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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. [ABSTRACT FROM AUTHOR]

Aims: To investigate the 1-year risks of Staphylococcus aureus bacteraemia (SAB), sepsis, and pneumonia in patients who underwent percutaneous coronary intervention and were treated with ticagrelor vs. clopidogrel., Methods and Results: In this nationwide observational cohort study, 26 606 patients who underwent urgent or emergent percutaneous coronary intervention (January 2011-December 2017) and initiated treatment with ticagrelor [N = 20 073 (75.5%); median age 64 years (25th-75th percentile 55-72 years); 74.8% men] or clopidogrel [N = 6533 (24.5%); median age 68 years (25th-75th percentile 58-77 years); 70.2% men] were identified using Danish nationwide registries. The 1-year standardized absolute risks of outcomes was calculated based on cause-specific Cox regression models, and average treatment effects between treatment groups were obtained as standardized differences in absolute 1-year risks. The absolute 1-year risk of SAB was 0.10% [95% confidence interval (CI), 0.05-0.15%] in the ticagrelor group and 0.29% (95% CI, 0.17-0.42%) in the clopidogrel group. Compared with clopidogrel, treatment with ticagrelor was associated with a significantly lower absolute 1-year risk of SAB [absolute risk difference -0.19% (95% CI, -0.32% to -0.05%), P value 0.006]. Likewise, treatment with ticagrelor was associated with a significantly lower absolute 1-year risk of sepsis [0.99% (95% CI, 0.83-1.14%) vs. 1.49% (95% CI, 1.17-1.80%); absolute risk difference -0.50% (95% CI, -0.86% to -0.14%), P value 0.007] and pneumonia [3.13% (95% CI, 2.86-3.39%) vs. 4.56% (95% CI, 4.03-5.08%); absolute risk difference -1.43% (95% CI, -2.03% to -0.82%), P value < 0.001] compared with clopidogrel., Conclusion: Treatment with ticagrelor was associated with a significantly lower 1-year risk of SAB, sepsis, and pneumonia compared with clopidogrel., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Introduction: Staphylococcus aureus bacteremia (SAB) is a high-risk infection and feared complication related to hemodialysis. This study aimed to investigate incidence and risk factors for SAB depending on hemodialysis access type., Methods: The Danish National Registry on Regular Dialysis and Transplantation was used to identify patients from January 1, 1996 to December 31, 2011 with end-stage kidney disease. Patients were followed until death, the first episode of SAB, or end of study (December 31, 2011). Independent risk factors were assessed by multivariable Poisson regression with time-updated exposure variables., Findings: Total of 9997 patients were included. The initial modality of renal replacement therapy was hemodialysis in 6826 patients and peritoneal dialysis in 2882 patients; 289 patients had preemptive kidney transplantation. SAB occurred in 1278 patients (12.8%). The incidence rate of SAB declined after 90 days and leveled off after 270 days in hemodialysis, peritoneal dialysis, and kidney transplanted. As compared to peritoneal dialysis, the adjusted rate ratio (RR) for SAB was 7.42 (95% CI 5.63-9.79) in uncuffed central venous catheter (CVC), 5.68 (95% CI 4.39-7.36) in cuffed CVC, 4.43 (95% CI 2.10-9.53) in arteriovenous graft, and 3.40 (95% CI 2.79-4.15) in arteriovenous fistula. SAB risk did not differ between uncuffed and cuffed CVC. The risk of SAB was increased during the first three months of renal replacement therapy especially for CVC (RR 11.37 [95% CI7.09-18.22]) compared with peritoneal dialysis. Diabetes mellitus (RR 1.35 [95% CI 1.20-1.51]) and male sex (RR 1.15 [95% CI 1.03-1.29]) were also associated with SAB., Discussion: Patients on hemodialysis had a high incidence rate of SAB, particularly those undergoing hemodialysis via CVC. SAB risk was comparable for cuffed and uncuffed CVC. Diabetes mellitus, male sex, and the first three months in renal replacement therapy were independently associated with SAB., (© 2019 International Society for Hemodialysis.)

Background: Livestock-associated methicillin-resistant Staphylococcus aureus clonal complex 398 (LA-MRSA CC398) is causing an increasing number of skin and soft tissue infections (SSTIs) in Denmark and other European countries with industrial pig production. Yet, its impact on MRSA bloodstream infections (BSIs) has not been well studied., Methods: We investigated the clinical epidemiology of all human cases of LA-MRSA CC398 BSI during 2010-2015. Cases of LA-MRSA CC398 BSI were compared to cases of BSI caused by other types of MRSA and cases of SSTI caused by LA-MRSA CC398. Whole-genome sequence analysis was used to assess the phylogenetic relationship among LA-MRSA CC398 isolates from Danish pigs and cases of BSI and SSTI., Results: The number of LA-MRSA CC398 BSIs and SSTIs increased over the years, peaking in 2014, when LA-MRSA CC398 accounted for 16% (7/44) and 21% (211/985) of all MRSA BSIs and SSTIs, corresponding to 1.2 and 37.4 cases of BSI and SSTI per 1000000 person-years, respectively. Most patients with LA-MRSA CC398 BSI had no contact to livestock, although they tended to live in rural areas. LA-MRSA CC398 caused 24.3 BSIs per 1000 SSTIs among people with no livestock contact, which is similar to the ratio observed for other types of MRSA. Whole-genome sequence analysis showed that most of the BSI and SSTI isolates were closely related to Danish pig isolates., Conclusions: This study demonstrates that the increasing number of LA-MRSA CC398 BSIs occurred in parallel with a much larger wave of LA-MRSA CC398 SSTIs and an expanding pig reservoir.

Methicillin-resistant Staphylococcus aureus (MRSA) is the common name for a heterogeneous group of highly drug-resistant staphylococci. Two major MRSA classes are distinguished based on epidemiology, namely community-associated (CA) and hospital-associated (HA) MRSA. Notably, the distinction of CA- and HA-MRSA based on molecular traits remains difficult due to the high genomic plasticity of S. aureus. Here we sought to pinpoint global distinguishing features of CA- and HA-MRSA through a comparative genome and proteome analysis of the notorious MRSA lineage USA300. We show for the first time that CA- and HA-MRSA isolates can be distinguished by 2 distinct extracellular protein abundance clusters that are predictive not only for epidemiologic behavior, but also for their growth and survival within epithelial cells. This 'exoproteome profiling' also groups more distantly related HA-MRSA isolates into the HA exoproteome cluster. Comparative genome analysis suggests that these distinctive features of CA- and HA-MRSA isolates relate predominantly to the accessory genome. Intriguingly, the identified exoproteome clusters differ in the relative abundance of typical cytoplasmic proteins, suggesting that signatures of cytoplasmic proteins in the exoproteome represent a new distinguishing feature of CA- and HA-MRSA. Our comparative genome and proteome analysis focuses attention on potentially distinctive roles of 'liberated' cytoplasmic proteins in the epidemiology and intracellular survival of CA- and HA-MRSA isolates. Such extracellular cytoplasmic proteins were recently invoked in staphylococcal virulence, but their implication in the epidemiology of MRSA is unprecedented.

Background: Panton-Valentine leucocidin is a Staphylococcus aureus virulence factor encoded by lukF-PV and lukS-PV that is infrequent in S aureus bacteremia (SAB), and, therefore, little is known about risk factors and outcome of lukF-PV / lukS-PV -positive SAB., Methods: This report is a register-based nationwide observational cohort study. lukF-PV was detected by polymerase chain reaction. Factors associated with the presence of lukF-PV were assessed by logistic regression analysis. Adjusted 30-day hazard ratios of mortality associated with lukF-PV status were computed by Cox proportional hazards regression analysis., Results: Of 9490 SAB cases, 129 were lukF-PV -positive (1.4%), representing 14 different clonal complexes. lukF-PV was associated with younger age, absence of comorbidity, and methicillin-resistant S aureus . In unadjusted analysis, mortality associated with lukF-PV -positive SAB was comparable to SAB. However, lukF-PV -positive SAB nonsurvivors were significantly older and had more comorbidity. Consequently, by adjusted analysis, the risk of 30-day mortality was increased by 70% for lukF-PV -positive SAB compared with SAB (hazard ratio, 1.70; 95% confidence interval, 1.20-2.42; P = .003)., Conclusions: lukF-PV -positive SAB is rare in Denmark but associated with a significantly increased risk of mortality. Although the risk of lukF-PV -positive SAB was highest in the younger age groups, >80% of deaths associated with lukF-PV -positive SAB occurred in individuals older than 55 years., (© The Author 2016. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

The tetracycline resistance gene tet(K) was shown to be integrated within the predominant staphylococcal cassette chromosome mec (SCCmec) element of Danish livestock-associated methicillin-resistant Staphylococcus aureus CC398 (LA-MRSA CC398). These LA-MRSA CC398 isolates already possessed tet(M), but the acquisition of tet(K) significantly improved their fitness at sublethal concentrations of tetracycline. Because tet(K) is genetically linked to SCCmec, the use of tetracycline in food animals may have contributed to the successful spread of LA-MRSA CC398., (Copyright © 2016 Larsen et al.)