Longridge NS. Topical gentamicin vestibular toxicity. J Otolaryngol 1994:23:444-445
Linder TE, Zwicky S, Brandle P. Ototoxicity of ear drops: A clinical perspective.
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A commented chronological listing of papers related to topical ototoxicity
Wright, Meyerhoff and Halama (1987) examined the effects of polymyxin B with
neomycin and found greater toxic effect from polymyxin B in chinchilla and primates.
Primates were less affected than rodents.
Morizono (1988) reviewed the ototoxicity of topical ear drops. There is good
evidence for ototoxicity in animals of the aminoglycosides and chloramphenicol.
Morizono pointed out that there is less evidence for ototoxicity in humans than
in animals, and suggested that this might be related to a less exposed round
window in humans, a thinner membrane, and other factors such as the presence
of infection or effusion.
Podoshin and others (1989) compared patients treated with an otic mixture containing
neomycin, polymyxin B and dexamethasone to a control group of 26 getting dexamethasone
only. Duration of followup was 1-2 years. Patients treated continuously
had a mean hearing loss of 10 DB, compared to 3.6 DB in patients treated intermittently
and 1.8 DB in patients treated with long intermissions. Control patients hearing
changed by -0.9 DB (improved), and was not related to intermissions in treatment.
Comment: this is the only human study available. It suggests that there is a
modest long-term risk of hearing decline with COS drops in perforation.
Morizono (1990) compared 10 minutes of exposure of the middle ear of COS, Vosol,
and Colymyxin, in Guinea pigs. In this situation one would expect Colymyxin,
which contains neomycin, to be the most toxic. Evoked responses were used as
the measurement, at 24 hours. Colymyxin was found to be twice as toxic as COS,
and Vosol, 4 times. This result would seem to suggest that the Colistin component
of Colymyxin, is ototoxic, and also that propylene glycol in Vosol is ototoxic,
but little conclusion can be drawn about long term effects.
Halama and others (1991) examined the cochlear ototoxicity of a single application
of COS in baboons. They also examined separate comparisons of polymyxin-B and
neomycin, which are components of COS. They examined the cochlea post-mortem,
at 5 or 6 weeks They found that polymyxin B caused greater damage than did neomycin,
and that both caused clear ototoxic damage including complete loss of inner
and outer hair cells in the lower basal turn.
Lundy and Graham (1993) surveyed 2235 otolaryngologists regarding their opinions
about the use of ototopical agent. 84.1% used these agents in the presence of
a perforation, and many also used them during intraoperative packing. 80% indicated
that the risks of hearing loss from otitis media was as great as or greater
than the risks of ototoxicity of an ototopical preparation. Only 3.4% of respondents
had witnessed irreversible inner ear damage caused by ototopicals.
Barlow and others (1994) compared injections of 0.2 ml of COs, GOS and Ofloxacin
in guinea pigs into the middle ear, and measured hair cell damage at 7 days.
The mean cochlear hair cell damage was 66% for COs, 6.5% for GOS, and 1.1% for
Ofloxacin. This study documents toxicity for drug that penetrates the middle
ear in animals. It does not address the question of whether there is a difference
between human and animal toxicity, or relative vestibulotoxicity.
Linder and others (1995) reviewed 134 patient charts where ear drops were administered
for potential ototoxicity. Two cases were found with bilateral profound hearing
loss "directly attributable to topical ear drops". Ten other suspected
cases were insufficiently documented. Comment: this study suggests
an incidence somewhere between 2-10%.
Hui and others (1997) reported two cases of hearing loss attributed to gentamicin,
Corticosporin, and sofracort otic drops, administered for for several years,
in patients with tubes or perforations.
Wong and Rutka (1997) reported 5 patients with tympanic membrane perforations
who they believed sustained ototoxicity from GOS. Case 1 developed vertigo after
3 weeks of treatment. Case 2 also developed unilateral vestibular loss
and worsening of hearing. Cases 3, 4 and 5 developed bilateral vestibular loss
after bilateral instillation over weeks to months. In a later article,
Rutka commented that he had encountered 29 patients with topical gentamicin
ototoxicity (Rutka, 2002). COMMENT: These cases are quite relevant and suggest
that unilateral or bilateral vestibular loss can be associated with use of
gentamicin based ear drops.
Pickett, Shinn and Smith (1997) considered evidence for and against ototoxicity
from ear drops in a comprehensive review. They noted abundant animal evidence
for ototoxicity of aminoglycosides, solvents such as propylene glycol (found
in Vosol). They concluded that from animal data, it is clear that most ear drops
that are used for treatment or prophylaxis of infection have ototoxic potential
and point out the puzzling relative lack of common ototoxicity in humans. They
suggest that either ototoxicity is not recognized as hearing loss is attributed
to underlying disease, or because of anatomic differences between animals and
humans in the thickness of the round window membrane, there is less susceptibility
to topical ototoxicity in humans. They pointed out that there was a lack of
well-controlled studies on the use of ear drops in humans.
Ozagar and others (1997) found no cochlear ototoxicity of either ciprofloxacin
or gentamicin drops in 20 patients with chronic otitis media. COMMENT: This
is hardly surprising as gentamicin is not very cochleotoxic in humans and ciprofloxacin
is not ototoxic in animals. A more interesting study would have been to look
at vestibular function 1 year after use of gentamicin drops.
Bath and others (1999) documented 16 patients with vestibulotoxicity, possibly
related to topical drops containing gentamicin/steroid containing drops. An
additional case was presented reporting intentional ablation of vestibular function
using commercially available ear drops, in a patient with unilateral Meniere's
disease. Two drops, twice a day were instilled through a ventilation tube over
3 weeks.