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Effects of ceftazidime, a betalactam antibiotic, on murine haemopoiesis in vitro
Author(s) -
Hauser Simon P.,
Udupa Kodetthoor B.,
Lipschitz David A.
Publication year - 1994
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1994.tb04822.x
Subject(s) - myelopoiesis , cfu gm , antibiotics , ceftazidime , myeloid , haematopoiesis , colony forming unit , in vitro , microbiology and biotechnology , biology , chemistry , immunology , biochemistry , bacteria , stem cell , genetics , pseudomonas aeruginosa
Summary. 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 μg/ml (267 μ m ) for CFU‐GM, 132 μg/ml (241 μ m ) for BFU‐E and 180 μg/ml (329 μ 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 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.