Jump to content

Chloramphenicol

From Wikipedia, the free encyclopedia
(Redirected from Synthomycetine)

For the episode of The Americans, see Chloramphenicol (The Americans).
Chloramphenicol
Clinical data
Trade namesChloromycetin, Abeed, others[1]
Other namesC/CHL/CL[2]
AHFS/Drugs.comMonograph
MedlinePlusa608008
License data
Pregnancy
category
  • AU: A
Routes of
administration		Topical (eye drops), by mouth, intravenous therapy (IV), intramuscular injection (IM)
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability75–90%
Protein binding60%
MetabolismLiver
Elimination half-life1.6–3.3 hours
ExcretionKidney (5–15%), faeces (4%)
Identifiers
  • 2,2-dichloro-N-[(1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]acetamide[4]
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.000.262 Edit this at Wikidata
Chemical and physical data
FormulaC11H12Cl2N2O5
Molar mass323.13 g·mol−1
3D model (JSmol)
  • c1cc(ccc1[C@H]([C@@H](CO)NC(=O)C(Cl)Cl)O)[N+](=O)[O-]
  • InChI=1S/C11H12Cl2N2O5/c12-10(13)11(18)14-8(5-16)9(17)6-1-3-7(4-2-6)15(19)20/h1-4,8-10,16-17H,5H2,(H,14,18)/t8-,9-/m1/s1 checkY
  • Key:WIIZWVCIJKGZOK-RKDXNWHRSA-N checkY
  (verify)

Chloramphenicol is an antibiotic useful for the treatment of a number of bacterial infections.[5] This includes use as an eye ointment to treat conjunctivitis.[6] By mouth or by injection into a vein, it is used to treat meningitis, plague, cholera, and typhoid fever.[5] Its use by mouth or by injection is only recommended when safer antibiotics cannot be used.[5] Monitoring both blood levels of the medication and blood cell levels every two days is recommended during treatment.[5]

Common side effects include bone marrow suppression, nausea, and diarrhea.[5] The bone marrow suppression may result in death.[5] To reduce the risk of side effects treatment duration should be as short as possible.[5] People with liver or kidney problems may need lower doses.[5] In young infants, a condition known as gray baby syndrome may occur which results in a swollen stomach and low blood pressure.[5] Its use near the end of pregnancy and during breastfeeding is typically not recommended.[7] Chloramphenicol is a broad-spectrum antibiotic that typically stops bacterial growth by stopping the production of proteins.[5]

Chloramphenicol was discovered after being isolated from Streptomyces venezuelae in 1947.[8] Its chemical structure was identified and it was first synthesized in 1949. It is on the World Health Organization's List of Essential Medicines.[9] It is available as a generic medication.[5]

Medical uses

[edit]

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]

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.[10]

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.[11]

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.[12]

Spectrum

[edit]

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.[13]

  • 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.[14][15]

Resistance

[edit]

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;[16] 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]

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]

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.[17]

Some other resistance genes beyond cat are known, such as chloramphenicol hydrolase,[18] and chloramphenicol phosphotransferase.[19]

Adverse effects

[edit]

Aplastic anemia

[edit]

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.[20] Chloramphenicol should be discontinued if the complete blood count drops. The highest risk is with oral chloramphenicol (affecting 1 in 24,000–40,000)[21] and the lowest risk occurs with eye drops (affecting less than one in 224,716 prescriptions).[22]

Thiamphenicol, a related compound with a similar spectrum of activity, is available in Italy and 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, but is not approved for use in humans.[citation needed]

Bone marrow suppression

[edit]

Chloramphenicol may cause bone marrow suppression during treatment; this is a direct toxic effect of the drug on human mitochondria.[23] 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.[24]

Leukemia

[edit]

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,[25] and the risk increases with length of treatment.

Gray baby syndrome

[edit]

Intravenous chloramphenicol use has been associated with the so-called gray baby syndrome.[26] 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.[27] 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.[28][29][30]

Hypersensitivity reactions

[edit]

Fever, macular and vesicular rashes, angioedema, urticaria, and anaphylaxis may occur. Herxheimer's reactions have occurred during therapy for typhoid fever.[31]

Neurotoxic reactions

[edit]

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.[31] It is theorized that this is caused by chloramphenicol's effects on the metabolism of B-Vitamins, specifically B-12.[32]

Pharmacokinetics

[edit]

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.[31] 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]

Chloramphenicol increases the absorption of iron.[33]

Use in special populations

[edit]

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.[34] Chloramphenicol passes into breast milk, so should therefore be avoided during breast feeding, if possible.[35]

Dose monitoring

[edit]

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 > 40 μg/mL; trough levels (taken immediately before a dose) should be 5–10 μg/mL.[36][37]

Drug interactions

[edit]

Administration of chloramphenicol concomitantly with bone marrow depressant drugs is contraindicated, although concerns over aplastic anaemia associated with ocular chloramphenicol have largely been discounted.[38]

Chloramphenicol is a potent inhibitor of the cytochrome P450 isoforms CYP2C19 and CYP3A4 in the liver.[39] 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.[31][40]

Drug antagonistic

[edit]

Chloramphenicol is antagonistic with most cephalosporins and using both together should be avoided in the treatment of infections.[41]

Drug synergism

[edit]

Chloramphenicol has been demonstrated a synergistic effect when combined with fosfomycin against clinical isolates of Enterococcus faecium.[42]

Mechanism of action

[edit]

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[43] in the 23S rRNA of the 50S ribosomal subunit, preventing peptide bond formation.[44] Chloramphenicol directly interferes with substrate binding in the ribosome, as compared to macrolides, which sterically block the progression of the growing peptide.[45][46][47]

History

[edit]

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.[8]: 26 [48][49]

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.[50]

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.[51]

Society and culture

[edit]

Names

[edit]

Chloramphenicol is available as a generic worldwide under many brandnames[52] and also under various generic names in eastern Europe and Russia, including chlornitromycin, levomycetin, and chloromycetin; the racemate is known as synthomycetin.[53]

Formulations

[edit]
Pure chloramphenicol

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]

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.[54]

In molecular biology, chloramphenicol is prepared in ethanol.[citation needed]

Intravenous

[edit]

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.[55] 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.[56]

Oily

[edit]

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.[57]

Oily chloramphenicol was first used to treat meningitis in 1975[58] and numerous studies since have demonstrated its efficacy.[59][60][61] 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.[62]

Eye drops

[edit]

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.[22] In Mexico, this is the treatment used prophylactically in newborns for neonatal conjunctivitis.[63]

Veterinary uses

[edit]

Although its use in veterinary medicine is highly restricted, chloramphenicol still has some important veterinary uses.[64] It is currently considered the most useful treatment of chlamydial disease in koalas.[65][66] The pharmacokinetics of chloramphenicol have been investigated in koalas.[67]

Biosynthesis

[edit]

The biosynthetic gene cluster and pathway for chloroamphenicol was characterized from Streptomyces venezuelae ISP5230[68][69] a.k.a. ATCC 17102.[70] Currently the chloramphenicol biosynthetic gene cluster has 17 genes with assigned roles.[71]

References

[edit]
  1. ^ Woods AL (2008). Delmar nurse's drug handbook (2009 ed.). Clifton Park, N.Y.: Delmar. p. 296. ISBN 9781428361065. Archived from the original on 2016-03-05.
  2. ^ "Antibiotic abbreviations list". Retrieved 22 June 2023.
  3. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  4. ^ "Chloramphenicol". PubChem. Archived from the original on 2016-11-15.
  5. ^ a b c d e f g h i j k "Chloramphenicol". The American Society of Health-System Pharmacists. Archived from the original on 2015-06-24. Retrieved Aug 1, 2015.
  6. ^ Edwards KH (2009). Optometry: Science, Techniques and Clinical Management. Elsevier Health Sciences. p. 102. ISBN 978-0750687782. Archived from the original on 2017-03-07.
  7. ^ "Chloramphenicol Pregnancy and Breastfeeding Warnings". Multum Information Services. Archived from the original on 8 September 2015. Retrieved 26 August 2015.
  8. ^ a b Pongs O (1979). "Chapter 3: Chloramphenicol". In Hahn FE (ed.). Mechanism of Action of Antibacterial Agents. Antibiotics Volume V Part 1. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 26–42. ISBN 978-3-642-46403-4.
  9. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  10. ^ "WHO meningitis epidemic guidelines Africa". Archived from the original on 5 March 2016. Retrieved 29 February 2016.
  11. ^ Čivljak R, Giannella M, Di Bella S, Petrosillo N (February 2014). "Could chloramphenicol be used against ESKAPE pathogens? A review of in vitro data in the literature from the 21st century". Expert Review of Anti-Infective Therapy. 12 (2): 249–264. doi:10.1586/14787210.2014.878647. PMID 24392752. S2CID 34134573. Archived from the original on 2022-03-03. Retrieved 2021-07-02.
  12. ^ Gower EW, Lindsley K, Tulenko SE, Nanji AA, Leyngold I, McDonnell PJ (February 2017). "Perioperative antibiotics for prevention of acute endophthalmitis after cataract surgery". The Cochrane Database of Systematic Reviews. 2017 (2): CD006364. doi:10.1002/14651858.CD006364.pub3. PMC 5375161. PMID 28192644.
  13. ^ "Chloramphenicol (Chloromycetin) | the Antimicrobial Index Knowledgebase - TOKU-E". Archived from the original on 2014-04-23. Retrieved 2014-04-21.
  14. ^ Carone BR, Xu T, Murphy KC, Marinus MG (January 2014). "High incidence of multiple antibiotic resistant cells in cultures of in enterohemorrhagic Escherichia coli O157:H7". Mutation Research. 759: 1–8. Bibcode:2014MRFMM.759....1C. doi:10.1016/j.mrfmmm.2013.11.008. PMC 3913999. PMID 24361397.
  15. ^ Moore AM, Patel S, Forsberg KJ, Wang B, Bentley G, Razia Y, et al. (2013). "Pediatric fecal microbiota harbor diverse and novel antibiotic resistance genes". PLOS ONE. 8 (11): e78822. Bibcode:2013PLoSO...878822M. doi:10.1371/journal.pone.0078822. PMC 3827270. PMID 24236055.
  16. ^ Gil JA, Kieser HM, Hopwood DA (1985). "Cloning of a chloramphenicol acetyltransferase gene of Streptomyces acrimycini and its expression in Streptomyces and Escherichia coli". Gene. 38 (1–3): 1–8. doi:10.1016/0378-1119(85)90197-0. PMID 3905512.
  17. ^ "Chloramphenicol spectrum of bacterial susceptibility and Resistance" (PDF). Product Data Safety Sheet. TOKU-E. December 2010. Archived from the original (PDF) on 11 February 2014. Retrieved 15 May 2012.
  18. ^ Mosher RH, Ranade NP, Schrempf H, Vining LC (February 1990). "Chloramphenicol resistance in Streptomyces: cloning and characterization of a chloramphenicol hydrolase gene from Streptomyces venezuelae". Journal of General Microbiology. 136 (2): 293–301. doi:10.1099/00221287-136-2-293. PMID 2324705.
  19. ^ Mosher RH, Camp DJ, Yang K, Brown MP, Shaw WV, Vining LC (November 1995). "Inactivation of chloramphenicol by O-phosphorylation. A novel resistance mechanism in Streptomyces venezuelae ISP5230, a chloramphenicol producer". The Journal of Biological Chemistry. 270 (45): 27000–27006. doi:10.1074/jbc.270.45.27000. PMID 7592948.
  20. ^ Hammett-Stabler CA, Johns T (May 1998). "Laboratory guidelines for monitoring of antimicrobial drugs. National Academy of Clinical Biochemistry". Clinical Chemistry. 44 (5): 1129–1140. doi:10.1093/clinchem/44.5.1129. PMID 9590397.
  21. ^ Wallerstein RO, Condit PK, Kasper CK, Brown JW, Morrison FR (June 1969). "Statewide study of chloramphenicol therapy and fatal aplastic anemia". JAMA. 208 (11): 2045–2050. doi:10.1001/jama.208.11.2045. PMID 5818983.
  22. ^ a b Lancaster T, Swart AM, Jick H (February 1998). "Risk of serious haematological toxicity with use of chloramphenicol eye drops in a British general practice database". BMJ. 316 (7132): 667. doi:10.1136/bmj.316.7132.667. PMC 28473. PMID 9522792.
  23. ^ Yunis AA (September 1989). "Chloramphenicol toxicity: 25 years of research". The American Journal of Medicine. 87 (3N): 44N–48N. PMID 2486534.
  24. ^ Morley A, Trainor K, Remes J (April 1976). "Residual marrow damage: possible explanation for idiosyncrasy to chloramphenicol". British Journal of Haematology. 32 (4): 525–531. doi:10.1111/j.1365-2141.1976.tb00955.x. PMID 1259934. S2CID 40234293.
  25. ^ Shu XO, Gao YT, Linet MS, Brinton LA, Gao RN, Jin F, et al. (October 1987). "Chloramphenicol use and childhood leukaemia in Shanghai". Lancet. 2 (8565): 934–937. doi:10.1016/S0140-6736(87)91420-6. PMID 2889862. S2CID 3217082.
  26. ^ McIntyre J, Choonara I (2004). "Drug toxicity in the neonate". Biology of the Neonate. 86 (4): 218–221. doi:10.1159/000079656. PMID 15249753. S2CID 29906856.
  27. ^ Piñeiro-Carrero VM, Piñeiro EO (April 2004). "Liver" (PDF). Pediatrics. 113 (4 Suppl): 1097–1106. doi:10.1542/peds.113.S3.1097. PMID 15060205. S2CID 264867934. Archived (PDF) from the original on 2021-08-28. Retrieved 2012-01-09.
  28. ^ Feder HM (September 1986). "Chloramphenicol: what we have learned in the last decade". Southern Medical Journal. 79 (9): 1129–1134. doi:10.1097/00007611-198609000-00022. PMID 3529436.
  29. ^ Mulhall A, de Louvois J, Hurley R (November 1983). "Chloramphenicol toxicity in neonates: its incidence and prevention". British Medical Journal. 287 (6403): 1424–1427. doi:10.1136/bmj.287.6403.1424. PMC 1549666. PMID 6416440.
  30. ^ Forster J, Hufschmidt C, Niederhoff H, Künzer W (April 1985). "[Need for the determination of chloramphenicol levels in the treatment of bacterial-purulent meningitis with chloramphenicol succinate in infants and small children]". Monatsschrift Kinderheilkunde (in German). 133 (4): 209–213. PMID 4000136.
  31. ^ a b c d "Drug Insert from DailyMed". Archived from the original on 19 April 2014. Retrieved 18 April 2014.
  32. ^ Ramilo O, Kinane BT, McCracken GH (May 1988). "Chloramphenicol neurotoxicity". The Pediatric Infectious Disease Journal. 7 (5): 358–359. doi:10.1097/00006454-198805000-00015. PMID 3380586.
  33. ^ Silverman HM, ed. (2006). "Iron Supplements". Pill Book, The (12th revised ed.). New York: Bantam Dell. pp. 593–596. ISBN 978-0-553-58892-7.
  34. ^ Yogev R, Kolling WM, Williams T (May 1981). "Pharmacokinetic comparison of intravenous and oral chloramphenicol in patients with Haemophilus influenzae meningitis". Pediatrics. 67 (5): 656–660. doi:10.1542/peds.67.5.656. PMID 6973130. S2CID 8701518.
  35. ^ "Drugs and Other Substances in Breast Milk". kidsgrowth.org. Archived from the original on 23 June 2007. Retrieved 19 June 2009.
  36. ^ Hammett-Stabler CA, Johns T (May 1998). "Laboratory guidelines for monitoring of antimicrobial drugs. National Academy of Clinical Biochemistry". Clinical Chemistry. 44 (5): 1129–1140. doi:10.1093/clinchem/44.5.1129. PMID 9590397.
  37. ^ "Chloramphenicol (Lexi-Drugs)". Lexi-Comp Online. Archived from the original on 26 July 2013. Retrieved 18 April 2014.
  38. ^ "Practice Guidance: OTC Chloramphenicol Eye Drops" (PDF). Royal Pharmaceutical Society of Great Britain (RPSGB). June 2005. Archived from the original (PDF) on 2005-10-22.
  39. ^ Park JY, Kim KA, Kim SL (November 2003). "Chloramphenicol is a potent inhibitor of cytochrome P450 isoforms CYP2C19 and CYP3A4 in human liver microsomes". Antimicrobial Agents and Chemotherapy. 47 (11): 3464–3469. doi:10.1128/AAC.47.11.3464-3469.2003. PMC 253795. PMID 14576103.
  40. ^ "Fakta för förskrivare" [Facts for prescribers] (in Swedish). FASS – Swedish National Drug Formulary. Archived from the original on 2002-06-11.
  41. ^ Asmar BI, Prainito M, Dajani AS (September 1988). "Antagonistic effect of chloramphenicol in combination with cefotaxime or ceftriaxone". Antimicrobial Agents and Chemotherapy. 32 (9): 1375–8. doi:10.1128/AAC.32.9.1375. PMC 175871. PMID 3195999.
  42. ^ Lagatolla C, Milic J, Imperi F, Cervoni M, Bressan R, Luzzati R, et al. (February 2021). "Synergistic activity of fosfomycin and chloramphenicol against vancomycin-resistant Enterococcus faecium (VREfm) isolates from bloodstream infections". Diagnostic Microbiology and Infectious Disease. 99 (2): 115241. doi:10.1016/j.diagmicrobio.2020.115241. hdl:11368/2973877. PMID 33130503. S2CID 225174927.
  43. ^ Schifano JM, Edifor R, Sharp JD, Ouyang M, Konkimalla A, Husson RN, et al. (May 2013). "Mycobacterial toxin MazF-mt6 inhibits translation through cleavage of 23S rRNA at the ribosomal A site". Proceedings of the National Academy of Sciences of the United States of America. 110 (21): 8501–8506. Bibcode:2013PNAS..110.8501S. doi:10.1073/pnas.1222031110. PMC 3666664. PMID 23650345.
  44. ^ "Chloramphenicol". The Merck Manual. Rahway, NJ, USA: Merck & Co., Inc. Archived from the original on 2010-03-10.
  45. ^ Jardetzky O (July 1963). "Studies on the mechanism of action of chloramphenicol. I. The conformation of chlioramphenicol in solution" (PDF). The Journal of Biological Chemistry. 238 (7): 2498–2508. doi:10.1016/S0021-9258(19)68000-2. PMID 13957484. Archived (PDF) from the original on 2015-12-11.
  46. ^ Wolfe AD, Hahn FE (January 1965). "Mode of action of chloramphenicol IX. Effects of chloramphenicol upon a ribosomal amino acid polymerization system and its binding to bacterial ribosome". Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis. 95: 146–155. doi:10.1016/0005-2787(65)90219-4. PMID 14289020.
  47. ^ Hahn FE, Wisseman CL, Hopps HE (February 1955). "Mode of action of chloramphenicol. III. Action of chloramphenicol on bacterial energy metabolism". Journal of Bacteriology. 69 (2): 215–223. doi:10.1128/JB.69.2.215-223.1955. PMC 357505. PMID 14353832.
  48. ^ Mildred C, Crooks HM, John C, Quentin RB (July 1949). "Chloramphenicol (Chloromycetin).IV.Chemical Studies". Journal of the American Chemical Society. 71 (7): 2458–2462. doi:10.1021/ja01175a065.
  49. ^ Controulis J, Rebstock MC, Crooks HM (July 1949). "Chloramphenicol (Chloromycetin). V. Synthesis". Journal of the American Chemical Society. 71 (7): 2463–2468. doi:10.1021/ja01175a066.
  50. ^ ""Kennedy Says 45 Babies Died in a Test"". The New York Times. New York. October 12, 1972. Retrieved 18 December 2022.
  51. ^ Fraunfelder FW, Fraunfelder FT (September 2013). "Restricting topical ocular chloramphenicol eye drop use in the United States. Did we overreact?". American Journal of Ophthalmology. 156 (3): 420–422. doi:10.1016/j.ajo.2013.05.004. PMID 23953152.
  52. ^ "International listings for chloramphenicol". Drugs.com. Archived from the original on 2015-07-11. Retrieved 9 July 2015.
  53. ^ The Great Soviet Encyclopedia, 3rd Edition, 1970–1979 (3rd ed.). The Gale Group, Inc. Archived from the original on 11 July 2015. Retrieved 10 July 2015.
  54. ^ "Chloramphenicol". go.drugbank.com. June 23, 2023. Retrieved 23 June 2023.
  55. ^ Glazko AJ, Dill WA, Kinkel AW (1977). "Absorption and excretion of parenteral doses of chloramphenicol sodium succinate in comparison with per oral doses of chloramphenicol (abstract)". Clinical Pharmacological Therapy. 21: 104.
  56. ^ Bhutta ZA, Niazi SK, Suria A (March–April 1992). "Chloramphenicol clearance in typhoid fever: implications for therapy". Indian Journal of Pediatrics. 59 (2): 213–219. doi:10.1007/BF02759987. PMID 1398851. S2CID 13369284.
  57. ^ Lewis RF, Dorlencourt F, Pinel J (September 1998). "Long-acting oily chloramphenicol for meningococcal meningitis". Lancet. 352 (9130): 823. doi:10.1016/S0140-6736(05)60723-4. PMID 9737323. S2CID 42224633.
  58. ^ 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 (in French). 6 (4): 120–124. doi:10.1016/S0399-077X(76)80134-5.
  59. ^ Wali SS, Macfarlane JT, Weir WR, Cleland PG, Ball PA, Hassan-King M, et al. (1979). "Single injection treatment of meningococcal meningitis. 2. Long-acting chloramphenicol". Transactions of the Royal Society of Tropical Medicine and Hygiene. 73 (6): 698–702. doi:10.1016/0035-9203(79)90024-5. PMID 538813.
  60. ^ Puddicombe JB, Wali SS, Greenwood BM (1984). "A field trial of a single intramuscular injection of long-acting chloramphenicol in the treatment of meningococcal meningitis". Transactions of the Royal Society of Tropical Medicine and Hygiene. 78 (3): 399–403. doi:10.1016/0035-9203(84)90132-9. PMID 6464136.
  61. ^ Pécoul B, Varaine F, Keita M, Soga G, Djibo A, Soula G, et al. (October 1991). "Long-acting chloramphenicol versus intravenous ampicillin for treatment of bacterial meningitis". Lancet. 338 (8771): 862–866. doi:10.1016/0140-6736(91)91511-R. hdl:10144/19393. PMID 1681224. S2CID 31211632.
  62. ^ Nathan N, Borel T, Djibo A, Evans D, Djibo S, Corty JF, et al. (2005). "Ceftriaxone as effective as long-acting chloramphenicol in short-course treatment of meningococcal meningitis during epidemics: a randomised non-inferiority study" (PDF). Lancet. 366 (9482): 308–313. doi:10.1016/S0140-6736(05)66792-X. hdl:10144/23232. PMID 16039333. S2CID 20885088. Archived from the original on 2021-08-28. Retrieved 2019-09-24.
  63. ^ Kaštelan S, Anić Jurica S, Orešković S, Župić T, Herman M, Gverović Antunica A, et al. (November 2018). "A Survey of Current Prophylactic Treatment for Ophthalmia Neonatorum in Croatia and a Review of International Preventive Practices". Medical Science Monitor. 24: 8042–8047. doi:10.12659/MSM.910705. PMC 6240167. PMID 30413681. 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
  64. ^ Boothe DM (March 2012). "Chloramphenicol and Congeners". Rahway, NJ, USA: Merck & Co., Inc. Archived from the original on 31 October 2014. Retrieved 31 October 2014.
  65. ^ Govendir M, Hanger J, Loader JJ, Kimble B, Griffith JE, Black LA, et al. (April 2012). "Plasma concentrations of chloramphenicol after subcutaneous administration to koalas (Phascolarctos cinereus) with chlamydiosis". Journal of Veterinary Pharmacology and Therapeutics. 35 (2): 147–154. doi:10.1111/j.1365-2885.2011.01307.x. PMID 21569052.
  66. ^ Griffith JE, Higgins DP (November 2012). "Diagnosis, treatment and outcomes for koala chlamydiosis at a rehabilitation facility (1995-2005)". Australian Veterinary Journal. 90 (11): 457–463. doi:10.1111/j.1751-0813.2012.00963.x. PMID 23106328.
  67. ^ Black LA, McLachlan AJ, Griffith JE, Higgins DP, Gillett A, Krockenberger MB, et al. (October 2013). "Pharmacokinetics of chloramphenicol following administration of intravenous and subcutaneous chloramphenicol sodium succinate, and subcutaneous chloramphenicol, to koalas (Phascolarctos cinereus)". Journal of Veterinary Pharmacology and Therapeutics. 36 (5): 478–485. doi:10.1111/jvp.12024. PMID 23157306.
  68. ^ He J, Magarvey N, Piraee M, Vining LC (October 2001). "The gene cluster for chloramphenicol biosynthesis in Streptomyces venezuelae ISP5230 includes novel shikimate pathway homologues and a monomodular non-ribosomal peptide synthetase gene". Microbiology. 147 (Pt 10): 2817–2829. doi:10.1099/00221287-147-10-2817. PMID 11577160.
  69. ^ Piraee M, White RL, Vining LC (January 2004). "Biosynthesis of the dichloroacetyl component of chloramphenicol in Streptomyces venezuelae ISP5230: genes required for halogenation". Microbiology. 150 (Pt 1): 85–94. doi:10.1099/mic.0.26319-0. PMID 14702400.
  70. ^ Vining L, Stuttard C (1995). Genetics and Biochemistry of Antibiotic Production. Boston: Butterworth-Heinemann. ISBN 978-0-7506-9095-9.
  71. ^ Fernández-Martínez LT, Borsetto C, Gomez-Escribano JP, Bibb MJ, Al-Bassam MM, Chandra G, et al. (December 2014). "New insights into chloramphenicol biosynthesis in Streptomyces venezuelae ATCC 10712". Antimicrobial Agents and Chemotherapy. 58 (12): 7441–7450. doi:10.1128/AAC.04272-14. PMC 4249514. PMID 25267678.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Chloramphenicol&oldid=1258996604"