Aplastic anaemia chloramphenicol

Q50 Systemic use of chloramphenicol is reserved for life-threatening infections. Chloramphenicol may cause reversible aplastic anaemia. 

The systemic use of chloramphenicol is reserved only for life-threatening infections where other anti-microbial therapy has failed or is inadequate, since chloramphenicol may cause reversible aplastic anaemia as a side-effect. 

McGhee CN, Anastas CN. Widespread ocular use of topical chloramphenicol is there justifiable concern regarding idiosyncratic aplastic anaemia Br J Ophthalmol 1996 80 182-184. 

Laporte JR, Vidal X, Ballarin E, Ibanez L. Possible association between ocular chloramphenicol and aplastic anaemia—the absolute risk is very low. Br J Clin Pharmacol 1998 46(2) 181. ... 

Wiholm BE, Kelly JP, Kaufman D, IssaragrisU S, Levy M, Anderson T, Shapiro S. Relation of aplastic anaemia to use of chloramphenicol eye drops in two international case-control studies. BMJ 1998 316(7132) 666. 

Chloramphenicol causes two distinct forms of toxicity in humans. The most serious form is an irreversible aplastic anaemia. This rare idiosyncratic response (the incidence is 25,000-60,000) may have an immunological component however, the meehanism of chloramphenicol-induced aplastic anemia remains unknown. Neither a dose-response relationship nor a threshold dose for the induction of aplastic anaemia has been established. Aplastic anemia is associated with reduced numbers of erythrocytes, leukocytes, and platelets (pancytopaenia), with resultant bleeding disorders and secondary infections. The condition tends to be irreversible and fatal. By comparison, leukemia may be a sequel of hypoplastic anemia. Because thiamphenicol and florfenicol lack the p-nitro moiety, they do not induce irreversible aplastic anemia in humans. 

As a successor to chloramphenicol, florfenicol is now used extensively in food-producing species, particularly calves, chickens, and young pigs. It lacks the para-nitro group of chloramphenicol, which seems to be an essential molecular feature for causing aplastic anaemia. Therefore, there is no public health risk relating to aplastic anaemia arising from the use of florfenicol. 

Isolated reports describe fatal aplastic anaemia in two patients given intravenous chloramphenicol and cimetidine. 

Chloramphenicol can cause two forms of bone marrow depression. One is serious and irreversible, and can result in fatal aplastic anaemia, whereas the other is probably unrelated, milder and reversible, and appears to occur at chloramphenicol serum levels of 25 micrograms/mL or more. This occurs because chloramphenicol can inhibit protein synthesis, the first sign of which is a fall in the reticulocyte count, which reflects inadequate red cell maturation. This response to chloramphenicol has been seen in animals healthy individuals, a series of patients with liver disease," and in anaemic patients being treated with iron dextran or vitamin Bj2. 

Chloramphenicol was the first broad-spectrum antibiotic to be used in medicine, but it came under a cloud when long-continued administration produced many cases of aplastic anaemia, which can be life endangering. Its use is now restricted to diseases where it is the most active known remedy, and which are likely to be cured quickly, within the safe period of the drug. Hence it is used to cure typhoid fever, bacterial meningitis, and anaerobic infections of the brain such as those caused by B.fragilis. It is the only common antibiotic to pass freely into the cerebrospinal fluid and to cross the blood—brain barrier. It also serves as a useful alternative to the tetracyclines in cholera and the rickettsial diseases such as typhus or Rocky Mountain spotted fever. 

Bone marrow cells from patients showing the delayed type of reaction (aplastic anaemia), and cultured in vitro, have been found to be resistant to chloramphenicol. As compared with normal bone marrow cells, the resistant cells showed a reduced capacity for proliferation. On the basis of these observations the theory has been advanced that during treatment with chloramphenicol the sensitive cells are eliminated, leaving a population of blood-cell precursors with poor proliferative activity (SO -). 

Chloramphenicol may cause retinal bleeding (as a symptom of aplastic anaemia), alterations in the perception of colours, and optic neuritis. The latter type of side effect has been observed especially in children with cystic fibrosis receiving chloramphenicol in relatively high doses for fairly long periods (38 ). Deficiency of B vitamins is believed to be the cause of the optic neuritis, and perhaps also of the polyneuritis, peripheral neuritis, and paraesthesiae of the legs sometimes seen after prolonged courses of treatment with chloramphenicol and thiam-phenicoL Administration of extra vitamins may protect patients from this type of reversible side effect (SED VIII, p. 610 38 ). 

Howell, A., Andrews, T. W. and Watts, R.W. E. (1975) Bone-marrow cells resistairt to dilotamphenicol in chloramphenicol-induced aplastic anaemia Lancet, 1, 65. 

Chloramphenicol was originally obtained from Streptomyces Venezuela but is now produced by chemical synthesis. Although it has a broad spectrum of activity, it is rarely used systemically due to a high incidence of aplastic anaemia. 

---