Topical Antibiotic Ear Drops: Are They Safe?

S. Pappas; T.P. Nikolopoulos; S. Korres; G. Papacharalampous; A. Tzangarulakis; E. Ferekidis

Disclosures

Int J Clin Pract. 2006;60(9):1115-1119. 

In This Article

Human Studies

Considering the significant advantages and the popular use of ear drops, it is important to know which are the safer drops and their limitations, in order to avoid complications. In the English literature there are at least nine published papers reporting more than 165 documented patients who developed sensorineural hearing loss from the use of otic drops in otitis media.[25] Lundy and Graham published a survey by 2235 otolaryngologists,[26] 3.4% of whom reported irreversible cochlear damage attributable to otic drops. Toxicity from gentamycin ear drops usually involves the vestibular system rather than the cochlea.[27] If placed in the round window niche of patients immediately before labyrinthectomy or translabyrinthine surgery, it can be identified in the labyrinthine fluids in significant levels.[28] This is so well recognised that it is currently used as a standard form of treating vertigo in severe Meniere's disease.[29]

The crucial question is what happens to the permeability of otic drops in middle ears of patients with otitis media. The round window membrane in otitis media undergoes the same histopathological changes as the mucoperiostium of the middle ear mucosa as it is part of it. These changes suggest that in the early stages (the first 3-5 days of active inflammation), there may be an increase in permeability but that, as the inflammatory process progresses (1 week of inflammation and thereafter), the membrane becomes thicker and develops protective mechanisms in terms of decreased permeability. As the active inflammatory process decreases, the thickness and the protective mechanisms developed by the membrane decrease and the membrane reverts to normal. Experimental evidence in cats, chinchillas and guinea-pigs using tracers and neomycin has confirmed this finding.[15,20,30]

Hui et al.[31] reported two cases of hearing loss attributable to gentamicin, and Wong and Rutka[32] reported five patients with tympanic membrane perforations who, according to the authors, sustained ototoxicity from Garasone (gentamicin sulphate 0.3%, betamethasone, sodium sulphate).[31,32]

Marais et al.[33] similarly presented nine cases (12 ears in total) of iatrogenic topical vestibulotoxicity, all patients having been treated with Garasone for prolonged periods. Toxicity was found to be primarily vestibular rather than cochlear.

Bath et al.[27] identified 16 patients with well-documented histories, physical findings and laboratory investigations consistent with topical gentamicin-induced ototoxicity. One patient with incapacitating unilateral Meniere's disease underwent successful planned vestibular ablation using topical gentamicin/steroid drops. In all cases of inadvertent ototoxicity, patients had used drops for longer than 7 days (average 20.7 days) prior to symptoms developing, and vestibulotoxicity was confirmed by electronystagmogram testing.[27]

According to the Canadian Medical Association, 20 cases have been reported in Canada since 1981, 17 of which involved vestibular disorders and three hearing loss. In most cases the conditions being treated were middle ear disorders with otorrhoea; in one case however, gentamicin ear drops were given to treat Meniere's disease (along with high-dose intratympanic gentamicin infusions). Six patients had used the drops for no more than 5-7 days, and in 16 patients the symptoms had not resolved at the time the cases were reported to the Canadian health authority.

In a very thorough review of the literature in March 2004, Matz et al. found a total of 54 cases of gentamicin vestibular toxicity, 24 of whom displayed associated auditory toxicity.[34]

Ototoxicity of gentamicin drops is therefore well documented in the literature; however, if we take into account the wide use of such preparations all over the world, it would seem that this complication is rare.

In normal middle ears dexamethasone, hydrocortisone, and methylprednisolone have been documented as capable of traversing the round window membrane but appear to be safe.[35,36]

Neomycin/polymyxin B ear drops may cause severe inner ear damage even in low concentration in patients who are known not to be hyper-susceptible to aminoglycosides, rare though the phenomenon is.[37]

In a review of the literature Matz et al. found 11 patients of cochlear and two cases of vestibular toxicity in neomycin-based ear drops.[34]

Quinolone ear drops appear to be an effective alternative, and there is good evidence from randomised controlled trials that they may be the best choice for treating chronic middle ear infections.[38] They are already in use in the United States, Canada, New Zealand, Japan and other countries.

Ciprofloxacin and ofloxacin ear drops have several advantages over aminoglycosides. The Cochrane systematic review on therapies for chronic otitis media shows that quinolone ear drops are more effective than non-quinolone agents both in reducing ear discharge and in eradicating bacteria.[38] It also confirmed that antibiotic ear drops were more effective than systemic antibiotics in chronic otitis media and results from studies in animals and humans have so far failed to show any ototoxicity resulting from quinolone ear drops.[39]

Among the quinolones, apart from having the greatest activity against Pseudomonas, ciprofloxacin is effective against S. aureus, the other major pathogen in chronic otitis media. Recent studies have failed to show that oral ciprofloxacin has any deleterious effects on growing cartilage in children, and with the comparatively small doses used in topical application, it is likely soon to be officially recognised as safe for paediatric use.[40] In the United States topical ofloxacin has already been approved for the treatment of otorrhoea after grommet insertion in children older than 1 year (although in chronic middle ear infections it can only be used in children over the age of 12).

Resistance to ciprofloxacin in Pseudomonas strains (arising from mutation of the bacterial enzymes involved in DNA replication, namely gyrase and topoisomerase), is a growing problem. Roughly 20% or more of Pseudomonas isolates identified in hospitals in Europe and the United States are resistant to ciprofloxacin, and most of these strains are multidrug resistant.[41] Although topical use can ensure the continued effectiveness of the antibiotic in the face of possible resistance, inappropriate systemic use of quinolones can eventually cause resistance to topical quinolone preparations as well.[7]

Ciprofloxacin is already commonly used in respiratory, gastrointestinal and ophthalmic practice, and its more frequent use in otolaryngology would not therefore add greatly to the pool of resistant bacteria. Curative doses of topical ciprofloxacin or ofloxacin might actually help eradicate chronic Pseudomonas infections, thus reducing the problem of resistance associated with less effective antibiotics. Concentrations achieved through topical use are substantially higher than those achieved by other forms of administration, and thus there is a better chance of eradicating the infection.[1]

The quinolones are superior to the aminoglycosides in terms of safety, bacterial eradication and clinical cure, and seem therefore to be the drops of choice for treating otorrhoea.[42,43]

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