Journal Article

Procalcitonin, mid-regional proadrenomedullin and C-reactive protein in predicting treatment outcome in community-acquired febrile urinary tract infection

Leyten, Eliane Madeleine Sophie, Stalenhoef, Janneke Evelyne, van der Reijden, Tanny J. K., Koster, Ted, van Nieuwkoop, Cees, van der Starre, Willize Elizabeth, van Dissel, Jaap Tamino, Wilson, Darius Cameron, Delfos, Nathalie Manon, van ‘t Wout, Johannes (Jan) Willem, Ablij, Hans Christiaan

2019

Overview

Background A reduction in duration of antibiotic therapy is crucial in minimizing the development of antimicrobial resistance, drug-related side effects and health care costs. The minimal effective duration of antimicrobial therapy for febrile urinary tract infections (fUTI) remains a topic of uncertainty, especially in male patients, those of older age or with comorbidities. Biomarkers have the potential to objectively identify the optimal moment for cessation of therapy. Methods A secondary analysis of a randomized placebo-controlled trial among 35 primary care centers and 7 emergency departments of regional hospitals in the Netherlands. Women and men aged ≥18 years with a diagnosis of fUTI were randomly assigned to receive antibiotic treatment for 7 or 14 days. Patients indicated to receive antimicrobial treatment for more than 14 days were excluded from randomization. The biomarkers procalcitonin (PCT), mid-regional proadrenomedullin (MR-proADM), and C-reactive protein (CRP) were compared in their ability to predict clinical cure or failure through the 10–18 day post-treatment visit. Results Biomarker concentrations were measured in 249 patients, with a clinical cure rate of 94% in the 165 randomized and 88% in the 84 non-randomized patients. PCT, MR-proADM and CRP concentrations did not differ between patients with clinical cure and treatment failure, and did not predict treatment outcome, irrespective of 7 or 14 day treatment duration (ROC AUC 0.521; 0.515; 0.512, respectively). PCT concentrations at presentation were positively correlated with bacteraemia (τ = 0.33, p  < 0.001) and presence of shaking chills (τ = 0.25, p  < 0.001), and MR-proADM levels with length of hospital stay (τ = 0.40, p  < 0.001), bacteraemia (τ = 0.33, p  < 0.001), initial intravenous treatment (τ = 0.22, p  < 0.001) and time to defervescence (τ = 0.21, p  < 0.001). CRP did not display any correlation to relevant clinical parameters. Conclusions Although the biomarkers PCT and MR-proADM were correlated to clinical parameters indicating disease severity, they did not predict treatment outcome in patients with community acquired febrile urinary tract infection who were treated for either 7 or 14 days. CRP had no added value in the management of patients with fUTI. Trial registration The study was registered at ClinicalTrials.gov [ NCT00809913 ; December 16, 2008] and trialregister.nl [ NTR1583 ; December 19, 2008].

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adrenomedullin / Adrenomedullin - analysis / Adrenomedullin - blood / Aged / Anti-Bacterial Agents - therapeutic use / Antibiotic stewardship / Antibiotic therapy / Antibiotics / Antiinfectives and antibacterials / Antimicrobial agents / Antimicrobial resistance / Bacteremia / Bacterial and fungal diseases / Biological markers / Biomarkers / Biomarkers, Pharmacological - analysis / Biomarkers, Pharmacological - blood / C-reactive protein / C-Reactive Protein - analysis / C-Reactive Protein - metabolism / Care and treatment / Chills / Clinical outcomes / Communities / Community-Acquired Infections - blood / Community-Acquired Infections - diagnosis / Community-Acquired Infections - drug therapy / Community-Acquired Infections - epidemiology / Comorbidity / Correlation / Disease / Emergency medical services / Failure / Female / Fever / Fever - blood / Fever - diagnosis / Fever - drug therapy / Fever - epidemiology / Health care costs / Hospitals / Humans / Infectious Diseases / Intensive care / Internal Medicine / Intravenous administration / Male / Medical Microbiology / Medical research / Medicine / Medicine & Public Health / Microbial drug resistance / Middle Aged / Netherlands - epidemiology / Parameters / Parasitology / Patient outcomes / Patients / Primary care / Procalcitonin / Procalcitonin - analysis / Procalcitonin - blood / Prognosis / Protein Precursors - analysis / Protein Precursors - blood / Proteins / Pyelonephritis / Randomization / Research Article / Retrospective Studies / Risk factors / Secondary analysis / Sepsis / Shaking / Side effects / Studies / Therapy / Treatment duration / Treatment Outcome / Tropical Medicine / Urinary tract / Urinary tract diseases / Urinary tract infections / Urinary Tract Infections - blood / Urinary Tract Infections - diagnosis / Urinary Tract Infections - drug therapy / Urinary Tract Infections - epidemiology / Urogenital system / Womens health