Cefotetan Therapy for Escherichia Coli Infections

Официальное название

Cefotetan Therapy for Escherichia Coli Bacteremia and Genitourinary Infections: a Prospective Phase II Pilot Study

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Cefotetan
  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
• Препарат Carbapenems
  Preferred antibiotic for ESBL E. coli infections: ertapenem. Minimum 1 dose within 24 hours of randomization.
• Препарат Beta Lactam Antibiotics
  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.

Первичные конечные точки

• Clinical success [Срок оценки: From randomization through 30 days.]

Вторичные конечные точки (2)

• Cefotetan MIC [Срок оценки: Baseline]
• Cefotetan trough [Срок оценки: Day 1 through 7]

Критерии участия

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Oregon Health & Science University — Portland

Публикации

• Tamma PD, Heil EL, Justo JA, Mathers AJ, Satlin MJ, Bonomo RA. Infectious Diseases Society of America 2024 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections. Clin Infect Dis. 2024 Aug 7:ciae403. doi: 10.1093/cid/ciae403. Online ahead of print. PMID 39108079
• Harris PNA, Tambyah PA, Lye DC, Mo Y, Lee TH, Yilmaz M, Alenazi TH, Arabi Y, Falcone M, Bassetti M, Righi E, Rogers BA, Kanj S, Bhally H, Iredell J, Mendelson M, Boyles TH, Looke D, Miyakis S, Walls G, Al Khamis M, Zikri A, Crowe A, Ingram P, Daneman N, Griffin P, Athan E, Lorenc P, Baker P, Roberts L, Beatson SA, Peleg AY, Harris-Brown T, Paterson DL; MERINO Trial Investigators and the Australasi PMID 30208454
• Stewart AG, Cottrell K, Henderson A, Vemuri K, Bauer MJ, Paterson DL, Harris PNA. In Vitro Activity of Cefotetan against ESBL-Producing Escherichia coli and Klebsiella pneumoniae Bloodstream Isolates from the MERINO Trial. Microbiol Spectr. 2021 Sep 3;9(1):e0022621. doi: 10.1128/Spectrum.00226-21. Epub 2021 Jul 7. PMID 34232101

Идентификаторы

NCT: NCT07318584 · STUDY00028869

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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