Chloramphenicol toxicity

Both chloramphenicol and thiamphenicol cause reversible bone marrow suppression (9). The irreversible, often fatal, aplastic anemia, however, is only seen for chloramphenicol (9). This rare (1 in 10,000—45,000) chloramphenicol toxicity has been linked to the nitroaromatic function (1,9). Thiamphenicol, which is less toxic than chloramphenicol in regard to aplastic anemia, lacks potency as can be seen in Table 1, and thiamphenicol has never found much usage in the United States. An analogue of thiamphenicol having antimicrobial potencies equivalent to chloramphenicol was sought. Florfenicol (2) was selected for further development from a number of closely related stmctures. 

Holt D., D. Harvey, and R. Hurley (1993). Chloramphenicol toxicity. Adverse Drug Reactions and Toxicological Reviews 12 83-95. 

TACROLIMUS CHLORAMPHENICOL Toxic blood levels of tacrolimus, usually on the second day of starting chloramphenicol Attributed to impaired clearance of tacrolimus by chloramphenicol. Dose i of nearly 80% of tacrolimus may be required to prevent toxicity. Watch for adverse effects. Monitor tacrolimus plasma concentrations... 

By 1950 it became evident that chloramphenicol could cause serious and fatal blood dyscrasias. Its use has therefore steadily fallen during the past 50 years. Since the risk of serious chloramphenicol toxicity is so small (1 18 000 or probably less) it is of more than historical interest. There are still many areas in which its benefits outweigh its risks. These include ... 

The early, dose-related type of chloramphenicol toxicity is usually seen after the second week of treatment, and is characterized by inhibited proliferation of erythroid cells and reduced incorporation of iron into heme. The clinical correlates in the peripheral blood are anemia, reticulo-cytopenia, normoblastosis, and a shift to early erythrocyte forms. The plasma iron concentration is increased. Early erythroid forms and granulocyte precursors show cytoplasmic vacuolation. After withdrawal, complete recovery is the rule. Leukopenia and thrombocytopenia are less frequent. 

Nahata MC. Lack of predictability of chloramphenicol toxicity in paediatric patients. J Clin Pharm Ther 1989 14(4) 297-303. 

Brown RT. Chloramphenicol toxicity in an adolescent. J Adolesc Health Care 1982 3(l) 53-5. 

Daum RS, Cohen DL, Smith AL. Fatal aplastic anemia following apparent dose-related chloramphenicol toxicity. J Pediatr 1979 94(3) 403-6. 

Linezolid has been associated with reversible myelosup-pression (14), which appears to be related to the duration of therapy, with a higher risk after more than 2 consecutive weeks of treatment (15). Myelosuppression with red cell hypoplasia has been reported in three patients taking linezolid 600 mg bd. The bone marrow changes were similar to those seen in reversible chloramphenicol toxicity. Another patient had sideroblastic anemia after taking linezolid for 2 months (16,17). 

Yunis AA, Miller AM, Salem Z, Arimura GK. Chloramphenicol toxicity pathogenetic mechanisms and the role of the P-NO2 in aplastic anemia. Clin Toxicol 1980 17(3) 359-73. 

Two mechanisms contribute to chloramphenicol toxicity in neonates (1) a developmental deficiency of glucuronyl transferase, the hepatic enzyme that metabolizes chloramphenicol and (2) inadequate renal excretion of unconjugated drug. At the onset, plasma chloramphenicol concentrations usually exceed 100 pg/mL but may be only 75 pg/mL. For children under 2 weeks of age, the maximum daily chloramphenicol dose is 25 mg/kg of body weight thereafter, fuU-term infants may receive up to 50 mg/kg daily. 

The second form of chloramphenicol toxicity in humans involves dose-dependent and reversible bone marrow suppression. With this toxicity, erythroid and myeloid precursors do not mature normally, serum iron concentration is increased, and phenylalanine concentrations are decreased. These signs of toxicity usually disappear when chloramphenicol is discontinued. Chronic dosing with thiamphenicol or florfenicol may also cause dose-dependent bone marrow suppression. 

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