination of RAST with a lateral flow assay (LFA) for extended-spectrum beta-lactamase (ESBL) detection. A total of 530 E. coli and 112 K. pneumoniae complex strains were analyzed, generating 2,641 and 558 readable RAST zones, respectively. RAST results categorized according to antimicrobial sensitivity/resistance (S/R) were obtained for 83.1% (2,194/2,641) and 87.5% (488/558) of E. coli and K. pneumoniae complex strains, respectively. The RAST result categorization to S/R for piperacillin-tazobactam was poor (37.2% for E. coli and 66.1% for K. pneumoniae complex). CA with the standard DD method was over 97% for all tested antibiotics. Using RAST, we detected 15/26 and 1/10 of the E. coli and K. pneumoniae complex strains that were resistant to the EAT. For patients treated with cefotaxime, RAST was used to detect 13/14 cefotaxime-resistant E. coli strains and 1/1 cefotaxime-resistant K. pneumoniae complex strain. ESBL positivity was reported the same day as blood culture positivity with RAST and LFA. EUCAST RAST provides accurate and clinically relevant susceptibility results after 4 h of incubation and can accelerate the assessment of resistance patterns.IMPORTANCE Early effective antimicrobial treatment has been shown to be crucial for improving the outcome of bloodstream infections (BSI) and sepsis. In combination with the rise of antibiotic resistance, this calls for accelerated methods for antibiotic susceptibility testing (AST) for effective treatment of BSI. This study assesses EUCAST RAST, an AST method that yields results in 4, 6, or 8 h after blood culture positivity. We analyzed a high number of clinical samples of Escherichia coli and Klebsiella pneumoniae complex strains and confirm that the method delivers reliable results after 4 h of incubation for the relevant antibiotics for treating E. coli and K. pneumoniae complex bacteremia. Furthermore, we conclude that it is an important tool for antibiotic treatment decision-making and early detection of ESBL-producing isolates. Early effective antimicrobial treatment has been shown to be crucial for improving the outcome of bloodstream infections (BSI) and sepsis. In combination with the rise of antibiotic resistance, this calls for accelerated methods for antibiotic susceptibility testing (AST) for effective treatment of BSI.
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| 2. |
- Fenhammar, Johan, et al.
(författare)
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Renal effects of treatment with a TLR4-inhibitor in conscious septic sheep
- 2014
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 18:5, s. 488-
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Acute kidney injury (AKI) is a common and feared complication of sepsis. The pathogenesis of sepsis-induced AKI is largely unknown, and therapeutic interventions are mainly supportive. In the present study, we tested the hypothesis that pharmacological inhibition of Toll-like receptor 4 (TLR4) would improve renal function and reduce renal damage in experimental sepsis, even after AKI had already developed. Methods: Sheep were surgically instrumented and subjected to a 36-hour intravenous infusion of live Escherichia coli. After 12 hours, they were randomized to treatment with a selective TLR4 inhibitor (TAK-242) or vehicle. Results: The E. coli caused normotensive sepsis characterized by fever, increased cardiac index, hyperlactemia, oliguria, and decreased creatinine clearance. TAK-242 significantly improved creatinine clearance and urine output. The increase in N-acetyl-beta-D-glucosaminidas, a marker of tubular damage, was attenuated. Furthermore, TAK-242 reduced the renal neutrophil accumulation and glomerular endothelial swelling caused by sepsis. These effects were independent of changes in renal artery blood flow and renal microvascular perfusion in both cortex and medulla. TAK-242 had no effect per se on the measured parameters. Conclusions: These results show that treatment with a TLR4 inhibitor is able to reverse a manifest impairment in renal function caused by sepsis. In addition, the results provide evidence that the mechanism underlying the effect of TAK-242 on renal function does not involve improved macro-circulation or micro-circulation, enhanced renal oxygen delivery, or attenuation of tubular necrosis. TLR4-mediated inflammation resulting in glomerular endothelial swelling may be an important part of the pathogenesis underlying Gram-negative septic acute kidney injury.
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| 3. |
- Hanson, Mikael G. V., et al.
(författare)
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A short-term dietary supplementation with high doses of vitamin E increases NK cell cytolytic activity in advanced colorectal cancer patients
- 2007
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Ingår i: Cancer Immunology and Immunotherapy. - : Springer Science and Business Media LLC. - 0340-7004 .- 1432-0851. ; 56:7, s. 973-984
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Tidskriftsartikel (refereegranskat)abstract
- Cancer patients with advanced disease display signs of immune suppression, which constitute a major obstacle for effective immunotherapy. Both T cells and NK cells are affected by a multitude of mechanisms of which the generation of reactive oxygen species is of major importance. Therefore, we hypothesized that two weeks of high-dose treatment with the anti-oxidant vitamin E may enhance NK cell function in cancer patients by protecting from oxidative stress. Seven patients with colorectal cancer (Dukes stage C and D) received a daily dose of 750 mg of vitamin E during a period of two weeks and the function, phenotype and receptor expression of NK cells were analyzed. The short-term vitamin E treatment significantly improved NK cell cytolytic activity in six out of the seven patients analyzed. The increased NK cell activity in patients' PBMC was not due to increased numbers of NK cells or an increase in the proportion of the CD56(dim) NK cell subpopulation. Furthermore, neither an increased perforin expression nor an enhanced ability of NK cells to produce IFN-gamma was observed as a result of vitamin E treatment. Finally, vitamin E treatment was associated with a minor, but consistent, induction of NKG2D expression in all patients analyzed. In conclusion, this pilot study demonstrates that vitamin E may boost NK cell function in patients with colorectal cancer. Further studies are warranted to explore the potential of vitamin E as an adjuvant for immunotherapy against cancer and to determine the underlying mechanism(s) behind vitamin E induced NK cell activation.
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| 5. |
- Skorup, Paul, et al.
(författare)
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Evaluation of an extracorporeal ozone-based bactericide system for the treatment of Escherichia coli sepsis
- 2022
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Ingår i: Intensive Care Medicine Experimental. - : Springer Nature. - 2197-425X. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sepsis is associated with substantial mortality rates. Antibiotic treatment is crucial, but global antibiotic resistance is now classified as one of the top ten global public health risks facing humanity. Ozone (O-3) is an inorganic molecule with no evident function in the body. We investigated the bactericide properties of ozone, using a novel system of extracorporeal ozone blood treatment. We hypothesized that ozone would decrease the concentration of viable Escherichia coli (E. coli) in human whole blood and that the system would be technically feasible and physiologically tolerable in a clinically relevant model of E. coli sepsis in swine. Methods: The E. coli strain B09-11822, a clinical isolate from a patient with septic shock was used. The in vitro study treated E. coli infected human whole blood (n = 6) with ozone. The in vivo 3.5-h sepsis model randomized swine to E. coli infusion and ozone treatment (n = 5) or E. coli infusion and no ozone treatment (n = 5). Live E. coli, 5 x 10(7) colony-forming units (CFU/mL) was infused in a peripheral vein. Ozone treatment was initiated with a duration of 30 min after 1.5 h. Results: The single pass in vitro treatment decreased E. coli by 27%, mean 1941 to 1422 CFU/mL, mean of differences - 519.0 (95% CI - 955.0 to - 82.98,P= 0.0281). pO(2) increased (95% CI 31.35 to 48.80, P= 0.0007), pCO(2) decreased (95% CI -3.203 to - 1.134, P= 0.0069), oxyhemoglobin increased (95% CI 1.010 to 3.669, P= 0.0113). Methemoglobin was not affected. In the sepsis model, 9/10 swine survived. One swine randomized to ozone treatment died from septic shock before initiation of the treatment. Circulatory, respiratory, and metabolic parameters were not affected by the ozone treatment. E. coli in arterial blood, in organs and in aerobic and anaerobic blood cultures did not differ. Hemoglobin, leucocytes, and methemoglobin were not affected by the treatment. Conclusions: Ozone decreased the concentration of viable E. coli in human whole blood. The system was technically feasible and physiologically tolerable in porcine sepsis/septic shock and should be considered for further studies towards clinical applications.
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| 6. |
- Zimmer, Christine L., et al.
(författare)
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A biliary immune landscape map of primary sclerosing cholangitis reveals a dominant network of neutrophils and tissue-resident T cells
- 2021
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Ingår i: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 13:599
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Tidskriftsartikel (refereegranskat)abstract
- The human biliary system, a mucosal barrier tissue connecting the liver and intestine, is an organ often affected by serious inflammatory and malignant diseases. Although these diseases are linked to immunological processes, the biliary system represents an unexplored immunological niche. By combining endoscopy-guided sampling of the biliary tree with a high-dimensional analysis approach, comprehensive mapping of the human biliary immunological landscape in patients with primary sclerosing cholangitis (PSC), a severe biliary inflammatory disease, was conducted. Major differences in immune cell composition in bile ducts compared to blood were revealed. Furthermore, biliary inflammation in patients with PSC was characterized by high presence of neutrophils and T cells as compared to control individuals without PSC. The biliary T cells displayed a CD103(+)CD69(+) effector memory phenotype, a combined gut and liver homing profile, and produced interleukin-17 (IL-17) and IL-22. Biliary neutrophil infiltration in PSC associated with CXCL8, possibly produced by resident T cells, and CXCL16 was linked to the enrichment of T cells. This study uncovers the immunological niche of human bile ducts, defines a local immune network between neutrophils and biliary-resident T cells in PSC, and provides a resource for future studies of the immune responses in biliary disorders.
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