A 2019 randomized controlled trial demonstrated noninferiority amongst patients treated with seven versus 14 days of antibiotics for uncomplicated bacteremia caused by Gram-negative organisms. The primary composite outcome, including all-cause mortality, infectious complications, and hospital readmissions, occurred in 46% of patients in the seven-day group vs 48% in the 14-day group. Most of the 600 study patients in this trial had infections caused by Enterobacterales organisms such as E. coli from a urinary source and were transitioned to an oral fluoroquinolone for step-down therapy. The study concluded that reducing antibiotic treatment durations for uncomplicated Gram-negative bacteremia to seven days was non-inferior to longer durations and represented an important antibiotic stewardship intervention (Yahav et al., 2019).
Trial results informed the Carolina Antibiotic Stewardship Program’s (CASP) Best Practices for Duration of Antimicrobial Therapy were updated to recommend a seven-day duration for treatment of pyelonephritis with bacteremia caused by Enterobacterales organisms such as E. coli. Clinical scenarios such as complicated bacteremias with sequelae of infection or the presence of infected renal stones or foreign material may require treatment durations beyond seven days.
In 2023, CASP conducted a study led by Ashley Marx, PharmD, and Stephanie Hill, PharmD, to assess the median treatment durations for patients hospitalized at the University of North Carolina Hospitals with E. coli bacteremia from a urinary source in 2022. Adult patients 18 years or older were included if they had positive blood cultures for E. coli with a diagnosis of UTI, pyelonephritis, or positive urine culture during the admission. Immunocompromised patients were excluded. A total of 64 patients met the inclusion criteria, of which 70% were females with a median age of 64 years and a median length of hospital admission of six days. Some 18% of patients required ICU-level care during their admission.
Approximately one-third of patients completed their treatment course with intravenously administered antibiotics, and the remaining two-thirds received a combination of intravenous and oral antibiotics. The most common oral step-down agents included fluoroquinolones (72%), β-lactams (23%), or trimethoprim-sulfamethoxazole (5%). A subgroup analysis of 31 patients with uncomplicated bacteremia found the median antibiotic treatment duration for uncomplicated E. coli bacteremia from a urinary source was ten days (IQR: 8-12; range 7-17). Findings from this study will serve as a duration of antimicrobial therapy baseline for future opportunities to optimize treatment durations for uncomplicated Gram-negative bacteremia.
Stephanie Hill, PharmD is a PGY2 with UNC Hospitals.