Combination of antibiotic treatment with the thrombin inhibitor recombinant hirudin for the therapy of experimental Klebsiella pneumoniae sepsis

Thromb Haemost. 1994 Jun;71(6):768-72.

Abstract

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.

MeSH terms

  • Animals
  • Disseminated Intravascular Coagulation / drug therapy*
  • Disseminated Intravascular Coagulation / etiology
  • Drug Therapy, Combination
  • Female
  • Hirudin Therapy*
  • Hirudins* / analogs & derivatives*
  • Klebsiella Infections / complications
  • Klebsiella Infections / drug therapy*
  • Klebsiella Infections / mortality
  • Klebsiella pneumoniae*
  • Multiple Organ Failure / drug therapy
  • Multiple Organ Failure / etiology
  • Rats
  • Recombinant Proteins / therapeutic use
  • Sepsis / complications
  • Sepsis / drug therapy*
  • Sepsis / etiology
  • Sepsis / mortality
  • Tobramycin / therapeutic use*

Substances

  • Hirudins
  • Recombinant Proteins
  • Tobramycin
  • lepirudin