Antibiotic-induced release of inflammatory mediators from bacteria in experimental Klebsiella pneumoniae-induced sepsis.

In a fibrin-clot model of sepsis, developed in mice, treatment with the antibiotics ceftazidime (Cfz) and ofloxacin (Ofl) caused significant (p < 0.01) release of endotoxin and TNF-alpha after 4.5 h when compared with control (untreated) and amikacin (Ami) treated group. Except for control group, the level of bacteremia declined in all three antibiotic-treated groups. The results suggest that antibiotic therapy, irrespective of the agent used, results in an increase in endotoxin levels in vivo. The amount of endotoxin liberated by Ami was much smaller than with Cfz and Ofl therapy, which makes it an appropriate agent for the treatment of sepsis. An increase in the level of TNF-alpha along with endotoxin is suggestive of increased inflammatory response.

Establishment of a sepsis model following implantation of Klebsiella pneumoniae-infected fibrin clot into the peritoneal cavity of mice.

Successful establishment of sepsis by entrapping a dose of 150 colony forming units of Klebsiella pneumoniae in a fibrin clot following implantation into the peritoneal cavity of mice is reported. The dose in the fibrin clot gave 50% mortality in mice, spread over a period of one week. All the infected mice showed positive blood culture up to 6 d post-infection; histopathology revealed inflammatory changes in both liver and spleen. Introduction of K. pneumoniae into experimental mice without entrapment in fibrin clot caused no mortality and blood culture remained positive only up to 2 d; histopathology of liver and spleen throughout the period of study showed relatively mild inflammatory changes, which almost cleared during 14 d post-infection. The use of the fibrin-clot model may thus be considered to be useful in studying both the initial and the persisting stage of infection in the peritoneum, whence a slow release of bacteria into the blood takes place which finally leads to sepsis and septicemia.