Cumulative antibiotic exposure is associated with ceftriaxone resistance among patients with urinary source Gram-negative bloodstream infection: A retrospective cohort study.

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We investigated the relationship between cumulative, historical antibiotic therapy and the presence of ceftriaxone-resistant (CRO-R) Enterobacterales bloodstream infections (BSI) from urinary sources. Adult patients established with primary care at Mayo Clinic with a first episode of monomicrobial Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, or Proteus mirabilis BSI from a urinary source from May 2019-May 2023 were included. Antibiotic therapy over the year prior to BSI was quantified as days of therapy (DOT), cumulative modified Antibiotic Spectrum Index (mASI), and cumulative Days of Antibiotic Spectrum Coverage (DASC) using prescription data. Patients with CRO-R urinary pathogens prior to antibiotic therapy assessment were excluded. 721 adults had monomicrobial Gram-negative BSI, including 70 patients (9.7%) with a CRO-R pathogen and 651 patients (90.3%) with a ceftriaxone-susceptible (CRO-S) pathogen. In the 12 months prior to BSI, levels of antibiotic DOT, mASI, and DASC were significantly greater among patients with CRO-R BSI than CRO-S BSI (p<0.001). The median time from blood culture collection to appropriate antibiotic therapy was significantly longer in the CRO-R group (24 hours, IQR 16-48) than the CRO-S group (1 hour, IQR 0-2) (p <0.001). Increasing cumulative antibiotic therapy prior to BSI, as quantified by the mASI, was significantly associated with increased risk of 1-year CDI after BSI (P = 0.027). Patients with first episode CRO-R Enterobacterales BSI had significantly greater prior antibiotic exposure than patients with CRO-S BSI and experienced significant delay of appropriate therapy. Routine quantitation and reporting of prior antibiotic therapy may improve empiric prescribing.