NationMaster - Encyclopedia: Chloramphenicol

Chloramphenicol is a bacteriostatic antibiotic originally derived from the bacterium Streptomyces venezuelae, isolated by David Gottlieb, and introduced into clinical practice in 1949. In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ... In medicine, a topical medication is applied to body surfaces such as the skin or mucous membranes such as the vagina, nasopharynx, or the eye. ... Intravenous therapy or IV therapy is the administration of liquid substances directly into a vein. ... Intramuscular injection is the injection of a substance directly into a muscle. ... Bacteriostatic antibiotics hamper the growth of bacteria by interfering with bacteria protein production, interfering with bacteria DNA production interfering with bacteria cellular metabolism Bacteriostatic antibiotics inhibit growth and repoduction of the bacteria, though do not kill it, while bactericidal antibiotics kill bacteria. ... Staphylococcus aureus - Antibiotics test plate. ... Phyla/Divisions Actinobacteria Aquificae Bacteroidetes/Chlorobi Chlamydiae/Verrucomicrobia Chloroflexi Chrysiogenetes Cyanobacteria Deferribacteres Deinococcus-Thermus Dictyoglomi Fibrobacteres/Acidobacteria Firmicutes Fusobacteria Gemmatimonadetes Nitrospirae Omnibacteria Planctomycetes Proteobacteria Spirochaetes Thermodesulfobacteria Thermomicrobia Thermotogae Bacteria (singular, bacterium) are a major group of living organisms. ... David Gottlieb (* 1911; â€ 1982), a professor of plant pathology at the University of Illinois at Urbana-Champaign (1946-1982), was a pioneer in the field of fungi physiology and antibiotics for plants. ...

It was the first antibiotic to be manufactured synthetically on a large scale. Chloramphenicol is effective against a wide variety of microorganisms; it is still very widely used in low income countries because it is exceedingly cheap, but has fallen out of favour in the West due to a very rare but very serious side effect: aplastic anemia. Aplastic anemia is a condition where bone marrow does not produce sufficient new cells to replenish blood cells. ...

In the West, the main use of chloramphenicol is in eye drops or ointment for bacterial conjunctivitis. Eye drops are saline-containing drops used as a vector to administer medication in the eye. ... An ointment is a viscous semisolid preparation used topically on a variety of body surfaces. ...

Dosage

The usual dose is 50 mg/kg/day in four divided doses: the usual dose in an adult male is therefore around 750 mg four times daily; this dose is doubled in severe illness. Half the dose is used in premature babies or neonates, because they do not metabolise the drug as effectively.

Chloramphenicol is available as 250 mg capsules or as a liquid (125 mg/5 ml). In some countries, chloramphenicol is sold as chloramphenicol palmitate ester. Chloramphenicol palmitate ester is inactive, and is hydrolysed to active chloramphenicol in the small intestine. There is no difference in bioavailability between chloramphenicol and chloramphenicol palmitate. It has been suggested that this article or section be merged into Palmitic acid. ... General formula of a carboxylate ester. ... Hydrolysis is a chemical reaction or process in which a molecule is split into two parts by reacting with a molecule of water, which has the chemical formula H2O. One of the parts gets an OH- from the water molecule and the other part gets an H+ from the water. ... In biology the small intestine is the part of the gastrointestinal tract (gut) between the stomach and the large intestine. ... In pharmacology, bioavailability is used to describe the fraction of an administered dose of medication that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ...

The intravenous (IV) preparation of chloramphenicol is the succinate ester, because pure chloramphenicol does not dissolve in water. This creates a problem: chloramphenicol succinate ester is an inactive prodrug and must first be hydrolysed to chloramphenicol; the hydrolysis process is incomplete and 30% of the dose is lost unchanged in the urine, therefore serum concentrations of chloramphenicol are only 70% of those achieved when chloramphenicol is given orally.^[1] For this reason, the chloramphenicol dose needs to be increased to 75 mg/kg/day when administered IV in order to achieve levels equivalent to the oral dose.^[2] The oral route is therefore preferred to the intravenous route. Succinate is the anion of succinic acid. ... General formula of a carboxylate ester. ... A prodrug is a pharmacological substance (drug) which is administered in an inactive (or significantly less active) form. ...

Manufacture of oral chloramphenicol in the U.S. stopped in 1991, because the vast majority of chloramphenicol-associated cases of aplastic anaemia are associated with the oral preparation. There is now no oral formulation of chloramphenicol available in the U.S., although there is no theoretical reason why the intravenous preparation should not be equally effective (or perhaps even more effective) when taken by mouth.

Dose monitoring

Plasma levels of chloramphenicol must be monitored in neonates and in patients with abnormal liver function. It is recommended that plasma levels be monitored in all children under the age of 4, the elderly and patients with renal failure. Peak levels (1 hour after the dose is given) should be 15–25 mg/l; trough levels (taken immediately before a dose) should be less than 15 mg/l. Blood plasma is the liquid component of blood, in which the blood cells are suspended. ...

Chloramphenicol and the liver

Chloramphenicol is metabolised by the liver to chloramphenicol glucuronate (which is inactive). In liver impairment, the dose of chloramphenicol must therefore be reduced. There is no standard dose reduction for chloramphenicol in liver impairment, and the dose should be adjusted according to measured plasma concentrations. The Î±-D form of glucuronic acid. ...

Chloramphenicol and the kidneys

The majority of the chloramphenicol dose is excreted by the kidneys as the inactive metabolite, chloramphenicol glucuronate. Only a tiny fraction of the chloramphenicol is excreted by the kidneys unchanged. It is suggested that plasma levels be monitored in patients with renal impairment, but this is not mandatory. Chloramphenicol succinate ester (the inactive intravenous form of the drug) is readily excreted unchanged by the kidneys, more so than chloramphenicol base, and this is the major reason why levels of chloramphenicol in the blood are much lower when given intravenously than orally.

Oily chloramphenicol

Dose: 100 mg/kg (maximum dose 3 g) as a single intramuscular injection. The dose is repeated if there is no clinical response after 48 hours. A single injection costs approximately US$5. ISO 4217 Code USD User(s) the United States, the British Indian Ocean Territory[1], the British Virgin Islands, East Timor, Ecuador, El Salvador, the Marshall Islands, Micronesia, Palau, Panama, Turks and Caicos Islands, and the insular areas of the United States Inflation 2. ...

Oily chloramphenicol (or chloramphenicol oil suspension) is a long-acting preparation of chloramphenicol first introduced by Roussel in 1954; marketed as Tifomycine®, it was originally used as a treatment for typhoid. Roussel stopped production of oily chloramphenicol in 1995; the International Dispensary Association has manufactured it since 1998, first in Malta and then in India from December 2004. This is about the disease typhoid fever. ...

Oily chloramphenicol is recommended by the World Health Organization (WHO) as the first line treatment of meningitis in low-income countries and appears on the essential drugs list. It was first used to treat meningitis in 1975^[3] and there have been numerous studies since demonstrating its efficacy.^[4]^[5]^[6] It is the cheapest treatment available for meningitis (US$5 per treatment course, compared to US$30 for ampicillin and US$15 for five days of ceftriaxone). It has the great advantage of requiring only a single injection, whereas ceftriaxone is traditionally given daily for five days. This recommendation may yet change now that a single dose of ceftriaxone (cost US$3) has been shown to be equivalent to one dose of oily chloramphenicol.^[7] The World Health Organization (WHO) is a specialized agency of the United Nations that acts as a coordinating authority on international public health, headquartered in Geneva, Switzerland. ... Meningitis is inflammation of the meninges, caused by microorganisms that have spread into the blood and into the cerebrospinal fluid (CSF). ... The World Health Organization (WHO) Model List of Essential Medicines is a guideline for national governments that want to ensure they have an inventory of medicines needed by every health system. ... Ampicillin is a beta-lactam antibiotic that has been used extensively to treat bacterial infections since 1961. ... Ceftriaxone (trade name RocephinÂ®) is a third-generation cephalosporin antibiotic. ...

Chloramphenicol eye drops

In the West, chloramphenicol is still widely used in topical preparations (ointments and eye drops) for the treatment of bacterial conjunctivitis. Isolated case report of aplastic anaemia following chloramphenicol eyedrops exist, but the risk is estimated to be less than 1 in 224,716 prescriptions.^[8] An ointment is a viscous semisolid preparation used topically on a variety of body surfaces. ... Eye drops are saline-containing drops used as a vector to administer medication in the eye. ... Aplastic anemia is a condition where the bone marrow does not produce enough, or any, new cells to replenish the blood cells. ...

Pharmacology

Chloramphenicol is extremely lipid soluble, it remains relatively unbound to protein and is a small molecule: it has a large apparent volume of distribution of 100 litres and penetrates effectively into all tissues of the body, including the brain. The concentration achieved in brain and cerebrospinal fluid (CSF) is around 30 to 50% even when the meninges are not inflamed; this increases to as high as 89% when the meninges are inflamed. Many drugs are bound to Blood plasma proteins. ... The volume of distribution (VD) is a pharmacological term used to quantify the distribution of a drug throughout the body after oral or intravenous dosing. ... Cerebrospinal fluid (CSF), Liquor cerebrospinalis, is a clear bodily fluid that occupies the subarachnoid space in the brain (the space between the skull and the cerebral cortexâ€”more specifically, between the arachnoid and pia layers of the meninges). ...

Uses

Because it functions by inhibiting bacterial protein synthesis, chloramphenicol has a very broad spectrum of activity: it is active against Gram-positive bacteria (including most strains of MRSA), Gram-negative bacteria and anaerobes.^[9] It is not active against Pseudomonas aeruginosa or Enterobacter species. It has some activity against Burkholderia pseudomallei, but is no longer routinely used to treat infections caused by this organism (it has been superseded by ceftazidime and meropenem). In the West, chloramphenicol is mostly restricted to topical uses because of the worries about the risk of aplastic anaemia. A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Gram-positive bacteria are those that are stained dark blue or violet by gram staining, in contrast to gram-negative bacteria, which are not affected by the stain. ... Electron micrograph of MRSA Methicillin-resistant Staphylococcus aureus (MRSA) is a specific strain of the Staphylococcus aureus bacterium that has developed antibiotic resistance to all penicillins, including methicillin and other narrow-spectrum Î²-lactamase-resistant penicillin antibiotics. ... Bacteria that are Gram-negative are not stained dark blue or violet by Gram staining, in contrast to Gram-positive bacteria. ... An anaerobic organism or anaerobe is any organism that does not require oxygen for growth. ... Binomial name Pseudomonas aeruginosa (Schroeter 1872) Migula 1900 Pseudomonas aeruginosa is Gram-negative, aerobic, rod-shaped bacteria with unipolar motility. ... Species etc. ... Binomial name Burkholderia pseudomallei (Whitmore 1913) Yabuuchi et al. ... Ceftazidime is an antibiotic which eliminates bacteria that cause many kinds of infections, including lung, skin, bone, joint, stomach, blood, gynecological, and urinary tract infections. ... Meropenem is an ultra-broad spectrum injectable antibiotic used to treat a wide variety of infections, including meningitis and pneumonia. ... Aplastic anemia is a condition where the bone marrow does not produce enough, or any, new cells to replenish the blood cells. ...

The original indication of chloramphenicol was in the treatment of typhoid, but the now almost universal presence of multi-drug resistant Salmonella typhi has meant that it is seldom used for this indication except when the organism is known to be sensitive. Chloramphenicol may be used as a second-line agent in the treatment of tetracycline-resistant cholera. This is about the disease typhoid fever. ... Binomial name Salmonella enterica Salmonella enterica is a species of Salmonella bacterium. ... Tetracycline (INN) (IPA: ) is a broad-spectrum antibiotic produced by the streptomyces bacterium, indicated for use against many bacterial infections. ... Cholera (frequently called Asiatic cholera or epidemic cholera) is a severe diarrheal disease caused by the bacterium Vibrio cholerae. ...

Because of its excellent CSF penetration (far superior to any of the cephalosporins), chloramphenicol remains the first choice treatment for staphylococcal brain abscesses. It is also useful in the treatment of brain abscesses due to mixed organisms or when the causative organism is not known. Cerebrospinal fluid (CSF), Liquor cerebrospinalis, is a clear bodily fluid that occupies the subarachnoid space in the brain (the space between the skull and the cerebral cortexâ€”more specifically, between the arachnoid and pia layers of the meninges). ... The cephalosporins, are a class of Î²-lactam antibiotics. ... Binomial name Staphylococcus aureus Rosenbach 1884 Staphylococcus aureus, the most common cause of staph infections, is a spherical bacterium, frequently living on the skin or in the nose of a healthy person, that can cause a range of illnesses from minor skin infections (such as pimples, boils, and cellulitis) and... Brain abscess (or cerebral abscess) is an abscess caused by inflammation and collection of infected material coming from local (ear infection, infection of paranasal sinuses, infection of the mastoid air cells of the temporal bone, epidural abscess) or remote (lung, heart, kidney etc. ...

Chloramphenicol is active against the three main bacterial causes of meningitis: Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae. In the West, chloramphenicol remains the drug of choice in the treatment of meningitis in patients with severe penicillin or cephalosporin allergy and GPs are recommended to carry intravenous chloramphenicol in their bag. In low income countries, the WHO recommend that oily chloramphenicol be used first-line to treat meningitis. Meningitis is inflammation of the meninges, caused by microorganisms that have spread into the blood and into the cerebrospinal fluid (CSF). ... Binomial name Neisseria meningitidis Albrecht & Ghon, 1901 Neisseria meningitidis, also simply known as meningococcus is a gram-negative bacterium best known for its role in meningitis. ... Binomial name Streptococcus pneumoniae (Klein 1884) Chester 1901 Streptococcus pneumoniae is a species of Streptococcus that is a major human pathogen. ... Binomial name Haemophilus influenzae (Lehmann & Neumann 1896) Winslow 1917 Haemophilus influenzae, formerly called Pfeiffers bacillus or Bacillus influenzae, is a non-motile Gram-negative coccobacillus first described in 1892 by Dr. Richard Pfeiffer during an influenza pandemic. ... Penicillin nucleus Penicillin (sometimes abbreviated PCN) refers to a group of Î²-lactam antibiotics used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms. ... The cephalosporins, are a class of Î²-lactam antibiotics. ... This article or section does not cite its references or sources. ... Meningitis is inflammation of the meninges, caused by microorganisms that have spread into the blood and into the cerebrospinal fluid (CSF). ...

Chloramphenicol has been used in the U.S. in the initial empirical treatment of children with fever and a petechial rash, when the differential diagnosis includes both Neisseria meningitidis septicaemia as well as Rocky Mountain spotted fever, pending the results of diagnostic investigations. Empirical treatment is medical treatment (usually antibiotics) started before a diagnosis is confirmed. ... Purpura is the appearance of purple discolorations on the skin caused by bleeding underneath the skin. ... In medicine, differential diagnosis (sometimes abbreviated DDx or Î”Î”) is the systematic method physicians use to identify the disease causing a patients symptoms. ... Binomial name Neisseria meningitidis Albrecht & Ghon, 1901 Neisseria meningitidis, also simply known as meningococcus is a gram-negative bacterium best known for its role in meningitis. ... Sepsis (in Greek Σήψις) is a serious medical condition caused by a severe systemic infection leading to a systemic inflammatory response. ... Binomial name Rickettsia rickettsii Wolbach, 1919 Wikispecies has information related to: Ixodidae Wikispecies has information related to: Rickettsia Rocky Mountain spotted fever is the most severe and most frequently reported rickettsial illness in the United States, and has been diagnosed throughout the Americas. ...

Chloramphenicol is also effective against Enterococcus faecium, which has led to it being considered for treatment of vancomycin-resistant enterococci. SEM micrograph of vancomycin-resistant enterococci. ...

Adverse effects

Aplastic anemia

The most serious side effect of chloramphenicol treatment is aplastic anaemia.^[10] This effect is rare and is generally fatal: there is no treatment and there is no way of predicting who may or may not get this side effect. The effect usually occurs weeks or months after chloramphenicol treatment has been stopped and there may be a genetic predisposition.^[11] It is not known whether monitoring the blood counts of patients can prevent the development of aplastic anaemia, but it is recommended that patients have a blood count checked twice weekly while on treatment. The highest risk is with oral chloramphenicol^[12] (affecting 1 in 24,000–40,000)^[13] and the lowest risk occurs with eye drops (affecting less than 1 in 224,716 prescriptions).^[8] An adverse drug reaction (abbreviated ADR) is a term to describe the unwanted, negative consequences sometimes associated with the use of medications. ... Aplastic anemia is a condition where the bone marrow does not produce enough, or any, new cells to replenish the blood cells. ... A full blood count (FBC) or complete blood count (CBC) is a test requested by a doctor or other medical professional that gives information about the cells in a patients blood. ...

Thiamphenicol is a related compound with a similar spectrum of activity that is available in China for human use, and has never been associated with aplastic anaemia. Thiamphenicol is available in the U.S. and Europe as a veterinary antibiotic, and is not approved for use in humans. Thiamphenicol is an antibiotic. ... Veterinary medicine is the application of medical diagnostic and therapeutic principles to companion, domestic, exotic, wildlife, and production animals. ...

Bone marrow suppression

It is common for chloramphenicol to cause bone marrow suppression during treatment: this is a direct toxic effect of the drug on human mitochondria. This effect manifests first as a fall in haemoglobin levels and occurs quite predictably once a cumulative dose of 20 g has been given. This effect is fully reversible once the drug is stopped and does not predict future development of aplastic anaemia. Bone marrow suppression is a serious side effect of chemotherapy and certain drugs affecting the immune system such as azathioprine. ... In cell biology, a mitochondrion is an organelle found in the cells of most eukaryotes. ... 3-dimensional structure of hemoglobin Hemoglobin or haemoglobin is the iron-containing oxygen-transport metalloprotein in the red cells of the blood in mammals and other animals. ...

Leukaemia

There is an increased risk of childhood leukaemia as demonstrated in a Chinese case-controlled study,^[14] and the risk increases with length of treatment. Leukemia (leukaemia in Commonwealth English) is a group of blood diseases characterized by malignancies (cancer) of the blood-forming tissues. ... Case-control studies are one type of epidemiological study design. ...

Gray baby syndrome

Intravenous chloramphenicol use has been associated with the so called gray baby syndrome.^[15] This phenomenon occurs in newborn infants because they do not yet have fully functional liver enzymes, and so chloramphenicol remains unmetabolized in the body.^[16] This causes several adverse effects, including hypotension and cyanosis. The condition can be prevented by using chloramphenicol at the recommended doses and monitoring blood levels.^[17]^[18]^[19] Gray baby syndrome (also termed Gray or Grey syndrome) is a rare but serious side effect that occurs in newborn infants (especially premature babies) following the intravenous administration of the antibiotc chloramphenicol. ... In physiology and medicine, hypotension refers to an abnormally low blood pressure. ... Cyanosis refers to the bluish coloration of the skin due to the presence of deoxygenated hemoglobin in blood vessels near the skin surface. ...

Mechanism and resistance

Chloramphenicol is bacteriostatic (that is, it stops bacterial growth) by inhibiting the enzyme peptidyl transferase, which inhibits ribosomal activity and protein synthesis by preventing the binding of amino acyl-tRNA to the A site on the 50S subunit.^[20] While chloramphenicol and the macrolide class of antibiotics function ultimately in the same manner of affecting the 50S ribosomal subunit, chloramphenicol is not a macrolide. Bacteriostatic antibiotics hamper the growth of bacteria by interfering with bacteria protein production, interfering with bacteria DNA production interfering with bacteria cellular metabolism Bacteriostatic antibiotics inhibit growth and reproduction of bacteria without killing them; killing is done by bacteriocidal agents. ... ... Figure 1: Ribosome structure indicating small subunit (A) and large subunit (B). ... Transfer RNA (abbreviated tRNA) is a small RNA chain (74-93 nucleotides) that transfers a specific amino acid to a growing polypeptide chain at the ribosomal site of protein synthesis during translation. ...

There are three mechanisms of resistance to chloramphenicol: reduced membrane permeability, mutation of the 50S ribosomal subunit and elaboration of chloramphenicol acetyltransferase. It is easy to select for reduced membrane permability to chloramphenicol in vitro by serial passage of bacteria, and this is the most common mechanism of low-level chloramphenicol resistance. High level resistance is conferred by the cat-gene; this gene codes for an enzyme called "chloramphenicol acetyltransferase" which inactivates chloramphenicol by covalently linking one or two acetyl groups, derived from acetyl-S-coenzyme A, to the hydroxyl groups on the chloramphenicol molecule. The acetylation prevents chloramphenicol from binding to the ribosome. Resistance-conferring mutations of the 50S ribosomal subunit are rare. Antibiotic resistance is the ability of a micro-organism to withstand the effects of an antibiotic. ... For other meanings of this term, see gene (disambiguation). ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... Chloramphenicol acetyltransferase is a bacterial enzyme that detoxifies the antibiotic chloramphenicol. ... Acetyl is the radical of acetic acid. ... // Hydroxyl group The term hydroxyl group is used to describe the functional group -OH when it is a substituent in an organic compound. ...

Chloramphenicol resistance may be carried on a plasmid that also codes for resistance to other drugs. One example is the ACCoT plasmid (A=ampicillin, C=chloramphenicol, Co=co-trimoxazole, T=tetracycline) which mediates multi-drug resistance in typhoid (also called R factors). Ampicillin is a beta-lactam antibiotic that has been used extensively to treat bacterial infections since 1961. ... Co-trimoxazole (abbreviated SXT) is a bacteriostatic antibiotic combination of trimethoprim and sulfamethoxazole, in the ratio of 1 to 5, used in the treatment of a variety of bacterial infections. ... Tetracycline (INN) (IPA: ) is a broad-spectrum antibiotic produced by the streptomyces bacterium, indicated for use against many bacterial infections. ... R-factor is an old name for a plasmid that codes for antibiotic resistance. ...

Trade names

Chloramphenicol has a long history and therefore a multitude of alternative names in many different countries:

References

^ Glazko AJ, Dill WA, Kinkel AW, et al. (1977). "Absorption and excretion of parenteral doses of chloramphenicol sodium succinate in comparison with per oral doses of chloramphenicol (abstract)". Clin Pharmacol Ther 21: 104.
^ Bhutta Z, Niazi S, Suria A (Mar-Apr 1992). "Chloramphenicol clearance in typhoid fever: implications for therapy.". Indian J Pediatr 59 (2): 213-9. PMID 1398851.
^ Rey M, Ouedraogo L, Saliou P, Perino L (1976). "Traitement minute de la méningite cérébrospinale épidémique par injection intramusculaire unique de chloramphénicol (suspension huileuse)". Médecine et Maladies Infectieuses 6: 120–24.
^ Wali S, Macfarlane J, Weir W, Cleland P, Ball P, Hassan-King M, Whittle H, Greenwood B (1979). "Single injection treatment of meningococcal meningitis. 2. Long-acting chloramphenicol.". Trans R Soc Trop Med Hyg 73 (6): 698-702. PMID 538813.
^ Puddicombe J, Wali S, Greenwood B (1984). "A field trial of a single intramuscular injection of long-acting chloramphenicol in the treatment of meningococcal meningitis.". Trans R Soc Trop Med Hyg 78 (3): 399-403. PMID 6464136.
^ Pécoul B, Varaine F, Keita M, Soga G, Djibo A, Soula G, Abdou A, Etienne J, Rey M (Oct 5 1991). "Long-acting chloramphenicol versus intravenous ampicillin for treatment of bacterial meningitis.". Lancet 338 (8771): 862-6. PMID 1681224.
^ Nathan N, Borel T, Djibo A, et al. (2005). "Ceftriaxone as effective as long-acting chloramphenicol in short-course treatment of meningococcal meningitis during epidemics: a randomised non-inferiority study". Lancet 366 (9482): 308–13. PMID 16039333.
^ ^a ^b Lancaster T, Stewart AM, Jick H (1998). "Risk of serious haematological toxicity with use of chloramphenicol eye drops in a British general practice database". Brit Med J 316: 667. PMID 9522792.
^ Neu HC, Gootz TD (1996). Antimicrobial Chemotherapy:Antimicrobial Inhibitors of Ribosome Function.. In: Baron's Medical Microbiology (Baron S et al, eds.), 4th ed., Univ of Texas Medical Branch. (via NCBI Bookshelf) ISBN 0-9631172-1-1.
^ Rich M, Ritterhoff R, Hoffmann R (Dec 1950). "A fatal case of aplastic anemia following chloramphenicol (chloromycetin) therapy.". Ann Intern Med 33 (6): 1459-67. PMID 14790529.
^ Nagao T, Mauer A (1969). "Concordance for drug-induced aplastic anemia in identical twins.". N Engl J Med 281 (1): 7-11. PMID 5785754.
^ Holt R (1967). "The bacterial degradation of chloramphenicol". Lancet i: 1259.
^ Wallerstein R, Condit P, Kasper C, Brown J, Morrison F (Jun 16 1969). "Statewide study of chloramphenicol therapy and fatal aplastic anemia.". JAMA 208 (11): 2045-50. PMID 5818983.
^ Shu X, Gao Y, Linet M, Brinton L, Gao R, Jin F, Fraumeni J (Oct 24 1987). "Chloramphenicol use and childhood leukaemia in Shanghai.". Lancet 2 (8565): 934-7. PMID 2889862.
^ McIntyre J, Choonara I (2004). "Drug toxicity in the neonate.". Biol Neonate 86 (4): 218-21. PMID 15249753.
^ Piñeiro-Carrero V, Piñeiro E (2004). "Liver.". Pediatrics 113 (4 Suppl): 1097-106. PMID 15060205.
^ Feder H (1986). "Chloramphenicol: what we have learned in the last decade.". South Med J 79 (9): 1129-34. PMID 3529436.
^ Mulhall A, de Louvois J, Hurley R (1983). "Chloramphenicol toxicity in neonates: its incidence and prevention." (Scanned copy & PDF). Br Med J (Clin Res Ed) 287 (6403): 1424-7. PMID 6416440.
^ Forster J, Hufschmidt C, Niederhoff H, Künzer W (1985). "[Need for the determination of chloramphenicol levels in the treatment of bacterial-purulent meningitis with chloramphenicol succinate in infants and small children]". Monatsschr Kinderheilkd 133 (4): 209-13. PMID 4000136.
^ Petska, S. (1971). Inhibitors of ribosome functions. Annual Review of Microbiology 25:1580.

Contents

Dosage

Dose monitoring

Chloramphenicol and the liver

Chloramphenicol and the kidneys

Oily chloramphenicol

Chloramphenicol eye drops

Pharmacology

Uses

Adverse effects

Aplastic anemia

Bone marrow suppression

Leukaemia

Gray baby syndrome

Mechanism and resistance

Trade names

References

External links

Contents

Dosage GA_googleFillSlot("encyclopedia_square");

Dose monitoring

Chloramphenicol and the liver

Chloramphenicol and the kidneys

Oily chloramphenicol

Chloramphenicol eye drops

Pharmacology

Uses

Adverse effects

Aplastic anemia

Bone marrow suppression

Leukaemia

Gray baby syndrome

Mechanism and resistance

Trade names

References

External links

Dosage