Wed . 18 Nov 2018

Gentamicin

gentamicin, gentamicin sulfate ophthalmic solution
Gentamicin, sold under brand names Garamycin among others, is an antibiotic used to treat several types of bacterial infections1 This may include bone infections, endocarditis, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, and sepsis among others It is not effective for gonorrhea or chlamydia infections It can be given intravenously, by injection into a muscle, or topically1 Topical formulations may be used in burns or for infections of the outside of the eye2 In the developed world it is often only used for two days until bacterial cultures determine what antibiotics the infection is sensitive3 The dose required should be monitored by blood testing1

Gentamicin can cause inner ear problems and kidney problems1 The inner ear problems can include problems with balance and problems with hearing These problems may be permanent If used during pregnancy it can cause harm to the baby1 It appears to be safe for use during breastfeeding4 Gentamicin is a type of aminoglycoside It works by stopping the bacteria from making protein, which typically kills the bacteria1

Gentamicin was discovered in 19635 It is made from the bacteria Micromonospora purpurea1 Gentamicin is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system6 It is available as a generic medication7 The injectable's wholesale cost in the developing world in 2014 was between US$005 and US$058 per ml8

Contents

  • 1 Medical uses
  • 2 Adverse effects
    • 21 Kidney damage
    • 22 Inner ear
  • 3 Mechanism of action
    • 31 Components
  • 4 Contraindications
  • 5 Special populations
    • 51 Pregnancy and breastfeeding
    • 52 Geriatrics
    • 53 Pediatrics
  • 6 History
  • 7 Research
  • 8 References

Medical usesedit

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 Staphylococcus9 Gentamicin is used in the treatment of respiratory tract infections, urinary tract infections, blood, bone and soft tissues infections of these susceptible bacteria10

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 trappers11

Some Enterobacteriaceae, Pseudomonas spp, Enterococci, Staphylococcus aureus and other Staphylococci are resistant to gentamicin sulfate, to varying degrees12

Adverse effectsedit

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 toxicity9 These two toxicities may have delayed presentation, sometimes not appearing until after completing treatment9

Kidney damageedit

Kidney damage is a problem in 10-25% of people who receive aminoglycosides, and gentamicin is one of the most nephrotoxic of the class13 Oftentimes acute nephrotoxicity is reversible, but it may be fatal9 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 vancomycin13

Factors that increase risk of nephrotoxicity include:13

  • 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 blood13

Inner earedit

11% of the population who receives aminoglycosides experience damage to their inner ear14 The common symptoms of inner ear damage are: tinnitus, hearing loss, vertigo, trouble with coordination, dizziness15 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 problems15 To reduce the risk of ototoxicity it is recommended to stay hydrated9

Factors that increase risk of inner ear damage include:910

  • High blood uric acid levels
  • Kidney dysfunction
  • Liver dysfunction
  • Higher doses
  • Long courses of therapy
  • Elderly
  • Also taking strong diuretics eg furosemide

Mechanism of actionedit

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 aminoglycosides16

Componentsedit

Gentamicin is composed of a number of related gentamicin components and fractions which have varying degrees of antimicrobial potency17 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 complex18 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 compounds19

Contraindicationsedit

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 aminoglycosides10

Special populationsedit

Pregnancy and breastfeedingedit

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 newborn10

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 babies10

Geriatricsedit

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 dysfunction9

Pediatricsedit

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 injection9

Historyedit

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, NJ working with source material soil samples provided by Rico Woyciesjes20 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

Researchedit

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 mediacitation needed

Referencesedit

  1. ^ a b c d e f g "Gentamicin sulfate" The American Society of Health-System Pharmacists Retrieved Aug 15, 2015 
  2. ^ Bartlett, Jimmy 2013 Clinical Ocular Pharmacology s ed Elsevier p 214 ISBN 9781483193915 
  3. ^ Moulds, Robert; Jeyasingham, Melanie October 2010 "Gentamicin: a great way to start" Australian Prescriber 33: 134–135 
  4. ^ "Gentamicin use while breastfeeding" 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 CS1 maint: Extra text: authors list link
  6. ^ "WHO Model List of Essential Medicines 19th List" PDF World Health Organization April 2015 Retrieved 8 December 2016 
  7. ^ Burchum, Jacqueline 2014 Lehne's pharmacology for nursing care Elsevier Health Sciences p 1051 ISBN 9780323340267 
  8. ^ "Gentamicin sulfate" International Drug Price Indicator Guide Retrieved 15 August 2015 
  9. ^ a b c d e f g h i "Gentamicin" PDF Baxter Corporation Retrieved 2 November 2015 
  10. ^ a b c d e "Product Monograph" PDF Sandoz Canada Inc Retrieved 2 November 2015 
  11. ^ Goljan, Edward F 2011 Rapid Review Pathology 3rd ed Philadelphia, Pennsylvania: Elsevier p 241 ISBN 978-0-323-08438-3 
  12. ^ "Gentamicin spectrum of bacterial susceptibility and Resistance" PDF Retrieved 15 May 2012 
  13. ^ 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 PMID 20861826 doi:101038/ki2010337 
  14. ^ 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 ISSN 1355-6037 PMC 1768868  PMID 15831617 doi:101136/hrt2003028308 
  15. ^ a b Selimoglu, Erol 2007-01-01 "Aminoglycoside-induced ototoxicity" Current Pharmaceutical Design 13 1: 119–126 ISSN 1873-4286 PMID 17266591 doi:102174/138161207779313731 
  16. ^ "DrugBank-Gentamicin" 
  17. ^ Weinstein, Marvin J 1967 "Biological Activity of the Antibiotic Components of the Gentamicin Complex" Journal of Bacteriology 943: 789–790  |access-date= requires |url= help
  18. ^ Vydrin, A F 2003 "Component Composition of Gentamicin Sulfate Preparations" Pharmaceutical Chemistry Journal 378: 448–449  |access-date= requires |url= help
  19. ^ Isoherranen, Nina; Eran, Lavy 2000 "Pharmacokinetics of Gentamicin C1, C1a, and C2 in Beagles after a Single Intravenous Dose" Antimicrobial Agents and Chemotherapy 446: 1443–1447 doi:101128/aac4461443-14472000 
  20. ^ Weinstein, Marvin; Wagman 1963 "Gentamicin, A New Antimicrobial Complex from Micromonospora" J Med Chem 6: 463–464 doi:101021/jm00340a034 

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Gentamicin


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