Agranulocytosis during antibiotic therapy: drug sensitivity or sepsis?

Forty-three patients reviewed from the literature and five cases of agranulocytosis during antibiotic therapy studied by the author are presented. Time required to develop agranulocytosis with antibiotics was < 19 days in comparison to > 40 days required with nonantibiotic drugs. In all, agranulocytosis occurred concomitantly with drug treatment and became normal as treatment was discontinued. Retrospective rechallenge studies suggest that agranulocytosis may be dose related. In all cases PMNs were almost completely deleted and marrows were devoid of granulocyte precursors. In contrast, leukopenia secondary to overwhelming sepsis displayed persisting granulocytes in peripheral blood and marrow. While leukagglutinins were not found in nine cited cases, four serums were toxic to test PMNs as measured by suppression of postphagocytosis respiratory burst. Clindamycin directly suppressed development of CFU-G in one sensitive patient but not in 16 normal controls. The hazard of antibiotics in suppressing granulocytopoiesis is emphasized by these observations.