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 pneumoniae develop disseminated intravascular coagulation (DIC), multi-organ failure (MOF) and finally die in a septic shock. We investigated the therapeutic effect of antibiotic (tobramycin) treatment combined with the infusion of the highly specific thrombin inhibitor rec. hirudin. Although administration of 2 mg/kg tobramycin alone leads to a decrease of the bacterial burden, DIC could not be prevented. Infusion of rec. hirudin (0.25 mg/kg x h) for 4 h (start of treatment 1 h post infection), in addition to a bolus administration of tobramycin, led to an amelioration of DIC parameters as fibrinogen, thrombin-antithrombin complex (TAT) and platelets. Serum transaminase levels (GOT, GPT) as a marker of MOF were significantly improved by rec. hirudin, the T50 value increased from 17 h in the tobramycin group to 42 h in the tobramycin+rec. hirudin group, mortality rates were 90% or 60%, respectively. Combination of heparin (100 U/kg x h) and tobramycin was not effective on survival.
Research Laboratories of Behringwerke AG, Marburg, Germany.
G
G
Dickneite
J
J
Czech
D000818:Animals; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy* / Q000209:etiology; D004359:Drug Therapy, Combination; D005260:Female; D024764:Hirudin Therapy; D006629:Hirudins / Q000031:analogs & derivatives*; D007710:Klebsiella Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D007711:Klebsiella pneumoniae; D009102:Multiple Organ Failure / Q000188:drug therapy / Q000209:etiology; D051381:Rats; D011994:Recombinant Proteins / Q000627:therapeutic use; D018805:Sepsis / Q000150:complications / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D014031:Tobramycin / Q000627:therapeutic use*
D006629:Hirudins; D011994:Recombinant Proteins; D014031:Tobramycin; C083544:lepirudin