Procalcitonin-Guided Treatment on Duration of Antibiotic Therapy and Cost in Septic Patients (PRODA): a Multi-Center Randomized Controlled Trial

Abstract

Background The objective of this study was to establish the efficacy and safety of procalcitonin (PCT)-guided antibiotic discontinuation in critically ill patients with sepsis in a country with a high prevalence of antimicrobial resistance and a national health insurance system. Methods In a multi-center randomized controlled trial, patients were randomly assigned to a PCT group (stopping antibiotics based on a predefined cut-off range of PCT) or a control group. The primary end-point was antibiotic duration. We also performed a cost-minimization analysis of PCT-guided antibiotic discontinuation. Results The two groups (23 in the PCT group and 29 in the control group) had similar demographic and clinical characteristics except for need for renal replacement therapy on ICU admission (46% vs. 14%; P = 0.010). In the per-protocol analysis, the median duration of antibiotic treatment for sepsis was 4 days shorter in the PCT group than the control group (8 days; interquartile range [IQR], 6–10 days vs. 14 days; IQR, 12–21 days; P = 0.001). However, main secondary outcomes, such as clinical cure, 28-day mortality, hospital mortality, and ICU and hospital stays were not different between the two groups. In cost evaluation, PCT-guided therapy decreased antibiotic costs by USD 30 (USD 241 in the PCT group vs. USD 270 in the control group). The results of the intention-to-treat analysis were similar to those obtained for the per-protocol analysis. Conclusion PCT-guided antibiotic discontinuation in critically ill patients with sepsis could reduce the duration of antibiotic use and its costs with no apparent adverse outcomes. Trial Registration ClinicalTrials.gov Identifier: NCT02202941

Procalcitonin for individualizing antibiotic treatment: an update with a focus on COVID-19

“…[ 42 ]. Similarly, two recent trials from Greece and South Korea found a reduction in antibiotic use of up to 5 days but only the larger Greek study found a reduction in mortality [ 62 , 120 ]. Despite the heterogeneity of the data, overall results suggest that PCT is a good and safe complementary tool to discontinue antibiotics in sepsis, thus reducing antibiotic exposure, while its possible positive effect on mortality requires further research [ 47 , 121 ].…”

A 2020 review on the role of procalcitonin in different clinical settings: an update conducted with the tools of the Evidence Based Laboratory Medicine

“…The use and usefulness of PCT as a biomarker is covered extensively in literature in two main areas: as an early marker of sepsis (differentiating bacterial and non bacterial etiologies) and as a guide to the management of antibiotic therapy (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). In recent decades, there has been a shift in the focus on PCT as a biomarker able to guide the discontinuation of antibiotic therapy, particularly in critically ill patients (5,7,9,10,(12)(13)(14)(15)(16)18), demonstrating its safety and efficacy either alone or in association with other biomarkers, such as C-reactive protein (CRP), alpha 2 macroglobulin (A2M) and presepsin (19,21,22).…”

“…Conversely, in other trials the real efficacy provided by PCT in guiding the clinician's diagnosis has been questioned (7,8,10,11,19,23). Jeon et al (9) confirmed the role of PCT as a biomarker capable of reducing the duration of antibiotic treatment, but found that its use did not impact on clinical cure, 28-day mortality, in-hospital mortality, ICU length of stay and overall hospital length of stay, when comparing the PCT-guided and the control group of patients. Pepper et al evaluated the PCT-guided antibiotic discontinuation approach in a systematic review including 16 randomized clinical trials (RCTs) (23); they found that this approach was associated with decreased mortality (risk ratio, 0.89; 95% CI, 0.83-0.97) and with a decrease in antibiotics' duration (mean difference, 1.31 days; 95% CI, −2.27 to −0.35).…”

Procalcitonin to Guide Antibiotic Therapy for Critically Ill Patients in Korea

“…Herein, a prospective, randomized, controlled trial was performed by Jeon et al7 to assess the efficacy and safety of using PCT to guide antibiotic duration in the Korean ICU setting 7. From 4 sites in South Korea, 62 adult patients admitted to the ICU with presumed or proven infection were enrolled.…”

“…Despite the strength of evidence described above,237 there are a few limitations to these studies that clinicians should be aware of before using PCT in practice 8. First, protocol adherence in the ICU based trials has been approximately 50% 237. How closely physicians outside of clinical trials adhere to evidence-based algorithms is unclear.…”