E Coli Infection, ESBL Producing E.Coli
Conditions
Keywords
cefotetan, cephamycin, ESBL producing E. coli, E. coli infection
Brief summary
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.
Detailed description
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.
Interventions
DRUGCefotetan
Minimum 1 dose cefotetan within 24 hours of randomization. Creatinine clearance (CrCl) \>30 mL/minute: 2 g IV every 12 hours; CrCl 10-30 mL/minute: 2 g IV every 24 hours; CrCl \<10 mL/minute: 2 g IV every 48 hours
DRUGCarbapenems
Preferred antibiotic for ESBL E. coli infections: ertapenem. Minimum 1 dose within 24 hours of randomization.
Beta lactam antibiotics for non-ESBL E. coli infections include preferred ceftriaxone or alternative cephalosporins (cefepime, ceftazidime), penicillins (piperacillin-tazobactam, ampicillin-sulbactam), and carbapenems (ertapenem, meropenem). Minimum 1 dose within 24 hours of randomization.
Sponsors
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical success | From randomization through 30 days. | Absence of death, recurrent E. coli, bacteremia, or need for antibiotic treatment for recurrent E.coli genitourinary infection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cefotetan MIC | Baseline | Cefotetan MIC from E. coli isolated from blood and/or urine culture |
| Cefotetan trough | Day 1 through 7 | Cefotetan serum trough obtained from a subset of participants randomized to cefotetan arm |
Countries
United States
Contacts
Primary ContactKristina L. Bajema
Backup ContactJames Lewis
Outcome results
None listed