Abstract |
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.
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Authors | S P Hauser, K B Udupa, D A Lipschitz |
Journal | British journal of haematology
(Br J Haematol)
Vol. 86
Issue 4
Pg. 733-9
(Apr 1994)
ISSN: 0007-1048 [Print] England |
PMID | 7918065
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
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Topics |
- Animals
- Bone Marrow Cells
- Ceftazidime
(antagonists & inhibitors, pharmacology)
- Cell Division
(drug effects)
- Cells, Cultured
- Colony-Forming Units Assay
- Dose-Response Relationship, Drug
- Erythroid Precursor Cells
(drug effects)
- Female
- Guinea Pigs
- Hematopoiesis
(drug effects)
- Hematopoietic Stem Cells
(cytology, drug effects)
- In Vitro Techniques
- Mice
- Mice, Inbred C57BL
- Time Factors
- Tretinoin
(pharmacology)
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