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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.

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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].

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Last Update: January 24, 2017.



Chloramphenicol is a broad spectrum antibiotic introduced into clinical practice in 1948, but which was subsequently shown to cause serious and fatal aplastic anemia and is now used rarely and reserved for severe, life-threatening infections for which other antibiotics are not available. Chloramphenicol has also been linked to cases of acute, clinically apparent liver injury with jaundice, largely in association with aplastic anemia.


Chloramphenicol (klor" am fen' i kol) is an antibiotic initially isolated from Streptomyces venezuelae and later characterized biochemically and synthesized. Chloramphenicol was introduced into clinical practice in 1948 under the brand name Chloromycetin and became a widely used antibiotic because of its oral availability, excellent tolerability and wide spectrum of activity. Chloramphenicol has bacteriostatic activity against many gram positive and gram negative organisms, both aerobic and anaerobic including H. influenza, N meningitides, S. pneumoniae, N gonorrhoeae, Brucella species and Bordetella pertussis. It also has activity against many spirochaetes, rickettsiae, chlamydiae and mycoplasmas. Chloramphenicol is thought to act by binding to the 50S ribosomal subunit in bacteria, thus inhibiting bacterial protein synthesis. A similar inhibition of protein synthesis may occur in mitochondria. Within a few years of its introduction, chloramphenicol was linked to rare cases of aplastic anemia and later to other fatal blood dyscrasias including thrombocytopenia, neutropenia and pure red cell aplasia. In addition, cases of leukemia were identified in children who had recovered from blood dyscrasias attributed to chloramphenicol. By the early 1960s, more than 1000 cases of severe bone marrow aplasia were attributed to use of chloramphenicol and it was widely banned or placed under restrictions, particularly in children. Currently, chloramphenicol is available only in parenteral forms, and its use is restricted to severe, life-threatening infections for which no other antibiotic is available because of antibiotic resistance or drug allergy. Several generic forms of chloramphenicol for intravenous administration are available and the recommended dose is 50 mg/kg daily in 4 divided doses. Monitoring for blood counts is recommended and prompt discontinuation for any evidence of myelosuppression.


A proportion of patients with blood dyscrasias due to chloramphenicol also developed clinically apparent liver injury with jaundice, usually occurring before the appearance of aplastic anemia or severe thrombocytopenia. Jaundice arises in 10% to 25% of cases of aplastic anemia, usually within 1 to 2 months of starting chloramphenicol and often shortly after it is stopped. Aplastic anemia and the accompanying liver injury occur most frequently in patients who receive multiple courses of chloramphenicol or prolonged therapy. The serum enzyme pattern is usually hepatocellular and the clinical presentation is an acute hepatitis-like syndrome with onset of fatigue, nausea, anorexia and abdominal discomfort followed by dark urine and jaundice. Rare instances have a cholestatic pattern of presentation with jaundice and itching and prominent elevations in alkaline phosphatase. Some cases occur in the absence of bone marrow involvement. Immunoallergic and autoimmune features are rarely present. The course is self-limited in most instances, but examples of acute liver failure have been reported, particularly in patients without aplastic anemia. In most cases, however, the liver injury associated with chloramphenicol use is eclipsed by the severe bone marrow aplasia.

Likelihood score: B (highly likely cause of clinically apparent liver injury, now rarely seen).

Mechanism of Injury

The etiology of liver injury associated with chloramphenicol is likely idiosyncratic and probably immunological. The hepatitis that accompanies chloramphenicol induced aplastic anemia is similar to the hepatitis that occurs with spontaneous or idiopathic aplastic anemia, suggesting a common pathogenesis of bone marrow and hepatic progenitor cell injury and loss. The marrow toxicity of chloramphenicol has been attributed to the nitrophenyl group in the molecule which is unique among microbial derived antibiotics.

Outcome and Management

The liver injury accompanying blood dyscrasias caused by chloramphenicol is often severe, but resolves rapidly in most cases only to be followed by signs and symptoms of bone marrow failure. Acute liver failure can result, but the role of liver transplantation in this situation is difficult because of the accompanying marrow damage and aplasia.

Drug Class: Antiinfective Agents, Miscellaneous



Chloramphenicol – Generic, Chloromycetin®


Antiinfective Agents


Product labeling at DailyMed, National Library of Medicine, NIH


Chloramphenicol 56-75-7 C11-H12-Cl2-N2-O5
Chloramphenicol chemical structure


References updated: 24 January 2017

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    (Expert review of hepatotoxicity published in 1999 mentions that the hepatic injury from chloramphenicol is eclipsed by its vastly more important myelotoxicity, but that at least 25 cases of liver injury with jaundice have been reported, usually with hepatocellular injury).
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    (Review of the metabolism of chloramphenicol and its toxicity to bone marrow elements leads to the hypothesis that a toxic metabolite of the drug is responsible for damage and loss of marrow stem cells).
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    (Review of the evidence for and against the association of chloramphenicol eye drops and aplastic anemia).
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    (Analyses of registries from two international case control studies of aplastic anemia found none of 426 cases [but 7 of 3118 controls] had a recent history of use of chloramphenicol eye drops).
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    (Among 442,543 patients who received chloramphenicol eye drops over a 7 year period in the UK, 3 patients had a subsequent diagnosis of severe hematologic toxicity within the following 3 months, but in each case an alternative diagnosis was possible and the maximal calculated risk was <1 per 100,000 persons exposed).
  • Wareham DW, Wilson P. Chloramphenicol in the 21st century. Hosp Med 2002; 63 (3): 157-61. [PubMed: 11933819]
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  • Doshi B, Sarkar S. Topical administration of chloramphenicol can induce acute hepatitis. BMJ 2009; 338: 1699. [PubMed: 19525305]
    (37 year old man developed fatigue and jaundice, 1 week after a 5 day course of chloramphenicol eye drops [bilirubin 1.9 mg/dL, AST 868 U/L, Alk P 224 U/L], resolving over the next 10 months).


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