Agranulocytosis associated with semisynthetic penicillins and cephalosporines

Abstract

Within one year we observed in the same intensive care unit seven severely polytraumatized patients with agranulocytosis (AG) associated with treatment by semisynthetic penicillins or cephalosporins combined with aminoglycosides. Antibiotics were given because of severe bacterial respiratory or generalised infections. Five patients died, four of them without haematological remission. Bone marrow aspirates showed hypoplasia of granulopoiesis due to a lack of mature cells. Leukocyte and granulocyte counts in the blood declined continuously over a period of 8 to 11 days. In average, minimal granulocyte counts occurred after 21 days of hospitalisation and 14 days of antibiotic drug exposure. Beside the incriminated antibiotics all patients were treated sporadically with other agents of which may cause AG. Granulocyte kinetics and serial bone marrow examinations of one patient suggest a phenothiazine type of AG, which is caused by a toxic damage of granulopoiesis. Declining absolute granulocyte counts in the blood together with persisting high temperatures during antibiotic treatment should give rise to the suspicion of a beginning AG.

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

“…It remains unclear how this inhibition of cell proliferation is achieved. Because the effect can be abolished by thorough washing after preincubation, stable • criteria in which death occurred from various causes before the peripheral granulocyte count rose again [73]. Nevertheless, the risk for important sequelae off3-lactam antibiotic-induced neutropenia appears to be low.…”

Transient pancytopenia

“…When observed, the kinetics of decline were similar to agranulocytosis induced by chlorpromazine [21] or by beta-lactamates [19,24] suggesting a suppression of hemopoetic cell production rather than increased peripheral destruction. When observed, the kinetics of decline were similar to agranulocytosis induced by chlorpromazine [21] or by beta-lactamates [19,24] suggesting a suppression of hemopoetic cell production rather than increased peripheral destruction.…”

Drug-Induced Agranulocytosis

“…Agranulocytosis induced by~-lactam antibiotics is almost exclusively observed during hospital 459 treatment, in particular in intensive care units, when high doses are given parenterally over prolonged periods (Editorial 1985;Kirkwood & Lasezkay 1985;Neftel et al 1985;Schmid et al 1984). The patients are usually under close clinical control, and secondary infections seldom arise.…”

“…For some drugs, evidence is equivocal: data 458 suggesting both immune mediation and direct toxicity have been presented for quinidine (Ascensao et al 1984;Eisner et al 1977;Kelton et al 1979;Sutherland et al 1977), thyrostatics (Berkman et al 1983;Bilezikian et al 1976;Guffy et al 1984;Wiberg & Nuttall 1972), {j-Iactam antibiotics (Editorial 1985Murphy et al 1983;Neftel et al 1985;Rouveix et al 1983;Schmid et al 1984)and aprindine (Bodenheimer & Samarel 1979;Boogaerts et al 1984;Pisciotta & Cronkite 1983). For some drugs, evidence is equivocal: data 458 suggesting both immune mediation and direct toxicity have been presented for quinidine (Ascensao et al 1984;Eisner et al 1977;Kelton et al 1979;Sutherland et al 1977), thyrostatics (Berkman et al 1983;Bilezikian et al 1976;Guffy et al 1984;Wiberg & Nuttall 1972), {j-Iactam antibiotics (Editorial 1985Murphy et al 1983;Neftel et al 1985;Rouveix et al 1983;Schmid et al 1984)and aprindine (Bodenheimer & Samarel 1979;Boogaerts et al 1984;Pisciotta & Cronkite 1983).…”