Procalcitonin Versus C-Reactive Protein for Guiding Antibiotic Therapy in Sepsis: A Randomized Trial

Objective: We sought to evaluate whether procalcitonin was superior to C-reactive protein in guiding antibiotic therapy in intensive care patients with sepsis. Design: Randomized open clinical trial. Setting: Two university hospitals in Brazil. Patients: Patients with severe sepsis or septic shock. Interventions: Patients were randomized in two groups: the procalcitonin group and the C-reactive protein group. Antibiotic therapy was discontinued following a protocol based on serum levels of these markers, according to the allocation group. The procalcitonin group was considered superior if the duration of antibiotic therapy was at least 25% shorter than in the C-reactive protein group. For both groups, at least seven full-days of antibiotic therapy were ensured in patients with Sequential Organ Failure Assessment greater than 10 and/or bacteremia at inclusion, and patients with evident resolution of the infectious process had antibiotics stopped after 7 days, despite biomarkers levels. Measurements and Main Results: Ninety-four patients were randomized: 49 patients to the procalcitonin group and 45 patients to the C-reactive protein group. The mean age was 59.8 (sd, 16.8) years. The median duration of antibiotic therapy for the first episode of infection was 7.0 (Q1-Q3, 6.0-8.5) days in the procalcitonin group and 6.0 (Q1-Q3, 5.0-7.0) days in the C-reactive protein group (p = 0.13), with a hazard ratio of 1.206 (95% CI, 0.774-1.3; p = 0.13). Overall, protocol overruling occurred in only 13 (13.8%) patients. Twenty-one patients died in each group (p = 0.836). Conclusions: C-reactive protein was as useful as procalcitonin in reducing antibiotic use in a predominantly medical population of septic patients, causing no apparent harm.s