Association of Daily Body Temperature, White Blood Cell Count, and C-reactive Protein With Mortality and Persistent Bacteremia in Patients With Staphylococcus Aureus Bacteremia: A Post Hoc Analysis of the CAMERA2 Randomized Clinical Trial

Abstract

Introduction: Classification of patients with Staphylococcus aureus bacteremia as complicated versus uncomplicated is based on a combination of clinical and microbiologic variables. Whether daily body temperature and common laboratory tests such as C-reactive protein (CRP) and white blood cell (WBC) can improve risk stratification algorithms is unclear.

Methods: We conducted a post hoc secondary analysis of the CAMERA2 trial, which enrolled hospitalized adult patients with methicillin-resistant S aureus bacteremia and prospectively collected daily body temperature and peripheral blood WBC and CRP. We evaluated the prognostic relevance of each parameter by calculating crude and adjusted odds ratios for 90-day all-cause mortality comparing patients with the abnormal parameter of interest versus those with normal parameters on each day of illness.

Results: A total of 345 patients were included in this analysis, of whom 63 (18.3%) died within 90 days. Fever (body temperature ≥38.0 °C) was associated with increased odds of 90-day mortality from day 4 and onwards. Fever later in the illness course was associated with higher adjusted odds of mortality (8.78; 95% confidence interval, 2.78-27.7 on day 7 vs adjusted odds ratio 3.70; 95% CI, 1.58-8.67 on day 4). In contrast, CRP and abnormal WBC count did not demonstrate a consistent or temporal association with mortality.

Conclusions: Persistent fever after 72 hours is associated with increased mortality in patients with methicillin-resistant S aureus bacteremia, supporting recommendations that this should be kept as a criterion for classifying patients as either "high-risk" or "complicated." Within this dataset, there was limited additional predictive value in WBC or CRP.

Keywords: MRSA; c-reactive protein; risk stratification; staphylococcus aureus bacteremia; white blood cell.

Figure 1.

Mean temperature on each day of illness, for all patients (A) and stratified by presence of persistent bacteremia (B) and 90-d mortality (C). Points depict mean values for each day of illness for each subgroup, whereas error bars depict the 95% confidence interval around the mean. Corresponding numbers below each graph show the number of patients with available observations per subgroup for each day (eg, on day 8 there were 239 patients who were no longer bacteremic with available temperature readings and 17 patients who were still bacteremic on day 8 and had available temperature readings).

Figure 2.

Crude and adjusted odds ratios for 90-day all-cause mortality comparing patients with fever to patients without fever, for each day of illness. Points reflect the crude or odds ratio while error bars reflect the 95% confidence interval. Blue points and bars show the crude odds ratio while orange points and bars show the adjusted odds ratio after adjustment for age, sex, treatment group, immunosuppression status, and Charlson comorbidity index. Annotated numbers beside each point shows the point effect estimate of the odd ratio.

Figure 3.

Crude and adjusted odds ratios for 90-day all-cause mortality using different CRP interpretation criteria, for each day of illness. Points reflect the crude or odds ratio while error bars reflect the 95% confidence interval. Blue points and bars show the crude odds ratio while orange points and bars show the adjusted odds ratio after adjustment for age, sex, treatment group, immunosuppression status, and Charlson comorbidity index. Arrow points indicate that the limit of the confidence interval extends beyond the range of the y-axis. The X-symbol indicates that the model for that day did not converge (due to insufficient data points). CRP = C-reactive protein.

Figure 4.

Crude and adjusted odds ratios for 90-day all-cause mortality, comparing patients with abnormal WBC count versus those with normal WBC count. Points reflect the crude or odds ratio while error bars reflect the 95% confidence interval. Blue points and bars show the crude odds ratio while orange points and bars show the adjusted odds ratio after adjustment for age, sex, treatment group, immunosuppression status, and Charlson comorbidity index. WBC = white blood cell.