Association between patient characteristics and outcome for 270 patients with <i>S. aureus</i> infection.

<p>Data are number (%) unless otherwise stated.</p>*<p>¹p value for the comparison between all-cause deaths and survivors.</p>*<p>²Denominator for occupation is number of patients over the age of 16 years which is given in each square.</p>*<p>³Past medical history of any underlying chronic medical conditions reported by the patient/relative or recorded in the medical notes.</p>*<p>⁴Immunosuppression from HIV (5 untreated, 3 on anti-retroviral therapy), chemotherapy (n = 3), untreated leukaemia (n = 1), radiotherapy (n = 1) or immunosuppressive medication including prednisolone more than 30 mg/day for more than 1 week (n = 17).</p>*<p>⁵Renal disease included end stage renal failure on long-term dialysis (n = 3; 2 on haemodialysis, 1 on peritoneal dialysis) and chronic renal failure (not on dialysis) due to diabetes mellitus (n = 14), systemic lupus erythematosus (n = 1), multiple myeloma (n = 1), glomerulonephritis (n = 1) or an unknown aetiology (n = 5).</p>*<p>⁶Cardiac disease comprised congenital heart disease (n = 4), valvular heart disease including rheumatic heart disease (n = 8), ischaemic heart disease (n = 8), or arrhythmias including heart block requiring pacemaker (n = 4).</p>*<p>⁷Lung disease comprised previously treated tuberculosis (n = 9), previous empyema (n = 1), lung cancer (n = 2), long-term tracheostomy (n = 1), chronic obstructive pulmonary disease (n = 2) or asthma (n = 1).</p

Significant risk factors for mortality from <i>S. aureus</i> infection from multiple logistic regression analysis.

*<p>¹95% confidence intervals.</p>*<p>²p value from Likelihood ratio test.</p

The range of sites of infection in patients and outcome associated with each clinical presentation.

*<p>¹p value for the comparison between all-cause deaths and survivors.</p>*<p>²Site of deep abscesses were muscle (n = 20), retroperitoneal space (n = 7), parotid gland (n = 7), liver (n = 3), lung (n = 2), epidural space (n = 2), eye (n = 2), oropharynx (n = 2) and spleen (n = 1).</p>*<p>³Other skin and soft tissue infections includes: necrotising fasciitis (n = 9), bedsore(s) (n = 6), pustules and carbuncles (n = 5), infected wound from trauma (n = 3), infected wound from tophi (n = 2), gangrene (n = 2), cellulitis (without other skin or soft tissue lesion) (n = 2) and infection of exfoliated skin following a severe drug reaction (n = 2).</p>*<p>⁴Orthopaedic material includes: internal fixation metalwork (n = 8) and a hip replacement (n = 1).</p>*<p>⁵Intravenous devices were peripheral cannulas (n = 4), central catheters (n = 3) and an umbilical catheter (n = 1).</p>*<p>⁶Endocarditis from transthoracic echocardiographic evidence of vegetations (n = 7); 1 case clinically but died prior to echocardiogram.</p>*<p>⁷Other infections include: urinary tract infection (n = 3), tenosynovitis (n = 2), Lemierre's syndrome (n = 1) and corneal ulcer (n = 1).</p>*<p>⁸Post-operative infections include: mediastinitis (n = 4; 3 following mitral valve replacement and 1 after coronary artery bypass graft), meningitis from infected bone flap surgical wound (n = 1) and abdominal wound (n = 1).</p

Timely effective antibiotic therapy and procedures for infectious source control significantly improved outcome.

<p>Administration of an effective antibiotic on the same day as the positive culture was taken significantly reduced all-cause mortality (p<0.001), as did undergoing a procedure for infectious source control (p<0.001).</p

Higher all-cause mortality associated with methicillin-resistant <i>S. aureus</i> (MRSA) but not with Panton-Valentine Leukocidin (PVL).

<p>Patients infected by MRSA had a greater all-cause mortality compared with patients infected by methicillin-susceptible <i>S. aureus</i> (MSSA) (p<0.001). Conversely, patients infected by PVL gene-positive <i>S. aureus</i> had a lower all-cause mortality compared with patients infected by PVL gene-negative <i>S. aureus</i> (p<0.001), an association that remained after adjustment for MRSA (p = 0.001).</p

WBC-normalized plasma cytokine concentrations induced by stimulation of whole blood from 300 healthy subjects at 37°C for six hours with medium alone, <i>E. coli</i> O111:B4 LPS 10 ng/ml (as a positive control), heat-killed <i>B. pseudomallei</i> 1026b 2.5 × 10⁶ CFU/ml, or heat-killed <i>B. pseudomallei</i> K96243 2.5 × 10⁶ CFU/ml.

<p>Boxes show the median and interquartile range; whiskers show upper and lower adjacent values; outside values are not shown for clarity.</p

Blockade of the LPS-TLR4 axis markedly impairs TNF-α production induced by <i>B. pseudomallei</i> in human monocytes.

<p>Human monocytes (50,000/well) were stimulated with <i>B. pseudomallei</i> K96243 LPS 1 ng/ml (LPS) or heat-killed <i>B. pseudomallei</i> K96243 (bacteria:monocyte ratio of 1:1) (BP), with or without polymyxin B 100 μg/ml (PB) or a TLR4/MD2 neutralizing antibody 20 μg/ml (Ab) or isotype control 20 μg/ml (Iso). TNF-α was assayed in duplicate cell supernatants after 4 hours. Given substantial inter-individual variation in cytokine release, all TNF-α values for each individual were normalized to LPS-induced levels from the same subject. Relative TNF- α units for each individual (N=4) and mean values are displayed. Statistically significant differences were determined by ANOVA and a Bonferroni post-test. For clarity, only differences between each agonist alone (LPS or BP) and each agonist with polymyxin B or an antibody are shown. ***, p≤0.001. NS, p>0.05.</p

Plasma cytokine concentrations induced by stimulation of whole blood with <i>B. pseudomallei</i> K96243 LPS 10 ng/ml (BPlps), <i>E. coli</i> O111:B4 LPS 10 ng/ml (EClps), or <i>S. minnesota</i> Re595 LPS 10 ng/ml (SMlps).

<p>Boxes show the median and interquartile range; whiskers show upper and lower adjacent values; outside values are not shown for clarity. Statistical comparisons are made by ANOVA with a Bonferroni post test on log₁₀ transformed data. *, p≤0.05; **, p≤0.01; ***, p≤0.001.</p

WBC-normalized plasma cytokine concentrations induced by stimulation of whole blood from 300 healthy subjects at 37°C for six hours with heat-killed <i>B. pseudomallei</i> 1026b 2.5 × 10⁶ CFU/ml, stratified by age and sex.

<p>Boxes show the median and interquartile range; whiskers show upper and lower adjacent values; outside values are not shown for clarity.</p

Heat map of correlation between cytokine concentration induced by stimulation of whole blood with a panel of purified innate immune ligands and heat-killed bacteria (as specified in the methods) with dendrogram of hierarchichal clustering results for the correlation matrix.

<p>Lowest correlation is red and highest correlation is white.</p