Mode of bacterial killing affects the inflammatory response and associated organ dysfunctions in a porcine E. coli intensive care sepsis model

BACKGROUND: Sepsis is often treated with penicillin-binding protein 3 (PBP-3) acting β-lactam antibiotics, such as piperacillin-tazobactam, cefotaxime, and meropenem. They cause considerable bacterial structural changes and have in vitro been associated with an increased inflammatory response. In a clinically relevant large animal sepsis model, our primary aim was to investigate whether bacteria killed by a PBP-3-active antibiotic has a greater effect on the early inflammatory response and organ dysfunction compared with corresponding amounts of live or heat-killed bacteria. A secondary aim was to determine whether the addition of an aminoglycoside could mitigate the cefuroxime-induced response.

METHOD: Killed or live Escherichia coli were administrated as a 3-h infusion to 16 healthy pigs in a prospective, randomized controlled interventional experimental study. Cefuroxime was chosen as the PBP-3-active antibiotic and tobramycin represented the aminoglycosides. The animals were randomized to receive (I) bacteria killed by cefuroxime, (II) live bacteria, (III) bacteria killed by heat, or (IV) bacteria killed by the combination of cefuroxime and tobramycin. Plasma endotoxin, tumor necrosis factor alpha, interleukin-6, interleukin-10, leukocytes, and organ function were recorded at the start of the experiment and then hourly for 6 h.

RESULTS: Differences in dynamics of concentration over time between the four treatment groups were found for the three cytokines (p < 0.001). Animals receiving cefuroxime-killed bacteria demonstrated higher responses than those receiving live (p < 0.05) or heat-killed bacteria (p < 0.01). The addition of tobramycin reduced the cefuroxime-induced responses (p < 0.001). The cytokine responses were associated with leucocyte activation that was further associated with pulmonary dysfunction and increases in lactate (p < 0.01).

CONCLUSIONS: In comparison with live or heat-killed bacteria, bacteria killed by a PBP-3-active antibiotic induced an increased inflammatory response that appears to be associated with deteriorated organ and cellular function. The addition of an aminoglycoside to the PBP-3-active antibiotic reduced that response.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:24

Enthalten in:

Critical care (London, England) - 24(2020), 1 vom: 14. Nov., Seite 646

Sprache:

Englisch

Beteiligte Personen:

Skorup, Paul [VerfasserIn]
Maudsdotter, Lisa [VerfasserIn]
Lipcsey, Miklós [VerfasserIn]
Larsson, Anders [VerfasserIn]
Sjölin, Jan [VerfasserIn]

Links:

Volltext

Themen:

130068-27-8
Antibiotics
Bacteria
Cefuroxime
Cytokines
Endotoxins
Inflammation
Interleukin-10
Interleukin-6
Journal Article
O1R9FJ93ED
Penicillin-Binding Proteins
Porcine
Research Support, Non-U.S. Gov't
Sepsis
Tobramycin
Tumor Necrosis Factor-alpha
VZ8RRZ51VK

Anmerkungen:

Date Completed 14.07.2021

Date Revised 14.07.2021

published: Electronic

Citation Status MEDLINE

doi:

10.1186/s13054-020-03303-9

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM317565664