Novel evidence on sepsis-inducing pathogens: from laboratory to bedside

Abstract

Sepsis is a life-threatening condition and a significant cause of preventable morbidity and mortality globally. Among the leading causative agents of sepsis are bacterial pathogens Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus pyogenes, along with fungal pathogens of the Candida species. Here, we focus on evidence from human studies but also include in vitro and in vivo cellular and molecular evidence, exploring how bacterial and fungal pathogens are associated with bloodstream infection and sepsis. This review presents a narrative update on pathogen epidemiology, virulence factors, host factors of susceptibility, mechanisms of immunomodulation, current therapies, antibiotic resistance, and opportunities for diagnosis, prognosis, and therapeutics, through the perspective of bloodstream infection and sepsis. A list of curated novel host and pathogen factors, diagnostic and prognostic markers, and potential therapeutical targets to tackle sepsis from the research laboratory is presented. Further, we discuss the complex nature of sepsis depending on the sepsis-inducing pathogen and host susceptibility, the more common strains associated with severe pathology and how these aspects may impact in the management of the clinical presentation of sepsis.

Keywords: diagnostics; immunology; inflammation; microorganisms; prognosis; sepsis; therapy.

Figure 1

Selection of the latest figures on sepsis-associated pathogen epidemiology worldwide. Streptococcus pyogenes-associated TSS is reported in the United States with an uneven distribution between adults (22.5%) and pediatrics (7.1%; Meehan et al., 2018). TSST-1 has been identified in 67% of MRSA and 4% of MSSA blood isolates in the Democratic Republic of the Congo (Vandendriessche et al., 2017) and in 23.1% of MRSA and 6.7% of MSSA blood isolates in China (Liu et al., 2018). PVL ⁺ TSST-1⁺ isolates have been found in 0.4% of all MRSA isolates in Japan (Kaneko et al., 2023). A high prevalence of PVL⁺ MRSA strains in adults has been found in New Caledonia Island (Imauven et al., 2022). An escalating number of countries in Latin America have reported the detection of Candida auris (Riera et al., 2022).