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{{Drugbox
| Verifiedfields = changed
| verifiedrevid = 443833957
| IUPAC_name = (3''R'',4''R'',5''R'')-2-{[(1''S'',2''S'',3''R'',4''S'',6''R'')-4,6-<br />diamino-3-{[(2''R'',3''R'',6''S'')-<br />3-amino-6-[(1''R'')-<br />1-(methylamino)ethyl]oxan-2-yl]oxy}-<br />2-hydroxycyclohexyl]oxy}-5-methyl-<br />4-(methylamino)oxane-3,5-diol
| image = Gentamicin C2.svg
| image2 = Gentamicin.png
<!--Clinical data-->
| tradename = Genticyn, Garamycin, Magenta, Merigenta and others
| Drugs.com = {{drugs.com|monograph|gentamicin-sulfate}}
| MedlinePlus = a682275
| pregnancy_category = D
| legal_UK = POM
| routes_of_administration = [[Intravenous therapy|IV]], [[eye drop]], [[Intramuscular injection|IM]], [[topical]]
<!--Pharmacokinetic data-->
| bioavailability = limited oral bioavailability
| protein_bound = 0-10%
| elimination_half-life = 2 hrs
| excretion = renal
<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 1403-66-3
| ATC_prefix = D06
| ATC_suffix = AX07
| ATC_supplemental =  {{ATC|J01|GB03}} {{ATC|S01|AA11}} {{ATC|S02|AA14}} {{ATC|S03|AA06}} {{ATCvet|A07|AA91}} {{ATCvet|G01|AA91}} {{ATCvet|G51|AA04}} {{ATCvet|J51|GB03}}
| PubChem = 3467
| IUPHAR_ligand = 2427
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB00798
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 390067
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = T6Z9V48IKG
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D08013
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 27412
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 195892
<!--Chemical data-->
| C=21 | H=43 | N=5 | O=7
| molecular_weight = 477.596 g/mol
| smiles = O[C@]3(C)[C@H](NC)[C@@H](O)[C@@H](O[C@H]2[C@H](N)C[C@H](N)[C@@H](O[C@H]1O[C@H](C(NC)C)CC[C@H]1N)[C@@H]2O)OC3
| InChI = 1/C21H43N5O7/c1-9(25-3)13-6-5-10(22)19(31-13)32-16-11(23)7-12(24)17(14(16)27)33-20-15(28)18(26-4)21(2,29)8-30-20/h9-20,25-29H,5-8,22-24H2,1-4H3/t9?,10-,11+,12-,13+,14+,15-,16-,17+,18-,19-,20-,21+/m1/s1
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C21H43N5O7/c1-9(25-3)13-6-5-10(22)19(31-13)32-16-11(23)7-12(24)17(14(16)27)33-20-15(28)18(26-4)21(2,29)8-30-20/h9-20,25-29H,5-8,22-24H2,1-4H3/t9?,10-,11+,12-,13+,14+,15-,16-,17+,18-,19-,20-,21+/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = CEAZRRDELHUEMR-URQXQFDESA-N
}}
<!-- Definition and uses -->
'''Gentamicin''', sold under the brandname '''Garamycin''' among other, is an [[antibiotic]] used to treat many types of [[bacteria]]l infections.<ref name=AHFS2015/> This may include [[osteomyelitis|bone infections]], [[endocarditis]], [[pelvic inflammatory disease]], [[meningitis]], [[pneumonia]], [[urinary tract infections]], and [[sepsis]] among others.<!-- <ref name=AHFS2015/> --> It is not effective for [[gonorrhea]] or [[chlamydia infection]]s.<!-- <ref name=AHFS2015/> --> It can be given [[Intravenous therapy|intravenously]], [[Intramuscular injection|by injection into a muscle]], or [[topical]]ly.<ref name=AHFS2015/> Topical formulations may be used in burns or for infections of the outside of the eye.<ref>{{cite book|last1=Bartlett|first1=Jimmy|title=Clinical Ocular Pharmacology|date=2013|publisher=Elsevier|isbn=9781483193915|page=214|edition=s|url=https://books.google.com/books?id=kA8lBQAAQBAJ&pg=PA214}}</ref> In the developed world it is often only used for two days until [[bacterial culture]]s determine what antibiotics the infection is sensitive to.<ref name="ap01">{{cite journal |author=Moulds, Robert and Jeyasingham, Melanie |journal=Australian Prescriber |title=Gentamicin: a great way to start |date=October 2010 |volume=33 |issue=5 |pages=134–135 |doi=10.18773/austprescr.2010.062 |url=http://www.australianprescriber.com/magazine/33/5/134/5}}</ref> The dose required should be monitored by blood testing.<ref name=AHFS2015/>

<!-- Side effects and mechanism -->
Gentamicin can cause [[ototoxic|inner ear problems]] and [[nephrotoxic|kidney problems]].<ref name=AHFS2015/> The inner ear problems can include problems with balance and [[hearing loss|problems with hearing]].<!-- <ref name=AHFS2015/> --> These problems may be permanent.<!-- <ref name=AHFS2015/> --> If used during [[pregnancy]] it can cause harm to the baby.<ref name=AHFS2015/> It appears to be safe for use during [[breastfeeding]].<ref name=GenB>{{cite web|title=Gentamicin use while Breastfeeding|url=http://www.drugs.com/breastfeeding/gentamicin.html|accessdate=15 August 2015}}</ref> Gentamicin is a type of [[aminoglycoside]].<!-- <ref name=AHFS2015/> --> It works by stopping the bacteria from making protein which typically [[bactericidal|kills the bacteria]].<ref name=AHFS2015>{{cite web|title=Gentamicin Sulfate|url=http://www.drugs.com/monograph/gentamicin-sulfate.html|publisher=The American Society of Health-System Pharmacists|accessdate=Aug 15, 2015}}</ref>

<!-- Society and culture -->
Gentamicin was discovered in 1963.<ref>{{cite book|last1=Pucci|first1=edited by Thomas Dougherty, Michael J.|last2=Weinstein|first2=Marvin J.|title=Handbook of antibiotic discovery and development|date=2011|publisher=Springer|location=New York|isbn=9781461413998|page=238|edition=2012|url=https://books.google.com/books?id=E6Dv5XsXU-IC&pg=PA238}}</ref> It is made from the bacteria ''[[Micromonospora purpurea]]''.<ref name=AHFS2015/> Gentamicin is on the [[World Health Organization's List of Essential Medicines]], the most important medication needed in a basic [[health system]].<ref>{{cite web|title=WHO Model List of EssentialMedicines|url=http://apps.who.int/iris/bitstream/10665/93142/1/EML_18_eng.pdf?ua=1|work=World Health Organization|accessdate=22 April 2014|date=October 2013}}</ref> It is available as a [[generic medication]].<ref>{{cite book|last1=Burchum|first1=Jacqueline|title=Lehne's Pharmacology for Nursing Care|date=2014|publisher=Elsevier Health Sciences|isbn=9780323340267|page=1051|url=https://books.google.com/books?id=C7_NBQAAQBAJ&pg=PA1052}}</ref> It wholesale cost is between 0.05 and 0.58 USD per day.<ref>{{cite web|title=Gentamicin Sulfate|url=http://erc.msh.org/dmpguide/resultsdetail.cfm?language=english&code=GEN10A&s_year=2014&year=2014&str=10%20mg%2Fml&desc=Gentamicin%20Sulfate&pack=new&frm=AMPOULE&rte=INJ&class_code2=06%2E2%2E2%2E&supplement=&class_name=%2806%2E2%2E2%2E%29Other%20antibacterials%3Cbr%3E|website=International Drug Price Indicator Guide|accessdate=15 August 2015}}</ref>

==Medical uses==
Active against a wide range of bacterial infections, mostly Gram-negative bacteria including ''[[Pseudomonas]]'', ''[[Proteus (bacterium)|Proteus]]'', ''[[Serratia]]'', and the Gram-positive ''[[Staphylococcus]]''.<ref>[http://www.merck.com/mmpe/lexicomp/gentamicin.html Gentamicin: Drug Information Provided by Lexi-Comp: Merck Manual Professional]</ref>

Gentamicin is not used for ''[[Neisseria gonorrhoeae]]'', ''[[Neisseria meningitidis]]'' or ''[[Legionella pneumophila]]'' bacterial infections (because of the risk of the person going into shock from lipid A [[endotoxin]] found in certain Gram-negative organisms). Gentamicin is also useful against ''[[Yersinia pestis]]'', its relatives, and ''[[Francisella tularensis]]'' (the organism responsible for [[tularemia]] seen often in hunters and/or trappers).<ref>{{cite book|last=Goljan|first=Edward F.|title=Rapid Review Pathology|edition=3rd|year=2011|publisher=Elsevier|location=Philadelphia, PA|isbn=978-0-323-08438-3|pages=241}}</ref>

Some ''[[Enterobacteriaceae]]'', ''[[Pseudomonas]] spp.'', ''[[enterococci]]'', ''[[Staphylococcus aureus]]'' and other ''[[staphylococci]]'' are resistant to gentamicin sulfate, to varying degrees.<ref>{{cite web|title=Gentamicin spectrum of bacterial susceptibility and Resistance|url=http://www.toku-e.com/Upload/Products/PDS/20120604005203.pdf|accessdate=15 May 2012}}</ref>

==Side effects==
[[Side effects]] of gentamicin toxicity vary between people. Side effects may become apparent shortly after or up to months after gentamicin is administered. Symptoms of gentamicin toxicity include:
* Balance difficulty
* Bouncing, unsteady vision
* Ringing in the ears ([[tinnitus]])
* Difficulty multi-tasking, particularly when standing
Gentamicin is [[nephrotoxic]]. Risk factors for aminoglycoside nephrotoxicity include patient factors such as: 
* increased age
* reduced renal function
* pregnancy
* hypothyroidism
* hepatic dysfunction
* volume depletion
* metabolic acidosis
* concurrent use of other drugs: vancomycin, NSAIDs, cisplatin, cyclosporin, cephalosporin, diuretics
* Concurrent use of iodinated contrast agents
Treatment factors can also affect toxicity. Important factors such as dose, frequency, levels and duration of therapy can affect level of toxicity.

Psychiatric symptoms related to gentamicin can occur. These include anorexia, confusion, depression, disorientation and visual hallucinations.<ref>{{cite book|first1=A.J.|last1=Giannini|first2=H.R.|last2=Black|title=Psychiatric, Psychogenic and Somatopsychic Disorders Handbook|location=Garden City, New York|publisher=Medical Examination Publishing Co.|date=1978| pages=136–137| isbn=0-87488-596-5}}</ref>

A number of factors and determinants should be taken into account when using gentamicin, including differentiation between empirical and directed therapy which will affect dosage and treatment period.<ref name="ap01" /> Many medical practitioners freely administer gentamicin as an antibiotic without advising people of the severe and permanent potential ramifications of its use. Gentamicin is a low-cost medicine when compared with alternatives, and is typically US$3–6 per dosage less than alternatives.

===Inner ear===
Aminoglycosides are toxic to the sensory cells of the ear, but they vary greatly in their relative effects on hearing versus balance. Gentamicin is a vestibulotoxin, and can cause permanent loss of [[equilibrioception]], caused by damage to the vestibular apparatus of the inner ear, usually if taken at high doses or for prolonged periods of time, but there are well documented cases in which gentamicin completely destroyed the vestibular apparatus after three to five days.{{Citation needed|date=May 2010}}  A small number of affected individuals have a normally harmless mutation in their [[mitochondrion|mitochondrial]] DNA encoding the 12S [[ribosomal RNA]] (m.1555 A>G), that allows the gentamicin to affect their cells.<ref>{{Cite journal
 | pmid = 20301595
| year = 1993
| last1 = Pandya
| first1 = A
| title = Nonsyndromic Hearing Loss and Deafness, Mitochondrial
| editor-last1 = Pagon
| editor-first1 = R. A.
| editor-last2 = Adam
| editor-first2 = M. P.
| editor-last3 = Ardinger
| editor-first3 = H. H.
| editor-last4 = Bird
| editor-first4 = T. D.
| editor-last5 = Dolan
| editor-first5 = C. R.
| editor-last6 = Fong
| editor-first6 = C. T.
| editor-last7 = Smith
| editor-first7 = R. J. H.
| editor-last8 = Stephens
| editor-first8 = K
}}</ref> The cells of the [[ear]] are particularly sensitive to this, sometimes causing complete hearing loss.<ref>[http://american-hearing.org/disorders/gentamicin-toxicity/ Gentamicin Toxicity] at the American Hearing Research Foundation</ref> However, gentamicin is sometimes used intentionally for this purpose in severe [[Ménière's disease]], to disable the [[vestibular apparatus]]. These side effects are most common when the drug is administered via drops directly to the ear.

===Kidneys===
Prevention of nephrotoxicity includes judicious use of IV fluids to correct and avoid volume depletion, correction of hypokalemia and hypomagnesemia. Once daily dosing has been shown to be less toxic than multiple daily doses. Gentamicin is usually dosed by [[ideal body weight]]. Various formulae exist for calculating gentamicin dosage. Trough and peak serum levels of gentamicin are monitored during treatment to individualize therapy and prevent excess exposure.<ref>{{Cite journal|url = http://www.ncbi.nlm.nih.gov/pubmed/20861826|title = New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view.|last = Lopez-Novoa|first = Jose|date = 2011|journal = Kidney International|accessdate = September 30, 2014|doi = 10.1038/ki.2010.337|pmid = 20861826|volume=79|issue = 1|pages=33–45}}</ref>

Gentamicin, like other [[aminoglycosides]], causes [[nephrotoxicity]] by inhibiting protein synthesis in renal cells.  This mechanism specifically causes necrosis of cells in the [[proximal tubule]], resulting in [[acute tubular necrosis]] which can lead to [[acute renal failure]].<ref>{{cite journal|last1=Sundin|first1= D.P.|last2= Sandoval|first2= R.|last3= Molitoris|first3= B.A.|title=Gentamicin Inhibits Renal Protein and Phospholipid Metabolism in Rats: Implications Involving Intracellular Trafficking|url=|journal=J Am Soc Nephrol|volume= 12|pages=114–123|date=2001|issue= 1|accessdate=|doi=|pmid= 11134257}}</ref>

==Mechanism of action==
Gentamicin is a bactericidal antibiotic that works by irreversibly binding the 30S subunit of the bacterial ribosome, interrupting protein synthesis.  This mechanism of action is similar to other [[aminoglycosides]].<ref>{{cite web|url=http://www.drugbank.ca/drugs/DB00798|title=|date=|accessdate=|publisher=|author=}}</ref> Gentamicin is a [[bactericidal]] antibiotic.

===Components===
Gentamicin is composed of a number of related gentamicin components and fractions which have varying degrees of antimicrobial potency.<ref>{{cite journal|last=Weinstein|first=Marvin J.|title=Biological Activity of the Antibiotic Components of the Gentamicin Complex|url=|journal=Journal of Bacteriology|volume=94|date=1967|issue=3|pages=789–790|doi=10.1128/JB.94.3.789-790.1967|pmid=4962848|pmc=251956}}</ref> The main components of gentamicin include members of the gentamicin C complex: gentamicin C1, gentamicin C1a, and gentamicin C2 which compose approximately 80% of gentamicin and have been found to have the highest antibacterial activity. Gentamicin A, B, X, and a few others make up the remaining 20% of gentamicin and have lower antibiotic activity than the gentamicin C complex.<ref>{{cite journal|last=Vydrin|first=A. F.|title=Component Composition of Gentamicin Sulfate Preparations|url=|journal=Pharmaceutical Chemistry Journal|volume=37|date=2003|issue=8|pages=448–449|doi=10.1023/A:1027372416983|s2cid=43731658}}</ref> The exact composition of a given sample or lot of gentamicin is not well defined, and the level of gentamicin C components or other components in gentamicin may differ from lot-to-lot depending on the gentamicin manufacturer or manufacturing process. Because of this lot-to-lot variability, it can be difficult to study various properties of gentamicin including pharmacokinetics and microorganism susceptibility if there is an unknown combination of chemically related but different compounds.<ref>{{cite journal|last1=Isoherranen|first1=Nina|last2=Eran|first2=Lavy|title=Pharmacokinetics of Gentamicin C<sub>1</sub>, C<sub>1a</sub>, and C<sub>2</sub> in Beagles after a Single Intravenous Dose|url=|journal=Antimicrobial Agents and Chemotherapy|volume=44|date=2000|issue=6|pages=1443–1447|accessdate=|doi=10.1128/AAC.44.6.1443-1447.2000|pmid=10817690|pmc=89894}}</ref>

==History==
[[File:Gentamicin for injection.jpg|thumb|Gentamicin for injection]]

Gentamicin is produced by the fermentation of ''[[Micromonospora purpurea]]''. It was discovered in 1963 by Weinstein, Wagman ''et al''. at Schering Corporation in Bloomfield, N.J. working with source material (soil samples) provided by Rico Woyciesjes.<ref>{{cite journal|last=Weinstein|first=Marvin|author2=Wagman|title=Gentamicin, A New Antimicrobial Complex from Micromonospora|journal=J Med Chem|year=1963|volume=6|pages=463–464|doi=10.1021/jm00340a034|pmid=14184912}}</ref> Subsequently it was purified and the structures of its three components determined by Cooper, ''et al''., also at the Schering Corporation. It was initially used as a topical treatment for burns at the Atlanta and San Antonio burn units and was introduced into IV usage in 1971. It remains a mainstay for use in sepsis.

It is synthesized by ''[[Micromonospora]]'', a genus of [[Gram-positive bacteria]] widely present in the environment (water and soil). To highlight their specific biological origins, gentamicin and other related antibiotics produced by this genus ([[verdamicin]], [[mutamicin]], [[sisomicin]], [[netilmicin]], [[retymicin]]) generally have their spellings ending in ''~micin'' and not in ''~mycin''.

==Research==
Gentamicin is also used in [[molecular biology]] research as an antibacterial agent in tissue and cell culture, to prevent contamination of sterile cultures. Gentamicin is one of the few heat-stable antibiotics that remain active even after [[autoclave|autoclaving]], which makes it particularly useful in the preparation of some microbiological growth media.{{citation needed|date=September 2015}}

==References==
{{Reflist|30em}}

{{Antibiotics and chemotherapeutics for dermatological use}}
{{AminoglycosideAntiBiotics}}
{{Otologicals}}