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) a, 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‐a, MDP, and ampicillinsulbactam 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.