Hand eczema and temporal variation of Staphylococcus aureus clonal complexes: A prospective observational study.

BACKGROUND: Hand eczema (HE) is frequently associated with Staphylococcus aureus; however, its role in the pathogenesis of HE is poorly understood. OBJECTIVE: To investigate the temporal variation in S aureus subtypes, ie, clonal complex (CC) types, on the hands and relate it to S aureus colonization in the nose and severity in a cohort of HE patients. METHODS: S aureus from the hands and nose of 50 adult HE patients and 50 controls was prospectively identified at 5 visits over 3 weeks. RESULTS: S aureus was identified on the hands of 23 (46%) patients at 2 or more visits and on the hands of 1 control once. Of the HE patients with S aureus colonization, 78% had the same S aureus CC type over time. Twenty-one patients had the same S aureus CC type on the hands and in the nose. Persistent colonization was strongly related to an increased disease severity. LIMITATIONS: A relatively small S aureus culture-positive population. CONCLUSION: The temporal stability of S aureus CC type and high occurrence of the identical subtypes on the hands and in the nose imply that S aureus colonization in patients with HE is of a more permanent nature. Taken together with the finding that persistent colonization and HE severity are clearly related, our results indicate that S aureus may contribute to the perpetuating course of HE.

Altered Maturation of the Skin Microbiome in Infants with Atopic Dermatitis.

The aim of this study was to investigate the early-life development of the skin microbiome in atopic dermatitis. Nineteen infants with atopic dermatitis and 19 healthy infants were evaluated 3 times, at 3 months intervals, within the first 30 months of life. Tape-strips were collected from volar forearms, cheeks, and eczema lesions, and the skin microbiome was assessed by 16S rRNA sequencing. Both the community structure and richness of the skin microbiome of infants with atopic dermatitis differed significantly from that of healthy infants, with greater richness in healthy infants. For infants with atopic dermatitis, the community composition was not dominated by Staphylococci. For healthy infants, community composition and richness correlated significantly with age, while such a pattern was not revealed in infants with atopic dermatitis. This suggests a slower maturation of the skin microbiome in atopic dermatitis, which precedes the staphylococcal predominance observed in older children and adults.

Dabigatran and the Risk of Staphylococcus aureus Bacteremia: A Nationwide Cohort Study.

BACKGROUND: Treatment with dabigatran, an oral direct thrombin inhibitor, reduces the virulence of Staphylococcus aureus in in vitro and in vivo models. However, it remains to be determined whether dabigatran reduces the risk of S. aureus infections in humans. We investigated the incidence rate of S. aureus bacteremia (SAB) in patients with atrial fibrillation treated with the direct thrombin inhibitor dabigatran compared with patients treated with the factor Xa-inhibitors rivaroxaban, apixaban, and edoxaban. METHODS: In this observational cohort study, 112 537 patients with atrial fibrillation who initiated treatment with direct oral anticoagulants (August 2011-December 2017) were identified from Danish nationwide registries. The incidence rates of SAB in patients treated with dabigatran versus patients treated with the factor Xa-inhibitors were examined by multivariable Cox regression accounting for time-dynamic changes in exposure status during follow-up. RESULTS: A total of 112 537 patients were included. During a median follow-up of 2.0 years, 186 patients in the dabigatran group and 356 patients in the factor Xa-inhibitor group were admitted with SAB. The crude incidence rate of SAB was lower in the dabigatran group compared with the factor Xa-inhibitor group (22.8 [95% confidence interval [CI], 19.7-26.3] and 33.8 [95% CI, 30.5-37.6] events per 10 000 person-years, respectively). In adjusted analyses, dabigatran was associated with a significantly lower incidence rate of SAB compared with factor Xa-inhibitors (incidence rate ratio, .76; 95% CI, .63-.93). CONCLUSIONS: Treatment with dabigatran was associated with a significantly lower incidence rate of SAB compared with treatment with factor Xa-inhibitors.

Human genetic variation in GLS2 is associated with development of complicated Staphylococcus aureus bacteremia.

The role of host genetic variation in the development of complicated Staphylococcus aureus bacteremia (SAB) is poorly understood. We used whole exome sequencing (WES) to examine the cumulative effect of coding variants in each gene on risk of complicated SAB in a discovery sample of 168 SAB cases (84 complicated and 84 uncomplicated, frequency matched by age, sex, and bacterial clonal complex [CC]), and then evaluated the most significantly associated genes in a replication sample of 240 SAB cases (122 complicated and 118 uncomplicated, frequency matched for age, sex, and CC) using targeted sequence capture. In the discovery sample, gene-based analysis using the SKAT-O program identified 334 genes associated with complicated SAB at p<3.5 x 10-3. These, along with eight biologically relevant candidate genes were examined in the replication sample. Gene-based analysis of the 342 genes in the replication sample using SKAT-O identified one gene, GLS2, significantly associated with complicated SAB (p = 1.2 x 10-4) after Bonferroni correction. In Firth-bias corrected logistic regression analysis of individual variants, the strongest association across all 10,931 variants in the replication sample was with rs2657878 in GLS2 (p = 5 x 10-4). This variant is strongly correlated with a missense variant (rs2657879, p = 4.4 x 10-3) in which the minor allele (associated here with complicated SAB) has been previously associated with lower plasma concentration of glutamine. In a microarray-based gene-expression analysis, individuals with SAB exhibited significantly lower expression levels of GLS2 than healthy controls. Similarly, Gls2 expression is lower in response to S. aureus exposure in mouse RAW 264.7 macrophage cells. Compared to wild-type cells, RAW 264.7 cells with Gls2 silenced by CRISPR-Cas9 genome editing have decreased IL1-ß transcription and increased nitric oxide production after S. aureus exposure. GLS2 is an interesting candidate gene for complicated SAB due to its role in regulating glutamine metabolism, a key factor in leukocyte activation.

Skin Microbiome in Atopic Dermatitis.

Atopic dermatitis is a common inflammatory skin disease with a complex pathogenesis that includes imbalanced immune system signalling, impaired skin barrier and enhanced Staphylococcus aureus skin colonization. The skin bacterial communities are characterized by increasing abundance of S. aureus, leading to reduced diversity compared with the bacterial communities on healthy skin, and increasing disease severity. In contrast, fungal communities are richer and more diverse on the skin of patients with atopic dermatitis, although distribution of the most common species is similar in patients and controls. Filaggrin deficiency in atopic dermatitis skin might be related to the enhanced skin colonization by S. aureus. In addition, S. aureus expressing variant virulence factors have been shown to elicit atopic dermatitis-like phenotypes in mice, indicating that specific S. aureus strains can induce flare-ups. This review aims to provide an overview of the recent literature on the skin microbiome in atopic dermatitis.

Colonization with Staphylococcus aureus in patients with hand eczema: Prevalence and association with severity, atopic dermatitis, subtype and nasal colonization.

BACKGROUND: While Staphylococcus aureus (S. aureus) colonization has been thoroughly studied in atopic dermatitis (AD), where S. aureus is related to flares and considered a trigger factor, S. aureus colonization in hand eczema (HE) has only been sparsely studied. OBJECTIVES: To examine the 1-week prevalence of S. aureus colonization in HE patients, and its association with severity, HE subtype, AD, and nasal S. aureus colonization compared with healthy controls. METHODS: In a case-control study of 50 adult HE patients and 50 healthy controls, bacterial swabs from lesional skin (patients only), non-lesional skin (dorsal hand), and the nasal cavity were sampled for culturing of S. aureus on days 1, 3, 5 and 8. Participants were characterized by demographics, AD, HE subtype, filaggrin gene mutation status, and HE severity. RESULTS: Twenty-seven HE patients (54%) were colonized with S. aureus on the hand compared to one control (2%) (P < .01). Nasal S. aureus colonization was found in 72% of patients and 22% of controls (P < .01). For patients, S. aureus colonization on the hands was associated with an atopic HE subtype and HE severity (P = .01 and P < .01, respectively). CONCLUSIONS: Both hand and nasal S. aureus colonization were highly prevalent among HE-patients and may have an impact on the persistence of HE.

In Vivo Selection of a Unique Tandem Repeat Mediated Azole Resistance Mechanism (TR120) in Aspergillus fumigatus cyp51A, Denmark.

We report a fatal aspergillosis case in which STRAf typing and whole-genome sequencing substantiated in vivo emergence of an azole-resistant Aspergillus fumigatus with a 120-bp tandem repeat in the promoter region of cyp51A. This event, previously restricted to the environment, challenges current understanding of azole resistance development in A. fumigatus.

The microbiome reflects diagnosis and predicts disease severity in paediatric onset inflammatory bowel disease.

Objectives: A microbiotic profile characterized by decreased abundance and richness has been described in inflammatory bowel disease (IBD). Recently, sequencing the microbiome to the species level has become possible, which can improve our understanding of the gut to host interaction in IBD. We aimed to describe the microbiotic profile in paediatric IBD and compare it to disease phenotype and disease course. Methods: Faecal samples were collected from a cross-sectional cohort. The microbiome analysis was performed using 16S and 18S rRNA sequencing with the miSeq instrument. Inflammatory activity was assessed by faecal calprotectin. Data regarding medical treatment and surgery in the year after faecal sampling were collected from patient charts. Results: One hundred and forty-three (143) paediatric IBD patients and 34 healthy controls (HC) were included. We found a reduced richness in IBD patients compared to HCs (controls vs. ulcerative colitis (UC), p < .001 and controls vs. Crohn's disease (CD), p = .04)). Moreover, a high degree of intestinal inflammation and extensive disease extent was associated with reduced richness in UC (p = .02 and p = .04, respectively). Nine species were significantly associated with a healthy microbiome and three species were associated with IBD. Lastly, we found that the composition of the microbiome could distinguish between CD, UC and HCs. Conclusions: In this study, we found that the microbiome could discriminate between IBD phenotypes and predict which patients were at risk of surgery. In the future, this could be included as part of the diagnostic work-up in IBD patients.

Dissemination and Characteristics of a Novel Plasmid-Encoded Carbapenem-Hydrolyzing Class D ß-Lactamase, OXA-436, Found in Isolates from Four Patients at Six Different Hospitals in Denmark.

The diversity of OXA-48-like carbapenemases is continually expanding. In this study, we describe the dissemination and characteristics of a novel carbapenem-hydrolyzing class D ß-lactamase (CHDL) named OXA-436. In total, six OXA-436-producing Enterobacteriaceae isolates, including Enterobacter asburiae (n = 3), Citrobacter freundii (n = 2), and Klebsiella pneumoniae (n = 1), were identified in four patients in the period between September 2013 and April 2015. All three species of OXA-436-producing Enterobacteriaceae were found in one patient. The amino acid sequence of OXA-436 showed 90.4 to 92.8% identity to the amino acid sequences of other acquired OXA-48-like variants. Expression of OXA-436 in Escherichia coli and kinetic analysis of purified OXA-436 revealed an activity profile similar to that of OXA-48 and OXA-181, with activity against penicillins, including temocillin; limited or no activity against extended-spectrum cephalosporins; and activity against carbapenems. The blaOXA-436 gene was located on a conjugative ∼314-kb IncHI2/IncHI2A plasmid belonging to plasmid multilocus sequence typing sequence type 1 in a region surrounded by chromosomal genes previously identified to be adjacent to blaOXA genes in Shewanella spp. In conclusion, OXA-436 is a novel CHDL with functional properties similar to those of OXA-48-like CHDLs. The described geographical spread among different Enterobacteriaceae and the plasmid location of blaOXA-436 illustrate its potential for further dissemination.

Staphylococcus aureus Bacteremia in Children Aged 5-18 Years-Risk Factors in the New Millennium.

OBJECTIVES: To assess the association between comorbidities and Staphylococcus aureus bacteremia in children aged 5-18 years, thus, in children with a matured immune system. Further, we aimed to identify presumably healthy children acquiring bacteremia. STUDY DESIGN: By cross-linking nationwide registries, we consecutively included all children born from 1995 onward at their 5-year birthday or date of immigration during 2000-2015. We examined incidence rate ratios (IRR) between preselected exposures and microbiologically verified S aureus bacteremia (reference = children without exposure) using Poisson regression models. RESULTS: We followed 1 109 169 children in 2000-2015 during which 307 children (incidence rate: 3.7 per 100 000 person-years) acquired S aureus bacteremia (methicillin-resistant S aureus = 8; 2.6%). Children without known comorbidities or recent contact with the healthcare system comprised 37.1% of infected children. The highest IRRs were observed in children undergoing dialysis or plasmapheresis (IRR = 367.2 [95% CI) = 188.5-715.3]), children with organ transplantation (IRR = 149.5 [95% CI = 73.9-302.2]), and children with cancer (IRR = 102.9 [95% CI = 74.4-142.2]). Positive associations also were observed in children with chromosomal anomalies (IRR = 7.16 [95% CI = 2.96-17.34]), atopic dermatitis (IRR = 4.89 [95% CI = 3.11-7.69]), congenital heart disease (IRR = 3.14 [95% CI = 1.92-5.11]), and in children undergoing surgery (IRR = 3.34 [95% CI = 2.59-4.28]). Neither premature birth nor parental socioeconomic status was associated with increased disease rates. CONCLUSIONS: S aureus bacteremia is uncommon in children between 5 and 18 years of age. Risk factors known from the adult population, such as dialysis, plasmapheresis, organ transplantation, and cancer, were associated with the highest relative rates. However, prematurity and parental socioeconomic status were not associated with increased rates. Approximately one-third of infected children were presumably healthy.

Staphylococcus aureus CC395 harbours a novel composite staphylococcal cassette chromosome mec element.

Background: CoNS species are likely reservoirs of the staphylococcal cassette chromosome mec (SCC mec ) in Staphylococcus aureus . S . aureus CC395 is unique as it is capable of exchanging DNA with CoNS via bacteriophages, which are also known to mediate transfer of SCC mec . Objectives: To analyse the structure and putative origin of the SCC mec element in S . aureus CC395. Methods: The only MRSA CC395 strain described in the literature, JS395, was subjected to WGS, and its SCC mec element was compared with those found in CoNS species and other S. aureus strains. Results: JS395 was found to carry an unusually large 88 kb composite SCC mec element. The 33 kb region downstream of orfX harboured a type V SCC mec element and a CRISPR locus, which was most similar to those found in the CoNS species Staphylococcus capitis and Staphylococcus schleiferi . A 55 kb SCC element was identified downstream of the type V SCC mec element and contained a mercury resistance region found in the composite SCC element of some Staphylococcus epidermidis and S . aureus strains, an integrated S . aureus plasmid containing genes for the detoxification of cadmium and arsenic, and a stretch of genes that was partially similar to the type IVg SCC mec element found in a bovine S . aureus strain. Conclusions: The size and complexity of the SCC mec element support the idea that CC395 is highly prone to DNA uptake from CoNS. Thus CC395 may serve as an entry point for SCC mec and SCC structures into S . aureus .

Whole-genome comparison of urinary pathogenic Escherichia coli and faecal isolates of UTI patients and healthy controls.

The faecal flora is a common reservoir for urinary tract infection (UTI), and Escherichia coli (E. coli) is frequently found in this reservoir without causing extraintestinal infection. We investigated these E. coli reservoirs by whole-genome sequencing a large collection of E. coli from healthy controls (faecal), who had never previously had UTI, and from UTI patients (faecal and urinary) sampled from the same geographical area. We compared MLST types, phylogenetic relationship, accessory genome content and FimH type between patient and control faecal isolates as well as between UTI and faecal-only isolates, respectively. Comparison of the accessory genome of UTI isolates to faecal isolates revealed 35 gene families which were significantly more prevalent in the UTI isolates compared to the faecal isolates, although none of these were unique to one of the two groups. Of these 35, 22 belonged to a genomic island and three putatively belonged to a type VI secretion system (T6SS). MLST types and SNP phylogeny indicated no clustering of the UTI or faecal E. coli from patients distinct from the control faecal isolates, although there was an overrepresentation of UTI isolates belonging to clonal lineages CC73 and CC12. One combination of mutations in FimH, N70S/S78N, was significantly associated to UTI, while phylogenetic analysis of FimH and fimH identified no signs of distinct adaptation of UTI isolates compared to faecal-only isolates not causing UTI. In summary, the results showed that (i) healthy women who had never previously had UTI carried faecal E. coli which were overall closely related to UTI and faecal isolates from UTI patients; (ii) UTI isolates do not cluster separately from faecal-only isolates based on SNP analysis; and (iii) 22 gene families of a genomic island, putative T6SS proteins as well as specific metabolism and virulence associated proteins were significantly more common in UTI isolates compared to faecal-only isolates and (iv) evolution of fimH for these isolates was not linked to the clinical source of the isolates, apart from the mutation combination N70S/S78N, which was correlated to UTI isolates of phylogroup B2. Combined, these findings illustrate that faecal and UTI isolates, as well as faecal-only and faecal-UTI isolates, are closely related and can only be distinguished, if at all, by their accessory genome.

Familial Clustering of Staphylococcus aureus Bacteremia in First-Degree Relatives: A Danish Nationwide Cohort Study.

BACKGROUND: A genetic predisposition to Staphylococcus aureus bacteremia has been demonstrated in animals, suggesting that genetic differences might influence susceptibility to S aureus in humans. OBJECTIVE: To determine whether a history of S aureus bacteremia in first-degree relatives increases the rate of the disease, and whether this rate is affected by the type of family relationship (that is, parent or sibling) or by how the relative acquired the infection. DESIGN: Register-based nationwide cohort study (1992 to 2011). SETTING: Denmark. PARTICIPANTS: First-degree relatives (children or siblings) of patients previously hospitalized with S aureus bacteremia. MEASUREMENTS: Poisson regression models were used to calculate standardized incidence ratios (SIRs) of S aureus bacteremia, with the incidence rate in the population as a reference. RESULTS: 34 774 individuals (the exposed cohort) with a first-degree relative (index case patient) previously hospitalized with S aureus bacteremia were followed up for a median of 7.8 years (interquartile range, 3.6 to 13.0). A higher rate of S aureus bacteremia was observed among these first-degree relatives (SIR, 2.49 [95% CI, 1.95 to 3.19]) than in the background population. The estimate was significantly higher if the index case patient was a sibling (SIR, 5.01 [CI, 3.30 to 7.62]) than a parent (SIR, 1.96 [CI, 1.45 to 2.67]; interaction P < 0.0001). No interaction was observed regarding the sex of the first-degree relative (interaction P for parents = 0.85; interaction P for siblings = 0.92). Stratifying by disease acquisition revealed the highest rates in individuals exposed to index case patients with non-hospital-acquired infection. Few were infected with genetically identical bacteremia isolates. LIMITATION: The rarity of the outcome limited the number of variables in the multiple regression analysis, and whether nonsignificant interactions were true or caused by insufficient statistical power remains uncertain. CONCLUSION: A significant familial clustering of S aureus bacteremia was found, with the greatest relative rate of disease observed in individuals exposed to siblings with a history of the disease. PRIMARY FUNDING SOURCE: The Danish Heart Foundation and the Christian Larsen and Judge Ellen Larsen Foundation.

Evidence for Human Adaptation and Foodborne Transmission of Livestock-Associated Methicillin-Resistant Staphylococcus aureus.

We investigated the evolution and epidemiology of a novel livestock-associated methicillin-resistant Staphylococcus aureus strain, which colonizes and infects urban-dwelling Danes even without a Danish animal reservoir. Genetic evidence suggests both poultry and human adaptation, with poultry meat implicated as a probable source.

Use of WGS data for investigation of a long-term NDM-1-producing Citrobacter freundii outbreak and secondary in vivo spread of blaNDM-1 to Escherichia coli, Klebsiella pneumoniae and Klebsiella oxytoca.

OBJECTIVES: An outbreak of NDM-1-producing Citrobacter freundii and possible secondary in vivo spread of blaNDM-1 to other Enterobacteriaceae were investigated. METHODS: From October 2012 to March 2015, meropenem-resistant Enterobacteriaceae were detected in 45 samples from seven patients at Aalborg University Hospital, Aalborg, Denmark. In silico resistance genes, Inc plasmid types and STs (MLST) were obtained from WGS data from 24 meropenem-resistant isolates (13 C. freundii, 6 Klebsiella pneumoniae, 4 Escherichia coli and 1 Klebsiella oxytoca) and 1 meropenem-susceptible K. oxytoca. The sequences of the meropenem-resistant C. freundii isolates were compared by phylogenetic analyses. In vitro susceptibility to 21 antimicrobial agents was tested. Furthermore, in vitro conjugation and plasmid characterization was performed. RESULTS: From the seven patients, 13 highly clonal ST18 NDM-1-producing C. freundii were isolated. The ST18 NDM-1-producing C. freundii isolates were only susceptible to tetracycline, tigecycline, colistin and fosfomycin (except for the C. freundii isolates from Patient 2 and Patient 7, which were additionally resistant to tetracycline). The E. coli and K. pneumoniae from different patients belonged to different STs, indicating in vivo transfer of blaNDM-1 in the individual patients. This was further supported by in vitro conjugation and detection of a 154 kb IncA/C2 plasmid with blaNDM-1. Patient screenings failed to reveal any additional cases. None of the patients had a history of recent travel abroad and the source of the blaNDM-1 plasmid was unknown. CONCLUSIONS: To our knowledge, this is the first report of an NDM-1-producing C. freundii outbreak and secondary in vivo spread of an IncA/C2 plasmid with blaNDM-1 to other Enterobacteriaceae.

Adaptation of Escherichia coli traversing from the faecal environment to the urinary tract.

The majority of extraintestinal pathogenic Escherichia coli (ExPEC) causing urinary tract infections (UTI) are found in the patient's own gut flora, but only limited knowledge is available on the potential adaptation that may occur in the bacteria in order to traverse the perineum and successfully infect the urinary tract. Here, matching pairs of faecal and UTI isolates from 42 patients were compared pairwise using in-depth whole-genome sequencing to investigate whether genetic changes were evident for successful colonization in these two different environments. The identified non-synonymous mutations (0-12 substitutions in each pair) were primarily associated to genes encoding virulence factors and nutrient metabolism; and indications of parallel evolution were observed in genes encoding the major phase-variable protein antigen 43, a toxin/antitoxin locus and haemolysin B. No differences in virulence potential were observed in a mouse UTI model for five matching faecal and UTI isolates with or without mutations in antigen 43 and haemolysin B. Variations in plasmid content were observed in only four of the 42 pairs. Although, we observed mutations in known UTI virulence genes for a few pairs, the majority showed no detectable differences with respect to mutations or mobilome when compared to their faecal counterpart. The results show that UPECs are successful in colonizing both the bladder and gut without adaptation.

Investigation of a possible outbreak of carbapenem-resistant Acinetobacter baumannii in Odense, Denmark using PFGE, MLST and whole-genome-based SNPs.

OBJECTIVES: The objectives were to study a possible outbreak of carbapenem-resistant Acinetobacter baumannii by comparing three different typing methods (PFGE, MLST and whole-genome SNPs) and to compare the resistance gene profiles of the isolates. METHODS: From December 2012 to October 2013, eight carbapenem-resistant A. baumannii were detected at Odense University Hospital, Odense, Denmark. These isolates were typed by PFGE, with ApaI and SmaI, respectively, and subjected to WGS. The WGS data were used for in silico extraction of MLST types using two different schemes, resistance genes and SNPs, to which 31 publicly available A. baumannii genomes were added. RESULTS: Using ApaI, the eight isolates had four different PFGE profiles, which were further differentiated using SmaI, separating one of the profiles into two distinct PFGE types. Five ST2 (Pasteur MLST) OXA-23-producing isolates, two ST1 OXA-72-producing isolates and one ST158 OXA-23-producing isolate were detected. The five ST2 isolates were subdivided into ST195, ST208 and ST218 using the Oxford MLST scheme. The phylogenetic analysis based on the core genome showed that six of the eight Danish A. baumannii isolates were located in three distinct clusters. The two remaining isolates did not cluster with other Danish or international isolates included in the study. Isolates that clustered using PFGE, Oxford MLST and phylogenetic analysis also shared similar resistance gene profiles. CONCLUSIONS: The SNP profile, Oxford MLST, PFGE and resistance gene profiles clearly indicated spread of three different A. baumannii strains.

Role of urinary cathelicidin LL-37 and human ß-defensin 1 in uncomplicated Escherichia coli urinary tract infections.

Cathelicidin (LL-37) and human ß-defensin 1 (hBD-1) are important components of the innate defense in the urinary tract. The aim of this study was to characterize whether these peptides are important for developing uncomplicated Escherichia coli urinary tract infections (UTIs). This was investigated by comparing urinary peptide levels of UTI patients during and after infection to those of controls, as well as characterizing the fecal flora of participants with respect to susceptibility to LL-37 and in vivo virulence. Forty-seven UTI patients and 50 controls who had never had a UTI were included. Participants were otherwise healthy, premenopausal, adult women. LL-37 MIC levels were compared for fecal E. coli clones from patients and controls and were also compared based on phylotypes (A, B1, B2, and D). In vivo virulence was investigated in the murine UTI model by use of selected fecal isolates from patients and controls. On average, UTI patients had significantly more LL-37 in urine during infection than postinfection, and patient LL-37 levels postinfection were significantly lower than those of controls. hBD-1 showed similar urine levels for UTI patients and controls. Fecal E. coli isolates from controls had higher LL-37 susceptibility than fecal and UTI E. coli isolates from UTI patients. In vivo studies showed a high level of virulence of fecal E. coli isolates from both patients and controls and showed no difference in virulence correlated with the LL-37 MIC level. The results indicate that the concentration of LL-37 in the urinary tract and low susceptibility to LL-37 may increase the likelihood of UTI in a complex interplay between host and pathogen attributes.

Penetrance of hypertrophic cardiomyopathy in children and adolescents: a 12-year follow-up study of clinical screening and predictive genetic testing.

BACKGROUND: The penetrance of hypertrophic cardiomyopathy (HCM) during childhood and adolescence has been only sparsely described. We studied the penetrance of HCM and the short- and long-term outcomes of clinical screening and predictive genetic testing of child relatives of patients with HCM. METHODS AND RESULTS: Ninety probands and 361 relatives were included in a family screening program for HCM (1994-2001). Eleven sarcomere genes, CRYAB, α-GAL, and titin were screened. Sixty-six relatives and 4 probands were <18 years of age at inclusion. Twelve child relatives were mutation carriers (age, 12 ± 5 years), and 26 had unknown genetic status, ie, relatives from families without identified mutations (n = 21) or not tested (n = 5) (age, 11 ± 5 years). Twenty-eight noncarriers (42%; age, 10 ± 4 years) served as control subjects. Two of 38 child relatives (5%) at risk of developing HCM fulfilled diagnostic criteria for HCM at inclusion. After 12 ± 1 years of follow-up, 2 of the 36 (6%; 95% confidence interval, 2-18) at-risk child relatives who were phenotype negative at inclusion had developed the HCM phenotype at 26 and 28 years of age. During follow-up, none of the child relatives experienced serious cardiac events. Participation in the screening program had no long-term negative psychological impact. CONCLUSIONS: The penetrance of HCM in phenotype-negative child relatives at risk of developing HCM was 6% after 12 years of follow-up. The finding of phenotype conversion in the mid-20s warrants continued screening into adulthood. Forty-two percent of the child relatives were noncarriers, and repeat clinical follow-up could be safely limited to the remaining children.

Genome sequence of Staphylococcus aureus strain 11819-97, an ST80-IV European community-acquired methicillin-resistant isolate.

The European methicillin-resistant Staphylococcus aureus (MRSA) clone ST80-IV has historically dominated community-associated infections in major parts of Europe and is a lineage strongly linked to skin and soft tissue infections. Here, we report the genome sequence of an ST80-IV representative, 11819-97, isolated from a skin infection in Denmark in 1997.