vestibulotoxicity with gentamicin

Last edited 09/2022 and last reviewed 09/2022

Vestibulotoxicity with gentamicin

Gentamicin

• is an aminoglycoside antibiotic composed of a mixture of related gentamicin components and fractions and is used for many types of bacterial infections treatment, particularly those caused by Gram-negative organisms
  • aminoglycosides are bactericidal antimicrobial agents that disrupt the integrity of the bacterial cell wall and impair bacterial protein synthesis
• similar to all aminoglycosides, when gentamicin is given orally, it is not systemically active
  • is not absorbed to any appreciable extent from the small intestine
  • administered intravenously, intramuscularly, or topically to treat infections
  • eliminated, unchanged in the urine

Gentamicin is renally excreted within hours but accumulates over months in the inner ear

• evident ototoxicity (hearing and/or vestibular loss) is estimated to affect 11% of people taking daily treatment with gentamicin, and between 0.2% and 6.2% of patients who have received a single dose (1)
• vestibulotoxicity is considered to be dose dependent and commonly occurs when levels are high or renal clearance is poor
  • can occur in patients with preexisting renal damage and in patients with normal renal function treated at higher doses and/or for periods longer than those recommended (2)
  • other risk factors include increasing age, and concomitant use of other ototoxic drugs (3)
  • vestibulotoxic effect of gentamicin involves immediate inhibition of hair cell transmitter release by blocking mechanotransduction (3)
    • sustained exposure causes vestibular hair cell damage and death due to apoptosis
    • type I hair cells are more susceptible to loss than type II hair cells because they show an increased uptake and retention of gentamicin

Vestibulotoxicity with gentamicin:

• most patients present with gait disturbance and imbalance (1)
  • possibly because systemic administration of gentamicin tends to affect bilateral vestibular function (1)
    • with acute bilateral vestibular loss will be unable to stand unaided
  • imbalance is worse while walking in the dark, and oscillopsia occurs during head movements (3)
    • vertigo is infrequent (3)
    • oscillopsia is a disabling condition in patients with bilateral vestibular hypofunction (BVH) (3)
      • when the vestibulo-ocular reflex (VOR) is bilaterally impaired, its ability to compensate for rapid head movements must be supported by refixation saccades
• gentamicin is primarily toxic to the vestibular rather than auditory system (1)
  • majority (90%) of patients will not have accompanying hearing loss or tinnitus
  • vestibular loss is permanent in most patients
    

A review notes (1)

• enquire about a history of gentamicin administration in patients who experience vestibular symptoms such as imbalance while walking or wobbly vision
• gentamicin related vestibulotoxicity is often permanent, but prompt diagnosis and early physical rehabilitation can improve gait and balance
• avoid gentamicin, if possible, for surgical prophylaxis and in patients with risk factors such as pre-existing kidney disease, overweight, or using other drugs that can potentiate its effects (such as vancomycin)

Reference:

• Ferreira K, Forbes S, Kaski D. Vestibulotoxicity with gentamicin BMJ 2022; 378 :e070873
• Saleh P, Abbasalizadeh S, Rezaeian S, Naghavi-Behzad M, Piri R, Pourfeizi HH. Gentamicin-mediated ototoxicity and nephrotoxicity: A clinical trial study. Niger Med J. 2016 Nov-Dec;57(6):347-352.
• Ferreira-Cendon S, Martinez-Carranza R, Fernandez-Nava MJ, Villaoslada-Fuente R, Sanchez-Gomez H, Santa Cruz-Ruiz S, Sanchez-Ledesma M, Batuecas-Caletrio A. Prevention of Severe Vestibular Hypofunction after Systemic Gentamicin. J Clin Med. 2022 Jan 25;11(3):586.