Protein synthesis inhibiting clindamycin improves outcome in a mouse model of Staphylococcus aureus sepsis compared with the cell wall active ceftriaxone.
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.


METHODS
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).


METHODS
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.


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.
Department of Neurology, Georg-August-University, Goettingen, Germany.
Ivo
I
Azeh
Joachim
J
Gerber
Andreas
A
Wellmer
Malte
M
Wellhausen
Brigitte
B
Koenig
Helmut
H
Eiffert
Roland
R
Nau
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002443:Ceftriaxone / Q000627:therapeutic use*; D002473:Cell Wall / Q000187:drug effects; D002511:Cephalosporins / Q000627:therapeutic use*; D002981:Clindamycin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011500:Protein Synthesis Inhibitors / Q000627:therapeutic use*; D018805:Sepsis / Q000188:drug therapy*; D013203:Staphylococcal Infections / Q000188:drug therapy*; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D011500:Protein Synthesis Inhibitors; D002981:Clindamycin; D002443:Ceftriaxone