COMBINATION OF ANTIBIOTIC-TREATMENT WITH THE THROMBIN INHIBITOR RECOMBINANT HIRUDIN FOR THE THERAPY OF EXPERIMENTAL KLEBSIELLA-PNEUMONIAE SEPSIS

Rats which were infected with the gramnegative pathogen Klebsiella pne umoniae develop disseminated intravascular coagulation (DIC), multi-or gan failure (MOF) and finally die in a septic shock. We investigated t he therapeutic effect of antibiotic (tobramycin) treatment combined wi th the infusion of the highly specific thrombin inhibitor rec. hirudin . Although administration of 2 mg/kg tobramycin alone leads to a decre ase of the bacterial burden, DIC could not be prevented. Infusion of r ec. hirudin (0.25 mg/kg x h) for 4 h (start of treatment 1 h post infe ction), in addition to a bolus administration of tobramycin, led to an amelioration of DIC parameters as fibrinogen, thrombin-antithrombin c omplex (TAT) and platelets. Serum transaminase levels (GOT, GPT) as a marker of MOF were significantly improved by rec. hirudin, the T-50 va lue increased from 17 h in the tobramycin group to 42 h in the tobramy cin + rec. hirudin group, mortality rates were 90% or 60%, respectivel y. Combination of heparin (100 U/kg x h) and tobramycin was not effect ive on survival.