Inhibition of granulopoiesis in vivo and in vitro by beta-lactam antibiotics

J Infect Dis. 1985 Jul;152(1):90-8. doi: 10.1093/infdis/152.1.90.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agranulocytosis / chemically induced*
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / pharmacology*
  • Bone Marrow / pathology
  • Bone Marrow Cells
  • Cells, Cultured
  • Cephalosporins / pharmacology
  • Granulocytes*
  • Hematopoiesis / drug effects*
  • Humans
  • Neutropenia / chemically induced*
  • Neutropenia / pathology
  • Penicillins / pharmacology
  • Time Factors

Substances

  • Anti-Bacterial Agents
  • Cephalosporins
  • Penicillins