Improved survival in simulated surgical infection with combined cytokine, antibiotic and immunostimulant therapy.
A study was performed to find an ideal combination and sequence of cytokines, antibiotics and immunorestorative agents to enhance survival from serious infection. The effects of combinations of granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor (TNF) alpha, the immune adjuvant muramyl dipeptide (MDP) and two systemic antibiotics were studied in a validated murine model of surgical infection. A single cotton suture containing absorbed Klebsiella pneumoniae was placed into the thighs of mice to produce local and systemic infection. Control mice received a volume of subcutaneous saline equal to that of the therapeutic agent; only 18 per cent survived 9 days after infection. The survival time of mice treated with any single agent was similar to that of controls. The group given maximal combined therapy (65 mice) received GM-CSF, TNF-alpha, MDP, and ampicillin-sulbactam or cefoxitin for 6 days. The survival rate in this group 9 days after the introduction of infection was 84-90 per cent (P < 0.0001), suggesting that specific combinations of cytokines, immunostimulants and antibiotics may be useful in combating lethal infection.
Price Institute of Surgical Research, University of Louisville School of Medicine, Kentucky 40292.
E
E
Gaar
W
W
Naziri
W G
WG
Cheadle
J D
JD
Pietsch
M
M
Johnson
H C
HC
Polk
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000627:therapeutic use; D000667:Ampicillin / Q000627:therapeutic use; D000818:Animals; D016470:Bacteremia / Q000188:drug therapy* / Q000401:mortality; D002440:Cefoxitin / Q000627:therapeutic use; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D007710:Klebsiella Infections / Q000188:drug therapy*; D051379:Mice; D013407:Sulbactam / Q000627:therapeutic use; D013530:Surgical Wound Infection / Q000401:mortality / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
D014409:Tumor Necrosis Factor-alpha; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C035444:sultamicillin; D002440:Cefoxitin; D000667:Ampicillin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013407:Sulbactam