Aplastic anemia following two days of chloramphenicol therapy

Cone, Thomas E.; Abelson, Sol M.

doi:10.1016/s0022-3476(52)80011-3

Cited by 25 publications

(6 citation statements)

References 8 publications

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“…Shortly thereafter, a flurry of case reports describing one or several individuals attributed aplastic anemia to chloramphenicol. 23,35,41,50,59,84,116,122,131,140,155,203,223,224,276,305,306 These case reports differed from Volini's and associates' observations in several ways. All of the patients had chronic, nonremitting, even fatal bone marrow suppression.…”

Section: Clinical Pharmacology and Therapeuticsmentioning

confidence: 68%

Drug‐induced leukopenia and aplastic anemia

Pisciotta

1971

Clin Pharma and Therapeutics

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Hematopoietic damage following treatment with certain medications remains a major problem of drug therapy. As long as drugs remain indispensable in the treatment of disease, this problem cannot be resolved simply by avoiding their use. Instead, development of information that pertains to the mechanism and prediction of drug‐induced blood dyscrasias must be acquired for the safe use of drugs. Forewarned is forearmed; if it were possible to identify a susceptible patient or a potentially dangerous drug, then the potential risk of producing a serious blood re action with treatment would be minimized. A precedent for this concept was established with the discovery that patients whose erythrocytes are deficient in glucose‐6‐phosphate dehydrogenase are unusually susceptible to hemolytic anemia if treated with oxidant drugs.41 For most of the other toxic blood dyscrasias, knowledge of the pathogenesis remains obscure because certain difficulties limit acquisition of such information. The mechanisms of a drug reaction produced by one drug may differ from that produced by another drug. Also, the rare incidence of druginduced blood dyscrasias has made very few patients available for studies. Few papers have appeared which deal with the mechanism of drug‐induced hematopoietic disease. In addition, the difficulties entailed in obtaining bone marrow and other specimens in sufficient quantity has restricted effective investigation. Since the technique required to study mechanisms of drug reactions may be complex and expensive, it may be logistically unsound for a laboratory to “tool up” and then sit back and wait for the first patient to arrive.

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Section: Clinical Pharmacology and Therapeuticsmentioning

confidence: 68%

Drug‐induced leukopenia and aplastic anemia

Pisciotta

1971

Clin Pharma and Therapeutics

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“…The authors assumed that the severe aplastic anaemia resulted either from absorption of chloramphenicol through the conjuctival membranes or from drainage down the lachrymal duct with eventual gastrointestinal absorption. They stipulated that is was remarkable that a small amount of chloramphenicol could have such a devastating effect, and mentioned that the lack of dose-response relationships has been noted before by Cone and Abelson (1952) and that this supports the hypothesis for an individual, possibly genetic predisposition to this toxicity. It was also noted that the longer the interval between the last dose of chloramphenicol and the first sign of haematological abnormality, the greater the mortality, and that nearly all patients with intervals longer than two months died.…”

Section: Case Studies Upon Topical Ophthalmic Administrationmentioning

confidence: 99%

“…A fatal case of aplastic anaemia in a six-year-old girl following two days of chloramphenicol therapy was described by Cone and Abelson (1952). The patient received four doses of 250 mg chloramphenicol during two consecutive days.…”

Section: Case Studies Following Clinical Chloramphenicol Administrationmentioning

confidence: 99%

Scientific Opinion on Chloramphenicol in food and feed

2014

EFS2

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Chloramphenicol is an antibiotic not authorised for use in food-producing animals in the European Union (EU). However, being produced by soil bacteria, it may occur in plants. The European Commission asked EFSA for a scientific opinion on the risks to human and animal health related to the presence of chloramphenicol in food and feed and whether a reference point for action (RPA) of 0.3 µg/kg is adequate to protect public and animal health. Data on occurrence of chloramphenicol in food extracted from the national residue monitoring plan results and from the Rapid Alert System for Food and Feed (RASFF) were too limited to carry out a reliable human dietary exposure assessment. Instead, human dietary exposure was calculated for a scenario in which chloramphenicol is present at 0.3 µg/kg in all foods of animal origin, foods containing enzyme preparations and foods which may be contaminated naturally. The mean chronic dietary exposure for this worst-case scenario would range from 11 to 17 and 2.2 to 4.0 ng/kg b.w. per day for toddlers and adults, respectively. The potential dietary exposure of livestock to chloramphenicol was estimated to be below 1 µg/kg b.w. per day. Chloramphenicol is implicated in the generation of aplastic anaemia in humans and causes reproductive/hepatotoxic effects in animals. Margins of exposure for these effects were calculated at 2.4 × 10 5 or greater and the CONTAM Panel concluded that it is unlikely that exposure to food contaminated with chloramphenicol at or below 0.3 µg/kg is a health concern for aplastic anaemia or reproductive/hepatotoxic effects. Chloramphenicol exhibits genotoxicity but, owing to the lack of data, the risk of carcinogenicity cannot be assessed. The SUMMARYChloramphenicol is a broad-spectrum antibiotic effective against Gram-positive and Gram-negative bacteria and, in the past, has been widely used to treat infections in both humans and animals. Chloramphenicol is not authorised for use in food-producing animals in the European Union (EU) but may be used in human medicine and in treatments for non-food-producing animals. Apart from its potential occurrence as a residue in food from illicit treatment of food-producing animals, chloramphenicol has also been used in feed and food enzyme products and may occur naturally in plants from its production by the soil bacterium Streptomyces venezuelae.The EFSA Scientific Opinion entitled "Guidance on methodological principles and scientific methods to be taken into account when establishing Reference Points for Action (RPAs) for non-allowed pharmacologically active substances present in food of animal origin" identified an approach for establishing RPAs for various categories of non-allowed pharmacologically active substances. However, the opinion also identified certain categories of non-allowed pharmacologically active substances that are considered to be outside the scope of the procedure, including substances causing blood dyscrasias (aplastic anaemia) such as chloramphenicol. As chloramphenicol is excluded fro...

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“…However, what distinguishes chloramphenicol-associated aplastic anaemia from many other serious adverse drug events is the apparent absence of relationship to dose. Cone and Abelson (1952) first alluded to this, when they described a case of fatal aplastic anaemia in a 6-year-old girl, who had received a total of 2 g chloramphenicol orally over two days. This they compared with previous reports of aplastic anaemia, which had only been described following prolonged and intermittent treatment with chloramphenicol.…”

Section: Adverse Reactions In Manmentioning

confidence: 99%

Chloramphenicol 1. Hazards of use and the current regulatory environment

Page

1991

Aust Veterinary J

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Chloramphenicol is a broad-spectrum antibiotic which has enjoyed extensive use in both medical and veterinary practice. Shortly after its introduction in the late 1940s, the use of chloramphenicol was associated with the induction of an idiosyncratic form of aplastic anaemia in man. This rare and unpredictable adverse effect has since been associated not only with systemic use but with topical applications, as well as occupational exposure. Recognition of the small risk of a potentially fatal adverse reaction, together with the risk of selection of chloramphenicol-resistant pathogens, has led to restrictions on the veterinary uses of chloramphenicol. In Australia at present, the use of chloramphenicol is only permitted in small animals. Its use is specifically prohibited in food-producing animals, including horses.

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Aplastic anemia following two days of chloramphenicol therapy

Cited by 25 publications

References 8 publications

Drug‐induced leukopenia and aplastic anemia

Drug‐induced leukopenia and aplastic anemia

Scientific Opinion on Chloramphenicol in food and feed

Chloramphenicol 1. Hazards of use and the current regulatory environment

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