Personalized Antibiotic Therapy in the Emergency Department: PANTHER Trial

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Project Summary Urinary tract infections (UTIs) are one of the most common infections seen in the emergency department (ED) and one of the most common reasons antibiotics are prescribed in the U.S. Inappropriate antibiotic prescribing and excessively long durations of therapy are two major causes of increasing antimicrobial resistance. Standard treatment for patients discharged home from the ED is an oral course of antimicrobial therapy for a set number of days. Physicians recommend that patients complete the full-course of antimicrobial therapy regardless of the time of symptom resolution. However, this approach disregards host and pathogen factors that affect an individual’s unique response to treatment. An alternative approach would be to direct a patient to discontinue their antibiotics upon symptom resolution, i.e., patient-directed antimicrobial duration (PDAD). A critical evidence gap is that a patient-centered approach has not been evaluated in clinical trials, but may decrease unnecessary antibiotic exposure, lowering the risk of adverse events (AEs) and resistance promotion, while resulting in similar outcomes as those treated with a standard approach. Antimicrobial resistance has complicated UTI treatment with the prevalence of fluoroquinolone (FQ)-resistant Escherichia coli now exceeding 20% in some US locations. The Infectious Diseases Society of America guidelines identified a research gap to understand the role of 3rd generation cephalosporins for outpatient treatment of acute uncomplicated pyelonephritis (AUP) in the setting of high rates of FQ resistance. The need for FQ alternative treatments is particularly pressing because of increasing reports of FQ-associated serious adverse events (SAEs). A critical need exists to identify alternative antimicrobial strategies that could improve patient outcomes and decrease the risk of AEs and resistance promotion. As opposed to short-course FQ treatment, for β-lactam regimens, IDSA recommends a 10-14 day treatment duration, thus allowing an opportunity to explore PDAD to minimize collateral antibiotic damage. To overcome the inertia associated with the traditional recommendation to complete a full-course treatment and demonstrate the safety and feasibility of conducting a large randomized controlled trial, we propose a pilot study comparing PDAD to a fixed indication-specific duration using an oral 3rd generation cephalosporin for women with AUP treated as outpatients. If our study hypothesis is confirmed, then results from a large clinical trial will support a paradigm shift in the way antimicrobial therapy is prescribed for patients with AUP and other common infectious diseases.