A prospective study of neutropenia induced by high doses of β-lactam antibiotics

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Abstract
A prospective study on the effect of β-lactam antibiotics on granulopoiesis was carried out in 29 consecutive patients with bacterial endocarditis. Fourteen patients received a high dose of benzylpenicillin, up to 18 g/day, but in only three of them could the treatment be fulfilled as planned, for a mean time of 25 days. In 11 benzylpenicillin treated patients treatment had to be discontinued because of fever, rash or neutropenia. Neutropenia appeared in seven patients after 14–24 (mean 22) days. No superinfection occurred during the neutropenic phase which lasted 2–12 days. Patients with neutropenia differed significantly from others in having a lowered pretreatment neutrophil count (3·2 vs 10·4). In 15 patients treated with other β-lactams, three cases of fever and rash and one case of neutropenia were seen in patients treated with cloxacillin 12 g daily. It was concluded that a daily dose of 18 g of benzylpenicillin is too high for longer treatment periods and that patients with initial low counts of neutrophils have an increased risk of developing neutropenia.

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