Early identification of intensive care unit-acquired infections with daily monitoring of C-reactive protein: a prospective observational study

Abstract

Introduction: Manifestations of sepsis are sensitive but are poorly specific of infection. Our aim was to assess the value of daily measurements of C-reactive protein (CRP), temperature and white cell count (WCC) in the early identification of intensive care unit (ICU)-acquired infections.

Methods: We undertook a prospective observational cohort study (14 month). All patients admitted for > or =72 hours (n = 181) were divided into an infected (n = 35) and a noninfected group (n = 28). Infected patients had a documented ICU-acquired infection and were not receiving antibiotics for at least 5 days before diagnosis. Noninfected patients never received antibiotics and were discharged alive. The progression of CRP, temperature and WCC from day -5 to day 0 (day of infection diagnosis or of ICU discharge) was analyzed. Patients were divided into four patterns of CRP course according to a cutoff value for infection diagnosis of 8.7 mg/dl: pattern A, day 0 CRP >8.7 mg/dl and, in the previous days, at least once below the cutoff; pattern B, CRP always >8.7 mg/dl; pattern C, day 0 CRP < or =8.7 mg/dl and, in the previous days, at least once above the cutoff; and pattern D, CRP always < or =8.7 mg/dl.

Results: CRP and the temperature time-course showed a significant increase in infected patients, whereas in noninfected it remained almost unchanged (P < 0.001 and P < 0.001, respectively). The area under the curve for the maximum daily CRP variation in infection prediction was 0.86 (95% confidence interval: 0.752-0.933). A maximum daily CRP variation >4.1 mg/dl was a good marker of infection prediction (sensitivity 92.1%, specificity 71.4%), and in combination with a CRP concentration >8.7 mg/dl the discriminative power increased even further (sensitivity 92.1%, specificity 82.1%). Infection was diagnosed in 92% and 90% of patients with patterns A and B, respectively, and in only two patients with patterns C and D (P < 0.001).

Conclusion: Daily CRP monitoring and the recognition of the CRP pattern could be useful in the prediction of ICU-acquired infections. Patients presenting maximum daily CRP variation >4.1 mg/dl plus a CRP level >8.7 mg/dl had an 88% risk of infection.

Figure 1

Patterns of C-reactive protein (CRP) course before infection diagnosis or intensive care unit discharge. Four patterns of CRP course between day -5 and day 0 before infection diagnosis or intensive care unit discharge of individual patients are displayed according to a previously defined CRP cutoff value for infection diagnosis of 8.7 mg/dl [19]. See text for definition of patterns A–D. Dashed line, CRP cutoff value for infection diagnosis.

Figure 2

C-reactive protein (CRP), temperature and white cell count (WCC) progression before infection diagnosis or discharge. The time-dependent analysis of CRP, temperature and WCC (mean ± standard deviation) from day -5 to day 0 of infected patients and noninfected patients is presented. Both the CRP and temperature course clearly differentiate infected patients from noninfected patients (P < 0.001 and P < 0.001, respectively). Although the WCC time-dependent analysis was significantly different (P = 0.005), its progression was unpredictable and erratic both in infected patients as well as in noninfected patients.

Figure 3

Clinical course evaluated by the Sequential Organ Failure Assessment (SOFA) score in infected and noninfected patients. The SOFA score (mean ± standard deviation) between day -5 and day 0 of infected patients and noninfected patients is shown. In infected patients the SOFA score remained almost unchanged, whereas a significant decrease was observed in noninfected patients (P < 0.001).