Idiosyncratic reactions with chloramphenicol

Chloramphenicol commonly causes a dose-related reversible suppression of red cell production at dosages exceeding 50 mg/kg/d after 1-2 weeks. Aplastic anemia, a rare consequence (1 in 24,000 to 40,000 courses of therapy) of chloramphenicol administration by any route, is an idiosyncratic reaction unrelated to dose, although it occurs more frequently with prolonged use. It tends to be irreversible and can be fatal. 

Blood dyscrasias, mostly dose independent, are among the most important allergic-type adverse reactions to drugs. Aplastic anemia is a serious but rare (presumably) idiosyncratic reaction. It has been reported in association with chloramphenicol, quinacrine, phenylbutazone, mephenytoin, gold compounds, and potassium chlorate. Hemolytic anemia, thrombocytopenia, and agranulocytosis may result from an unusual, acquired sensitivity to a variety of widely used drugs including aminopyrine, phenylbutazone, phenothiazines, propylthiouracil, diphenylhydantoin, penicillins, chloramphenicol, sulfisoxazole, and tolbutamide. 

Mostly chloramphenicol is well tolerated with only mild gastrointestinal disturbances. However this antibiotic inhibits mitochondrial protein synthesis in red blood cell precursors in the bone marrow and thus may cause dose-dependent anemia. This dose dependent reaction should not be confused with the idiosyncratic aplastic anemia which is dose-independent and usually fatal. The onset of this idiosyncrasy which has an incidence of about 1 20 000-1 50 000 may be during the treatment or weeks to months after therapy. 

There is controversy about the risk of aplastic anemia with topical chloramphenicol. In a prospective case-control surveillance of aplastic anemia in a population of patients who had taken chloramphenicol for a total of 67.2 million person-years, 145 patients with aplastic anemia and 1226 controls were analysed. Three patients and five controls had been exposed to topical chloramphenicol, but two had also been exposed to other known causes of aplastic anemia. Based on these findings, an association between ocular chloramphenicol and aplastic anemia could not be excluded, but the risk was less than one per million treatment courses (38). In another study, a review of the literature identified seven cases of idiosyncratic hemopoietic reactions associated with topical chloramphenicol. However, the authors failed to find an association between the epidemiology of acquired aplastic anemia and topical chloramphenicol. Furthermore, after topical therapy they failed to detect serum accumulation of chloramphenicol by high performance hquid chromatography. They concluded that these findings support the view that topical chloramphenicol was not a risk factor for dose-related bone marrow toxicity and that calls for abolition of treatment with... 

Idiosyncratic aplastic anemia occurs only in humans exposed to chloramphenicol. The reaction is rare (1 in 30000) and not dose related. The toxic effects are related to the presence of the para-nitro group on the chloramphenicol molecule. Florfenicol lacks this group and is not associated with aplastic anemia in any species. Long-term chloramphenicol therapy (>14 days) is associated with dose-related anemia and pancytopenia through a decrease in protein synthesis in the bone marrow, especially in cats. Florfenicol may cause similar reversible suppression of the myeloid series in bone marrow, but this does not appear to be clinically significant during shortterm treatment regimens. 

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