w:chloramphenicol

The original indication of chloramphenicol was in the treatment of typhoid, but the presence of multiple drug-resistant Salmonella typhi has meant it is seldom used for this indication except when the organism is known to be sensitive.{{medical citation needed|date=August 2022}}

In low-income countries, the WHO no longer recommends only chloramphenicol as first-line to treat meningitis, but recognises it may be used with caution if there are no available alternatives.{{cite web|title=WHO meningitis epidemic guidelines Africa|url=https://www.who.int/csr/resources/publications/HSE_GAR_ERI_2010_4/en/|access-date=29 February 2016|url-status=dead|archive-url=https://web.archive.org/web/20160305134645/http://www.who.int/csr/resources/publications/HSE_GAR_ERI_2010_4/en/|archive-date=5 March 2016}}

During the last decade chloramphenicol has been re-evaluated as an old agent with potential against systemic infections due to multidrug-resistant gram positive microorganisms (including vancomycin resistant enterococci). In vitro data have shown an activity against the majority (> 80%) of vancomycin resistant E. faecium strains.{{cite journal | vauthors = Čivljak R, Giannella M, Di Bella S, Petrosillo N | title = Could chloramphenicol be used against ESKAPE pathogens? A review of in vitro data in the literature from the 21st century | journal = Expert Review of Anti-Infective Therapy | volume = 12 | issue = 2 | pages = 249–264 | date = February 2014 | pmid = 24392752 | doi = 10.1586/14787210.2014.878647 | url = http://www.tandfonline.com/doi/full/10.1586/14787210.2014.878647 | access-date = 2021-07-02 | url-status = live | s2cid = 34134573 | archive-url = https://web.archive.org/web/20220303115239/https://www.tandfonline.com/doi/full/10.1586/14787210.2014.878647 | archive-date = 2022-03-03 }}

In the context of preventing endophthalmitis, a complication of cataract surgery, a 2017 systematic review found moderate evidence that using chloramphenicol eye drops in addition to an antibiotic injection (cefuroxime or penicillin) will likely lower the risk of endophthalmitis, compared to eye drops or antibiotic injections alone.{{cite journal | vauthors = Gower EW, Lindsley K, Tulenko SE, Nanji AA, Leyngold I, McDonnell PJ | title = Perioperative antibiotics for prevention of acute endophthalmitis after cataract surgery | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | issue = 2 | pages = CD006364 | date = February 2017 | pmid = 28192644 | pmc = 5375161 | doi = 10.1002/14651858.CD006364.pub3 }}

Chloramphenicol has a broad spectrum of activity and has been effective in treating ocular infections such as conjunctivitis, blepharitis etc. caused by a number of bacteria including Staphylococcus aureus, Streptococcus pneumoniae, and Escherichia coli. It is not effective against Pseudomonas aeruginosa. The following susceptibility data represent the minimum inhibitory concentration for a few medically significant organisms.{{cite web |url=http://antibiotics.toku-e.com/antimicrobial_507.html |title=Chloramphenicol (Chloromycetin) {{pipe}} the Antimicrobial Index Knowledgebase - TOKU-E |access-date=2014-04-21 |url-status=live |archive-url=https://web.archive.org/web/20140423055139/http://antibiotics.toku-e.com/antimicrobial_507.html |archive-date=2014-04-23 }}

• Escherichia coli: 0.015 – 10,000 μg/mL
• Staphylococcus aureus: 0.06 – 128 μg/mL
• Streptococcus pneumoniae: 2 – 16 μg/mL

Each of these concentrations is dependent upon the bacterial strain being targeted. Some strains of E coli, for example, show spontaneous emergence of chloramphenicol resistance.{{cite journal | vauthors = Carone BR, Xu T, Murphy KC, Marinus MG | title = High incidence of multiple antibiotic resistant cells in cultures of in enterohemorrhagic Escherichia coli O157:H7 | journal = Mutation Research | volume = 759 | pages = 1–8 | date = January 2014 | pmid = 24361397 | pmc = 3913999 | doi = 10.1016/j.mrfmmm.2013.11.008 | bibcode = 2014MRFMM.759....1C }}{{cite journal | vauthors = Moore AM, Patel S, Forsberg KJ, Wang B, Bentley G, Razia Y, Qin X, Tarr PI, Dantas G | title = Pediatric fecal microbiota harbor diverse and novel antibiotic resistance genes | journal = PLOS ONE | volume = 8 | issue = 11 | pages = e78822 | date = 2013 | pmid = 24236055 | pmc = 3827270 | doi = 10.1371/journal.pone.0078822 | doi-access = free | bibcode = 2013PLoSO...878822M }}

Three mechanisms of resistance to chloramphenicol are known: reduced membrane permeability, mutation of the 50S ribosomal subunit, and elaboration of chloramphenicol acetyltransferase. It is easy to select for reduced membrane permeability 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;{{cite journal | vauthors = Gil JA, Kieser HM, Hopwood DA | title = Cloning of a chloramphenicol acetyltransferase gene of Streptomyces acrimycini and its expression in Streptomyces and Escherichia coli | journal = Gene | volume = 38 | issue = 1–3 | pages = 1–8 | date = 1985 | pmid = 3905512 | doi = 10.1016/0378-1119(85)90197-0 }} 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.{{medical citation needed|date=August 2022}}

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 multiple drug resistance in typhoid (also called R factors).{{medical citation needed|date=August 2022}}

As of 2014 some Enterococcus faecium and Pseudomonas aeruginosa strains are resistant to chloramphenicol. Some Veillonella spp. and Staphylococcus capitis strains have also developed resistance to chloramphenicol to varying degrees.{{cite web |title= Chloramphenicol spectrum of bacterial susceptibility and Resistance |url=http://www.toku-e.com/Upload/Products/PDS/20120618001452.pdf|access-date=15 May 2012|url-status=dead|archive-url=https://web.archive.org/web/20140211211304/http://www.toku-e.com/Upload/Products/PDS/20120618001452.pdf | work = Product Data Safety Sheet | publisher = TOKU-E | date = December 2010 |archive-date=11 February 2014}}

Some other resistance genes beyond cat are known, such as chloramphenicol hydrolase,{{cite journal | vauthors = Mosher RH, Ranade NP, Schrempf H, Vining LC | title = Chloramphenicol resistance in Streptomyces: cloning and characterization of a chloramphenicol hydrolase gene from Streptomyces venezuelae | journal = Journal of General Microbiology | volume = 136 | issue = 2 | pages = 293–301 | date = February 1990 | pmid = 2324705 | doi = 10.1099/00221287-136-2-293 | doi-access = free }} and chloramphenicol phosphotransferase.{{cite journal | vauthors = Mosher RH, Camp DJ, Yang K, Brown MP, Shaw WV, Vining LC | title = Inactivation of chloramphenicol by O-phosphorylation. A novel resistance mechanism in Streptomyces venezuelae ISP5230, a chloramphenicol producer | journal = The Journal of Biological Chemistry | volume = 270 | issue = 45 | pages = 27000–27006 | date = November 1995 | pmid = 7592948 | doi = 10.1074/jbc.270.45.27000 | doi-access = free }}

The most serious side effect of chloramphenicol treatment is aplastic anaemia ('AA'). This effect is rare but sometimes fatal. The risk of AA is high enough that alternatives should be strongly considered. Treatments are available but expensive. No way exists to predict who may or may not suffer this side effect. The effect usually occurs weeks or months after treatment has been stopped, and a genetic predisposition may be involved. It is not known whether monitoring the blood counts of patients can prevent the development of aplastic anaemia, but patients are recommended to have a baseline blood count with a repeat blood count every few days while on treatment.{{cite journal | vauthors = Hammett-Stabler CA, Johns T | title = Laboratory guidelines for monitoring of antimicrobial drugs. National Academy of Clinical Biochemistry | journal = Clinical Chemistry | volume = 44 | issue = 5 | pages = 1129–1140 | date = May 1998 | pmid = 9590397 | doi = 10.1093/clinchem/44.5.1129 | doi-access = free }} Chloramphenicol should be discontinued if the complete blood count drops. The highest risk is with oral chloramphenicol (affecting 1 in 24,000–40,000){{cite journal | vauthors = Wallerstein RO, Condit PK, Kasper CK, Brown JW, Morrison FR | title = Statewide study of chloramphenicol therapy and fatal aplastic anemia | journal = JAMA | volume = 208 | issue = 11 | pages = 2045–2050 | date = June 1969 | pmid = 5818983 | doi = 10.1001/jama.208.11.2045 }} and the lowest risk occurs with eye drops (affecting less than one in 224,716 prescriptions).

Chloramphenicol may cause bone marrow suppression during treatment; this is a direct toxic effect of the drug on human mitochondria.{{cite journal | vauthors = Yunis AA | title = Chloramphenicol toxicity: 25 years of research | journal = The American Journal of Medicine | volume = 87 | issue = 3N | pages = 44N–48N | date = September 1989 | pmid = 2486534 }} This effect manifests first as a fall in hemoglobin levels, which occurs quite predictably once a cumulative dose of 20 g has been given. The anaemia is fully reversible once the drug is stopped and does not predict future development of aplastic anaemia. Studies in mice have suggested existing marrow damage may compound any marrow damage resulting from the toxic effects of chloramphenicol.{{cite journal | vauthors = Morley A, Trainor K, Remes J | title = Residual marrow damage: possible explanation for idiosyncrasy to chloramphenicol | journal = British Journal of Haematology | volume = 32 | issue = 4 | pages = 525–531 | date = April 1976 | pmid = 1259934 | doi = 10.1111/j.1365-2141.1976.tb00955.x | s2cid = 40234293 }}

Leukemia, a cancer of the blood or bone marrow, is characterized by an abnormal increase of immature white blood cells. The risk of childhood leukemia is increased, as demonstrated in a Chinese case–control study,{{cite journal | vauthors = Shu XO, Gao YT, Linet MS, Brinton LA, Gao RN, Jin F, Fraumeni JF | title = Chloramphenicol use and childhood leukaemia in Shanghai | journal = Lancet | volume = 2 | issue = 8565 | pages = 934–937 | date = October 1987 | pmid = 2889862 | doi = 10.1016/S0140-6736(87)91420-6 | s2cid = 3217082 }} and the risk increases with length of treatment.

Intravenous chloramphenicol use has been associated with the so-called gray baby syndrome.{{cite journal | vauthors = McIntyre J, Choonara I | title = Drug toxicity in the neonate | journal = Biology of the Neonate | volume = 86 | issue = 4 | pages = 218–221 | year = 2004 | pmid = 15249753 | doi = 10.1159/000079656 | s2cid = 29906856 }}

This phenomenon occurs in newborn infants because they do not yet have fully functional liver enzymes (i.e. UDP-glucuronyl transferase), so chloramphenicol remains unmetabolized in the body.{{cite journal | vauthors = Piñeiro-Carrero VM, Piñeiro EO | title = Liver | journal = Pediatrics | volume = 113 | issue = 4 Suppl | pages = 1097–1106 | date = April 2004 | pmid = 15060205 | doi = 10.1542/peds.113.S3.1097 | s2cid = 264867934 | url = http://pediatrics.aappublications.org/content/113/Supplement_3/1097.full.pdf | access-date = 2012-01-09 | url-status = live | archive-url = https://web.archive.org/web/20210828032546/https://pediatrics.aappublications.org/content/pediatrics/113/Supplement_3/1097.full.pdf | archive-date = 2021-08-28 }}

This causes several adverse effects, including hypotension and cyanosis. The condition can be prevented by using the drug at the recommended doses, and monitoring blood levels.{{cite journal | vauthors = Feder HM | title = Chloramphenicol: what we have learned in the last decade | journal = Southern Medical Journal | volume = 79 | issue = 9 | pages = 1129–1134 | date = September 1986 | pmid = 3529436 | doi = 10.1097/00007611-198609000-00022 }}{{cite journal | vauthors = Mulhall A, de Louvois J, Hurley R | title = Chloramphenicol toxicity in neonates: its incidence and prevention | journal = British Medical Journal | volume = 287 | issue = 6403 | pages = 1424–1427 | date = November 1983 | pmid = 6416440 | pmc = 1549666 | doi = 10.1136/bmj.287.6403.1424 }}{{cite journal | vauthors = Forster J, Hufschmidt C, Niederhoff H, Künzer W | title = [Need for the determination of chloramphenicol levels in the treatment of bacterial-purulent meningitis with chloramphenicol succinate in infants and small children] | language = de | journal = Monatsschrift Kinderheilkunde | volume = 133 | issue = 4 | pages = 209–213 | date = April 1985 | pmid = 4000136 }}

Fever, macular and vesicular rashes, angioedema, urticaria, and anaphylaxis may occur. Herxheimer's reactions have occurred during therapy for typhoid fever.{{cite web|title=Drug Insert from DailyMed|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=08c16a42-1ad4-400f-b1b0-75303eb86713|access-date=18 April 2014|url-status=live|archive-url=https://web.archive.org/web/20140419012007/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=08c16a42-1ad4-400f-b1b0-75303eb86713|archive-date=19 April 2014}}

Headache, mild depression, mental confusion, and delirium have been described in patients receiving chloramphenicol. Optic and peripheral neuritis have been reported, usually following long-term therapy. If this occurs, the drug should be promptly withdrawn. It is theorized that this is caused by chloramphenicol's effects on the metabolism of B-Vitamins, specifically B-12.{{cite journal | vauthors = Ramilo O, Kinane BT, McCracken GH | title = Chloramphenicol neurotoxicity | language = en-US | journal = The Pediatric Infectious Disease Journal | volume = 7 | issue = 5 | pages = 358–359 | date = May 1988 | pmid = 3380586 | doi = 10.1097/00006454-198805000-00015 }}

Chloramphenicol is extremely lipid-soluble; it remains relatively unbound to protein and is a small molecule. It has a large apparent volume of distribution and penetrates effectively into all tissues of the body, including the brain. Distribution is not uniform, with highest concentrations found in the liver and kidney, with lowest in the brain and cerebrospinal fluid. The concentration achieved in brain and cerebrospinal fluid is around 30 to 50% of the overall average body concentration, even when the meninges are not inflamed; this increases to as high as 89% when the meninges are inflamed.{{citation needed|date=March 2023}}

Chloramphenicol increases the absorption of iron.{{cite encyclopedia | encyclopedia = Pill Book, The | title = Iron Supplements | pages = 593–596 | veditors = Silverman HM | publisher = Bantam Dell | location = New York | edition = 12th revised | year = 2006 | isbn = 978-0-553-58892-7 }}

Chloramphenicol is metabolized by the liver to chloramphenicol glucuronate (which is inactive). In liver impairment, the dose of chloramphenicol must therefore be reduced. No standard dose reduction exists for chloramphenicol in liver impairment, and the dose should be adjusted according to measured plasma concentrations.

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. Plasma levels should be monitored in patients with renal impairment, but this is not mandatory. Chloramphenicol succinate ester (an intravenous prodrug form) 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.{{cite journal | vauthors = Yogev R, Kolling WM, Williams T | title = Pharmacokinetic comparison of intravenous and oral chloramphenicol in patients with Haemophilus influenzae meningitis | journal = Pediatrics | volume = 67 | issue = 5 | pages = 656–660 | date = May 1981 | pmid = 6973130 | doi = 10.1542/peds.67.5.656 | s2cid = 8701518 }}

Plasma levels of chloramphenicol must be monitored in neonates and patients with abnormal liver function. Plasma levels should be monitored in all children under the age of four, the elderly, and patients with kidney failure.

Because efficacy and toxicity of chloramphenicol are associated with a maximum serum concentration, peak levels (one hour after the intravenous dose is given) should be 10–20 μg/mL with toxicity {{nowrap|> 40 μg/mL}}; trough levels (taken immediately before a dose) should be 5–10 μg/mL.{{cite journal | vauthors = Hammett-Stabler CA, Johns T | title = Laboratory guidelines for monitoring of antimicrobial drugs. National Academy of Clinical Biochemistry | journal = Clinical Chemistry | volume = 44 | issue = 5 | pages = 1129–1140 | date = May 1998 | pmid = 9590397 | doi = 10.1093/clinchem/44.5.1129 | doi-access = free }}{{cite web|title=Chloramphenicol (Lexi-Drugs)|url=http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6582|work=Lexi-Comp Online|access-date=18 April 2014|url-status=live|archive-url=https://web.archive.org/web/20130726053121/http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6582|archive-date=26 July 2013}}

Administration of chloramphenicol concomitantly with bone marrow depressant drugs is contraindicated, although concerns over aplastic anaemia associated with ocular chloramphenicol have largely been discounted.{{cite web | title = Practice Guidance: OTC Chloramphenicol Eye Drops | url = http://www.rpsgb.org.uk/pdfs/otcchlorampheneyedropsguid.pdf | date = June 2005 | publisher = Royal Pharmaceutical Society of Great Britain (RPSGB) | archive-url = https://web.archive.org/web/20051022000549/http://www.rpsgb.org.uk/pdfs/otcchlorampheneyedropsguid.pdf | archive-date = 2005-10-22 }}

Chloramphenicol is a potent inhibitor of the cytochrome P450 isoforms CYP2C19 and CYP3A4 in the liver.{{cite journal | vauthors = Park JY, Kim KA, Kim SL | title = Chloramphenicol is a potent inhibitor of cytochrome P450 isoforms CYP2C19 and CYP3A4 in human liver microsomes | journal = Antimicrobial Agents and Chemotherapy | volume = 47 | issue = 11 | pages = 3464–3469 | date = November 2003 | pmid = 14576103 | pmc = 253795 | doi = 10.1128/AAC.47.11.3464-3469.2003 }} Inhibition of CYP2C19 causes decreased metabolism and therefore increased levels of, for example, antidepressants, antiepileptics, proton-pump inhibitors, and anticoagulants if they are given concomitantly. Inhibition of CYP3A4 causes increased levels of, for example, calcium channel blockers, immunosuppressants, chemotherapeutic drugs, benzodiazepines, azole antifungals, tricyclic antidepressants, macrolide antibiotics, SSRIs, statins, cardiac antiarrhythmics, antivirals, anticoagulants, and PDE5 inhibitors.{{cite web | url = http://www.fass.se/LIF/produktfakta/fakta_lakare_artikel.jsp?articleID=18352 | trans-title = Facts for prescribers | title = Fakta för förskrivare | language = sv | publisher = FASS – Swedish National Drug Formulary | url-status = live | archive-url = https://web.archive.org/web/20020611044953/http://www.fass.se/LIF/produktfakta/fakta_lakare_artikel.jsp?articleID=18352 | archive-date = 2002-06-11 }}

Chloramphenicol is antagonistic with most cephalosporins and using both together should be avoided in the treatment of infections.{{cite journal | vauthors = Asmar BI, Prainito M, Dajani AS | title = Antagonistic effect of chloramphenicol in combination with cefotaxime or ceftriaxone | journal = Antimicrobial Agents and Chemotherapy | volume = 32 | issue = 9 | pages = 1375–8 | date = September 1988 | pmid = 3195999 | doi = 10.1128/AAC.32.9.1375 | pmc = 175871 }}

Chloramphenicol has been demonstrated a synergistic effect when combined with fosfomycin against clinical isolates of Enterococcus faecium.{{cite journal | vauthors = Lagatolla C, Milic J, Imperi F, Cervoni M, Bressan R, Luzzati R, Di Bella S | title = Synergistic activity of fosfomycin and chloramphenicol against vancomycin-resistant Enterococcus faecium (VREfm) isolates from bloodstream infections | journal = Diagnostic Microbiology and Infectious Disease | volume = 99 | issue = 2 | pages = 115241 | date = February 2021 | pmid = 33130503 | doi = 10.1016/j.diagmicrobio.2020.115241 | s2cid = 225174927 | hdl = 11368/2973877 | hdl-access = free }}

Chloramphenicol is a bacteriostatic agent, inhibiting protein synthesis. It prevents protein chain elongation by inhibiting the peptidyl transferase activity of the bacterial ribosome. It specifically binds to A2451 and A2452 residues{{cite journal | vauthors = Schifano JM, Edifor R, Sharp JD, Ouyang M, Konkimalla A, Husson RN, Woychik NA | title = Mycobacterial toxin MazF-mt6 inhibits translation through cleavage of 23S rRNA at the ribosomal A site | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 21 | pages = 8501–8506 | date = May 2013 | pmid = 23650345 | pmc = 3666664 | doi = 10.1073/pnas.1222031110 | doi-access = free | bibcode = 2013PNAS..110.8501S }} in the 23S rRNA of the 50S ribosomal subunit, preventing peptide bond formation.{{cite web | url = http://merck.com/mmpe/sec14/ch170/ch170d.html | title = Chloramphenicol | work = The Merck Manual | publisher = Merck & Co., Inc. | location = Rahway, NJ, USA | url-status = live | archive-url = https://web.archive.org/web/20100310105845/http://www.merck.com/mmpe/sec14/ch170/ch170d.html | archive-date = 2010-03-10 }} Chloramphenicol directly interferes with substrate binding in the ribosome, as compared to macrolides, which sterically block the progression of the growing peptide.{{cite journal | vauthors = Jardetzky O | title = Studies on the mechanism of action of chloramphenicol. I. The conformation of chlioramphenicol in solution | journal = The Journal of Biological Chemistry | volume = 238 | issue = 7 | pages = 2498–2508 | date = July 1963 | pmid = 13957484 | doi = 10.1016/S0021-9258(19)68000-2 | url = http://www.jbc.org/content/238/7/2498.full.pdf | url-status = live | doi-access = free | archive-url = https://web.archive.org/web/20151211033031/http://www.jbc.org/content/238/7/2498.full.pdf | archive-date = 2015-12-11 | author-link1 = Oleg Jardetzky }}{{cite journal | vauthors = Wolfe AD, Hahn FE | title = Mode of action of chloramphenicol IX. Effects of chloramphenicol upon a ribosomal amino acid polymerization system and its binding to bacterial ribosome | journal = Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis | volume = 95 | pages = 146–155 | date = January 1965 | pmid = 14289020 | doi = 10.1016/0005-2787(65)90219-4 }}{{cite journal | vauthors = Hahn FE, Wisseman CL, Hopps HE | title = Mode of action of chloramphenicol. III. Action of chloramphenicol on bacterial energy metabolism | journal = Journal of Bacteriology | volume = 69 | issue = 2 | pages = 215–223 | date = February 1955 | pmid = 14353832 | pmc = 357505 | doi = 10.1128/JB.69.2.215-223.1955 }}

Chloramphenicol was first isolated from Streptomyces venezuelae in 1947 and in 1949 a team of scientists at Parke-Davis including Mildred Rebstock published their identification of the chemical structure and their synthesis.{{rp|26}}{{cite journal| vauthors = Mildred C, Crooks HM, John C, Quentin RB |title=Chloramphenicol (Chloromycetin).IV.Chemical Studies|journal=Journal of the American Chemical Society|date=July 1949|volume=71|issue=7|pages=2458–2462|doi=10.1021/ja01175a065|bibcode=1949JAChS..71.2458R }}{{cite journal| vauthors = Controulis J, Rebstock MC, Crooks HM |title=Chloramphenicol (Chloromycetin). V. Synthesis|journal=Journal of the American Chemical Society|date=July 1949|volume=71|issue=7|pages=2463–2468|doi=10.1021/ja01175a066|bibcode=1949JAChS..71.2463C }}

In 1972, Senator Ted Kennedy combined the two examples of the Tuskegee Syphilis Study and the 1958 Los Angeles Infant Chloramphenicol experiments as initial subjects of a Senate Subcommittee investigation into dangerous medical experimentation on human subjects.{{cite news |author= |date=October 12, 1972 |title="Kennedy Says 45 Babies Died in a Test" |url=https://timesmachine.nytimes.com/timesmachine/1972/10/12/91352284.html?pageNumber=22 |work=The New York Times |location=New York |access-date=18 December 2022}}

In 2007, the accumulation of reports associating aplastic anemia and blood dyscrasia with chloramphenicol eye drops led to the classification of "probable human carcinogen" according to World Health Organization criteria, based on the known published case reports and the spontaneous reports submitted to the National Registry of Drug-Induced Ocular Side Effects.{{cite journal | vauthors = Fraunfelder FW, Fraunfelder FT | title = Restricting topical ocular chloramphenicol eye drop use in the United States. Did we overreact? | journal = American Journal of Ophthalmology | volume = 156 | issue = 3 | pages = 420–422 | date = September 2013 | pmid = 23953152 | doi = 10.1016/j.ajo.2013.05.004 }}

Chloramphenicol is available as a generic worldwide under many brandnames{{cite web | work = Drugs.com | url = https://www.drugs.com/international/chloramphenicol.html | title = International listings for chloramphenicol | archive-url = https://web.archive.org/web/20150711033900/http://www.drugs.com/international/chloramphenicol.html | archive-date=2015-07-11 | access-date = 9 July 2015 }} and also under various generic names in eastern Europe and Russia, including chlornitromycin, levomycetin, and chloromycetin; the racemate is known as synthomycetin.{{cite book|title=The Great Soviet Encyclopedia, 3rd Edition, 1970–1979 |publisher=The Gale Group, Inc. |edition=3rd |url=http://encyclopedia2.thefreedictionary.com/Levomycetin |access-date=10 July 2015|archive-date=11 July 2015|archive-url=https://web.archive.org/web/20150711130905/http://encyclopedia2.thefreedictionary.com/Levomycetin|url-status=live}}

File:Sample of Chloramphenicol.jpg

Chloramphenicol is available as a capsule or as a liquid. In some countries, it is sold as chloramphenicol palmitate ester (CPE). CPE is inactive, and is hydrolysed to active chloramphenicol in the small intestine. No difference in bioavailability is noted between chloramphenicol and CPE.{{citation needed|date=March 2023}}

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. No oral formulation of chloramphenicol is available in the U.S. for human use.{{cite web |title=Chloramphenicol |url=https://go.drugbank.com/drugs/DB00446 |website=go.drugbank.com |access-date=23 June 2023 |date=June 23, 2023}}

The intravenous (IV) preparation of chloramphenicol is the succinate ester. This creates a problem: Chloramphenicol succinate ester is an inactive prodrug and must first be hydrolysed to chloramphenicol; however, the hydrolysis process is often incomplete, and 30% of the dose is lost and removed in the urine. Serum concentrations of IV chloramphenicol are only 70% of those achieved when chloramphenicol is given orally.{{cite journal | vauthors = Glazko AJ, Dill WA, Kinkel AW | title = Absorption and excretion of parenteral doses of chloramphenicol sodium succinate in comparison with per oral doses of chloramphenicol (abstract) | journal = Clinical Pharmacological Therapy | year = 1977 | volume = 21 | pages = 104 }} For this reason, the dose needs to be increased to 75 mg/kg/day when administered IV to achieve levels equivalent to the oral dose.{{cite journal | vauthors = Bhutta ZA, Niazi SK, Suria A | title = Chloramphenicol clearance in typhoid fever: implications for therapy | journal = Indian Journal of Pediatrics | volume = 59 | issue = 2 | pages = 213–219 | date = March–April 1992 | pmid = 1398851 | doi = 10.1007/BF02759987 | s2cid = 13369284 }}

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 Foundation has manufactured it since 1998, first in Malta and then in India from December 2004.{{cite journal | vauthors = Lewis RF, Dorlencourt F, Pinel J | title = Long-acting oily chloramphenicol for meningococcal meningitis | journal = Lancet | volume = 352 | issue = 9130 | pages = 823 | date = September 1998 | pmid = 9737323 | doi = 10.1016/S0140-6736(05)60723-4 | s2cid = 42224633 | doi-access = free }}

Oily chloramphenicol was first used to treat meningitis in 1975{{cite journal | vauthors = Rey M, Ouedraogo L, Saliou P, Perino L | title = Traitement minute de la méningite cérébrospinale épidémique par injection intramusculaire unique de chloramphénicol (suspension huileuse) | journal = Médecine et Maladies Infectieuses | language = fr | year = 1976 | volume = 6 | pages = 120–124 | doi = 10.1016/S0399-077X(76)80134-5 | issue = 4 }} and numerous studies since have demonstrated its efficacy.{{cite journal | vauthors = Wali SS, Macfarlane JT, Weir WR, Cleland PG, Ball PA, Hassan-King M, Whittle HC, Greenwood BM | title = Single injection treatment of meningococcal meningitis. 2. Long-acting chloramphenicol | journal = Transactions of the Royal Society of Tropical Medicine and Hygiene | volume = 73 | issue = 6 | pages = 698–702 | year = 1979 | pmid = 538813 | doi = 10.1016/0035-9203(79)90024-5 }}{{cite journal | vauthors = Puddicombe JB, Wali SS, Greenwood BM | title = A field trial of a single intramuscular injection of long-acting chloramphenicol in the treatment of meningococcal meningitis | journal = Transactions of the Royal Society of Tropical Medicine and Hygiene | volume = 78 | issue = 3 | pages = 399–403 | year = 1984 | pmid = 6464136 | doi = 10.1016/0035-9203(84)90132-9 }}{{cite journal | vauthors = Pécoul B, Varaine F, Keita M, Soga G, Djibo A, Soula G, Abdou A, Etienne J, Rey M | title = Long-acting chloramphenicol versus intravenous ampicillin for treatment of bacterial meningitis | journal = Lancet | volume = 338 | issue = 8771 | pages = 862–866 | date = October 1991 | pmid = 1681224 | doi = 10.1016/0140-6736(91)91511-R | hdl-access = free | s2cid = 31211632 | hdl = 10144/19393 }} 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.{{cite journal | vauthors = Nathan N, Borel T, Djibo A, Evans D, Djibo S, Corty JF, Guillerm M, Alberti KP, Pinoges L, Guerin PJ, Legros D | title = Ceftriaxone as effective as long-acting chloramphenicol in short-course treatment of meningococcal meningitis during epidemics: a randomised non-inferiority study | journal = Lancet | volume = 366 | issue = 9482 | pages = 308–313 | year = 2005 | pmid = 16039333 | doi = 10.1016/S0140-6736(05)66792-X | url = https://fieldresearch.msf.org/bitstream/10144/23232/1/187_Ceftriaxone_as_effective_as_long-acting_-_Lancet_9482_2005.pdf | access-date = 2019-09-24 | url-status = live | hdl-access = free | s2cid = 20885088 | archive-date = 2021-08-28 | archive-url = https://web.archive.org/web/20210828032549/https://fieldresearch.msf.org/bitstream/handle/10144/23232/187_Ceftriaxone_as_effective_as_long-acting_-_Lancet_9482_2005.pdf;jsessionid=4FA77D2A307B91A4436B8801D471FF05?sequence=1 | hdl = 10144/23232 }}

Chloramphenicol is used in topical preparations (ointments and eye drops) for the treatment of bacterial conjunctivitis. Isolated case reports of aplastic anaemia following use of chloramphenicol eyedrops exist, but the risk is estimated to be of the order of less than one in 224,716 prescriptions.{{cite journal | vauthors = Lancaster T, Swart AM, Jick H | title = Risk of serious haematological toxicity with use of chloramphenicol eye drops in a British general practice database | journal = BMJ | volume = 316 | issue = 7132 | pages = 667 | date = February 1998 | pmid = 9522792 | pmc = 28473 | doi = 10.1136/bmj.316.7132.667 }} In Mexico, this is the treatment used prophylactically in newborns for neonatal conjunctivitis.{{cite journal | vauthors = Kaštelan S, Anić Jurica S, Orešković S, Župić T, Herman M, Gverović Antunica A, Marković I, Bakija I | title = A Survey of Current Prophylactic Treatment for Ophthalmia Neonatorum in Croatia and a Review of International Preventive Practices | journal = Medical Science Monitor | volume = 24 | pages = 8042–8047 | date = November 2018 | pmid = 30413681 | pmc = 6240167 | doi = 10.12659/MSM.910705 | quote = According to current health policy in Mexico, preventive treatment for ophthalmia neonatorum in neonates is a medico-legal requirement and consists of the application of a single drop of ophthalmic chloramphenicol in both eyes shortly after birth }}

Although its use in veterinary medicine is highly restricted, chloramphenicol still has some important veterinary uses.{{cite web | date = March 2012 | vauthors = Boothe DM |title= Chloramphenicol and Congeners |url= http://www.merckmanuals.com/vet/pharmacology/antibacterial_agents/chloramphenicol_and_congeners.html|publisher=Merck & Co., Inc. | location = Rahway, NJ, USA|access-date=31 October 2014|url-status=live|archive-url=https://web.archive.org/web/20141031232305/http://www.merckmanuals.com/vet/pharmacology/antibacterial_agents/chloramphenicol_and_congeners.html|archive-date=31 October 2014}} It is currently considered the most useful treatment of chlamydial disease in koalas.{{cite journal | vauthors = Govendir M, Hanger J, Loader JJ, Kimble B, Griffith JE, Black LA, Krockenberger MB, Higgins DP | title = Plasma concentrations of chloramphenicol after subcutaneous administration to koalas (Phascolarctos cinereus) with chlamydiosis | journal = Journal of Veterinary Pharmacology and Therapeutics | volume = 35 | issue = 2 | pages = 147–154 | date = April 2012 | pmid = 21569052 | doi = 10.1111/j.1365-2885.2011.01307.x }}{{cite journal | vauthors = Griffith JE, Higgins DP | title = Diagnosis, treatment and outcomes for koala chlamydiosis at a rehabilitation facility (1995-2005) | journal = Australian Veterinary Journal | volume = 90 | issue = 11 | pages = 457–463 | date = November 2012 | pmid = 23106328 | doi = 10.1111/j.1751-0813.2012.00963.x | doi-access = free }} The pharmacokinetics of chloramphenicol have been investigated in koalas.{{cite journal | vauthors = Black LA, McLachlan AJ, Griffith JE, Higgins DP, Gillett A, Krockenberger MB, Govendir M | title = Pharmacokinetics of chloramphenicol following administration of intravenous and subcutaneous chloramphenicol sodium succinate, and subcutaneous chloramphenicol, to koalas (Phascolarctos cinereus) | journal = Journal of Veterinary Pharmacology and Therapeutics | volume = 36 | issue = 5 | pages = 478–485 | date = October 2013 | pmid = 23157306 | doi = 10.1111/jvp.12024 }}

The biosynthetic gene cluster and pathway for chloroamphenicol was characterized from Streptomyces venezuelae ISP5230{{cite journal | vauthors = He J, Magarvey N, Piraee M, Vining LC | title = The gene cluster for chloramphenicol biosynthesis in Streptomyces venezuelae ISP5230 includes novel shikimate pathway homologues and a monomodular non-ribosomal peptide synthetase gene | journal = Microbiology | volume = 147 | issue = Pt 10 | pages = 2817–2829 | date = October 2001 | pmid = 11577160 | doi = 10.1099/00221287-147-10-2817 | doi-access = free }}{{cite journal | vauthors = Piraee M, White RL, Vining LC | title = Biosynthesis of the dichloroacetyl component of chloramphenicol in Streptomyces venezuelae ISP5230: genes required for halogenation | journal = Microbiology | volume = 150 | issue = Pt 1 | pages = 85–94 | date = January 2004 | pmid = 14702400 | doi = 10.1099/mic.0.26319-0 | doi-access = free }} a.k.a. ATCC 17102.{{cite book | vauthors = Vining L, Stuttard C | title=Genetics and Biochemistry of Antibiotic Production | publisher=Butterworth-Heinemann | publication-place=Boston | date=1995 | isbn=978-0-7506-9095-9 | page=}} Currently the chloramphenicol biosynthetic gene cluster has 17 genes with assigned roles.{{cite journal | vauthors = Fernández-Martínez LT, Borsetto C, Gomez-Escribano JP, Bibb MJ, Al-Bassam MM, Chandra G, Bibb MJ | title = New insights into chloramphenicol biosynthesis in Streptomyces venezuelae ATCC 10712 | journal = Antimicrobial Agents and Chemotherapy | volume = 58 | issue = 12 | pages = 7441–7450 | date = December 2014 | pmid = 25267678 | pmc = 4249514 | doi = 10.1128/AAC.04272-14 }}

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