Aminoglycoside Antibiotics

Sunday, June 4, 2023 11:35 Written by Mariama F.

MECHANISM OF ACTION
The aminoglycosides are bactericidal antibiotics, all having the same general pattern
(a) Transport of the aminoglycoside through the bacterial cell wall and cytoplasmic membrane.
(b) Binding to ribosomes resulting in inhibition of protein synthesis. Streptomycin binds to 30S ribosomes,
but other aminoglycosides bind to additional sites on 50S subunit
TOXICITY
1. Ototoxicity
the most important adverse effect, drugs are concentrated in the labyrinthine fluid and are slowly
removed from it, contraindicated in patients with perforated eardrum, it's avoided during pregnancy
due to risk of fetal ototoxicity.
Kanamycin and amikacin produce greater cochlear damage
Streptomycin and gentamicin produce more vestibular toxicity
2. Nephrotoxicity
manifests as tubular damage resulting in loss of urinary concentrating power, low g.f.r., nitrogen
retention, albuminuria. Avoid concurrent use of other nephrotoxic drugs, e.g. NSAIDs, amphotericin
B, vancomycin.
In the elderly and in neonates who have low g.f.r. Reduction in dose or increase in dose-interval is
essential according to the measured CLcr
PHARMAKOKINETICS
Absorption: all systemically administered are neither absorbed nor destroyed in the g.i.t. However, i.m
absorption is rapid
Distribution: distributed only extracellularly, so that Vd (~0.3 L/kg), cross placenta and can be found in
foetal blood/ amniotic fluid
Metabolism: not metabolized in the body, plasma t½ ranges between 2–4 hours
Excretion: excreted unchanged in urine.
DOSING REGIMEN
the daily dose of systemically administered aminoglycosides must be precisely calculated accordingly to
body weight and level of renal function.
Considering the t½ (2–4 hr), the daily doses are conventionally divided into 3 equal parts and injected i.m
every 8 hrs. However, a single total daily dose regimen is now recommended for patients with normal
renal function
Gentamicin
The cheapest, more potent (its MIC values are lower) than streptomycin, kanamycin and amikacin
equally potent as tobramycin, sisomicin and netilmicin
ineffective against Mycobacterium tuberculosis and other mycobacteria
Mostly, it is added to a penicillin/cephalosporin or vancomycin to obtain synergistic bacterial killing.
Uses : respiratory infections, Meningitis caused by gram negative bacilli (+ 3rd generation Cephalosporins)
Dose: 3–5 mg/kg/day (single dose or divided in 3 doses) i.m. or in an i.v. line over 30–60 min.
Streptomycin
now practically restricted to treatment of tuberculosis, but the growth of M. tuberculosis is promoted
rather than inhibited if streptomycin is used alone, it's called Streptomycin dependence
the lowest nephrotoxicity among aminoglycosides
Contraindicated during pregnancy due to risk of foetal ototoxicity
Acute infections: 1 g (0.75 g in those above 50 yr age) i.m. OD or BD for 7–10 days.
Tuberculosis: 1 g or 0.75 g i.m. OD or thrice weekly for 30–60 days

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Tobramycin
spectrum and pharmacokinetic properties, as well as dosage are almost identical to gentamicin
it is 2–4 times more active against Pseudomonas and Proteus
It should be used only as an alternative to gentamicin and not useful for combining with penicillin
Ototoxicity and nephrotoxicity is probably less than gentamicin.
Dose: 3–5 mg/kg day in 1–3 doses. i.m. or i.v. infusion over 30–60 min

Kanamycin
occasionally used as a second line drug in resistant tuberculosis.
However, it is more toxic, both to the cochlea and to kidney. Hearing loss, which is irreversible, is more
common than vestibular disturbance.
Dose: 0.5 g i.m. BD (15 mg/kg/day)

Amikacin
it has the widest spectrum of activity, including many organisms resistant to other aminoglycosides
It is recommended as a reserve drug where gentamicin/tobramycin resistance is high
Amikacin is effective in tuberculosis, but used only for multidrug resistant infection.
More hearing loss than vestibular disturbance occurs in toxicity
Dose: 15 mg/kg/day in 1–3 doses i.m.; urinary tract infection 7.5 mg/kg/day

Neomycin
it is a wide-spectrum aminoglycoside active against most gram negative bacilli and some gram-positive cocci
highly toxic to the internal ear (mainly auditory) and to kidney, therefore, not used systemically.
Dose: 0.25–1 g QID oral, 0.3–0.5% topical
Uses
(a) Topically for infected wound, ulcers, burn, external ear infections (often in combination with polymyxin,
bacitracin)
(b) Orally for preparation of bowel before surgery and hepatic coma by suppressing intestinal flora
Neomycin is contraindicated if renal function is impaired

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