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Procalcitonin Versus C-Reactive Protein for Guiding Antibiotic Therapy in Sepsis: a Randomized Trial
Study Question: Is procalcitonin (PCT) superior to C-reactive protein (CRP) for guiding antibiotic therapy in intensive care patients with sepsis?
Study Description: This study was a controlled open randomized clinical trial conducted at two teaching ICUs in Brazil. Patients were included if they were greater than 18 years of age with suspected severe sepsis or septic shock between September 2009 and May 2012. Patients were monitored for 72 hours before randomization. Patients in the PCT group were divided into groups based on PCT < 1 ng/mL or > 1 ng/mL. In the first group, antibiotics were continued until PCT < 0.1 ng/mL or 7 days of antibiotics and the later group until PCT decreased > 90% or 7 days of antibiotic therapy. The CRP group was divided into initial CRP level < 100 mg/L or > 100 mg/L and antibiotics were discontinued once CRP < 25 mg/dL or 7 days of antibiotics received or CRP reduction > 50% or 7 days of antibiotics, respectively. Patients were followed up to 28 days or until their death or hospital discharge.
Results: A total of 94 patients met inclusion criteria and were randomized. There were 49 patients in the PCT group and 45 patients in the CRP group. The average age was 59.8 ± 16.8 years and 60.6% of the patients were men. There were no differences between patient characteristics in the two groups. Pulmonary sepsis was the most common infection site in both groups. The primary outcome of duration of antibiotic therapy for the first episode of infection was similar in both groups, with a median of 7 (Q1 – Q3, 6 – 8.5) days in the PCT group and 6 (Q1 – Q3, 5 – 7) days in the CRP group (p = 0.06). The total exposure to antibiotics was longer in the PCT group than in the CRP group. However, this difference was not significant (13 days versus 8 days respectively, p = 0.183). No significant differences were found in secondary outcomes between the two studied groups regarding clinical cure, recurrence of first episode of infection, antibiotic free period, prevalence of nosocomial infection during follow-up, ICU or hospital length of stay, or 28-day mortality. Protocol overruling by the treating physician occurred in 13 patients: six patients in the PCT and seven patients in the CRP group.
Conclusion(s): A PCT-based protocol for antibiotic therapy in patients with sepsis is not superior to a protocol based on serum CRP level for reducing the use of antibiotics.
Perspective: In this study of patients with sepsis in the ICU, there was no difference in the PCT group versus the CRP group for guiding the duration of antibiotic treatment. Both biomarkers may be in the context of other signs of sepsis, and the findings of this study further underscore the question of whether 7 days of antibiotic therapy is a safe limit for medical ICU patients with severe sepsis and septic shock.
Reducing the duration of antibiotic treatment is one of the most efficient ways to reduce creating multi-drug resistant bacteria. The use of inflammatory biomarkers such as PCT and CRP holds promise in guiding duration of antibiotic therapy. As with most biomarkers, there is still the risk for false positives and negatives. With PCT, there may be false negatives within < 6 hours of infection onset or in the setting of autoimmune disease, and with CRP, anti-inflammatory medication may cause false negatives. PCT and CRP can both be utilized for duration of antibiotic therapy depending on what is available through laboratory services. CRP is the cheaper of the two biomarkers. There are limitations to the study in that it was a small sample size including two medical ICUs in Brazil. Further studies might examine subgroups of interest such as those with P. aeruginosa and A. baumannii infections.