Penicillin-G degradation products inhibit in vitro granulopoiesis

38% of penicillin-G in solution decays at 20 degrees C within 24 h, 50% at 37 degrees C and 66% within 3 h at 56 degrees C. These degraded penicillin-G solutions strongly inhibit growth and maturation of granulocytic stem cells in vitro. Inhibitory concentrations are in the range obtainable with high dose penicillin therapy in vivo. No cytotoxicity of degraded penicillin solutions on bone marrow cells was seen over 24 h. It is suggested that penicillin-G degradation products are responsible for severe granulocytopenia observed after high dose penicillin-G therapy.