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. 2021 Mar 2;10(5):1027.
doi: 10.3390/jcm10051027.

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

Min Ji Lee  1 , Tae Nyoung Chung  1 , Ye Jin Park B  1 , Han A Reum Lee  1 , Jung Ho Lee  1 , Chang June Yune  1 , Jinkun Bae  1 , Sehwan Mun  1 , Jeong Su Park  2 , Kyuseok Kim  1
Affiliations

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

Min Ji Lee et al. J Clin Med. .

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.

Keywords: antibiotics; intraabdominal infection; mortality; sepsis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Survival effect of different antibiotic treatments on polymicrobial intra-abdominal infection (IAI) model. (A) Severe IAI model, n = 4 for no antibiotics, n = 13 for CTX + M, n = 14 for IMP. (B) Mild IAI model, n = 4 per group, * p < 0.05 compared with no antibiotics model, ** p compared with CTX + M model. IAI, intraabdominal infection; CTX + M, ceftriaxone with metronidazole; IMP, imipenem.
Figure 2
Figure 2
CFU in blood and spleen in severe IAI model. (A) CFU in blood, (B) CFU in spleen. * p < 0.05 compared with sham, ** p compared with CTX + M model. IAI, intraabdominal infection; CTX + M, ceftriaxone with metronidazole; IMP, imipenem; CFU, colony-forming unit.
Figure 3
Figure 3
Effects of different antibiotic treatments on organ injury in severe IAI model. (A) Plasma lactate, (B) serum ALT, (C) serum creatinine. n = 3 for sham, n = 14 for IMP and CTX + M, *p < 0.05 compared with sham, ** p compared with CTX + M model. IAI, intraabdominal infection; CTX + M, ceftriaxone with metronidazole; IMP, imipenem; ALT, alanine aminotransferase.
Figure 4
Figure 4
Inflammation and oxidative stress in severe IAI model. (A) IL-6, (B) IL-10, (C) ROS generation. n = 3 for sham, n = 14 for IMP and CTX + M, * p < 0.05 compared with sham, ** p compared with CTX + M model. IAI, intraabdominal infection; CTX + M, ceftriaxone with metronidazole; IMP, imipenem; ROS, reactive oxygen species; DCF-DA, 20,70-dichlorofluorescein diacetate.
Figure 5
Figure 5
Effects of different antibiotics on endotoxin tolerance of PBMC stimulated by LPS. (A) Baseline TNF-α in PBMCs after severe IAI induction, (B) endotoxin tolerance of PBMCs in severe IAI model, (C) endotoxin tolerance of PBMCs in mild or severe IAI model with CTX + M. n = 5 for sham, n = 6–11 for other groups; * p < 0.05 compared with sham, ** p compared with CTX + M model. IAI, intraabdominal infection; CTX + M, ceftriaxone with metronidazole; IMP, imipenem; PBMC, peripheral blood mononuclear cell; LPS, lipopolysaccharide.
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