Predictive Value of C-Reactive Protein (CRP) in Identifying Fatal Outcome and Deep Infections in Staphylococcus aureus Bacteremia

Peer reviewe

Pentraxin 3 (PTX3) Is Associated with Severe Sepsis and Fatal Disease in Emergency Room Patients with Suspected Infection: A Prospective Cohort Study

Background Early diagnostic and prognostic stratification of patients with suspected infection is a difficult clinical challenge. We studied plasma pentraxin 3 (PTX3) upon admission to the emergency department in patients with suspected infection. Methods The study comprised 537 emergency room patients with suspected infection: 59 with no systemic inflammatory response syndrome (SIRS) and without bacterial infection (group 1), 67 with bacterial infection without SIRS (group 2), 54 with SIRS without bacterial infection (group 3), 308 with sepsis (SIRS and bacterial infection) without organ failure (group 4) and 49 with severe sepsis (group 5). Plasma PTX3 was measured on admission using a commercial solid-phase enzyme-linked immunosorbent assay (ELISA). Results The median PTX3 levels in groups 1–5 were 2.6 ng/ml, 4.4 ng/ml, 5.0 ng/ml, 6.1 ng/ml and 16.7 ng/ml, respectively (p<0.001). The median PTX3 concentration was higher in severe sepsis patients compared to others (16.7 vs. 4.9 ng/ml, p<0.001) and in non-survivors (day 28 case fatality) compared to survivors (14.1 vs. 5.1 ng/ml, p<0.001). A high PTX3 level predicted the need for ICU stay (p<0.001) and hypotension (p<0.001). AUCROC in the prediction of severe sepsis was 0.73 (95% CI 0.66–0.81, p<0.001) and 0.69 in case fatality (95% CI 0.58–0.79, p<0.001). PTX3 at a cut-off level for 14.1 ng/ml (optimal cut-off value for severe sepsis) showed 63% sensitivity and 80% specificity. At a cut-off level 7.7 ng/ml (optimal cut-off value for case fatality) showed 70% sensitivity and 63% specificity in predicting case fatality on day 28.In multivariate models, high PTX3 remained an independent predictor of severe sepsis and case fatality after adjusting for potential confounders. Conclusions A high PTX3 level on hospital admission predicts severe sepsis and case fatality in patients with suspected infection.Public Library of Science open acces

Receiver-operating characteristic (ROC) curve analyses of C-reactive protein (CRP) concentrations and white blood cell counts (WBC) with respect to presence of any deep infection focus recorded during 30-days.

<p>The area under the curve (AUC) for the day of the positive blood culture, CRP was 0.074 (95% CI, 0.67–0.81; p<0.0001) with a cut-off value of 108 mg/L with sensitivity of 77% and specificity of 60%. For CRP on day 7, the AUC was 0.75 (95% CI, 0.68–0.81; p<0.0001) with a cut-off value of 44 mg/L with sensitivity of 68% and specificity of 67% and for CRP on day 14 the AUC was 0.70 (95% CI, 0.64–0.77; p<0.0001) with a cut-off value of 22 mg/L with sensitivity of 59% and specificity of 68%. The corresponding AUC for WBC on the day 1 was 0.55 (95% CI, 0.46–0.63; p = 0.236) and a cut-off value was not determined. For WBC on day 7 the AUC was 0.65 (95% CI, 0.58–0.72; p<0.0001) with a cut-off value of 8.5 x109/L with sensitivity of 59% and specificity of 62%. For WBC on 14 days, the AUC was 0.56 (95% CI, 0.49–0.63; p = 0.153) with a cut-off value of 7.25 x109/L with sensitivity of 44% and specificity of 75%.</p

Characteristics, predisposing factors and severity of illness in 430 patients with <i>Staphylococcus aureus</i> bacteremia (SAB) stratified according to 30-day mortality.

<p>OR = odds ratio for fatal outcome. HR = hazard ratio for fatal outcome, 95% CI = 95% confidence interval. All values are given as number of patients (%).</p

C-reactive protein (CRP) (Mean ±SEM) levels in patients with <i>Staphylococcus aureus</i> bacteremia (SAB) within 30 days of the positive blood culture.

<p>(A) All 430 SAB patients. (B) SAB patients with a fatal outcome within 30 days (n = 53) and survivors (n = 377). (C) Mean CRP levels stratified according to the presence (n = 351) or absence (n = 79) of deep infection focus. Stars indicate p-values of the Student’s T-test. * p<0.05, ** p<0.01 and *** p<0.001.</p

Cut-off values for C-reactive protein (CRP) levels (mg/L) and white blood cell counts (WBC) in finding patients with fatal outcome among 430 patients with <i>Staphylococcus aureus</i> bacteremia.

<p>OR = odds ratio for fatal outcome. HR = hazard ratio for fatal outcome, 95% CI = 95% confidence interval. All values are given as number of patients (%).</p

Receiver-operating characteristic (ROC) curve analyses of C-reactive protein (CRP) concentrations and white blood cell counts (WBC) with respect to 30-day mortality in <i>Staphylococcus aureus</i> bacteremia (n = 430).

<p>The area under the curve (AUC) for CRP on the day 4 was 0.65 (95% CI, 0.55–0.76; p = 0.016) with a cut-off value of 104 mg/L with sensitivity of 77% and specificity of 55%. For CRP on the day 7 the AUC was 0.68 (95% CI, 0.58–0.79; p = 0.004) with a cut-off value of 66 mg/L with sensitivity of 73% and specificity of 55% and for CRP on day 14 the AUC was 0.86 (95% CI, 0.79–0.94; p<0.0001) with a cut-off value of 61mg/L with sensitivity of 82% and specificity of 80%. The corresponding AUC for WBC on the day 4 was 0.60 (95% CI, 0.49–0.71; p = 0.116) with a cut-off value of 8.0 x10⁹/L with sensitivity of 86% and specificity of 41%. For WBC on the day 7 the AUC was 0.70 (95% CI, 0.62–0.78; p = 0.002) with a cut-off value of 9.8 x10⁹/L with sensitivity of 77% and specificity of 62%. For WBC on the day 14 the AUC was 0.80 (95% CI, 0.70–0.92; p<0.0001) with a cut-off value of 8.6 x10⁹/L with sensitivity of 77% and specificity of 78%.</p

Factors associated with a deep infection focus in 430 patients with <i>Staphylococcus aureus</i> bacteremia.

<p>OR = odds ratio for presence of deep infection, 95% CI = 95% confidence interval. All values are given as number of patients (%).</p

Plasma pentraxin 3 (PTX3) in patients admitted to emergency room with suspected infection stratified by diagnosis groups (N = 537).

a<p>SIRS (Systemic Inflammatory Response Syndrome): At least two of the following conditions. 1. Temperature >38°C OR <36°C, 2. Heart rate >90 beats per minute. 3. Respiratory rate >20 breaths per minute or PaCO2<32 mmHg (4.3 kPa). 4. White blood cell count >12×10⁹/l or <4×10⁹/l or >10% immature (band) forms).</p>b<p>Documented bacterial infection: Microbiologically confirmed bacterial infection (either pathogenic bacterial growth in blood culture or in normally sterile tissue or the same usually less pathogenic bacterium (e.g. Staphylococcus epidermidis) in two different samples).</p>c<p>Probable bacterial infection: A clinician suspected bacterial infection and either infection focus was confirmed or antimicrobial treatment was started and the response to treatment supported bacterial infection.</p><p>Differences between the five groups were studied using Kruskal-Wallis test (p<0.001).</p

Receiver operating characteristic (ROC) curve for plasma levels of pentraxin 3 (PTX3), procalcitonin (PCT), interleukin-6 (IL-6) and C-reactive protein (CRP) detected on admission in relation to severe sepsis and case fatality (d28) in patients with suspected infection.

<p>AUC (ROC) (95% confidence interval, p<0.001.</p