This pilot study will compare clinical outcomes among patients treated with cefotetan versus standard of care antibiotics for bacteremia or genitourinary infections caused by E. coli. It will also measure cefotetan minimum inhibitory concentration (MIC) distributions and cefotetan trough serum concentrations.

In this single-center pilot trial, we will study the efficacy of cefotetan versus standard of care antibiotic therapy for patients hospitalized at Oregon Health & Science University (OHSU) with bacteremia caused by extended-spectrum β-lactamase-producing (ESBL) and non-ESBL E. coli with a genitourinary source. Participants who consent for enrollment will be randomized 1:1 to receive either cefotetan or standard of care antibiotic therapy for their infection and followed for 30 days to determine clinical outcomes. In addition, we will measure cefotetan MIC distributions among patients with ESBL bloodstream or genitourinary infections. Finally, we will measure cefotetan trough serum concentrations in a subset of enrolled patients with ESBL and non-ESBL E. coli bacteremia who are treated with cefotetan.

Inclusion Criteria (clinical cohort):

• Identified within 48 hours of inpatient antibiotic administration for acute illness.
• Patient or legally authorized representative are able to provide informed consent for participation in the study.
• Monomicrobial E. coli bacteremia with a genitourinary source.
• Isolate susceptible to both ertapenem and cefotetan (ESBL infections) or ceftriaxone and cefotetan (non-ESBL infections).

Exclusion Criteria (clinical cohort):

• Allergy to cefotetan.
• History of cephalosporin-associated hemolytic anemia.
• Allergy to ertapenem or meropenem (among patients with ESBL E. coli infections).
• Allergy to ceftriaxone (among patients with non-ESBL E. coli infections). Includes allergy to antibiotics with a similar structure expected to confer cross reactivity to ceftriaxone (cefotaxime, cefpodoxime, ceftazidime).
• Admission within 30 previous days.
• Any bacteremia with the same organism in the previous 90 days.
• Pregnant or breastfeeding.
• Moderately to severely immunocompromised, including solid organ or stem cell transplant, hematologic malignancy, active chemotherapy.
• Admission with neutropenic fever.
• Severe illness, including shock and/or intensive care unit admission.
• Inability to complete at least 72 hours of appropriate parenteral therapy, including at least 1 dose cefotetan for patients randomized to the treatment arm or at least 1 dose of appropriate parenteral therapy following randomization for patients assigned to the standard of care arm.