Proteolytic enzymes as adjuncts to antimicrobial prophylaxis of contaminated wounds.
When a tissue is injured, its vessels exhibit a marked increase in vascular permeability. Blood proteins, including fibrinogen, traverse the vessel walls and lead to the development of a surface coagulum. This inflammatory response continues until primary closure of the wound edges is accomplished. The thickness of the surface coagulum is roughly proportional to the time interval between wounding and closure. This coagulum encompasses the surface contaminants, preventing contact with either topical or systemic antibiotics. The presence of this surface coagulum limits the time in which antibiotic prophylaxis is effective. At three hours after injury, antimicrobial prophylaxis of contaminated wounds has no therapeutic value. Hydrolysis of the protein coagulum by proteolytic enzymes enhances the activity of the antibiotic in experimental wounds. The success of proteolytic enzymes as adjuncts to delayed antibiotic treatment can be correlated with the clot lysis activity of the enzymes in vitro. Travase, the most potent fibrinolytic enzyme, is the most effective adjunct to delayed antibiotic therapy of contaminated wounds. In contrast, the active enzymes found in Elase, which exhibit no significant clot lysis activity in vitro, do not potentiate the activity of antibiotics in wounds subjected to a delay in treatment. Travase prolongs the period of effective topical antibiotic action for at least eight hours in experimental contaminated wounds. The therapeutic merit of Travase is also apparent when the antibiotic is administered systemically. Travase shows promise as an adjunct to a variety of antibiotics that are effective against both gram-positive and gram-negative organisms. The results of these experimental studies support our belief that clinical studies support our belief that clinical studies should now be initiated to test the therapeutic value of Travase as an adjunct to antibiotics in heavily contaminated wounds subjected to an unavoidable delay in treatment.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001412:Bacillus subtilis / Q000201:enzymology; D001419:Bacteria; D001424:Bacterial Infections / Q000517:prevention & control; D001777:Blood Coagulation / Q000187:drug effects; D001963:Bromelains / Q000627:therapeutic use; D002918:Chymotrypsin / Q000627:therapeutic use; D003851:Deoxyribonucleases / Q000627:therapeutic use; D004357:Drug Synergism; D005341:Fibrinolysin / Q000627:therapeutic use; D006168:Guinea Pigs; D006868:Hydrolysis; D010206:Papain / Q000627:therapeutic use; D010447:Peptide Hydrolases / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011489:Protein Denaturation; D013299:Streptodornase and Streptokinase / Q000627:therapeutic use; D013381:Subtilisins / Q000627:therapeutic use; D013530:Surgical Wound Infection / Q000517:prevention & control*; D013997:Time Factors; D014357:Trypsin / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D001963:Bromelains; D013299:Streptodornase and Streptokinase; D003851:Deoxyribonucleases; D010447:Peptide Hydrolases; D013381:Subtilisins; D002918:Chymotrypsin; D014357:Trypsin; D005341:Fibrinolysin; D010206:Papain