Effect of combination therapy with recombinant human granulocyte colony-stimulating factor (rG-CSF) and antibiotics in nentropenic mice unresponsive to antibiotics alone

The effect of recombinant human granulocyte colony-stimulating factor (rG-CSF) in enhancing antimicrobial chemotherapy was investigated. Combined treatments of rG-CSF with cefotaxime, cefazolin, fosfomycin, gentamicin or amphotericin B were evaluated in systemic infections with Pseudomonas aeruginosa, Escherichia coli, Serratia marcescens, Staphylococcus aureus and Candida albicans in leucopenic mice induced by pretreatment with cyclophosphamide. Administration of appropriate antibiotics afforded a dose-related inhibition of death from infection in normal mice and mice treated with rG-CSF after cyclophosphamide injection. In cyclophosphamide-treated mice, even larger doses of the antibiotics failed to provide protection against infection with the same inoculum size. These results suggest the possibility that rG-CSF could be of help in treatments with antimicrobial agents against infections in leucopenic patients.