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

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. 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). 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%). 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. A complicated urinary tract infection (cUTI) is a bacterial infection that is more likely to spread or cause serious problems than an uncomplicated bladder infection. The microorganisms that cause cUTIs are becoming resistant to available treatments (meaning the antibiotics do not kill the bacteria or are less able to), leaving few options for oral antibiotic treatment. This means that many patients need to be hospitalized to receive intravenous antibiotics. A particular group of microorganisms causing cUTIs, called ‘ESBL+’ microorganisms, are often resistant to treatment. This study provides information about patients with cUTIs, how often antibiotics failed to treat these infections, and what the consequences were for the patients. We used data from a US Electronic Health Record database to identify adults with cUTIs infected with an ESBL+ uropathogen who were prescribed an antibiotic for treatment. For 6 months after their diagnosis, we assessed their demographics, infection characteristics, treatments, and how often their treatment failed. Patients in the study had a moderate chance of their antibiotic treatment not working, and this was more likely to happen in hospitalized patients than non-hospitalized patients. Treating cUTIs caused by drug-resistant bacteria is difficult because few oral antibiotics work against these infections. New oral treatments are needed to help patients with these hard-to-treat infections receive care outside the hospital.