Impact of Antibiotic Treatment Intensity on Long-Term Sepsis-Associated Kidney Injury in a Polymicrobial Peritoneal Contamination and Infection Model

Abstract

Background/Aims: Long-term kidney affections after sepsis are poorly understood. Animal models for investigating kidney damage in the late phase of disease progression are limited. The aim of this study was to investigate the impact of two antibiotic regimes on persistence of kidney injury after peritonitis. Methods: Kidney damage was investigated 65 days after polymicrobial peritoneal contamination and infection (PCI) sepsis induction in C57BL/6 mice. Short-term antibiotic therapy (STA, 4 days) was compared to long-term (LTA, 10 days) treatment using plasma creatinine, plasma and urine neutrophil gelatinase-associated lipocalin (NGAL), urine albumin/creatinine ratio and renal histology. Results: Sepsis resulted in mortality rates of 68.2% (STA) and 61.0% (LTA). Surviving STA animals showed the most pronounced kidney damage indicated by significantly elevated levels of creatinine and acute tubular damage (ATD), whereas NGAL was significantly increased in LTA survivors only. A creatinine level above 0.3 mg/dl was used to define kidney injury, found in 21.4% of STA animals and 7.8% of LTA animals. While animals with kidney injury demonstrated significantly higher ATD scores and persistent tubular damage, no significant differences were found for plasma or urine NGAL levels or urine albumin/creatinine ratios. Conclusion: Prolonged antibiotic treatment reduced the rate of ongoing peritonitis-induced kidney injury in a C57BL/6 mouse model. Plasma or urine NGAL levels were not able to identify animals with or without persistent kidney injury. The kidney injury after the PCI mouse model represents prototypic clinical findings and should be used for further studies investigating disease mechanisms.

Monocyte-induced recovery of inflammation-associated hepatocellular dysfunction in a biochip-based human liver model

“…Next, we wanted to address whether effects in the liver organoid are similarly detectable in the in vivo situation. Murine peritoneal contamination and infection (PCI) is a well-established in vivo model for studies on systemic inflammation, sepsis-related liver dysfunction and its long-term sequelae with respect to tissue repair 42 43 44 45 . Similar to findings in the liver organoid, cytokine levels rapidly increased in the mouse model within 6 h after induction of systemic inflammation by PCI, however, dropped down to low levels until 72 h at the mRNA level ( Fig.…”

“…Severe sepsis was induced using a peritoneal contamination and infection model by administration of standardized fecal slurry as described previously 44 and approved by the local animal welfare committee (TLLV, 02-037/12). Female C57Bl/6 mice (aged 12–14 weeks, n = 55) undergoing sepsis were monitored and resuscitated for four days (25 μL/g B.W.…”

Plasma Neutrophil Gelatinase-Associated Lipocalin Is Primarily Related to Inflammation during Sepsis: A Translational Approach

“…Lipocalin-2 deficient mice demonstrated a higher susceptibility for bacterial infections, and in wild type animals undergoing sepsis, a strong correlation between plasma-NGAL, interleukin 6 (IL-6) and interleukin 10 (IL-10), but also with TNF alpha was found [ 15 , 16 ], which raised the question whether plasma-NGAL might be stronger related to inflammation than to AKI itself. The precise role of plasma-NGAL as marker or mediator in non-infectious/non-inflammatory compared to infectious/inflammatory-related types of AKI is currently unclear and controversially discussed [ 17 – 20 ].…”

A systematic review and meta-analysis of antibiotic prophylaxis in skin graft surgery: A protocol

“…The continued use of prophylactic antibiotics may contribute to this which could lead to ineffective antibiotic therapy when treating an actively infected wound. Furthermore, antibiotics can have a range of systemic effects on the body ranging from nephrotoxicity [17] to anaphylaxis [9] in some, potentially putting patients at risk of death.…”