Editing Chloramphenicol (section)

== Medical uses ==

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.<ref name="WHOMeningitis">{{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}}</ref>

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.<ref>{{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 }}</ref>

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.<ref name="Gower">{{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 }}</ref>

===Spectrum===
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.<ref>{{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 }}</ref>
* ''Escherichia coli'': 0.015&nbsp;–&nbsp;10,000&nbsp;μg/mL
* ''Staphylococcus aureus'': 0.06&nbsp;–&nbsp;128&nbsp;μg/mL
* ''Streptococcus pneumoniae'': 2&nbsp;–&nbsp;16&nbsp;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.<ref>{{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 }}</ref><ref>{{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 }}</ref>

===Resistance===

Three mechanisms of [[Antibiotic resistance|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;<ref name="m586">{{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 }}</ref> 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.<ref>{{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}}</ref>

Some other resistance genes beyond ''cat'' are known, such as chloramphenicol hydrolase,<ref name="b716">{{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 }}</ref> and chloramphenicol phosphotransferase.<ref name="u157">{{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 }}</ref>