By Ashley Dao, PharmD Candidate c/o 2024
Extraintestinal pathogenic Escherichia coli (ExPEC) is the most common gram-negative bacilli and is a leading bacterial cause of urinary tract infections (UTI), bacteremia and meningitis. E coli is the leading cause of deaths associated with antibiotic resistant bacterial pathogens and a common cause of resistant hospital-acquired infections.1
Older adults, especially those with a history of UTIs, have an increased risk of developing invasive extraintestinal pathogenic Escherichia coli disease (IED), including bacteremia and sepsis.2, 3 UTIs are the most common source of infection reported in 21-59% of patients. Higher rates of UTIs in older patients may be secondary to the increased prevalence of urinary catheters, incontinence, and neurological disorders. E. coli is the most common pathogen in community acquired blood stream infections in the elderly. Although older patients had higher mortality and complications rates, studies demonstrated they were less likely to undergo infectious disease consultations and imaging studies. They were also less likely to be hospitalized in a critical care setting, have surgical/ drainage procedures and have their foreign body/ catheter removed or replaced.4 Important aspects of managing infection in older patients are antimicrobial stewardship in long-term care facilities, active and invasive diagnostic work-up and treatment and infectious disease consultation in older patients. Novel vaccines for bacterial infections may also prevent systemic bacterial infection in older adults.4
There are four ExPEC vaccines in clinical development. The most advanced in development is ExPEC9V by Janssen Pharmaceutical, Inc. (Janssen). ExPEC9V is nine-valent-O-polysaccharide conjugate vaccine currently in phase 3 clinical trial (NCT04899336) which is expected to be completed in May 2027.1, 2 In 2023 Sanofi announced an agreement with Janssen Pharmaceuticals to develop and commercialize the vaccine candidate for ExPEC developed by Janssen.3
E.mbrace Study
The E.mbrace Study (NCT04899336) is a randomized, double-blind, placebo controlled, multicenter, global phase 3 study to assess the efficacy, safety, and immunogenicity of vaccination with ExPEC9V in the prevention of IED in adults aged 60 years and older with a history of UTI in the past 2 years. The study consists of a Screening Phase (performed 8 days prior to vaccination on Day 1), Randomization, Vaccination Phase (Day 1) and Follow-up Phase (up to 3 years post-vaccination).2
ExPEC9V is a vaccine candidate for active immunization for the prevention of IED in adults 60 years of age and older.Invasive ExPEC is defined as an acute illness consistent with systemic bacterial infection. This infection is microbiologically confirmed by either the isolation and identification of E. coli from blood or sterile body siter, or by the isolation and identification of E. coli from urine in patient with urosepsis and no other identifiable source of infection.2
Inclusion/Exclusion Criteria
Participants of the trial must have a history of UTI in the past 2 years. Recent history of UTI or acuter bacterial prostatitis must have resolved more than 14 days prior to randomization. Female participants must be either postmenopausal or permanently sterile, and not intending to conceive by any methods. Excluded participants were those with end-stage renal disease requiring dialysis, contraindication to intramuscular injections and blood draws (e.g. bleeding disorders or a history of difficult blood draws), history of acute polyneuropathy (e.g. Guillain-Barre syndrome) or chronic inflammatory demyelinating polyneuropathy. Participants were also excluded if they received any E. coli or ExPEC vaccine.2
Study Design
The experimental arm, ExPEC9V, received a single intramuscular injection of nine-valent extraintestinal pathogenic E. coli vaccine on Day 1, while the placebo arm received a single intramuscular injection of matching placebo on Day 1. The primary outcomes were the number of participants with first IED event with microbiological confirmation in blood, other sterile sites, or urine, and number of participants with first IED event with microbiological confirmation excluding urine.2
The E.mbrace Study will assess the efficacy and safety of ExPEC9V in prevention of IED in older adults. Sepsis is a life-threatening blood stream infections (BSI) and E. coli is the most common pathogen in community acquired BSI. However, a significant part of BSIs in older adults may be prevented by removal of unnecessary urinary catheters, adherence of infection control practice and appropriate inclusion of infection disease consultations. Since older patients are often under-represented in clinical trials, ExPEC9V may reduce the prevalence of IED in older patients, helping older adults live longer and healthier lives and reducing hospitalization costs.
References:
- Frost I, Sati H, Garcia-Vello P, et al. The role of bacterial vaccines in the fight against antimicrobial resistance: an analysis of the preclinical and clinical development pipeline. Lancet Microbe. 2023;4(2):e113-e125. doi:10.1016/S2666-5247(22)00303-2
- ClinicalTrials.gov. A study of vaccination with 9-valent extraintestinal pathogenic Escherichia coli vaccine (ExPEC9V) in the prevention of invasive extraintestinal pathogenic Escherichia coli disease in adults aged 60 years and older with a history of urinary tract infection in the past 2 years (NCT04899336). Last Updated November 8, 2023. https://clinicaltrials.gov/study/NCT04899336. Accessed January 18, 2024.
- Sanofi. Press Release: Sanofi announced agreement for potential first-in-class vaccine against extraintestinal pathogenic E. coli. October 3, 2023. https://www.sanofi.com/en/media-room/press-releases/2023/2023-10-03-05-30-00-2753274. Accessed January 18, 2024.
- Yahav D, Eliakim-Raz N, Leibovici L, Paul M. Bloodstream infections in older patients. Virulence. 2016;7(3):341-352. doi:10.1080/21505594.2015.1132142
