Inhibition of granulopoiesis in vivo and in vitro by beta-lactam antibiotics.
beta-Lactam antibiotics can induce severe neutropenia by a hitherto unknown mechanism. Fifty cases of beta-lactam antibiotic-induced neutropenia (less than 1,000 neutrophils/mm3) from 17 hospitals were analyzed and compared with 140 literature cases. The incidence of neutropenia was 5%-greater than 15% in patients treated for greater than or equal to 10 days with large doses of any beta-lactam antibiotic but less than 0.1% with shorter duration of therapy. In greater than 95% of cases recovery occurred between one to seven days after withdrawal of beta-lactam antibiotics. Bone marrow aspirates were characterized by a lack of well-differentiated myeloid elements in the presence of numerous immature granulocyte precursors. Nine penicillins and eight cephalosporins inhibited in vitro granulopoiesis in a dose-dependent manner. There was a good correlation between the inhibitory capacity of beta-lactam antibiotics in vitro and the doses inducing neutropenia in vivo. These observations may be relevant for therapy in the granulocytopenic patient.
D000380:Agranulocytosis / Q000139:chemically induced*; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology*; D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D002511:Cephalosporins / Q000494:pharmacology; D006098:Granulocytes; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D009503:Neutropenia / Q000139:chemically induced* / Q000473:pathology; D010406:Penicillins / Q000494:pharmacology; D013997:Time Factors
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D010406:Penicillins