Gentamicin

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Gentamicin

Clinical data

Pronunciat /ˌdʒɛntəˈmaɪsən/
ion

Trade Cidomycin, Septopal, Genticyn, Garamycin, others

names

AHFS/Dru Monograph
gs.com

MedlinePl a682275
us

 AU: D
Pregnancy

category US: D (Evidence of risk)

Routes of IV, eye drop, IM, topical

administra
tion

 D06AX07 (WHO) J01GB03 (WHO) S01AA11 (WHO) S02AA14 (WHO) S03AA06 (WHO) QA07AA91 (
ATC code

WHO) QG01AA91 (WHO) QG51AA04 (WHO) QJ51GB03 (WHO)

Legal status

Legal  In general: ℞ (Prescription only)

status
 Pharmacokinetic data

Bioavailabi limited bioavailability by mouth

lity

Protein 0–10%
binding

Eliminatio 2 h
n half-life

Excretion renal

Identifiers

IUPAC name[show]

CAS  1403-66-3
Number

 3467
PubChem
CID

 2427
IUPHAR/
BPS

 DB00798
DrugBank

 390067
ChemSpid
er

UNII  T6Z9V48IKG

KEGG  D08013

ChEBI  CHEBI:27412

 ChEMBL195892
ChEMBL

ECHA 100.014.332
InfoCard

Chemical and physical data

Formula C21H43N5O7

Molar 477.596 g/mol

mass


3D model Interactive image
(JSmol)

SMILES[show]

InChI[show]

(what is this?) (verify)

Gentamicin, sold under brand names Garamycin among others, is an antibiotic used to treat
several types of bacterial infections.[1]This may include bone infections, endocarditis, pelvic
 inflammatory disease, meningitis, pneumonia, urinary tract infections, and sepsisamong
others.[1] It is not effective for gonorrhea or chlamydia infections.[1] It can be
given intravenously, by injection into a muscle, or topically.[1] Topical formulations may be used in
burns or for infections of the outside of the eye.[2] In the developed world it is often only used for
two days until bacterial cultures determine what antibiotics the infection is sensitive to.[3] The
dose required should be monitored by blood testing.[1]
Gentamicin can cause inner ear problems and kidney problems.[1] The inner ear problems can
include problems with balance and problems with hearing.[1] These problems may be
permanent.[1] If used during pregnancy it can cause harm to the baby.[1] It appears to be safe for
use during breastfeeding.[4] Gentamicin is a type of aminoglycoside.[1] It works by stopping the
bacteria from making protein, which typically kills the bacteria.[1]
Gentamicin was discovered in 1963.[5] It is made from the bacteria Micromonospora
purpurea.[1] Gentamicin is on the World Health Organization's List of Essential Medicines, the
most effective and safe medicines needed in a health system.[6] It is available as a generic
medication.[7] The injectable's wholesale cost in the developing world in 2014 was
between US$0.05 and US$0.58 per ml.[8]

Contents

 1Medical uses
 2Adverse effects
o 2.1Kidney damage
o 2.2Inner ear
 3Mechanism of action
o 3.1Components
 4Contraindications
 5Special populations
o 5.1Pregnancy and breastfeeding
o 5.2Geriatrics
o 5.3Pediatrics
 6History
 7Research
 8References

Medical uses[edit]
Active against a wide range of bacterial infections, mostly Gram-negative bacteria
including Pseudomonas, Proteus, Escherichia coli, Klebsiella pneumoniae, Enterobacter
aerogenes, Serratia, and the Gram-positive Staphylococcus.[9] Gentamicin is used in the
treatment of respiratory tract infections, urinary tract infections, blood, bone and soft tissues
infections of these susceptible bacteria.[10]
There is insufficient evidence to support gentamicin as the first line treatment of Neisseria
gonorrhea infection.[11] Gentamicin is not used for 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).[12]
Some Enterobacteriaceae, Pseudomonas spp., Enterococcus spp., Staphylococcus aureus and
other Staphylococcus spp. are resistant to gentamicin to varying degrees.[13]

Adverse effects[edit]
Adverse effects of gentamicin can range from less severe reactions such as nausea and
vomiting to more severe reactions such as:[9]

 Low blood counts

 Allergic responses
 Neuromuscular problems
 Nerve damage
 Kidney damage (nephrotoxicity)
 Ear disorders (ototoxicity)
Nephrotoxicity and ototoxicity are thought to be dose related with higher doses causing greater
chance of toxicity.[9] These two toxicities may have delayed presentation, sometimes not
appearing until after completing treatment.[9]
Kidney damage[edit]
Kidney damage is a problem in 10-25% of people who receive aminoglycosides, and gentamicin
is one of the most nephrotoxic of the class.[14] Oftentimes acute nephrotoxicity is reversible, but it
may be fatal.[9] The risk of nephrotoxicity can be affected by the dose, frequency, duration of
therapy, and concurrent use of certain medications such as NSAIDs, diuretics, cisplatin,
ciclosporin, cephalosporin, amphotericin, iodide contrast media, and vancomycin.[14]
Factors that increase risk of nephrotoxicity include:[14]

 Increased age
 Reduced renal function
 Pregnancy
 Hypothyroidism
 Hepatic dysfunction
 Volume depletion
 Metabolic acidosis
 Sodium depletion
Kidney dysfunction is monitored by measuring creatinine in the blood, electrolyte levels, low urine
output, foamy urine, and concentrations of other chemicals in the blood.[14]
Inner ear[edit]
11% of the population who receives aminoglycosides experience damage to their inner
ear.[15] The common symptoms of inner ear damage are: tinnitus, hearing loss, vertigo, trouble
with coordination, dizziness.[16] Chronic use of gentamicin can affect two areas of the ears. First,
damage of the inner ear hair cells can result in irreversible hearing loss. Second, damage to
inner ear vestibular apparatus can lead to balance problems.[16] To reduce the risk of ototoxicity it
is recommended to stay hydrated.[9]
Factors that increase risk of inner ear damage include:[9][10]

 High blood uric acid levels

 Kidney dysfunction
 Liver dysfunction
 Higher doses
 Long courses of therapy
 Elderly
 Also taking strong diuretics (e.g. furosemide)

Mechanism of action[edit]
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.[17]
Components[edit]
Gentamicin is composed of a number of related gentamicin components and fractions which
have varying degrees of antimicrobial potency.[18] 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.[19] 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.[20]

Contraindications[edit]
Gentamicin should not be used if a person has a history of hypersensitivity such as anaphylaxis
shock or other serious toxic reaction to gentamicin or any other aminoglycosides.[10]

Special populations[edit]
Pregnancy and breastfeeding[edit]
Gentamicin is not recommended in pregnancy unless the benefits outweigh the risks for the
mother. Gentamicin can cross the placenta and several reports of irreversible bilateral congenital
deafness in children have been seen. Intramuscular injection of gentamicin in mothers can
cause muscle weakness in the newborn.[10]
The safety and efficacy for gentamicin in nursing mothers has not been established. Detectable
gentamicin levels are found in human breast milk and in nursing babies.[10]
Geriatrics[edit]
Renal function should be assessed before beginning therapy and during in elderly due to a
decline in glomerular filtration rate. This population can have longer than usual gentamicin levels
in the body. Use cautiously in persons with renal, auditory, vestibular,
or neuromuscular dysfunction.[9]
Pediatrics[edit]
Gentamicin may not be appropriate to use in children, including newborns and infants. Studies
have shown higher serum levels and a longer half-life in this population. Check renal
function periodically during therapy. Hypocalcemia, hypokalemia, and muscle weakness have
been reported after gentamicin injection.[9]

History[edit]

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.[21] 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,
and retymicin) generally have their spellings ending in ~micin and not in ~mycin.

Research[edit]
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 autoclaving, which makes it particularly useful in the
preparation of some microbiological growth media.[citation needed]

References[edit]
1. ^ Jump up to:a b c d e f g h i j k l "Gentamicin sulfate". The American Society of Health-System
Pharmacists. Archived from the original on 2015-08-16. Retrieved Aug 15, 2015.
2. ^ Bartlett, Jimmy (2013). Clinical Ocular Pharmacology (s ed.). Elsevier.
p. 214. ISBN 9781483193915. Archived from the original on 2015-12-22.
3. ^ Moulds, Robert; Jeyasingham, Melanie (October 2010). "Gentamicin: a great way to
start". Australian Prescriber (33): 134–135. Archived from the original on 2011-03-13.
4. ^ "Gentamicin use while breastfeeding". Archived from the original on 6 September 2015.
Retrieved 15 August 2015.
5. ^ Pucci, edited by Thomas Dougherty, Michael J.; Weinstein, Marvin J. (2011). Handbook of
antibiotic discovery and development (2012 ed.). New York: Springer.
p. 238. ISBN 9781461413998. Archived from the original on 2016-03-11.
6. ^ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April
2015. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016.
7. ^ Burchum, Jacqueline (2014). Lehne's pharmacology for nursing care. Elsevier Health Sciences.
p. 1051. ISBN 9780323340267. Archived from the original on 2016-03-11.
8. ^ "Gentamicin sulfate". International Drug Price Indicator Guide. Archived from the original on 22
January 2018. Retrieved 15 August 2015.
9. ^ Jump up to:a b c d e f g h i "Gentamicin" (PDF). Baxter Corporation. Archived from the
original(PDF) on 4 March 2016. Retrieved 2 November 2015.
10. ^ Jump up to:a b c d e "Product Monograph" (PDF). Sandoz Canada Inc. Archived (PDF) from the
original on 12 April 2015. Retrieved 2 November 2015.
11. ^ Emma, Hathorn; Divya, Dhasmana; Lelia, Duley; Jonathan, DC Ross (2014). "The effectiveness
of gentamicin in the treatment of Neisseria gonorrhoeae: a systematic review". Systematic
review. 3: 104. doi:10.1186/2046-4053-3-104. PMC 4188483. PMID 25239090.
12. ^ Goljan, Edward F. (2011). Rapid Review Pathology (3rd ed.). Philadelphia, Pennsylvania:
Elsevier. p. 241. ISBN 978-0-323-08438-3.
13. ^ "Gentamicin spectrum of bacterial susceptibility and Resistance" (PDF). Archived from the
original (PDF) on 20 February 2015. Retrieved 15 May 2012.
14. ^ Jump up to:a b c d Lopez-Novoa, Jose M; Quiros, Yaremi; Vicente, Laura; Morales, Ana I; Lopez-
Hernandez, Francisco J (Jan 2011). "New insights into the mechanism of aminoglycoside
nephrotoxicity: an integrative point of view". Kidney International. 79 (1): 33–
45. doi:10.1038/ki.2010.337. PMID 20861826. Archived from the original on 2016-03-10.
15. ^ East, J E; Foweraker, J E; Murgatroyd, F D (2005-05-01). "Gentamicin induced ototoxicity
during treatment of enterococcal endocarditis: resolution with substitution by
netilmicin". Heart. 91 (5): e32. doi:10.1136/hrt.2003.028308. ISSN 1355-
6037. PMC 1768868. PMID 15831617.
16. ^ Jump up to:a b Selimoglu, Erol (2007-01-01). "Aminoglycoside-induced ototoxicity". Current
Pharmaceutical Design. 13 (1): 119–126. doi:10.2174/138161207779313731. ISSN 1873-
4286. PMID 17266591.
17. ^ "DrugBank-Gentamicin". Archived from the original on 2013-10-04.
18. ^ Weinstein, Marvin J. (1967). "Biological Activity of the Antibiotic Components of the Gentamicin
Complex". Journal of Bacteriology. 94.3: 789–790.
19. ^ Vydrin, A. F. (2003). "Component Composition of Gentamicin Sulfate
Preparations". Pharmaceutical Chemistry Journal. 37 (8): 448–
449. doi:10.1023/a:1027372416983.
20. ^ Isoherranen, Nina; Eran, Lavy (2000). "Pharmacokinetics of Gentamicin C1, C1a, and C2in
Beagles after a Single Intravenous Dose". Antimicrobial Agents and Chemotherapy. 44.6: 1443–
1447. doi:10.1128/aac.44.6.1443-1447.2000. PMC 89894.
21. ^ Weinstein, Marvin; Wagman (1963). "Gentamicin, A New Antimicrobial Complex from
Micromonospora". J Med Chem. 6: 463–464. doi:10.1021/jm00340a034.