Progress toward a vaccine for extraintestinal pathogenic E. coli (ExPEC) II: efficacy of a toxin-autotransporter dual antigen approach

Abstract

Extraintestinal pathogenic Escherichia coli (ExPEC) represents the most prevalent Gram-negative bacterial pathogen and is a primary contributor to mortality due to antimicrobial resistance (AMR) globally (both deaths attributable to and associated with AMR) (1, 2). ExPEC comprises the pathotypes of uropathogenic E. coli (UPEC), neonatal meningitis E. coli, and septicemia-associated isolates (3). ExPEC is the primary cause of bacteremia and urinary tract infections (UTIs) and a frequent cause of neonatal meningitis (4, 5). In the United States, over 970,000 sepsis cases are admitted annually, with an 8.7% yearly increase in incidence among hospitalized patients, accounting for over 50% of hospital deaths (6, 7). Based on the Centers for Disease Control and Prevention (CDC) multiple cause-of-death data (1999–2014), 6% of all deaths involved sepsis, 22% of these cases listing sepsis as the underlying cause (8). Moreover, in 2017, approximately 48.9 million new cases of sepsis were recorded globally, with 11 million sepsis-related deaths reported, accounting for 19.7% of all worldwide deaths (9). In addition, sepsis management remains a major challenge for healthcare systems worldwide, resulting in a disproportionately high burden in terms of cost and hospital resource utilization. In the United States, sepsis management costs surpass those for any other disease, exceeding $24 billion in 2013, representing 13% of total hospital expenses and growing at three times the rate of other admissions (10). E. coli has emerged as the predominant causative agent of bloodstream infections (BSIs) in both community and hospital settings over the past decade, accounting for 27.1% of all bacteremia cases. Moreover, the incidence rate of E. coli bacteremia is estimated at 48 per 100,000 person-years, exhibiting a notable increase with advancing age (11).