The Need of Enterococcal Coverage in Severe Intra-Abdominal Infection: Evidence from Animal Study

Abstract

Intra-abdominal infection (IAI) is a common and important cause of infectious mortality in intensive care units. Adequate source control and appropriate antimicrobial regimens are key in the management of IAI. In community-acquired IAI, guidelines recommend the use of different antimicrobial regimens according to severity. However, the evidence for this is weak. We investigated the effect of enterococcal coverage in antimicrobial regimens in a severe polymicrobial IAI model. We investigated the effects of imipenem/cilastatin (IMP) and ceftriaxone with metronidazole (CTX+M) in a rat model of severe IAI. We observed the survival rate and bacterial clearance rate. We identified the bacteria in blood culture. We measured lactate, alanine aminotransferase (ALT), creatinine, interleukin (IL)-6, IL-10, and reactive oxygen species (ROS) in the blood. Endotoxin tolerance of peripheral blood mononuclear cells (PBMCs) was also estimated to determine the level of immune suppression. In the severe IAI model, IMP improved survival and bacterial clearance compared to CTX+M. Enterococcus spp. were more frequently isolated in the CTX+M group. IMP also decreased plasma lactate, cytokine, and ROS levels. ALT and creatinine levels were lower in IMP group. In the mild-to-moderate IAI model, however, there was no survival difference between the groups. Immune suppression of PBMCs was observed in IAI model, and it was more prominent in the severe IAI model. Compared to CTX+M, IMP improved the outcome of rats in severe IAI model.

Whey protein hydrolysate mitigates both inflammation and endotoxin tolerance in THP‐1 human monocytic leukemia cells

“…14,38,39 Recently, endotoxin tolerance has also been regarded as an important issue in COVID-19, 9,10 Furthermore, the direct relationship between mortality and the severity of endotoxin tolerance was demonstrated in the animal model with a severe polymicrobial intra-abdominal infection. 40 These findings concerned with endotoxin tolerance have attracted clinical attention. Although endotoxin tolerance has two different aspects, we focused on the latter (i.e., an unlikable effect on clinical outcomes in patients with severe insults) and demonstrated the suppression of endotoxin tolerance by WPH.…”

“…Meanwhile, lower cytokine production when blood was stimulated by LPS ex vivo, that is endotoxin tolerance, was related to poorer clinical outcomes in patients with trauma, sepsis, or in the intensive care unit 14,38,39 . Recently, endotoxin tolerance has also been regarded as an important issue in COVID‐19, 9,10 Furthermore, the direct relationship between mortality and the severity of endotoxin tolerance was demonstrated in the animal model with a severe polymicrobial intra‐abdominal infection 40 . These findings concerned with endotoxin tolerance have attracted clinical attention.…”