EFFECTS OF CEFTAZIDIME, A BETA-LACTAM ANTIBIOTIC, ON MURINE HEMATOPOIESIS IN-VITRO

Agranulocytosis has been reported in 5-15% of patients treated with hi gh-dose betalactam antibiotics (BLA). We investigated the toxic effect of ceftazidime (CEF) as a representative of these antibiotics on colo ny-forming unit-granulocyte/macrophage (CFU-GM), on burst-forming unit -erythroid (BFU-E) colony growth and on myelopoiesis in murine long-te rm bone marrow culture (mLTBMC). The CEF concentration resulting in a 50% inhibition of growth was 146 mu g/ml (267 mu M) for CFU-GM, 132 mu g/ml (241 mu M) for BFU-E and 180 mu g/ml (329 mu M) for myeloid cell production in the supernatant of mLTBMC. Following addition of CEF to mLTBMC, CFU-GM remained low for 1 week and total myeloid cell product ion remained low for 2 weeks after removal of CEF from culture. Therea fter the values returned to control levels. The myeloid differential c ounts in the supernatant and adherent layers demonstrated a 'maturatio n arrest', which could be overcome by simultaneously adding all-trans retinoic acid to culture. These results demonstrate that CEF has rever sible inhibitory effects on myelopoiesis and highlight the utility of in vitro haemopoietic assays as models to examine drug-induced haemopo ietic dyscrasias.