Procalcitonin, pyuria and proadrenomedullin in the management of urinary tract infections – ‘triple p in uti’: study protocol for a randomized controlled trial

Abstract

BackgroundUrinary tract infections (UTIs) are among the most common infectious diseases and drivers of antibiotic use and in-hospital days. A reduction of antibiotic use potentially lowers the risk of antibiotic resistance. An early and adequate risk assessment combining medical, biopsychosocial and functional risk scores has the potential to optimize site-of-care decisions and thus allocation of limited health-care resources. The aim of this factorial design study is twofold: first, for Intervention A, it investigates antibiotic exposure of patients treated with a protocol based on the type of UTI, procalcitonin (PCT) and pyuria. Second, for Intervention B, it investigates the usefulness of the prognostic biomarker proadrenomedullin (ProADM) integrated into an interdisciplinary assessment bundle for site-of-care decisions.Methods and designThis randomized controlled open-label trial has a factorial design (2 × 2). Randomization of patients will be based on a pre-specified computer-generated randomization list and independent for the two interventions. Adults with UTI presenting to the emergency department (ED) will be screened and enrolled after providing informed consent.For our first Intervention (A), we developed a protocol based on previous observational research to recommend initiation and duration of antibiotic use based on the clinical presentation of UTI, pyuria and PCT levels. For our second intervention (B), an algorithm was developed to support site-of care decisions based on the prognostic marker ProADM and distinct nursing factors on days 1 and 3. Both interventions will be compared with a control group conforming to the guidelines.The primary endpoints for the two interventions will be: (A) overall exposure to antibiotics and (B) length of physician-led hospitalization within a follow-up of 30 days. Endpoints are assessed at discharge from hospital, and 30 and 90 days after admission. We plan to screen 300 patients and enroll 250 for an anticipated estimated loss of follow-up of 20%. This will provide adequate power for the two interventions.DiscussionThis trial investigates two strategies for improved individualized medical care in patients with UTI. The minimally effective duration of antibiotic therapy is not known for UTIs, which is important for reducing the selection pressure for antibiotic resistance, costs and drug-related side effects. Triage decisions must be improved to reflect the true medical, biopsychosocial and functional risks in order to allocate patients to the most appropriate care setting and reduce hospital-acquired disability.Trial registrationTrial registration number: ISRCTN13663741

Procalcitonin testing to guide antibiotic therapy for the treatment of sepsis in intensive care settings and for suspected bacterial infection in emergency department settings: a systematic review and cost-effectiveness analysis

“…One additional publication was obtained through contact with the authors, 69 after searches had identified the study protocol. 47 Figure 1 shows the flow of studies through the review process, and Appendix 4 provides details, with reasons for exclusions, of all publications excluded at the full paper screening stage.…”

“…Ten RCTs, 39,42,44,49,[55][56][57]60,62,69 reported in 16 publications, 39,40,[42][43][44][47][48][49][55][56][57][58][59]62,69,70 provided data on the effectiveness of adding PCT testing to the information used to guide antibiotic therapy in ED settings. Two studies 39,49 were conducted in children, and the remainder 42,44,[55][56][57]60,62,69 were conducted in all adult populations.…”

Effectiveness of Proadrenomedullin Enhanced CURB65 Score Algorithm in Patients with Community-Acquired Pneumonia in “Real Life”, an Observational Quality Control Survey

“…We show the development, implementation and use of the algorithm with proadrenomedullin enhanced CURB65 score over four years in our publications. The description of the derivation of the biomarker enhanced score, clinical trial, and post-study surveillance could be used as a model for new clinical scores and algorithms in LRTI and other diagnosis [ 24 , 25 ]. The studies (OPTIMA I–III) had well characterized cohorts, similar methodology and overall 341 patients with radiologically confirmed CAP.…”

Procalcitonin and pyuria-based algorithm reduces antibiotic use in urinary tract infections: a randomized controlled trial

“…Herein, we focus on the efficacy of an algorithm based on clinical symptoms, PCT, and pyuria to safely reduce the duration of antibiotic therapy compared to current guidelines [ 6 , 15 , 28 ]. Details of the full trial design and methods have been published elsewhere [ 29 ].…”