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

Isabela Borges, Rafael Carneiro, Rafael Bergo, Larissa Martins, Enrico Colosimo, Carolina Oliveira, Saulo Saturnino, Marcus Vinícius Andrade, Cecilia Ravetti, Vandack Nobre, NIIMI – Núcleo Interdisciplinar de Investigação em Medicina Intensiva, Isabela N Borges, Rafael M Carneiro, Rafael Bergo, Larissa N Martins, Enrico A Colosimo, Carolina F Oliveira, Saulo F Saturnino, Marcus Vinícius M Andrade, Cecilia G Ravetti, Vandack Nobre, Isabela Borges, Rafael Carneiro, Rafael Bergo, Larissa Martins, Enrico Colosimo, Carolina Oliveira, Saulo Saturnino, Marcus Vinícius Andrade, Cecilia Ravetti, Vandack Nobre, NIIMI – Núcleo Interdisciplinar de Investigação em Medicina Intensiva, Isabela N Borges, Rafael M Carneiro, Rafael Bergo, Larissa N Martins, Enrico A Colosimo, Carolina F Oliveira, Saulo F Saturnino, Marcus Vinícius M Andrade, Cecilia G Ravetti, Vandack Nobre

Abstract

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.

Keywords: Antibiotic; Antibiotic stewardship; C-reactive protein; Critical illness; Infection; Sepsis.

Conflict of interest statement

The authors have disclosed that they do not have any conflicts of interest.

Figures

Fig. 1
Fig. 1
Decision-making flowchart for antibiotic discontinuation based on CRP levels. ICU, intensive care unit; CRP, C-reactive protein; SOFA, Sequential Organ Failure Assessment
Fig. 2
Fig. 2
Inclusion flow diagram
Fig. 3
Fig. 3
Proportion of patients (%) on antibiotics during the first 14 days of follow-up. p value for comparison of frequency between groups by the chi-square test
Fig. 4
Fig. 4
Cumulative curve of antibiotic suspension. Time-to-event analysis

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