Telephone IDS consultation is inferior to bedside IDS consultation.

Recent genomic studies have revealed extensive variation in natural populations of many pathogenic bacteria. However, the evolutionary processes which contribute to much of this variation remain unclear. A previous whole-genome DNA microarray study identified variation at a large chromosomal region (RD13) of Staphylococcus aureus which encodes a family of proteins with homology to staphylococcal and streptococcal superantigens, designated staphylococcal exotoxin-like (SET) proteins. In the present study, RD13 was found in all 63 S. aureus isolates of divergent clonal, geographic, and disease origins but contained a high level of variation in gene content in different strains. A central variable region which contained from 6 to 10 different set genes, depending on the strain, was identified, and DNA sequence analysis suggests that horizontal gene transfer and recombination have contributed to the diversification of RD13. Phylogenetic analysis based on the RD13 DNA sequence of 18 strains suggested that loss of various set genes has occurred independently several times, in separate lineages of pathogenic S. aureus, providing a model to explain the molecular variation of RD13 in extant strains. In spite of multiple episodes of set deletion, analysis of the ratio of silent substitutions in set genes to amino acid replacements in their products suggests that purifying selection (selective constraint) is acting to maintain SET function. Further, concurrent transcription in vitro of six of the seven set genes in strain COL was detected, indicating that the expression of set genes has been maintained in contemporary strains, and Western immunoblot analysis indicated that multiple SET proteins are expressed during the course of human infections. Overall, we have shown that the chromosomal region RD13 has diversified extensively through episodes of gene deletion and recombination. The coexpression of many set genes and the production of multiple SET proteins during human infection suggests an important role in host-pathogen interactions.

In Finland, Staphylococcus aureus bloodstream infections are caused predominantly (>99%) by methicillin-sensitive strains. In this study, laboratory-based surveillance data on Staphylococcus aureus bloodstream infections occurring in Finland from 1995 to 2001 were analyzed. Preceding hospitalizations for all persons with Staphylococcus aureus bloodstream infections were obtained from the national hospital discharge registry, and data on outcome was obtained from the national population registry. An infection was defined as nosocomial when a positive blood culture was obtained more than 2 days after hospital admission or within 2 days of admission if there was a preceding hospital discharge within 7 days. A total of 5,045 cases were identified. The annual incidence of Staphylococcus aureus bloodstream infection rose by 55%, from 11 per 100,000 population in 1995 to 17 in 2001. The increase was detected in all adult age groups, though it was most distinct in patients >74 years of age. Nosocomial infections accounted for 51% of cases, a proportion that remained unchanged. The 28-day death-to-case ratio ranged from 1% in the age group 1-14 years to 33% in patients >74 years of age. The 28-day death-to-case ratios for nosocomial and community-acquired infections were 22% and 13%, respectively, and did not change over time. The increase in incidence among elderly persons resulted in an increase in the annual rate of mortality associated with Staphylococcus aureus bloodstream infections, from 2.6 to 4.2 deaths per 100,000 population per year. Staphylococcus aureus bloodstream infections are increasing in Finland, a country with a very low prevalence of methicillin resistance. While the increase may be due in part to increased reporting, it also reflects a growing population at risk, affected by such factors as high age and/or severe comorbidity.

Abstract. Ruotsalainen E, Järvinen A, Koivula I, Kauma H, Rintala E, Lumio J, Kotilainen P, Vaara M, Nikoskelainen J, Valtonen V, the FINLEVO Main outcome measures. Primary end-points were mortality at 28 days and at 3 months. Clinical and laboratory parameters were analysed as secondary end-points. Results. Adding levofloxacin to the standard treatment offered no survival benefit. Case fatality rates were 14% in both groups at 28 days, and 21% in the standard treatment and 18% in the levofloxacin group at 3 months. Levofloxacin combination did not differ from the standard treatment in the number of complications, time to defervescence, decrease in serum C-reactive protein concentration or length of antibiotic treatment. Deep infection was found in 84% of patients within 1 week following randomization with no difference between the treatment groups. At 3 months, the case fatality rate for patients with deep infection was 17% amongst those who received rifampicin versus 38% for those without rifampicin

BackgroundEndocarditis is a common complication in Staphylococcus aureus bacteremia (SAB). We compared risk factors, clinical manifestations, and outcome in a large, prospective cohort of patients with S. aureus endocarditis in injection drug users (IDUs) and in nonaddicts.MethodsFour hundred and thirty consecutive adult patients with SAB were prospectively followed up for 3 months. Definite or possible endocarditis by modified Duke criteria was found in 74 patients: 20 patients were IDUs and 54 nonaddicts.ResultsEndocarditis was more common in SAB among drug abusers (46%) than in nonaddicts (14%) (odds ratio [OR], 5.12; 95% confidence interval [CI], 2.65–9.91; P < 0.001). IDUs were significantly younger (27 ± 15 vs 65 ± 15 years, P < 0.001), had less ultimately or rapidly fatal underlying diseases (0% vs 37%, P < 0.001) or predisposing heart diseases (20% vs 50%, P = 0.03), and their SAB was more often community-acquired (95% vs 39%, P < 0.001). Right-sided endocarditis was observed in 60% of IDUs whereas 93% of nonaddicts had left-sided involvement (P < 0.001). An extracardiac deep infection was found in 85% of IDUs and in 89% of nonaddicts (P = 0.70). Arterial thromboembolic events and severe sepsis were also equally common in both groups. There was no difference in mortality between the groups at 7 days, but at 3 months it was lower among IDUs (10%) compared with nonaddicts (39%) (OR, 5.73; 95% CI, 1.20–27.25; P = 0.02).ConclusionS. aureus endocarditis in IDUs was associated with as high complication rates including extracardiac deep infections, thromboembolic events, or severe sepsis as in nonaddicts. Injection drug abuse in accordance with younger age and lack of underlying diseases were associated with lower mortality, but after adjusting by age and underlying diseases injection drug abuse was not significantly associated with mortality.

The soluble form of urokinase-type plasminogen activator receptor (suPAR) is a new inflammatory marker. High suPAR levels have been shown to associate with mortality in cancer and in chronic infections like HIV and tuberculosis, but reports on the role of suPAR in acute bacteremic infections are scarce. To elucidate the role of suPAR in a common bacteremic infection, the serum suPAR levels in 59 patients with Staphylococcus aureus bacteremia (SAB) were measured using the suPARnostic ELISA assay and associations to 1-month mortality and with deep infection focus were analyzed. On day three, after the first positive blood culture for S. aureus, suPAR levels were higher in 19 fatalities (median 12.3; range 5.7-64.6 ng/mL) than in 40 survivors (median 8.4; range 3.7-17.6 ng/mL, p = 0.002). This difference persisted for 10 days. The presence of deep infection focus was not associated with elevated suPAR levels as compared to patients with no deep infection focus. suPAR was found to be prognostic for mortality in receiver operator characteristic (ROC) curve analysis, which was not observed for serum C-reactive protein (CRP); the area under the curve (AUC) for suPAR was 0.754 (95% confidence interval [CI], 0.615-0.894, p = 0.003) and for CRP, it was 0.596 (95% CI, 0.442-0.750, p = 0.253). The optimal suPAR cut-off value in predicting 1-month mortality was 9.25 ng/mL. In conclusion, our study demonstrates that the new promising biomarker, serum suPAR concentration, was able to predict mortality in SAB.

IntroductionAmong patients with bacteraemia or sepsis the plasma cell-free DNA (cf-DNA) biomarker has prognostic value and Pitt bacteraemia scores predict outcome. We evaluated the prognostic value of plasma cf-DNA in patients with Staphylococcus aureus bacteraemia (SAB) treated in the ICU or in the general ward.Methods418 adult patients with positive blood culture for S. aureus were prospectively followed for 90 days. SAB patients were grouped according to ICU treatment: 99 patients were treated in ICU within 7 days of documented SAB whereas 319 patients were managed outside ICU. Pitt bacteraemia scores were assessed at hospital arrival and cf-DNA was measured at days 3 and 5 from positive blood culture.ResultsSAB patients with high Pitt bacteraemia scores and ICU treatment presented higher cf-DNA values as compared to SAB patients with low Pitt bacteraemia scores and non-ICU treatment at both days 3 and 5. Among ICU patients cf-DNA >1.99 µg/ml at day 3 predicted death with a sensitivity of 67% and a specificity of 77% and had an AUC in receiver operating characteristic analysis of 0.71 (p<0.01). The cut-off cf-DNA >1.99 µg/ml value demonstrated a strong association to high Pitt bacteraemia scores (≥4 points) (p<0.000). After controlling for all prognostic markers, Pitt bacteraemia scores ≥4 points at hospital admission (OR 4.47, p<0.000) and day 3 cf-DNA (OR 3.56, p<0.001) were the strongest factors significantly predicting outcome in ICU patients. cf-DNA at day 5 did not predict fatal outcome.ConclusionHigh cf-DNA concentrations were observed among patients with high Pitt bacteraemia scores and ICU treatment. Pitt bacteraemia scores (≥4 points) and cf-DNA at day 3 from positive blood culture predicted death among SAB patients in ICU and were found to be independent prognostic markers. cf-DNA had no prognostic value among non-ICU patients.

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