Beta-lactam antibiotics inhibit human in vitro granulopoiesis and proliferation of some other cell types

Suppressive effect of antibiotics on colony formation from human megakaryocyte progenitors (CFU-M) and granulocyte-macrophage progenitors (CFU-GM).

“…Similar data were obtained with some of the other penicillins and cephalosporins (16). Therefore, it is possible to speculate that the degradation products have caused such a suppressive effect on CFU-M and CFU-GM.…”

“…In our study, the antibiotics also suppressed the granulocyte and macrophage colony formation in addition to the megakaryocyte formation. Neftel et al (16) reported that (3-lactam antibiotics suppressed the pro liferation of not only CFU-GM but also chicken embryo liver cells and human and murine lymphoid cell lines. It is conceivable that the potency of the effect is dependent on the chemical structure of drugs and in the range of the influence is widespread including all the eucaryotic cells.…”

Effects of beta-lactam antibiotics on eukaryotic cells

“…Thus, under conditions in which cells remain viable and biosynthetically active compared to control cultures, an apparent decline has been seen in both protein synthesis (Schwarze and Seglen, 1981;Vonen and Morland, 1982;Larson et al, 1980;Neftel et al, 1986;Cottagnoud and Neftel, 1986) and in thymidine incorporation (Chaperon and Sanders, 1978;Weston et al, 1986). However, studies in one cell line (K-562) have shown that cell numbers, protein and DNA synthesis do not always parallel one another in BLA-treated cultures.…”

Pharmacokinetics and Pharmacogenomics of β-Lactam-Induced Neutropenia

“…Bone marrow aspirates of subjects with β-lactam-induced neutropenia revealed a lack of well-differentiated myeloid elements with numerous granulocyte precursors still present, suggesting inhibition during the proliferation stage [1]. Also, in vitro the addition of β-lactam antibiotics to either a promyelocytic cell line or bone marrow cultures collected from hematologically normal human donors showed a dose-dependent inhibition of granulopoiesis [1,4,6]. The median concentrations of penicillins and cephalosporins to cause 50% inhibition of colony formation ranged from 105-550 μg/ml and 7-35 μg/ml, respectively, which is within the expected range of normally delivered parenteral doses [1] In fact, all but five of our 21 subjects with cephalosporin future science group Preliminary Communication Hahn, Fukuda, Hahn, Mizuno, Frenck & Vinks plasma concentrations obtained had approximated trough concentrations greater than that range (Table 4).…”

“…Drug-induced neutropenia is associated with an increased rate of localized infections, sepsis and even fatal complications [2,3]. A direct relationship between β-lactam antibiotic concentrations and inhibition of the progression of progenitor blood cells to neutrophils has been suggested [1,[4][5][6]. Therefore, development of drug-induced neutropenia effectively rules out use of another β-lactam for continued therapy.…”