Effects of ceftazidime, a betalactam antibiotic, on murine haemopoiesis in vitro.
Agranulocytosis has been reported in 5-15% of patients treated with high-dose betalactam antibiotics (BLA). We investigated the toxic effect of ceftazidime (CEF) as a representative of these antibiotics on colony-forming unit-granulocyte/macrophage (CFU-GM), on burst-forming unit-erythroid (BFU-E) colony growth and on myelopoiesis in murine long-term bone marrow culture (mLTBMC). The CEF concentration resulting in a 50% inhibition of growth was 146 micrograms/ml (267 microM) for CFU-GM, 132 micrograms/ml (241 microM) for BFU-E and 180 micrograms/ml (329 microM) 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 production remained low for 2 weeks after removal of CEF from culture. Thereafter the values returned to control levels. The myeloid differential counts in the supernatant and adherent layers demonstrated a 'maturation arrest', which could be overcome by simultaneously adding all-trans retinoic acid to culture. These results demonstrate that CEF has reversible inhibitory effects on myelopoiesis and highlight the utility of in vitro haemopoietic assays as models to examine drug-induced haemopoietic dyscrasias.
Hauser
S P
SP
Department of Medicine, University of Arkansas for Medical Sciences, Little Rock.
Udupa
K B
KB
Lipschitz
D A
DA
D000818:Animals; D001854:Bone Marrow Cells; D002442:Ceftazidime / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D015672:Erythroid Precursor Cells / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology
D014212:Tretinoin; D002442:Ceftazidime