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 : 130 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, https://clinicaltrials.gov/ct2/show/NCT02987790 .

Antimicrobial Stewardship in the Intensive Care Unit: The Role of Biomarkers, Pharmacokinetics, and Pharmacodynamics

“…However, lower AMT exposure was only related to the index infection episode. The findings did not reveal a benefit in total AMT exposure or antibiotic-free days [23].…”

“…Current evidence advocates shorter AMT courses without negative impact on clinical outcomes in different infections and clinical settings [23][24][25][26][27]. However, limitations, such as frequently insufficient microbiological information, can make therapeutic accuracy and duration questionable aspects of care [28].…”

“…AMT guidance with biomarkers can promote treatment individualization, thereby preventing nonessential antimicrobial exposure and reducing treatment failure rates [23]. In the setting of infectious diseases, they should be easily available for routine clinical use and provide diagnostic, prognostic, and therapy follow-up characteristics [28].…”

“…C-reactive protein (CRP) and procalcitonin (PCT) comprise the few biomarkers with adequate characteristics for clinical use in acute infections [11,28], although diagnostic accuracy is not optimal and neither possesses specificity for source of infection [37,39]. CRP can present a more attractive low-cost alternative to PCT, considering the high testing costs of the latter [23].…”

“…Studies of CRP-guided algorithms are scarce, namely in the adult ICU population [23]. Oliveira et al compared PCT and CRP guidance among ICU patients with sepsis in a singlecenter study.…”