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1.  Risk and prognosis of Staphylococcus aureus bacteremia among individuals with and without end-stage renal disease: a Danish, population-based cohort study 
Background
Staphylococcus aureus is a leading cause of bloodstream infections among hemodialysis patients and of exit-site infections among peritoneal dialysis patients. However, the risk and prognosis of Staphylococcus aureus bacteremia among end-stage renal disease patients have not been delineated.
Methods
In this Danish nationwide, population-based cohort study patients with end-stage renal disease and matched population controls were observed from end-stage renal disease diagnosis/sampling until first episode of Staphylococcus aureus bacteremia, death, or end of study period. Staphylococcus aureus positive blood cultures, hospitalization, comorbidity, and case fatality were obtained from nationwide microbiological, clinical, and administrative databases. Incidence rates and risk factors were assessed by regression analysis.
Results
The incidence rate of Staphylococcus aureus bacteremia was very high for end-stage renal disease patients (35.7 per 1,000 person-years; 95% CI, 33.8-37.6) compared to population controls (0.5 per 1,000 person-years; 95% CI, 0.5-0.6), yielding a relative risk of 65.1 (95% CI, 59.6-71.2) which fell to 28.6 (95% CI, 23.3-35.3) after adjustment for sex, age, and comorbidity. After stratification for type of renal replacement therapy, we found the highest incidence rate of Staphylococcus aureus bacteremia among hemodialysis patients (46.3 per 1,000 person-years) compared to peritoneal dialysis patients (22.0 per 1,000 person-years) and renal transplant recipients (8.9 per 1,000 person-years). In persons with Staphylococcus aureus bacteremia, ninety-day case fatality was 18.2% (95% CI, 16.2%-20.3%) for end-stage renal disease patients and 33.7% (95% CI, 30.3-37.3) for population controls.
Conclusions
Patients with end-stage renal disease, and hemodialysis patients in particular, have greatly increased risk of Staphylococcus aureus bacteremia compared to population controls. Future challenges will be to develop strategies to reduce Staphylococcus aureus bacteremia-related morbidity and death in this high-risk population.
Electronic supplementary material
The online version of this article (doi:10.1186/s12879-014-0740-8) contains supplementary material, which is available to authorized users.
doi:10.1186/s12879-014-0740-8
PMCID: PMC4296555  PMID: 25566857
Bacteremia; Staphylococcus aureus; End-stage renal disease; Dialysis
3.  Origin and Evolution of European Community-Acquired Methicillin-Resistant Staphylococcus aureus 
mBio  2014;5(5):e01044-14.
ABSTRACT
Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was recognized in Europe and worldwide in the late 1990s. Within a decade, several genetically and geographically distinct CA-MRSA lineages carrying the small SCCmec type IV and V genetic elements and the Panton-Valentine leukocidin (PVL) emerged around the world. In Europe, the predominant CA-MRSA strain belongs to clonal complex 80 (CC80) and is resistant to kanamycin/amikacin and fusidic acid. CC80 was first reported in 1993 but was relatively rare until the late 1990s. It has since been identified throughout North Africa, the Middle East, and Europe, with recent sporadic reports in sub-Saharan Africa. While strongly associated with skin and soft tissue infections, it is rarely found among asymptomatic carriers. Methicillin-sensitive S. aureus (MSSA) CC80 strains are extremely rare except in sub-Saharan Africa. In the current study, we applied whole-genome sequencing to a global collection of both MSSA and MRSA CC80 isolates. Phylogenetic analyses strongly suggest that the European epidemic CA-MRSA lineage is derived from a PVL-positive MSSA ancestor from sub-Saharan Africa. Moreover, the tree topology suggests a single acquisition of both the SCCmec element and a plasmid encoding the fusidic acid resistance determinant. Four canonical SNPs distinguish the derived CA-MRSA lineage and include a nonsynonymous mutation in accessory gene regulator C (agrC). These changes were associated with a star-like expansion into Europe, the Middle East, and North Africa in the early 1990s, including multiple cases of cross-continent imports likely driven by human migrations.
IMPORTANCE
With increasing levels of CA-MRSA reported from most parts of the Western world, there is a great interest in understanding the origin and factors associated with the emergence of these epidemic lineages. To trace the origin, evolution, and dissemination pattern of the European CA-MRSA clone (CC80), we sequenced a global collection of strains of the S. aureus CC80 lineage. Our study determined that a single descendant of a PVL-positive methicillin-sensitive ancestor circulating in sub-Saharan Africa rose to become the dominant CA-MRSA clone in Europe, the Middle East, and North Africa. In the transition from a methicillin-susceptible lineage to a successful CA-MRSA clone, it simultaneously became resistant to fusidic acid, a widely used antibiotic for skin and soft tissue infections, thus demonstrating the importance of antibiotic selection in the success of this clone. This finding furthermore highlights the significance of horizontal gene acquisitions and underscores the combined importance of these factors for the success of CA-MRSA.
doi:10.1128/mBio.01044-14
PMCID: PMC4173770  PMID: 25161186
4.  Novel Organization of the Arginine Catabolic Mobile Element and Staphylococcal Cassette Chromosome mec Composite Island and Its Horizontal Transfer between Distinct Staphylococcus aureus Genotypes 
Antimicrobial Agents and Chemotherapy  2013;57(11):5774-5777.
In this study, 425 methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered in the Dutch-German Euregio were investigated for the presence of the arginine catabolic mobile element (ACME). Sequence analysis by whole-genome sequencing revealed an entirely new organization of the ACME-staphylococcal cassette chromosome mec composite island (SCCmec-CI), with truncated ACME type II located downstream of SCCmec. An identical nucleotide sequence of ACME-SCCmec-CI was found in two distinct MRSA lineages (t064-ST8 and t002-ST5), which has not been reported previously in S. aureus.
doi:10.1128/AAC.01321-13
PMCID: PMC3811323  PMID: 24002094
5.  Outcome and reinfection after Staphylococcus aureus bacteraemia in individuals with and without HIV-1 infection: a case–control study 
BMJ Open  2014;4(4):e004075.
Objectives
Individuals infected with HIV-1 are at an increased risk of Staphylococcus aureus bacteraemia (SAB). The aim of this study was to investigate mortality rate and risk of reinfection associated with SAB in HIV-1-infected individuals compared to individuals without HIV-1 infection.
Setting
University hospital treating a third of the estimated 5000 individuals with HIV infection in Denmark.
Participants
HIV-1-infected (n=82) and sex-matched and age-matched uninfected (n=163) individuals with SAB in the time period 1 January 1995 to 31 December 2010.
Primary outcome measures
30-day and 365-day mortality rate ratio and relative risk of reinfection.
Results
Individuals with HIV had an increased risk of death at day 30 (OR 11.90 (95% CI 2.15 to 65.85)) compared to individuals without HIV. Other factors associated with mortality were age, a foreign device and Pitt score. HIV-related factors did not associate to mortality. During follow-up, there were 43 episodes of reinfection; in individuals with HIV infection at an incidence rate of 7.8 (95% CI 4.7 to 10.9)/100 person-years compared with 2.2 (95% CI 1.2 to 3.2)/100 person-years for individuals without HIV. In multivariate analysis, HIV status (OR 2.91 (95% CI 1.29 to 6.58) and injection drug use (OR 3.51 (95% CI 1.06 to 11.63) were independently associated with an increased risk of reinfection.
Conclusions
HIV-1 infection is associated with an increased risk of 30-day mortality after SAB and a very high rate of reinfection. Age, a foreign device and Pitt score predicted outcome. For patients infected with HIV, neither CD4 T-lymphocyte counts nor plasma HIV RNA levels were associated with 30-day outcome.
Trial registration number
The study was approved by the Danish Data Protection Agency (record no. 2007-41-1196).
doi:10.1136/bmjopen-2013-004075
PMCID: PMC4010819  PMID: 24760348
6.  Phylogenetic Analysis of Staphylococcus aureus CC398 Reveals a Sub-Lineage Epidemiologically Associated with Infections in Horses 
PLoS ONE  2014;9(2):e88083.
In the early 2000s, a particular MRSA clonal complex (CC398) was found mainly in pigs and pig farmers in Europe. Since then, CC398 has been detected among a wide variety of animal species worldwide. We investigated the population structure of CC398 through mutation discovery at 97 genetic housekeeping loci, which are distributed along the CC398 chromosome within 195 CC398 isolates, collected from various countries and host species, including humans. Most of the isolates in this collection were received from collaborating microbiologists, who had preserved them over years. We discovered 96 bi-allelic polymorphisms, and phylogenetic analyses revealed that an epidemic sub-clone within CC398 (dubbed ‘clade (C)’) has spread within and between equine hospitals, where it causes nosocomial infections in horses and colonises the personnel. While clade (C) was strongly associated with S. aureus from horses in veterinary-care settings (p = 2×10−7), it remained extremely rare among S. aureus isolates from human infections.
doi:10.1371/journal.pone.0088083
PMCID: PMC3913741  PMID: 24505386
7.  Evaluation of a Modular Multiplex-PCR Methicillin-Resistant Staphylococcus aureus Detection Assay Adapted for mecC Detection 
Journal of Clinical Microbiology  2013;51(6):1917-1919.
A mecC (mecALGA251)-adapted multiplex PCR-based methicillin-resistant Staphylococcus aureus (MRSA) detection assay was evaluated using an international, spa-typed Staphylococcus aureus collection comprising 51 mecC-positive MRSA, 240 mecA-positive MRSA, and 50 mecA- and mecC-negative methicillin-susceptible S. aureus (MSSA) isolates. The assay showed 100% sensitivity and specificity for S. aureus species identification as well as for mecA and mecC detection.
doi:10.1128/JCM.00075-13
PMCID: PMC3716076  PMID: 23515551
8.  Rapid Differentiation between Livestock-Associated and Livestock-Independent Staphylococcus aureus CC398 Clades 
PLoS ONE  2013;8(11):e79645.
Staphylococcus aureus clonal complex 398 (CC398) isolates cluster into two distinct phylogenetic clades based on single-nucleotide polymorphisms (SNPs) revealing a basal human clade and a more derived livestock clade. The scn and tet(M) genes are strongly associated with the human and the livestock clade, respectively, due to loss and acquisition of mobile genetic elements. We present canonical single-nucleotide polymorphism (canSNP) assays that differentiate the two major host-associated S. aureus CC398 clades and a duplex PCR assay for detection of scn and tet(M). The canSNP assays correctly placed 88 S. aureus CC398 isolates from a reference collection into the human and livestock clades and the duplex PCR assay correctly identified scn and tet(M). The assays were successfully applied to a geographically diverse collection of 272 human S. aureus CC398 isolates. The simple assays described here generate signals comparable to a whole-genome phylogeny for major clade assignment and are easily integrated into S. aureus CC398 surveillance programs and epidemiological studies.
doi:10.1371/journal.pone.0079645
PMCID: PMC3828327  PMID: 24244535
9.  Novel mutations in penicillin-binding protein genes in clinical Staphylococcus aureus isolates that are methicillin resistant on susceptibility testing, but lack the mec gene 
Objectives
Methicillin-resistant Staphylococcus aureus (MRSA) is an important global health problem. MRSA resistance to β-lactam antibiotics is mediated by the mecA or mecC genes, which encode an alternative penicillin-binding protein (PBP) 2a that has a low affinity to β-lactam antibiotics. Detection of mec genes or PBP2a is regarded as the gold standard for the diagnosis of MRSA. We identified four MRSA isolates that lacked mecA or mecC genes, but were still phenotypically resistant to pencillinase-resistant β-lactam antibiotics.
Methods
The four human S. aureus isolates were investigated by whole genome sequencing and a range of phenotypic assays.
Results
We identified a number of amino acid substitutions present in the endogenous PBPs 1, 2 and 3 that were found in the resistant isolates but were absent in closely related susceptible isolates and which may be the basis of resistance. Of particular interest are three identical amino acid substitutions in PBPs 1, 2 and 3, occurring independently in isolates from at least two separate multilocus sequence types. Two different non-conservative substitutions were also present in the same amino acid of PBP1 in two isolates from two different sequence types.
Conclusions
This work suggests that phenotypically resistant MRSA could be misdiagnosed using molecular methods alone and provides evidence of alternative mechanisms for β-lactam resistance in MRSA that may need to be considered by diagnostic laboratories.
doi:10.1093/jac/dkt418
PMCID: PMC3922151  PMID: 24216768
β-lactams; MRSA; mecA; mecC
10.  Livestock Origin for a Human Pandemic Clone of Community-Associated Methicillin-Resistant Staphylococcus aureus 
mBio  2013;4(4):e00356-13.
ABSTRACT
The importance of livestock as a source of bacterial pathogens with the potential for epidemic spread in human populations is unclear. In recent years, there has been a global increase in community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections of healthy humans, but an understanding of the different evolutionary origins of CA-MRSA clones and the basis for their recent expansion is lacking. Here, using a high-resolution phylogenetic approach, we report the discovery of two emergent clones of human epidemic CA-MRSA which resulted from independent livestock-to-human host jumps by the major bovine S. aureus complex, CC97. Of note, one of the new clones was isolated from human infections on four continents, demonstrating its global dissemination since the host jump occurred over 40 years ago. The emergence of both human S. aureus clones coincided with the independent acquisition of mobile genetic elements encoding antimicrobial resistance and human-specific mediators of immune evasion, consistent with an important role for these genetic events in the capacity to survive and transmit among human populations. In conclusion, we provide evidence that livestock represent a reservoir for the emergence of new human-pathogenic S. aureus clones with the capacity for pandemic spread. These findings have major public health implications highlighting the importance of surveillance for early identification of emergent clones and improved transmission control measures at the human-livestock interface.
IMPORTANCE
Animals are the major source of new pathogens affecting humans. However, the potential for pathogenic bacteria that originally were found in animals to switch hosts and become widely established in human populations is not clear. Here, we report the discovery of emergent clones of methicillin-resistant Staphylococcus aureus (MRSA) that originated in livestock and switched to humans, followed by host-adaptive evolution and epidemic spread in global human populations. Our findings demonstrate that livestock can act as a reservoir for the emergence of new human bacterial clones with potential for pandemic spread, highlighting the potential role of surveillance and biosecurity measures in the agricultural setting for preventing the emergence of new human pathogens.
doi:10.1128/mBio.00356-13
PMCID: PMC3747577  PMID: 23943757
11.  Use of Vitek 2 Antimicrobial Susceptibility Profile To Identify mecC in Methicillin-Resistant Staphylococcus aureus 
Journal of Clinical Microbiology  2013;51(8):2732-2734.
The emergence of mecC methicillin-resistant Staphylococcus aureus (MRSA) poses a diagnostic challenge for clinical microbiology laboratories. Using the Vitek 2 system, we tested a panel of 896 Staphylococcus aureus isolates and found that an oxacillin-sensitive/cefoxitin-resistant profile had a sensitivity of 88.7% and a specificity of 99.5% for the identification of mecC MRSA isolates. The presence of the mecC gene, determined by bacterial whole-genome sequencing, was used as the gold standard. This profile could provide a zero-cost screening method for identification of mecC-positive MRSA strains.
doi:10.1128/JCM.00847-13
PMCID: PMC3719650  PMID: 23720794
12.  Staphylococcus aureus CC398 Clade Associated with Human-to-Human Transmission 
Applied and Environmental Microbiology  2012;78(24):8845-8848.
Staphylococcus aureus clonal complex 398 (CC398) isolates colonize livestock and can spread to human contacts. Genetic analysis of isolates epidemiologically associated with human-to-human, but not livestock, transmission in multiple countries and continents identified a common clade that was negative for tet(M) and positive for bacteriophage ϕ3. Another group of human-to-human-transmitted isolates belonged to the common livestock-associated clade but had acquired a unique ϕ7 bacteriophage.
doi:10.1128/AEM.02398-12
PMCID: PMC3502926  PMID: 23042163
13.  Dynamic of Livestock-Associated Methicillin-Resistant Staphylococcus aureus CC398 in Pig Farm Households: A Pilot Study 
PLoS ONE  2013;8(5):e65512.
The aim of this study was to determine the long-term carriage rates and transmission dynamics of methicillin-resistant Staphylococcus aureus (MRSA) in pig farmers and their household members. During a 6-month period in 2009–2010, 4 pig farms in Denmark, Belgium, and the Netherlands, respectively, were studied for the presence of MRSA. The proportion of persistent carriers was significantly higher among farmers than among household members (87% vs. 11%) and significantly higher in household members from Belgium compared to those from Denmark and the Netherlands (29% vs. 0% vs. 6%). Determinant analysis of MRSA carriage revealed that pig contact was the most important determinant for MRSA carriage among household members and that the increased MRSA carriage rate observed among household members from Belgium is linked to country-specific differences in pig exposure.
These findings demonstrated that even in pig farms with very high carriage rates of MRSA both in livestock and farmers, the risk for household members to acquire MRSA is limited and still depends strongly on pig exposure. By restricting access to the stables and exposure to pigs, MRSA acquisition by household members could be greatly reduced.
doi:10.1371/journal.pone.0065512
PMCID: PMC3669288  PMID: 23741497
14.  Genome Analysis of Staphylococcus aureus ST291, a Double Locus Variant of ST398, Reveals a Distinct Genetic Lineage 
PLoS ONE  2013;8(5):e63008.
Staphylococcus aureus ST291 has been reported as a homologue recombinant double locus variant of the livestock associated S. aureus ST398. However, whole genome sequencing show that ST291 is a unique genetic lineage with highly variable content within its accessory genome compared to both human and livestock associated genome sequenced CC398s.
doi:10.1371/journal.pone.0063008
PMCID: PMC3660392  PMID: 23704886
15.  Staphylococcus epidermidis Isolated in 1965 Are More Susceptible to Triclosan than Current Isolates 
PLoS ONE  2013;8(4):e62197.
Since its introduction to the market in the 1970s, the synthetic biocide triclosan has had widespread use in household and medical products. Although decreased triclosan susceptibility has been observed for several bacterial species, when exposed under laboratory settings, no in vivo studies have associated triclosan use with decreased triclosan susceptibility or cross-resistance to antibiotics. One major challenge of such studies is the lack of strains that with certainty have not been exposed to triclosan. Here we have overcome this challenge by comparing current isolates of the human opportunistic pathogen Staphylococcus epidermidis with isolates collected in the 1960s prior to introduction of triclosan to the market. Of 64 current S. epidermidis isolates 12.5% were found to have tolerance towards triclosan defined as MIC≥0.25 mg/l compared to none of 34 isolates obtained in the 1960s. When passaged in the laboratory in the presence of triclosan, old and current susceptible isolates could be adapted to the same triclosan MIC level as found in current tolerant isolates. DNA sequence analysis revealed that laboratory-adapted strains carried mutations in fabI encoding the enoyl-acyl carrier protein reductase isoform, FabI, that is the target of triclosan, and the expression of fabI was also increased. However, the majority of the tolerant current isolates carried no mutations in fabI or the putative promoter region. Thus, this study indicates that the widespread use of triclosan has resulted in the occurrence of S. epidermidis with tolerance towards triclosan and that the adaptation involves FabI as well as other factors. We suggest increased caution in the general application of triclosan as triclosan has not shown efficacy in reducing infections and is toxic to aquatic organisms.
doi:10.1371/journal.pone.0062197
PMCID: PMC3628582  PMID: 23614034
17.  Whole genome sequencing identifies zoonotic transmission of MRSA isolates with the novel mecA homologue mecC 
EMBO Molecular Medicine  2013;5(4):509-515.
Several methicillin-resistant Staphylococcus aureus (MRSA) lineages that carry a novel mecA homologue (mecC) have recently been described in livestock and humans. In Denmark, two independent human cases of mecC-MRSA infection have been linked to a livestock reservoir. We investigated the molecular epidemiology of the associated MRSA isolates using whole genome sequencing (WGS). Single nucleotide polymorphisms (SNP) were defined and compared to a reference genome to place the isolates into a phylogenetic context. Phylogenetic analysis revealed two distinct farm-specific clusters comprising isolates from the human case and their own livestock, whereas human and animal isolates from the same farm only differed by a small number of SNPs, which supports the likelihood of zoonotic transmission. Further analyses identified a number of genes and mutations that may be associated with host interaction and virulence. This study demonstrates that mecC-MRSA ST130 isolates are capable of transmission between animals and humans, and underscores the potential of WGS in epidemiological investigations and source tracking of bacterial infections.
doi:10.1002/emmm.201202413
PMCID: PMC3628104  PMID: 23526809
cattle; mecC; MRSA; sheep; zoonosis
20.  Cross-contamination: Comparison of Nasal and Chronic Leg Ulcer Staphylococcus aureus Strains Isolated from the Same Patient 
The aim of this study was to investigate the occurrence of bacterial cross-contamination between the nasal cavity and leg ulcers. Sixteen patients were included in the study. Staphylococcus aureus was isolated from the leg ulcer of 13 patients and 6 of these patients also harboured S. aureus in the nasal cavity. Klebsiella oxytoca was found in the ulcer and the nasal cavity of one patient. PFGE analysis revealed that patients harbouring S. aureus both in the nasal cavity and the leg ulcer had the same bacterial type at both sites. None of the S. aureus isolates were methicillin resistant.
doi:10.2174/1874285801307010006
PMCID: PMC3580757  PMID: 23459213
Staphylococcus aureus; nasal carriage; chronic leg ulcers; cross-contamination; Klebsiella oxytoca.
21.  Stable incidence and continued improvement in short term mortality of Staphylococcus aureus bacteraemia between 1995 and 2008 
BMC Infectious Diseases  2012;12:260.
Background
The objective of this study was to assess temporal changes in incidence and short term mortality of Staphylococcus aureus bacteraemia (SAB) from 1995 through 2008.
Methods
The study was conducted as a nation-wide observational cohort study with matched population controls. The setting was hospitalized patients in Denmark 1995-2008. Uni- and multivariate analyses were used to analyze the hazard of death within 30 days from SAB.
Results
A total of 16 330 cases of SAB were identified: 57% were hospital-associated (HA), 31% were community-acquired (CA) and 13% were of undetermined acquisition. The overall adjusted incidence rate remained stable at 23 per 100 000 population but the proportion of SAB cases older than 75 years increased significantly. Comorbidity in the cohort as measured by Charlson comorbidity index (CCI) score and alcohol-related diagnoses increased over the study period. In contrast, among the population controls the CCI remained stable and alcohol-related diagnoses increased slightly. For HA SAB crude 30-day mortality decreased from 27.8% to 21.8% (22% reduction) whereas the change for CA SAB was small (26.5% to 25.8%). By multivariate Cox regression, age, female sex, time period, CCI score and alcohol-related diagnoses were associated with increased mortality regardless of mode of acquisition.
Conclusions
Throughout a 14-year period the overall incidence of SAB remained stable while the overall short term prognosis continued to improve despite increased age and accumulation of comorbidity in the cohort. However, age and comorbidity were strong prognostic indicators for short term mortality.
doi:10.1186/1471-2334-12-260
PMCID: PMC3507819  PMID: 23075215
Bacteraemia; Epidemiology; Incidence; Mortality; Comorbidity; Alcoholism; Staphylococcus aureus; Charlson comorbidity index
22.  Genome Sequence of Staphylococcus aureus Strain 11819-97, an ST80-IV European Community-Acquired Methicillin-Resistant Isolate 
Journal of Bacteriology  2012;194(6):1625-1626.
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.
doi:10.1128/JB.06653-11
PMCID: PMC3294860  PMID: 22374956
23.  Influence of Host Genetics and Environment on Nasal Carriage of Staphylococcus aureus in Danish Middle-Aged and Elderly Twins 
The Journal of Infectious Diseases  2012;206(8):1178-1184.
Background. Nasal carriage is a major risk factor for Staphylococcus aureus infection. Approximately, one-quarter of adults carry S. aureus. However, the role of host genetics on S. aureus nasal carriage is unknown.
Methods. Nasal swabs were obtained from a national cohort of middle-aged and elderly Danish twins. Subjects colonized with S. aureus were identified by growth on selective plates and spa typing. A second sample was obtained from twins initially concordant for carriage. Twins found to again be colonized with S. aureus were defined as persistent carriers.
Results. The prevalence of S. aureus carriage among 617 twin pairs (monozygotic/dizygotic pairs: 112/505) was 26.3% (95% confidence interval [CI], 24.0%–28.9%). The concordance rate for carriage did not differ significantly between pairs of monozygotic (37.5%; 95% CI, 22.3%–53.8%) twins and same sex (24.2%; 95% CI, 15.4%–34.5%), and opposite sex (21.4%; 95% CI, 12.0%–33.4%) dizygotic twins. Despite shared childhoods, only 1 of 617 pairs was concordant with respect to lineage. Although heritability increased for S. aureus and lineage persistency, no significant heritability was detected.
Conclusion. In this study, host genetic factors exhibited only a modest influence on the S. aureus carrier state of middle-aged and elderly individuals.
doi:10.1093/infdis/jis491
PMCID: PMC3448969  PMID: 22872733
24.  Prevalence of infective endocarditis in patients with Staphylococcus aureus bacteraemia: the value of screening with echocardiography 
Aims
Staphylococcus aureus infective endocarditis (IE) is a critical medical condition associated with a high morbidity and mortality. In the present study, we prospectively evaluated the importance of screening with echocardiography in an unselected S. aureus bacteraemia (SAB) population.
Methods and results
From 1 January 2009 to 31 August 2010, a total of 244 patients with SAB at six Danish hospitals underwent screening echocardiography. The inclusion rate was 73% of all eligible patients (n= 336), and 53 of the 244 included patients (22%; 95% CI: 17–27%) were diagnosed with definite IE. In patients with native heart valves the prevalence was 19% (95% CI: 14–25%) compared with 38% (95% CI: 20–55%) in patients with prosthetic heart valves and/or cardiac rhythm management devices (P= 0.02). No difference was found between Main Regional Hospitals and Tertiary Cardiac Hospitals, 20 vs. 23%, respectively (NS). The prevalence of IE in high-risk patients with one or more predisposing condition or clinical evidence of IE were significantly higher compared with low-risk patients with no additional risk factors (38 vs. 5%; P < 0.001). IE was associated with a higher 6 months mortality, 14(26%) vs. 28(15%) in SAB patients without IE, respectively (P < 0.05).
Conclusion
SAB patients carry a high risk for development of IE, which is associated with a worse prognosis compared with uncomplicated SAB. The presenting symptoms and clinical findings associated with IE are often non-specific and echocardiography should always be considered as part of the initial evaluation of SAB patients.
doi:10.1093/ejechocard/jer023
PMCID: PMC3117467  PMID: 21685200
Infective endocarditis; Echocardiography; Staphylococcus aureus; Screening
25.  Genetic Variability in Beta-Defensins Is Not Associated with Susceptibility to Staphylococcus aureus Bacteremia 
PLoS ONE  2012;7(2):e32315.
Introduction
Human beta-defensins are key components of human innate immunity to a variety of pathogens, including Staphylococcus aureus. The aim of the present study was to investigate a potential association between gene variations in DEFB1 and DEFB103/DEFB4 and the development of S. aureus bacteremia (SAB) employing a case-control design.
Methods
Cases were unique patients with documented SAB, identified with the National S. aureus Bacteremia Register, a comprehensive dataset of all episodes of community associated-SABs (CA-SAB) occurring in children (≤20 yrs) in Denmark from 1990 to 2006. Controls were age-matched healthy individuals with no history of SAB. DNA obtained from cases and controls using the Danish Newborn Screening Biobank were genotyped for functional polymorphisms of DEFB1 by Sanger sequencing and copy number variation of the DEFB103 and DEFB4 genes using Pyrosequencing-based Paralogue Ratio Test (P-PRT).
Results
193 ethnic Danish SAB cases with 382 age-matched controls were used for this study. S. aureus isolates represented a variety of bacterial (i.e., different spa types) types similar to SAB isolates in general. DEFB1 minor allele frequencies of rs11362 (cases vs. controls 0.47/0.44), rs1800972 (0.21/0.24), and rs1799946 (0.32/0.33) were not significantly different in cases compared with controls. Also, DEFB4/DEFB103 gene copy numbers (means 4.83/4.92) were not significantly different in cases compared with controls.
Conclusions
Using a large, unique cohort of pediatric CA-SAB, we found no significant association between DEFB1 genetic variation or DEFB4/DEFB103 gene copy number and susceptibility for SAB.
doi:10.1371/journal.pone.0032315
PMCID: PMC3285211  PMID: 22384213

Results 1-25 (48)