Outbreak of OXA-48-producing Enterobacteriaceae in a neonatal intensive care unit in Western Sweden

In 2015, an outbreak caused by OXA-48-producing Enterobacteriaceae affected a neonatal intensive care unit at a Swedish University Hospital. The aim was to explore the transmission of OXA-48-producing strains between infants and the transfer of resistance plasmids between strains during the outbreak. Twenty-four outbreak isolates from ten suspected cases were whole-genome sequenced. A complete assembly was created for the index isolate (Enterobacter cloacae) and used as a mapping reference to detect its plasmids in the remaining isolates (17 Klebsiella pneumoniae, 4 Klebsiella aerogenes, and 2 Escherichia coli). Strain typing was performed using core genome MLST and SNP analysis. As judged from sequencing and clinical epidemiological data, the outbreak involved nine cases (two developed sepsis) and four OXA-48-producing strains: E. cloacae ST1584 (index case), K. pneumoniae ST25 (eight cases), K. aerogenes ST93 (two cases), and E. coli ST453 (2 cases). Two plasmids from the index strain, pEclA2 and pEclA4, carrying blaOXA48 and blaCMY-4, respectively, were traced to all K. pneumoniae ST25 isolates. Klebsiella aerogenes ST93 and E. coli ST453 harboured either only pEclA2, or both pEclA2 and pEclA4. One suspected case harbouring OXA-162-producing K. pneumoniae ST37 could be excluded from the outbreak. Once initiated by an E. cloacae strain, the outbreak was caused by the dissemination of a K. pneumoniae ST25 strain and involved inter-species horizontal transfer of two resistance plasmids, one of which carried blaOXA-48. To our knowledge, this is the first description of an outbreak of OXA-48-producing Enterobacteriaceae in a neonatal setting in northern Europe

Maternal dietary selenium intake during pregnancy and neonatal outcomes in the norwegian mother, father, and child cohort study

Properly working antioxidant defence systems are important for fetal development. One of the nutrients with antioxidant activity is selenium. Increased maternal selenium intake has been associated with reduced risk for being small for gestational age and preterm delivery. Based on the Norwegian Mother, Father, and Child Cohort Study and the Medical Birth Registry of Norway, we in-vestigated the association of maternal selenium intake from food and dietary supplements during the first half of pregnancy (n = 71,728 women) and selenium status in mid-pregnancy (n = 2628 women) with neonatal health, measured as two composite variables (neonatal morbidity/mortality and neonatal intervention). Low maternal dietary selenium intake (<30 \ub5g/day) was associated with increased risk for neonatal morbidity/mortality (adjusted odds ratio (adjOR) 1.36, 95% confidence interval (95% CI) 1.08–1.69) and neonatal intervention (adjOR 1.16, 95% CI 1.01–1.34). Using continuous variables, there were no associations between maternal selenium intake (from diet or supplements) or whole-blood selenium concentration and neonatal outcome in the adjusted models. Our findings suggest that sufficient maternal dietary selenium intake is associated with neonatal outcome. Adher-ing to the dietary recommendations may help ensure an adequate supply of selenium for a healthy pregnancy and optimal fetal development

Angiotensin II receptor expression and relation to Helicobacter pylori-infection in the stomach of the Mongolian gerbil

<p>Abstract</p> <p>Background</p> <p>The role of the renin-angiotensin system in gastric physiology and disease has as yet been sparsely explored. The first aim of the study was to investigate the baseline presence and location of angiotensin II receptors (AT1R and AT2R) in the stomach of the Mongolian gerbil. A second aim was to elucidate whether the presence of <it>H. pylori </it>infection is associated with changes in the expression of these receptors.</p> <p>Methods</p> <p><it>H. pylori</it>-negative and <it>H. pylori-</it>infected (strain SS1 or TN2GF4) male Mongolian gerbils were investigated. The stomachs were examined at six or 12 months after inoculation by the use of immunohistochemistry, western blot and microscopic morphometry.</p> <p>Results</p> <p>AT1R and AT2R were located in a variety of cells in the gerbil gastric wall, including a subpopulation of endocrine cells in the antral mucosa and inflammatory cells infiltrating <it>H. pylori</it>-infected stomachs. Gerbils infected with the SS1 strain showed a significantly increased antral AT1R protein expression and an increased number of infiltrating polymorphonuclear leucocytes (PMNs) at 12 months. The AT1R protein expression correlated with the number of PMNs and the antral expression of myeloperoxidase.</p> <p>Conclusions</p> <p>Angiotensin II receptors are present in a variety of cells in the gastric wall of the Mongolian gerbil. The results indicate an influence dependent on the <it>H. pylori </it>strain on the gastric AT1R expression and a relationship between gastric AT1R expression and mucosal PMNs infiltration.</p

Virulence, phenotype and genotype characteristics of invasive group B Streptococcus isolates obtained from Swedish pregnant women and neonates

Group B streptococci (GBS) are bacteria that can cause preterm birth and invasive neonatal disease. Heterogeneous expression of virulence factors enables GBS to exist as both commensal bacteria and to become highly invasive. A molecular epidemiological study comparing GBS bacterial traits, genotype and host characteristics may indicate whether it is possible to predict the risk of perinatal invasive GBS disease and more accurately target intrapartum antibiotic prophylaxis. A total of 229 invasive GBS isolates from Swedish pregnant women or neonates were assessed for virulence and phenotypic traits: hemolysis zone, hemolytic pigment (Granada agar), Streptococcus B Carrot Broth (SBCB) assay, CAMP factor, and hyaluronidase activity. Genes regulating hemolytic pigment synthesis (covR/covS, abx1, stk1, stp1) were sequenced. Of the virulence factors and phenotypes assessed, a Granada pigment or SBCB score ≥ 2 captured more than 90% of EOD isolates with excellent inter-rater reliability. High enzyme activity of hyaluronidase was observed in 16% (36/229) of the invasive GBS isolates and notably, in one case of stillbirth. Hyaluronidase activity was also significantly higher in GBS isolates obtained from pregnant/postpartum individuals versus the stillbirth or neonatal invasive isolates (p < 0.001). Sequencing analysis found that abx1 (g.T106I), stk1 (g.T211N), stp1 (g.K469R) and covS (g.V343M) variants were present significantly more often in the higher (Granada pigment score ≥ 2) versus lower pigmented isolates (p < 0.001, each variant). Among the 203 higher Granada pigment scoring isolates, 22 (10.8%) isolates had 3 of the four sequence variants and 10 (4.9%) had 2 of the four sequence variants. Although heterogeneity in GBS virulence factor expression was observed, the vast majority were more highly pigmented and contained several common sequence variants in genes regulating pigment synthesis. High activity of hyaluronidase may increase risk for stillbirth and invasive disease in pregnant or postpartum individuals. Our findings suggest that testing for GBS pigmentation and hyaluronidase may, albeit imperfectly, identify pregnant people at risk for invasive disease and represent a step towards a personalized medical approach for the administration of intrapartum antibiotic prophylaxis

Helicobacter pylori associated effects on inflammatory radical formation and angiotensin II receptors in the stomach

Helicobacter pylori infection of the stomach always results in mucosal inflammation and a marked systemic immune response. Despite the profound host defence reactions the bacterium avoids elimination and persists in the mucosa. This results in chronic inflammation and an increased risk for peptic ulcers and adenocarcinoma. Still a majority of infected individuals never develop any symptomatic disease. Previous results from our laboratory indicate that H. pylori reduces the power of host defence by restricting gastric NO production by pathogen-derived competitive iNOS inhibitors. It was considered of interest to further investigate not only the H. pylori associated inhibition of nitro-radical formation, but also interactions with the oxy-radical formation in gastric carcinogenesis. Furthermore, because the renin angiotensin system (RAS) recently was ascribed immunomodulatory actions, it was considered of interest to also explore if H. pylori influences the presence and location of this regulatory system in the gastric mucosa. The H. pylori infected Mongolian gerbil was used as the experimental model and was followed up to 18 months after infection. A first aim of this thesis was to by use of histopathology validate the model’s suitability for studies of H. pylori (strains SS1 and TN2GF4) induced gastric mucosal pathology. The results indicate that the H. pylori infected Mongolian gerbil cannot be confirmed as being a cancer model, but it is suitable for studies of acute and chronic mucosal inflammation. The Mongolian gerbil model was then used to elucidate H. pylori strain dependency on the expression of the oxy- and nitro-radical forming enzymes, and to investigate whether H. pylori infection results in inhibition of either or both of the nitro- and oxy-radical formation. Western blotting was used to assess iNOS and MPO expressions as representatives for nitro- and oxy radicalforming pathways, respectively. Radical formation was assessed as presence of nitrotyrosine or by use of NO or H2O2 sensitive microelectrodes. The results confirm that H. pylori infection in Mongolian gerbils despite an up-regulation of nitro- and oxy-radical forming enzymes results in inhibition of radical formation. Response patterns differed over time in relation to the H. pylori strain under study. The results were confirmed in human gastric specimens using similar western blot assessing expression of nitro-and oxy-radical forming enzymes as well as nitrotyrosine. Finally, gene transcripts and immunoreactivity to the angiotensin II receptors AT1R and AT2R were found present in the antral wall of the Mongolian gerbil. The investigation indicated a possible H. pylori strain dependent influence on the AT1R expression. The present studies on experimentally infected Mongolian gerbils and asymptomatic human tissues support strongly that H. pylori avoids to be eliminated from the gastric mucosa by interfering with the nitro- and oxy-radical formation. In addition the investigations also suggest the presence of a H. pylori strain dependent influence on the AT1R expression constituting a novel immunomodulatory principle

Maternal, fetal and perinatal factors associated with necrotizing enterocolitis in Sweden : A national case-control study

Objective To analyze associations of maternal, fetal, gestational, and perinatal factors with necrotizing enterocolitis in a matched case-control study based on routinely collected, nationwide register data. Study design All infants born in 1987 through 2009 with a diagnosis of necrotizing enterocolitis in any of the Swedish national health care registers were identified. For each case up to 6 controls, matched for birth year and gestational age, were selected. The resulting study population consisted of 720 cases and 3,567 controls. Information on socioeconomic data about the mother, maternal morbidity, pregnancy related diagnoses, perinatal diagnoses of the infant, and procedures in the perinatal period, was obtained for all cases and controls and analyzed with univariable and multivariable logistic regressions for the whole study population as well as for subgroups according to gestational age. Results In the study population as a whole, we found independent positive associations with necrotizing enterocolitis for isoimmunization, fetal distress, cesarean section, neonatal bacterial infection including sepsis, erythrocyte transfusion, persistent ductus arteriosus, cardiac malformation, gastrointestinal malformation, and chromosomal abnormality. Negative associations were found for maternal weight, preeclampsia, maternal urinary infection, premature rupture of the membranes, and birthweight. Different patterns of associations were seen in the subgroups of different gestational age. Conclusion With some interesting exceptions, especially in negative associations, the results of this large, population based study, are in keeping with earlier studies. Although restrained by the limitations of register data, the findings mirror conceivable pathophysiological processes and underline that NEC is a multifactorial disease.Funding agencies: Region Ostergotland, Sweden [LiO-107641]; Medical Research Council of Southeast Sweden [FORSS-77481]; Futurum - the Academy of Health Care, Jonkoping County Council, Jonkoping, Sweden; Region Ostergotland [LIO-130291, LIO-204581, LIO-280451, LIO-361481, L</p

C-reactive protein- and clinical symptoms-guided strategy in term neonates with early-onset sepsis reduced antibiotic use and hospital stay: a quality improvement initiative

Background: Early-onset sepsis (EOS) is a potentially life-threatening complication of birth. Clinical symptoms are often unspecific and biomarkers have low predictive values for EOS. Therefore, clinical suspicion often leads to antibiotic therapy in neonates with a negative blood culture. In the study we evaluated if a quality improvement initiative could reduce unwarranted antibiotic use in a safe way in term neonates with culture-negative sepsis. Methods: The quality improvement initiative included new treatment guidelines and were introduced on 11 June 2018. The guidelines included C-reactive protein- and clinical symptoms-guided decision-making and shorter intravenous antibiotic therapy. All term neonates treated for EOS at Ryhov Hospital, Jonkoping, Sweden were studied before (period 1: 2016-2017) and after the introduction of the new guidelines (period 2: 11 June 2018 to 30 Sept 2019). Laboratory and clinical data were analysed. Results: There were 7618 term neonates in period 1 and 5005 term neonates in period 2. We identified 140 (1.8%) EOS in period 1 and 97 (1.9%) EOS in period 2. During period 1 and 2, there were 61 (61/140, 44%) and 59 (59/97, 61%) EOS neonates, respectively, who met the criteria for shorter antibiotic treatment. The number of positive blood cultures were seven (0.92/1000 live births) and five (1.0/1000 live births) in period 1 and 2. The median C-reactive protein were 52 mg/L (37-62) in period 1 and 42 mg/L (31-56) in period 2 in the group who met the criteria of the guidelines. The duration of antibiotic therapy (Median: seven vs. five days, p &amp;lt; 0.001) and hospital stay (Median: seven vs. five days, p &amp;lt; 0.001) as well as healthcare costs (decreased by euro122,000/year) was reduced in the group who met the criteria after the introduction of the guidelines. Conclusion: C-reactive protein- and clinical symptoms-guided decision-making for EOS significantly decreased the duration of antibiotic therapy and hospital stay, and hence reduced healthcare costs, with no reinfection in a cohort of term infants.Funding Agencies|Futurum -the academy for healthcare, Region Jonkoping County; Swedish government; county council, the ALF [117661]</p

The Significance of the FTO Gene for Weight and Body Composition in Swedish Women With Severe Anorexia Nervosa During Intensive Nutrition Therapy

Objective: The aim of this prospective study was to investigate the potential influence of the fat mass and obesity-associated gene (FTO), SNP rs9939609, on body mass index (BMI) and body composition in women with anorexia nervosa (AN) undergoing intensive nutrition therapy. Method: Twenty-five female patients with AN (20.1 +/- 2.3 years; BMI, 15.5 +/- 0.9 kg/m(2)) were included for 12 weeks of treatment with a high-energy diet. FTO was genotyped and body composition parameters were assessed by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography at baseline and after 12 weeks. Results: The distribution of the different FTO genotypes were as follows: AA, 24%; TA, 48%; and TT, 28%. Patients gained a median of 9.8 kg (range, 5.5-17.0 kg) and BMI increased to 19.0 +/- 0.9 kg/m(2). The increase in BMI, fat mass, and the quotient fat/muscle area was significant for the TT and TA genotype groups. Total lean mass was stable in all genotype groups. We could not demonstrate any difference among the 3 FTO genotypes related to the increases in BMI during nutrition therapy when the additive, dominant, and recessive models of inheritance were applied. Conclusions: Irrespective of the FTO genotype, there was no difference in weight response during nutrition therapy. Hence, in this small study there was limited support for individualized nutrition therapy for AN based on FTO genotype