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

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.

Impact of Multidisciplinary Team Escalating Approach on Antibiotic Stewardship in the United Arab Emirates

“…In another study, ASP MDT interventions led by a surgeon, and included a pharmacologist and an ID specialist, decreased the duration of carbapenem therapy in general surgery services by providing recommendations on appropriate antibiotic therapy [ 20 ]. A C-reactive protein (CRP)-based protocol for antibiotic therapy was compared with a control group in critical care settings, and it did not result in a statistically significant difference in the duration of antibiotic treatment days between both groups [ 21 ].…”

“…The relative availability of clinical pharmacists enabled this approach. Previous studies have been conducted on a specific group of patients, for example, those who are only on IV antibiotics, surgical patients, critical care setting patients, infectious disease ward, or specific cases of certain infections [ 15 , 20 , 21 , 31 ]. Therefore, the advantages of our approach encompass including a wider number of patients to benefit from the intervention offered by the ASP MDT, and this improved clinical outcomes and other measures such as therapy cost and IV-to-oral switching in the medical, intensive care, and burns units within a six-month period.…”

Antibiotic stewardship in the era of precision medicine

“…Another RCT compared daily monitoring of C-reactive protein (CRP) to best clinical practices in ICU patients for determining the need for antibiotics. 24 The median duration of antibiotic treatment was 6.0 days for the CRP group and 7.0 days in the control group ( P = 0.011). However, clinicians must be cautious when using CRP to evaluate for bacterial coinfection with COVID-19 after dexamethasone and tocilizumab treatment.…”

Antimicrobial Stewardship Using Biomarkers: Accumulating Evidence for the Critically Ill

“…Median antibiotic duration in the CRP group was seven days; clinical failure between the three arms of treatment was non-inferior. In another open-label RCT, CRP-guided antimicrobial treatment was compared to SOC in 130 ICU patients with sepsis and/or septic shock [81]. In the CRP arm, the biomarker was measured after five days from start of antibiotics and antibiotics were stopped when CRP decrease more than 50% or when it was found less than 35 mg/L.…”