Complicated Urinary Tract Infections Caused by Fluoroquinolone-Non-Susceptible/Trimethoprim-Sulfamethoxazole-Resistant Extended-Spectrum β-Lactamase-Producing Enterobacterales: Patient Characteristics, Resistance Phenotypes, Treatment Patterns, and Clinical Outcomes.

INTRODUCTION Patients with complicated urinary tract infections (cUTIs) caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBL-E) not susceptible (NS) to fluoroquinolones (FQ-NS) or resistant (R) to trimethoprim-sulfamethoxazole (TMP/SMX-R) have few effective oral treatment options.

Methods

Data from the Optum de-identified Electronic Health Record data set (Optum EHR) (January 2018-September 2023) were used. The primary objective was to describe cumulative incidence of treatment failure (TF) by care setting (hospital versus non-hospital) within 30 days of the initiation of the latest intravenous antibiotic treatment prescribed ± 7 days from the microbiology results (index).

Results

Among 7388 eligible patients, mean (standard deviation) age was 65.6 (17.7) years, and 66.3% were female. Most patients (5211, 70.5%) had a cUTI with a complicating factor; 3415 (46.2%) were diagnosed in hospital. Among the 7902 ESBL-E isolates from eligible patients with cUTIs, Escherichia coli was the predominant pathogen (75.1%), followed by Klebsiella pneumoniae (13.4%). Overall, 6384 (81.7%) isolates were FQ-NS, 5323 (68.0%) TMP/SMX-R, and 170 (2.2%) carbapenem-NS. Kaplan-Meier estimates revealed that the cumulative incidence of TF by day 30 post-index was 27.5% among hospitalized patients and 25.2% among non-hospitalized, with variation by resistance profile, driven primarily by receipt of another antibiotic (both settings). Most patients (5013, 67.9%) were prescribed an intravenous antibiotic at index, often carbapenems (2157, 43.0%), but treatment sequences were heterogeneous. Recurrence occurred in 2116 patients (28.6%), hospitalization (among those not hospitalized at index) in 975 (24.5%), and readmission in 663 (19.4%).

Conclusions

These data indicate a substantial burden of cUTIs caused by ESBL-E that were FQ-NS or TMP/SMX-R, characterized by high rates of treatment failures and hospitalization for IV antibiotic treatment.