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aminoglycoside antibiotic
Indications:
1) life-threatening infections
a) endocarditis, especially with prosthetic valves
b) synergy with nafcillin against Staphylococcus aureus (benefits obtained in 1st few days of therapy)
c) hepatic encephalopathy, hepatic coma [6]
d) meningitis
2) empiric therapy of neutropenic patients
3) synergy with penicillins against some Enterococci (obtain in-vitro sensitivities)
4) ancillary agents in treatment of Mycobacterial infections
- Mycobacterium avium complex
5) gram-negative organisms
a) Campylobacter fetus
b) Yersinia enterocolitica
c) Pseudomonas aeruginosa [6]
d) tularemia
e) brucellosis
f) plague
6) gram positive infections
- Staphylococcus aureus
- Listeria monocytogenes
- group B Streptococcus
7) skin infections
- furunculosis
- paronychia
- ecthyma gangrenosum
8) otic infections
- otitis externa
- chronic suppurative otitis media
9) eye infections
- keratoconjunctivitis
- conjunctivitis
- keratitis
- blepharoconjunctivitis
- meibomitis
- dacryocystitis
- corneal abrasion, corneal perforation
- anterior uveitis
10) intra-abdominal infections
- gastrointestinal infections
- proctitis
- diverticulitis
- bacterial peritonitis
- cholangitis
11) urogenital infections
- gonorrhea
- chancroid
- urinary tract infection
12) respiratory tract infections
- pneumonia
13) infectious arthritis, osteomyelitis
14) sepsis
15) infections in patients with cystic fibrosis [6]
16) infections in patients with burns or necrosis
17) prophylaxis for perioperative infection [6]
18) antibiotic prophylaxis for mastoidectomy
19) empiric treatment for fever of unknown origin [6]
Dosage:
- once daily dosing preferred
Monitor:
Therapeutic drug monitoring:
- monitor levels
- see serum gentamicin, serum amikacin
Antimicrobial activity:
1) gram-positive activity (synergy with penicillins)
1) gram-negative activity, including Acinetobacter baumannii, Pseudomonas aeruginosa & carbapenem-resistant Enterobacteriaceae
2) aminoglycosides have no anaerobic activity
Adverse effects:
1) ototoxicity
a) tinnitus
b) vestibular toxicity may occur up to 2-3 months after stopping drug
2) nephrotoxicity
a) occurs after 5-7 days of therapy & correlates with the cumulative dose
b) often non-oliguric acute tubular necrosis
- pigmented or brown granular casts & tubular epithelial cells in the urine sediment.
c) urine osmolality is ~300 mOsm/kg H2O
d) FENa is >1%
e) hypokalemia & hypomagnesemia also can occur due to due to K+ & Mg+2 wasting
f) once a day dosing may reduce nephrotoxicity
g) even low-dose aminoglycosides may be nephrotoxic [4]
Drug interactions:
1) neuromuscular blocking agents: aminoglycosides prolong paralysis
2) aminoglycosides are inactivated with mixed in same IV bag or tubing as penicillins
3) ototoxicity increased by loop diuretics
4) nephrotoxicity increased by coadministration of:
a) vancomycin
b) amphotericin B
c) cyclosporine
d) non-steroidal anti-inflammatory drugs [NSAIDs]
e) radiocontrast agents
Laboratory:
- aminoglycoside resistance gene
Mechanism of action:
1) bactericidal activity, concentration-dependent
2) ionic cell wall interactions & ribosomal binding
Interactions
drug interactions
drug adverse effects of aminoglycosides
Related
aminoglycoside nephrotoxicity
aminoglycoside-induced deafness
Specific
amikacin (Amikin)
gentamicin (Garamycin, Genoptic, G-Mycin)
isepamicin (Exacin)
kanamycin (Kantrex)
neomycin (Mycifradin)
netilmicin (Netromycin)
plazomicin (Zemdri)
spectinomycin (Trobicin, Actinospectacin)
streptomycin
tobramycin (Nebcin, Tobrex)
General
aminoglycoside family
antibacterial agent
References
- Medical Knowledge Self Assessment Program (MKSAP) 11, 16.
American College of Physicians, Philadelphia 1998, 2012
- Drug Information & Medication Formulary, Veterans Affairs,
Central California Health Care System, 1st ed., Ravnan et al
eds, 1998
- Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed)
Lippincott-Raven, Philadelphia, 1998, pg 597
- Cosgrove SE et al.
Initial low-dose gentamicin for Staphylococcus aureus
bacteremia and endocarditis is nephrotoxic.
Clin Infect Dis 2009 Mar 15; 48:713.
PMID: 19207079
- Bayer AS and Murray BE
Initial low-dose aminoglycosides in Staphylococcus aureus
bacteremia: Good science, urban legend, or just plain toxic?
Clin Infect Dis 2009 Mar 15; 48:722.
PMID: 19207080
- Chen LF, Kaye D.
Current use for old antibacterial agents: polymyxins,
rifamycins, and aminoglycosides.
Infect Dis Clin North Am. 2009 Dec;23(4):1053-75,
PMID: 19909897
- Deprecated Reference