Duration of antibiotic therapy in critically ill patients: a randomized controlled trial of a clinical and C-reactive protein-based protocol versus an evidence-based best practice strategy without biomarkers

Borges, Isabela; Carneiro, Rafael; Bergo, Rafael; Martins, Larissa; Colosimo, Enrico; Oliveira, Carolina; Saturnino, Saulo; Andrade, Marcus Vinícius; Ravetti, Cecilia; Nobre, Vandack

BACKGROUND: The rational use of antibiotics is one of the main strategies to limit the development of bacterial resistance. We therefore sought to evaluate the effectiveness of a C-reactive protein-based protocol in reducing antibiotic treatment time in critically ill patients. METHODS: A randomized, open-label, controlled clinical trial conducted in two intensive care units of a university hospital in Brazil. Critically ill infected adult patients were randomly allocated to (i) intervention to receive antibiotics guided by daily monitoring of CRP levels and (ii) control to receive antibiotics according to the best practices for rational use of antibiotics. RESULTS: One hundred thirty patients were included in the CRP (n = 64) and control (n = 66) groups. In the intention-to-treat analysis, the median duration of antibiotic therapy for the index infectious episode was 7.0 (5.0–8.8) days in the CRP and 7.0 (7.0–11.3) days in the control (p = 0.011) groups. A significant difference in the treatment time between the two groups was identified in the curve of cumulative suspension of antibiotics, with less exposure in the CRP group only for the index infection episode (p = 0.007). In the per protocol analysis, involving 59 patients in each group, the median duration of antibiotic treatment was 6.0 (5.0–8.0) days for the CRP and 7.0 (7.0–10.0) days for the control (p = 0.011) groups. There was no between-group difference regarding the total days of antibiotic exposure and antibiotic-free days. CONCLUSIONS: Daily monitoring of CRP levels may allow early interruption of antibiotic therapy in a higher proportion of patients, without an effect on total antibiotic consumption. The clinical and microbiological relevance of this finding remains to be demonstrated. TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT02987790. Registered 09 December 2016.