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Published on: December 9, 2022
Protein synthesis inhibiting clindamycin improves outcome in a mouse model of Staphylococcus aureus sepsis compared
Ivo Azeh1, Joachim Gerber, Andreas Wellmer
1Department of Neurology, Georg-August-University, Goettingen, Germany.
Objective:
The release of proinflammatory components from bacteria depends on the mode of action of the antibacterial therapy used. We studied whether this influences mortality in experimental sepsis.
Design:
In a lethal murine model of Staphylococcus aureus sepsis, animals were randomly assigned to receive the protein synthesis inhibitor clindamycin (CLI) or the beta-lactam ceftriaxone (CRO).
Setting:
Therapy was introduced subcutaneously 5 hrs after intraperitoneal injection of 10 colony forming units of S. aureus American Type Culture Collection 29213 and was continued every 8 hrs for 3 days.
Measurements And Results:
Survival was higher in mice receiving CLI (29/50 animals [58%]) than in mice receiving CRO (16/50 animals [32%]; p =.015). Mice treated with CRO died earlier than mice receiving CLI (p =.002). Eight hours after the first antibiotic dose, the motor performance of mice receiving CRO had deteriorated more than it did for mice receiving CLI (p =.009). Higher levels of tumor necrosis factor-alpha were measured in serum (p =.027) and peritoneal fluid (p =.001) of CRO-treated mice. In vitro, CLI released smaller amounts of staphylococcal enterotoxin A than CRO.
Conclusions:
Antibiotic treatment of Gram-positive sepsis with a protein synthesis inhibitor decreases morbidity and mortality compared with a bacteriolytic compound. This may be caused by a reduction of the concentrations of proinflammatory/toxic bacterial components and cytokines.
Insights
Protein synthesis inhibitors like clindamycin (CLI) reduced mortality in experimental Staphylococcus aureus sepsis compared to bacteriolytic antibiotics like ceftriaxone (CRO). This suggests CLI
Area of Science:
- Microbiology
- Immunology
- Pharmacology
Background:
- Bacterial component release during antibiotic therapy can influence sepsis outcomes.
- Different antibiotic classes have distinct mechanisms of action, potentially affecting host response.
Purpose of the Study:
- To investigate if the mechanism of action of antibacterial therapy impacts mortality in experimental sepsis.
- To compare the effects of a protein synthesis inhibitor (clindamycin) versus a bacteriolytic agent (ceftriaxone) in a murine model of Staphylococcus aureus sepsis.
Main Methods:
- A lethal murine model of Staphylococcus aureus sepsis was established.
- Animals were randomized to receive either clindamycin (CLI) or ceftriaxone (CRO) subcutaneously every 8 hours for 3 days, starting 5 hours post-infection.
- Survival rates, time to death, motor performance, and levels of pro-inflammatory cytokines (TNF-alpha) were assessed.
- In vitro studies evaluated the release of staphylococcal enterotoxin A by each antibiotic.
Main Results:
- Survival was significantly higher in the clindamycin group (58%) compared to the ceftriaxone group (32%) (p = .015).
- Mice treated with ceftriaxone exhibited earlier mortality (p = .002) and greater motor performance deterioration (p = .009).
- Ceftriaxone treatment led to higher serum and peritoneal fluid levels of tumor necrosis factor-alpha (p = .027 and p = .001, respectively).
- In vitro, clindamycin released lower amounts of staphylococcal enterotoxin A compared to ceftriaxone.
Conclusions:
- Antibiotic treatment of Gram-positive sepsis using a protein synthesis inhibitor (clindamycin) resulted in decreased morbidity and mortality compared to a bacteriolytic agent (ceftriaxone).
- This improved outcome may be attributed to the reduced release of pro-inflammatory bacterial components and cytokines with protein synthesis inhibitors.
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