![]() Bacteremia with no evident source is considered primary ( 13) secondary bacteremia can arise through dissemination from an infection, commonly pneumonia or urinary tract infections (UTIs), or through contaminated medical devices. The severity and high mortality for conditions associated with bacteremia underscore the importance of investigating these complex infections.īacteria can enter the blood by multiple routes. Further, bloodstream infections are also associated with a high mortality risk of 27% ( 12). Sepsis can result in permanent dysfunction, including cognitive impairment or organ failure ( 9, 10) and is associated with variable, yet incredibly high, mortality ( 7, 10, 11). Annually, there are an estimated 1.7 million sepsis cases ( 6) in the United States and more than 30 million cases globally ( 7), leading the World Health Organization (WHO) to declare sepsis a global health priority ( 8). Clinical bacteremia can result in sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection ( 5). Filling these knowledge gaps could uncover potential targets for future therapies to treat these destructive infections.īacteremia, the presence of bacteria in the bloodstream, is an urgent public health issue ( 1) that can initiate devastating diseases ( 2, 3) and costs the global economy billions of dollars each year ( 4). This review summarizes what has been learned from clinical studies, describes how animal models assess bacteremia fitness factors, and discusses major gaps in knowledge that limit insight into Gram-negative bacteremia. However, our understanding of shared and species-specific factors involved in the three steps of Gram-negative bacteremia pathogenesis is incomplete. Animal models have provided insights into bacterial fitness factors required for initial body site invasion and bloodstream fitness for a few species. Clinical studies have identified some host and bacterial factors that correlate with better patient outcome and with disease progression. To establish bacteremia, pathogens must (i) invade initial sites of infection or colonization, (ii) disseminate to the bloodstream, and (iii) survive in the blood. A small group of species cause the majority of Gram-negative bacteremia cases, and each species is uniquely adapted for initial infection or colonization at specific body sites. Among primary bacteremias, a significant subset are thought to arise from gut colonization. Clinical presentation of bacteremia can be primary, originating from an unknown source, or secondary, originating from infections such as pneumonia. Gram-negative bacteremia is a significant public health threat affecting both healthy individuals and those with underlying comorbidities but is especially dangerous in vulnerable populations like the elderly and hospitalized patients ( 1). This review provides an overview of Gram-negative bacteremia, compares animal models for bacteremia, and discusses prevalent Gram-negative bacteremia species. ![]() Capsule production, adhesins, and metabolic flexibility are common mediators, whereas only some species utilize toxins. The few bacteremia fitness factors identified in these prominent Gram-negative species demonstrate shared and unique pathogenic mechanisms at each phase of bacteremia progression. A small subset of species is responsible for the majority of Gram-negative bacteremia cases, including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. ![]() To develop new therapies, it is critical to define species-specific and multispecies fitness factors required for bacteremia in model systems that are relevant to human infection. Third, bacteria adapt to survive in the blood and blood-filtering organs. Second, bacteria overcome host barriers, such as immune responses, and disseminate from initial body sites to the bloodstream. First, bacteria invade or colonize initial sites of infection. Gram-negative bacteremia develops in three phases. Concerningly, rates of both Gram-negative bacteremia and antimicrobial resistance in the causative species are increasing. Gram-negative bacteremia is a devastating public health threat, with high mortality in vulnerable populations and significant costs to the global economy.
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