Inhibition of Granulopoiesis in Vivo and in Vitro by -Lactam Antibiotics

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Abstract
β-Lactam antibiotics can induce severe neutropenia by a hitherto unknown mechanism. Fifty cases of β-lactam antibiotic-induced neutropenia (15% in patients treated for ⩾10 days with large doses of any β-lactam antibiotic but 95% of cases recovery occurred between one to seven days after withdrawal of β-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 β-lactam antibiotics in vitro and the doses inducing neutropenia in vivo. These observations may be relevant for therapy in the granulocytopenic patient.