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.