Background. The impact of bacterial clonality on infections caused byStaphylococcus aureus is unclear. Methods. Three hundred seventy-nine S. aureus isolates (125 methicillin-resistant S. aureus [MRSA] and 254 methicillin-susceptible S. aureus [MSSA]) were genotyped by spa typing and multilocus sequence typing. For MRSA isolates, the staphylococcal chromosomal cassette mec (SCCmec) element was also typed. Three clinical categories were identified: nasal carriage only ( ), uncomplicated infection ( ), and bacteremia with hematogn p 118 n p 104 enous complications ( ). n p 157 Results. By use of eBURST, 18 clonal complexes (CCs) were found in 371 isolates. Eight CCs accounted for 89% of isolates and occurred in all clinical categories. CC5 () and CC30 ( ) exhibited a significant P p .0025 P p .0308 trend toward more frequent hematogenous complications. Isolates within spa types 2 and 16 showed the same significant trend and grouped within CC5 and CC30, respectively. SCCmec II isolates also showed the same significant trend compared with SCCmec IV; 96% were CC5 or CC30.Conclusions. Although most S. aureus genotypes exhibited the capacity to cause invasive disease, strains within CC5 and CC30 exhibited a significant trend toward increasing levels of hematogenous complications. Isolates within these CCs were also implicated by use of spa and SCCmec typing. The genetic determinants underlying these findings remain to be demonstrated.

The impact of bacterial genetic characteristics on the outcome of patients with Staphylococcus aureus infections is uncertain. This investigation evaluated potential associations between bacterial genotype and clinical outcome using isolates collected as part of an international phase 2 clinical trial (FAST II) evaluating telavancin for the treatment of complicated skin and skin structure infections (cSSSI). Ninety S. aureus isolates from microbiologically evaluable patients with cSSSI enrolled in the FAST II trial from 11 sites in the United States (56 isolates, or 62%) and 7 sites in South Africa (34 isolates, or 38%) were examined for staphylococcal cassette chromosome mec, agr, and the presence of 31 virulence genes and subjected to pulsed-field gel electrophoresis (PFGE). South African methicillin-susceptible S. aureus (MSSA) isolates were more likely to carry certain virulence genes, including sdrD (P ‫؍‬ 0.01), sea (P < 0.01), and pvl (P ‫؍‬ 0.01). All 44 (49%) methicillin-resistant S. aureus (MRSA) isolates were from the United States; 37 (84%) were strain USA 300 by PFGE. In the United States, MRSA isolates were more likely than MSSA isolates to carry genes for sdrC (P ‫؍‬ 0.03), map/eap (P ‫؍‬ 0.05), fnbB (P ‫؍‬ 0.11), tst (P ‫؍‬ 0.02), sea (P ‫؍‬ 0.04), sed (P ‫؍‬ 0.04), seg (P ‫؍‬ 0.11), sej (P ‫؍‬ 0.11), agr (P ‫؍‬ 0.09), V8 (P ‫؍‬ 0.06), sdrD, sdrE, eta, etb, and see (P < 0.01 for all). MRSA isolates were more often clonal than MSSA isolates by PFGE. Isolates from patients who were cured were significantly more likely to contain the pvl gene than isolates from patients that failed or had indeterminate outcomes (79/84 [94%] versus 3/6 [50%]; P ‫؍‬ 0.01). S. aureus strains from different geographic regions have different distributions of virulence genes.

CoNS have emerged as an important cause of NVE in both community and health care settings. Despite high rates of surgical therapy, NVE caused by CoNS is associated with poor outcomes.

Background The significance of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) is unknown. Using a multinational collection of isolates from methicillin-resistant S. aureus (MRSA) infective endocarditis (IE), we characterized IE patients with and without hVISA, and genotyped the infecting strains. Methods MRSA bloodstream isolates from 65 patients with definite IE from 8 countries underwent PCR for 31 virulence genes, pulsed-field gel electrophoresis, and multilocus sequence typing. hVISA was defined using population analysis profiling (PAP). Results Nineteen (29.2%) of 65 MRSA IE isolates exhibited hVISA by PAP. Isolates from Oceania and Europe were more likely to exhibit hVISA than isolates from the United States (77.8% vs. 35.0% vs. 13.9%; P < .001). The prevalence of hVISA was higher among isolates with a vancomycin minimum inhibitory concentration of 2 mg/L (P = .026). hVISA-infected patients were more likely to have persistent bacteremia (68.4% vs. 37.0%; P = .029) and heart failure (47.4% vs. 19.6%; P = .033). Mortality of hVISA- and non-hVISA-infected patients did not differ (42.1% vs. 34.8%, P = .586). hVISA and non-hVISA isolates were genotypically similar. Conclusions In these analyses, hVISA occurred in over one-quarter of MRSA IE isolates, was associated with certain IE complications, and varied in frequency by geographic region.

Importance Reperfusion times for ST elevation myocardial infarction (STEMI) occurring in outpatients have improved significantly, but quality improvement efforts have largely ignored STEMI occurring in hospitalized patients (inpatient-onset STEMI). Objective To define the incidence and variables associated with treatment and outcomes of patients who develop STEMI during hospitalization for conditions other than acute coronary syndromes (ACS). Design, Setting and Participants STEMIs were identified in the 2008–2011 California State Inpatient Database. Exposure STEMI were classified as inpatient-onset or outpatient-onset based on present-on-admission codes. Patients who developed STEMI after being hospitalized for ACS were excluded from the analysis. Main Outcome Measures Regression models were used to evaluate associations between location of onset of STEMI, resource utilization and outcomes. Adjustments were made for patient age, sex, comorbidities and hospital characteristics. Results 62021 STEMIs were identified from 303 hospitals of which 3068 (4.9%) occurred in patients hospitalized for non-ACS indications. Inpatient-onset STEMI patients were older (71.5 ± 13.5 vs 64.9 ± 14.1 years; p < 0.001) and more frequently female (47.4% vs 32%; p < 0.001) than outpatient-onset STEMI. Inpatient-onset STEMI had higher in-hospital mortality (33.6% vs 9.2%; adjusted odds ratio (AOR) = 3.05; 95% CI, 2.76 to 3.38; p < 0.001), were less likely to be discharged home (33.7% vs 69.4%; AOR = 0.38; 95% CI, 0.34 to 0.42; p < 0.001), and were less likely to undergo cardiac catheterization (33.8% vs 77.8%; AOR = 0.19; 95% CI, 0.16 to 0.21; p < 0.001) or percutaneous coronary intervention (21.6% vs 65%; AOR = 0.23; 95% CI, 0.21 to 0.26; p < 0.001). Length of stay (13.4 ± 17.8 vs 4.7 ± 6.3 days; adjusted multiplicative effect (AME) = 2.51; 95% CI, 2.35 to 2.69; p < 0.001) and inpatient charges ($245000 ± 258700 vs $129000 ± 129800; AME = 2.09; 95% CI, 1.93 to 2.28; p < 0.001) were higher for inpatient-onset STEMI. Conclusions and Relevance Patients who developed STEMI while hospitalized for a non-ACS condition, compared to those with onset of STEMI as an outpatient, were less likely to undergo invasive testing or intervention and had a higher in-hospital mortality rate.

We conclude that the selective use of intranasal mupirocin and daily chlorhexidine bathing for patients colonized with MRSA reduced the incidence of MRSA colonization and infection and contributed to reductions identified by active-surveillance cultures. This finding suggests that additional strategies to reduce the incidence of MRSA infection and colonization--beyond expanded surveillance--may be needed.

Background Clopidogrel’s effectiveness is likely reduced significantly for prevention of thrombotic events after acute coronary syndrome (ACS) in patients exhibiting a decreased ability to metabolize clopidogrel into its active form. A genetic mutation responsible for this reduced effectiveness is detectable by genotyping. Ticagrelor is not dependent on gene-based metabolic activation and demonstrated greater clinical efficacy than clopidogrel in a recent secondary prevention trial. In 2011, clopidogrel will lose its patent protection and likely will be substantially less expensive than ticagrelor. Objective To determine the cost-effectiveness of ticagrelor compared with a genotype-driven selection of antiplatelet agents. Methods A hybrid decision tree/Markov model was used to estimate the 5-year medical costs (in 2009 US$) and outcomes for a cohort of ACS patients enrolled in Medicare receiving either genotype-driven or ticagrelor-only treatment. Outcomes included life years and quality-adjusted life years (QALYs) gained. Data comparing the clinical performance of ticagrelor and clopidogrel were derived from the Platelet Inhibition and Patient Outcomes trial. Results The incremental cost-effectiveness ratio (ICER) for universal ticagrelor was $10,059 per QALY compared to genotype-driven treatment, and was most sensitive to the price of ticagrelor and the hazard ratio for death for ticagrelor compared with clopidogrel. The ICER remained below $50,000 per QALY until a monthly ticagrelor price of $693 or a 0.93 hazard ratio for death for ticagrelor relative to clopidogrel. In probabilistic analyses, universal ticagrelor was below $50,000 per QALY in 97.7% of simulations. Conclusion Prescribing ticagrelor universally increases quality-adjusted life years for ACS patients at a cost below a typically accepted threshold.

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