Gentamicin ototoxicity: a 23-year selected case series of 103 patients

Rebekah M Ahmed, Imelda P Hannigan, Hamish G MacDougall, Raymond C Chan and G Michael Halmagyi
Med J Aust 2012; 196 (11): 701-704. || doi: 10.5694/mja11.10850
Published online: 4 June 2012


Objective: To review patients with severe bilateral vestibular loss associated with gentamicin treatment in hospital.


Design and setting: A retrospective case series of presentations to a balance disorders clinic between 1988 and 2010.


Main outcome measures: Relationship between vestibulotoxicity and gentamicin dose or dosing profile; indications for prescribing gentamicin.


Results: 103 patients (age, 18–84 years; mean, 64 years) presented with imbalance, oscillopsia or both, but none had vertigo. Only three noted some hearing impairment after having gentamicin, but audiometric thresholds for all patients were consistent with their age. In all patients, the following tests gave positive results: a bilateral clinical head-impulse test, a vertical head-shaking test for vertical oscillopsia, and a foam Romberg test. In 21 patients, imbalance occurred during gentamicin treatment (ignored or dismissed by prescribers in 20) and in 66 after treatment; the remaining 16 could not recall when symptoms were first noticed, except that it was after gentamicin treatment in hospital. Total gentamicin dose range was 2–318 mg/kg (mean, 52 mg/kg), daily dose range was 1.5–5.6 mg/kg (mean, 3.5 mg/kg), and duration was 1–80 days (mean, 17 days). Six patients had only a single dose; 26 had five or fewer doses. Serum gentamicin levels, measured in 82 patients, were in the recommended range in 59. Time to diagnosis ranged from 4 days to 15 years. Nephrotoxicity developed in 43 patients. Gentamicin dosage complied with contemporary or current Australian antibiotic guidelines in under half the patients.


Conclusions: Gentamicin ototoxicity is vestibular, not cochlear, producing permanent loss of balance, but not of hearing. Gentamicin can be vestibulotoxic in any dose, in any regimen, at any serum level.



The 103 patients who fulfilled our criteria comprised 47 men, 56 women; mean age, 64 years (range, 18–84 years). Forty-eight presented with both imbalance and oscillopsia, 39 with imbalance only, and four with oscillopsia only; and in 12 patients we were unable to determine their main presenting symptom. In all patients, the following tests gave positive results: a bilateral clinical head impulse test,9 a vertical head-shaking test for vertical oscillopsia,10 and a foam Romberg test (Video 1, Video 2, Video 3, Video 4, Video 5, Video 6).11 Thirty-eight patients had recurrent falls or required a walking aid, and 44 required vestibular rehabilitation.14

Twenty-one patients first noted symptoms in hospital during gentamicin treatment (gentamicin treatment was stopped in only one patient); 29 patients had completed treatment but were still in hospital; 37 experienced symptoms after discharge; and 16 could not remember when they first noticed symptoms, except that it was after gentamicin treatment in hospital.

Absence of cochleotoxicity

Only three of the 103 patients with GVT complained of hearing impairment after gentamicin treatment, in each case while still in hospital. No patient had audiometry at the time gentamicin was given, but all had audiometry later as part of the assessment of vestibular loss. For the 73 patients whose audiograms were retrieved, hearing loss at each frequency, averaged for each age group and both ears, was not different from accepted age-group means (Box 2).15,16 Audiometry in the three patients who complained of hearing loss also showed thresholds consistent with age. The pure-tone thresholds in the 30 descriptive reports were reported as normal or showing only high-frequency hearing loss, consistent with age and noise exposure. We were unable to retrieve audiometry data from before gentamicin treatment for any of the patients.

Loss of balance, not of hearing

All these patients developed symptoms and signs of bilateral vestibular impairment after treatment with gentamicin, but only three noted any hearing impairment. Audiometric thresholds in the all patients were not significantly different from age-matched thresholds.15,16 Unless pre-gentamicin audiometry is available, high-frequency (4–8 kHz) hearing loss, especially in elderly men, cannot be assumed to be due to gentamicin; noise and ageing are much more common causes of hearing loss.1 Measuring hearing before and after gentamicin treatment17,18 shows only slight (about 15 dB) high-frequency (4–8 kHz), asymptomatic hearing loss. This suggests that any hearing loss from gentamicin ototoxicity would not be noticed by patients with normal hearing,19,20 and certainly not by those with pre-existing, high-frequency hearing loss. By contrast, symptoms of vestibular loss are obvious to patients, as are the clinical signs to the aware clinician.

Link with nephrotoxicity

The mean total dose and serum levels of gentamicin in the 43 patients with GVT who developed nephrotoxicity24,25 were substantially higher than in the 60 who did not. Patients who develop vestibulotoxicity seem more likely to develop nephrotoxicity (42%) than patients in general receiving gentamicin (5%–17%),26 suggesting a common mechanism or predisposing factor.

Guideline indications

The current (2010) Australian antibiotic guidelines advise that use of gentamicin for empirical treatment should be limited to 48 hours, pending the results of microbiological investigations. Directed therapy is indicated only for infections in which there is resistance to other, safer, antimicrobials; for combination therapy in serious Pseudomonas aeruginosa and Brucella infections; and as synergistic treatment for streptococcal or enterococcal endocarditis. It should be considered for prophylactic use only in patients at specific risk of developing endocarditis from genitourinary or gastrointestional procedures.13

Gentamicin was given according to current antibiotic guidelines13 in 47% of our 103 patients; 52% were given empirical gentamicin for longer than the recommended 48 hours; and in only 46% of patients was gentamicin given in accordance with contemporary antibiotic guidelines. Few medical and surgical specialists prescribed gentamicin based on culture results, and in some cases continued it even when culture showed that it was not indicated.

Previous studies have examined the inappropriate use of aminoglycosides;27,28 in one, 10.2% of antibiotic-days were deemed inappropriate.29 An education program for junior medical officers improved appropriate prescribing of gentamicin from 52% to 78%.30

Minimising vestibulotoxicity

As there is always a risk of vestibulotoxicity with gentamicin, regardless of dose or serum level, it should be given only as recommended by antibiotic guidelines13 and when there is no safer alternative. Clinicians prescribing gentamicin should use bedside methods to monitor for vestibulotoxicity,10,22 although this is possible only in conscious, cooperative patients. Stopping gentamicin treatment early could prevent further damage, allowing some hair cell regeneration and recovery of vestibular function.33

Our report of 103 cases seen over 23 years suggests that vestibulotoxicity is rare (Addendum). However, our criteria excluded patients in whom we were unable to obtain dosing and clinical details, those with pre-existing renal failure, and those with partial bilateral9 or unilateral vestibulotoxicity.34

GVT can occur with any dose, in any regimen, at any serum level, and is often not recognised. Vestibulotoxicity can be devastating and conscious patients should be warned of this risk before being treated with gentamicin.

Video 1: Head impulse test in a patient with moderately severe gentamicin vestibulotoxicity

While the patient stares at a distant target, the clinician turns the patient’s head briskly to the left, to the right, up and down. (The head turns need to be fast but small, only about 20° so they do not cause any discomfort.) A subject with a normal vestibulo-ocular reflex is able to keep his eyes fixed on the target by immediately making compensatory smooth eye movements.

This patient cannot do this, most obviously in response to leftward and downward head impulses. Instead, about 150 ms after each head impulse, he makes jerky compensatory eye movements — overt (ie, clinically obvious) “catch-up” saccades — to return his eyes to the target. He has vertical and horizontal impairment of the vestibulo-ocular reflex.

Video vestibulometry reveals that the head impulse test gave positive results in all four directions. The reason the catch-up saccades were not clinically apparent during rightward and upward head rotations was that they were covert (ie, they occurred early and during, rather than after, head rotation).

Video 2: Head impulse test of a patient with severe gentamicin vestibulotoxicity

This patient generates large overt saccades after head rotation to both sides, which are easy for a clinical observer to detect. In slow motion, during head rotation to both sides, the eyes move with the head and jump back to the target with a delayed overt saccade after head rotation. (Reproduced with permission from: Weber KP, Aw ST, Todd MJ, et al. Horizontal head impulse test detects gentamicin vestibulotoxicity. Neurology 2009; 72: 1417-1424.)

Video 3: Video measurement of a horizontal head impulse test of the patient in Video 2

While the patient stares at a distant target, the clinician (this time from behind) turns the patient’s head briskly to the left and to the right. The patient wears ICS video vestibulometric goggles (GN Otometrics, Schaumburg, Illinois, USA; and Tåstrup, Denmark.) and the clinician watches the results on a screen. These show that the eye velocity, inverted for ease of comparison (yellow traces), is much smaller than the head velocity (blue or red traces) indicating the measured deficit in the horizontal vestibulo-ocular reflex. These data are shown in more detail in Video 4.

Video 4: Horizontal vestibulo-ocular reflex deficit shown in three dimensions

The top two surfaces show the video-vestibulometric results from the patient in Video 2 and Video 3; for comparison, the lower two show results from a subject with a normal vestibulo-ocular reflex. The surfaces are rotating for easy inspection (blue surfaces = head velocity; red surfaces = eye velocity in three dimensions). The surfaces are superimposed eye velocity, which is inverted (ie, polarity reversed) for ease of comparison with head velocity. The lowest initial peaks of each surface represent the lowest stimulus (head) and response (eye) velocities, and the highest peaks are the highest velocities. In the normal subject, the red (eye) and blue (head) velocities are almost identical, indicating a vestibulo-ocular reflex that compensates perfectly. In the patient, the red surfaces are at first much smaller than the blue surfaces, indicating the severe deficit in the vestibulo-ocular reflex at all head velocities; then there is a shower of spikes — the “catch-up” saccades clinically evident in Video 1 and Video 2. (For more information about impulsive testing see

Video 5: A simulation of impaired dynamic visual acuity due to oscillopsia during vertical head shaking

The simulation shows the visual experience of a patient with severe bilateral vestibular impairment (left), compared with a normal subject (right), during vertical head movement. Note the decreased visual acuity caused by impairment of the vertical vestibulo-ocular reflex in the patient versus preserved visual acuity, with stabilisation of the line-of-sight by normal vestibulo-ocular reflex eye movements. In patients with bilateral vestibular loss, oscillopsia occurs during walking or running.

Video 6: Positive foam Romberg test in a patient with severe bilateral severe gentamicin vestibulotoxicity

The patient has no problem standing with feet together and eyes closed on a firm surface, but is unable to do so on a foam surface. The foam surface disrupts proprioception, the only means of postural stability when neither visual nor vestibular inputs are available to stabilise posture. A control subject is able to stand with eyes closed on a foam surface.

Received 5 July 2011, accepted 5 March 2012

  • Rebekah M Ahmed1
  • Imelda P Hannigan1
  • Hamish G MacDougall2
  • Raymond C Chan1
  • G Michael Halmagyi1

  • 1 Department of Neurology, Royal Prince Alfred Hospital, Sydney, NSW.
  • 2 Vestibular Research Laboratory, School of Psychology, University of Sydney, Sydney, NSW.



We thank Dr Richard Benn for helpful discussions over many years and Dr Vicki Levidiotis for reviewing the manuscript. The study was supported by Garnett Passe and Rodney Williams Memorial Foundation (Hamish MacDougall) and National Health and Medical Research Council Grant 245515 (Michael Halmagyi).

Competing interests:

Michael Halmagyi and Hamish MacDougall have acted as unpaid consultants for GN Otometrics.

  • 1. Dobie RA, Black FO, Pezsnecker SC, Stallings VL. Hearing loss in patients with vestibulotoxic reactions to gentamicin therapy. Arch Otolaryngol Head Neck Surg 2006; 132: 253-257.
  • 2. Seemungal BM, Bronstein AM. Aminoglycoside ototoxicity: vestibular function is also vulnerable. BMJ 2007; 335: 952.
  • 3. Halmagyi GM, Fattore CM, Curthoys IS, Wade S. Gentamicin vestibulotoxicity. Otolaryngol Head Neck Surg 1994; 111: 571-574.
  • 4. Black FO, Pesznecker S, Stallings V. Permanent gentamicin vestibulotoxicity. Otol Neurotol 2004; 25: 559-569.
  • 5. Ishiyama G, Ishiyama A, Kerber K, Baloh RW. Gentamicin ototoxicity: clinical features and the effect on the human vestibulo-ocular reflex. Acta Otolaryngol 2006; 126: 1057-1061.
  • 6. Ariano RE, Zelenitsky SA, Kassum D. Aminoglycoside-induced vestibular injury: maintaining a sense of balance. Ann Pharmacother 2008; 42: 1282-1289.
  • 7. Minor LB. Gentamicin-induced bilateral vestibular hypofunction. JAMA 1998; 279: 541-544.
  • 8. Zingler VC, Cnyrim C, Jahn K, et al. Causative factors and epidemiology of bilateral vestibulopathy in 255 patients. Ann Neurol 2007; 61: 524-532.
  • 9. Weber KP, Aw ST, Todd MJ, et al. Horizontal head impulse test detects gentamicin vestibulotoxicity. Neurology 2009; 72: 1417-1424.
  • 10. Vital D, Hegemann SC, Straumann D, et al. A new dynamic visual acuity test to assess peripheral vestibular function. Arch Otolaryngol Head Neck Surg 2010; 136: 686-691.
  • 11. Vereeck L, Truijen S, Wuyts FL, Van de Heyning PH. The dizziness handicap inventory and its relationship with functional balance performance. Otol Neurotol 2007; 28: 87-93.
  • 12. Halmagyi GM, Yavor RA, McGarvie LA. Testing the vestibulo-ocular reflex. Adv Otorhinolaryngol 1997; 53: 132-154.
  • 13. Antibiotic Expert Group. Therapeutic guidelines: antibiotic. Version 14. Melbourne: Therapeutic Guidelines Limited, 2010.
  • 14. Herdman SJ. Vestibular rehabilitation. 3rd ed. New York: Davis, 2007: 309-359.
  • 15. Gates, GA, Cooper JC, Kannel WB, Miller NJ. Hearing in the elderly: the Framingham cohort, 1983-1985. Part I. Basic audiometric test results. Ear Hear 1990; 11: 247-256.
  • 16. Pearson JD, Morrell CH, Gordon-Salant S, et al. Gender differences in a longitudinal study of age-associated hearing loss. J Acoust Soc Am 1995; 97: 1196-1205.
  • 17. Sha SH, Qiu JH, Schacht J. Aspirin to prevent gentamicin-induced hearing loss. N Engl J Med 2006; 354: 1856-1857.
  • 18. Moore RD, Smith CR, Lietman PS. Risk factors for the development of auditory toxicity in patients receiving aminoglycosides. J Infect Dis 1984; 149: 23-30.
  • 19. Lancaster JL, Mortimore S, McCormick M, Hart CA. Systemic absorption of gentamicin in the management of active mucosal chronic otitis media. Clin Otolaryngol Allied Sci 1999; 24: 435-439.
  • 20. Stavroulaki P, Apostolopoulos N, Dinopoulou D, et al. Otoacoustic emissions – an approach for monitoring aminoglycoside induced ototoxicity in children. Int J Pediatr Otorhinolaryngol 1999; 50: 177-184.
  • 21. JC. Living without a balancing mechanism. N Engl J Med 1952; 246: 458-460.
  • 22. MacDougall HG, Weber KP, McGarvie LA, et al. The video head impulse test: diagnostic accuracy in peripheral vestibulopathy. Neurology 2009; 73: 1134-1141.
  • 23. Gentamicin Information Center. About gentamicin poisoning. (accessed Mar 2012).
  • 24. Appel GB. Aminoglycoside nephrotoxicity. Am J Med 1990; 88: 16S-20S.
  • 25. Prins JM, Buller HR, Kuijper EJ, et al. Once versus thrice daily gentamicin in patients with serious infections. Lancet 1993; 341: 335-339.
  • 26. Raveh D, Koypt M, Hite Y, et al. Risk factors for nephrotoxicity in elderly patients receiving once-daily aminoglycosides. QJM 2002; 95: 291-297.
  • 27. English WP, Williams MD. Should aminoglycoside antibiotics be abandoned? Am J Surg. 2000; 180: 512-515.
  • 28. Leong CL, Buising K, Richards M, et al. Providing guidelines and education is not enough: an audit of gentamicin use at The Royal Melbourne Hospital. Intern Med J 2006; 36: 37-42.
  • 29. Dunagan WC, Woodward RS, Medoff G, et al. Antibiotic misuse in two clinical situations: positive blood culture and administration of aminoglycosides. Rev Infect Dis 1991; 13: 405-412.
  • 30. Johnson MW, Mitch WE, Heller AH, Spector R. The impact of an educational program on gentamicin use in a teaching hospital. Am J Med 1982; 73: 9-14.
  • 31. Wu WJ, Sha SH, Schacht J. Recent advances in understanding aminoglycoside ototoxicity and its prevention. Audiol Neurootol 2002; 7: 171-174.
  • 32. Chen FQ, Schacht J, Sha SH. Aminoglycoside-induced histone deacetylation and hair cell death in the mouse cochlea. J Neurochem 2009; 108: 1226-1236.
  • 33. Black FO, Gianna-Poulin C, Pesznecker SC. Recovery from vestibular ototoxicity. Otol Neurotol 2001; 22: 662-671.
  • 34. Ahmed RM, MacDougall HG, Halmagyi GM. Unilateral gentamicin vestibulotoxicity. Otol Neurotol 2011; 32: 1158-1162.


remove_circle_outline Delete Author
add_circle_outline Add Author

Do you have any competing interests to declare? *

I/we agree to assign copyright to the Medical Journal of Australia and agree to the Conditions of publication *
I/we agree to the Terms of use of the Medical Journal of Australia *
Email me when people comment on this article

Online responses are no longer available. Please refer to our instructions for authors page for more information.