BackgroundInfections caused by extended spectrum beta-lactamases (ESBL)-producing bacteria have been emerging worldwide and the majority of ESBL-producing E. coli strains are isolated from patients with urinary tracts infections. The purpose of this study was to compare the host-response mechanisms in human polymorphonucleated leukocytes (PMN) and renal epithelial cells when stimulated by ESBL- or non-ESBL-producing uropathogenic E. coli (UPEC) isolates. The host-pathogen interaction of these ESBL-producing strains in the urinary tract is not well studied.ResultsThe ability of ESBL strains to evoke ROS-production from PMN cells was significantly higher than that of the non-ESBL strains. The growth of ESBL strains was slightly suppressed in the presence of PMN compared to non-ESBL strains after 30 min and 2 h, but the opposite was observed after 5 and 6 h. The number of migrating PMN was significantly higher in response to ESBL strains compared to non-ESBL strains. Stimulation of A498 cells with ESBL strains elicited lower production of IL-6 and IL-8 compared to non-ESBL strains.ConclusionSignificant differences in host-response mechanisms were identified when host cells were stimulated by ESBL- or non-ESBL producing strains. The obtained results on the early interactions of ESBL-producing strains with the host immune system may provide valuable information for management of these infections.

BackgroundNitric 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.ResultsFour clinical isolates of multidrug-resistant extended-spectrum β-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.ConclusionAn NO-donor in combination with miconazole and PMBN showed enhanced antimicrobial effects and proved effective against multidrug-resistant ESBL-producing uropathogenic E. coli.

The purpose of this study was to compare the Quantiferon‐TB Gold Plus test analysed with chemiluminescence immunoassay (CLIA) to immunoassay (EIA). One hundred and twenty‐five clinical specimens submitted to Karolinska University Hospital for Quantiferon‐TB Gold Plus analysis were used to analyse agreement of the CLIA and EIA assays. The imprecision on CLIA was determined by analysis of pooled clinical samples of antigen tubes (TB1 and TB2), a reference material from National Institute for Biological Standards and Control (NIBSC 82/587) and two controls of the test. Recovery on CLIA was determined by analysis of the TB1 and TB2 samples and NIBSC 82/587. Concordant results were obtained for 110 (88.0%) of 125 samples with cut‐off including a borderline range. With no borderline range, 121 of 125 samples (96.8%) showed concordant results. Repeatability had a coefficient of variation (CV) of 14.9%. Reproducibility for pooled clinical samples TB1 and TB2 had a CV of 10.5% and 11.0%, respectively, and for the NIBSC 82/587 7.45%, and kit controls 31.0% respective 12.2%. Overall recovery had a mean of 94.1% (SD 12%). We concluded that Quantiferon‐TB Gold Plus analysed with the CLIA assay shows good concordance with EIA and acceptable imprecision.