2

Tobramycin is ototoxic and in some individuals with genetic predisposition Tobramycin can apparently cause rapid permanent balance and hearing loss.

Yet, at least where I live, Tobramycin is prescribed for ear infections both as drops and as gels/creams (as eye drops but applied to ear under doctor recommendation). Why is this?

  • 2
    Where do you live? An aminoglycoside is indeed an odd choice for an ear infection. I'm struggling to imagine a scenario where it would be appropriate, except perhaps when there is also severe, pussy conjunctivitis. Even then... – De Novo Jan 7 at 20:41
  • 1
    It seems like as long as the tympanic membrane is not perforated, aminoglycosides have little topical ototoxicity even in the (external) ear itself. To be ototoxic, the hair cells need to be exposed, which can occur via systemic but not topical (at least not in substantial quantities) routes. However, I've been unable to find anything that answers the title question explicitly, in particular relative to other options like ciprofloxacin. Seems like it would be a reasonable choice for something like ciprofloxacin-resistant Pseudomonas, but strange to me to use first line... – Bryan Krause Jan 7 at 22:51
  • @BryanK perforation is a relatively common complication of, e.g. otitis media, which is one of the reasons aminoglycisides are generally contraindicated. – De Novo Jan 8 at 2:48
  • @DeNovo I could have been more clear, but that's why I said "as long as the tympanic membrane is not perforated" - yes of course in case of otitis media there's risk of perforation so it would be riskier. – Bryan Krause Jan 8 at 6:29
  • 1
    @DeNovo Yeah, I got it. I like how you wrote your answer as a bit of a frame challenge that emphasizes the dangers. In my comment I was trying to come at it from the other side (that is, why would you even consider this given the potential dangers?) and some real-world studies show (perhaps surprisingly) low incidence of ototoxicity when applied topically to the ear. I think overall the summary is that there is really no clear reason to use first-line; in case of an unrelenting and resistant infection one might weigh the risk of ototoxicity against direct bacterial damage to the inner ear. – Bryan Krause Jan 8 at 23:27
4

Summary

Tobramycin is an aminoglycoside antibiotic. All aminoglycoside antibiotics carry a risk of irreversible ototoxicity. The risk is reduced when applied topically, but not eliminated. Even topical use should be avoided for middle ear infections (otitis media). For external ear infections (otitis externa), care should be taken, including ensuring an intact tympanic membrane. As this Canadian review suggests, it is important to discuss the risk of ototoxicity with patients when making a treatment decision.

Approval and use in the US, Canada, and the UK

There are no approved formulations of tobramycin for any ear infection in the US, but there is a suspension containing neomycin that is approved for otitis externa. It contains a warning:

WARNINGS: Neomycin can induce permanent sensorineural hearing loss due to cochlear damage, mainly destruction of hair cells in the organ of Corti. The risk is greater with prolonged use. Therapy should be limited to 10 consecutive days (see PRECAUTIONS-General). Patients being treated with eardrops containing neomycin should be under close clinical observation. CASPORYN HC Otic Suspension should not be used in any patient with a perforated tympanic membrane.

To summarize the main points: Ototoxicity is a risk. Patients should be carefully observed. If the tympanic membrane is perforated, this drug is absolutely contraindicated.

Gentamicin drops are approved in Canada for otitis externa, and are reported to be used off label for otitis media.

In this review, aminoglycoside drops are described as first line therapy in the UK for chronic suppurative otitis media, much to the review authors' chagrin.

Background on aminoglycosides and ototoxicity

Aminoglycosides are generally reserved for severe infections (e.g., sepsis, pneumonia, endocarditis). This is, in part, due to the challenging side effect profile common to all members of this drug class, including irreversible ototoxicity, reported in up to 25% of patients in some series. Ototoxicity appears to depend on rapid uptake and slow elimination by hair cells, which in turn depends on plasma concentration, but it is not predictable. Ototoxicity can occur after brief, low dose therapy, and may not manifest until after the drug has been withdrawn, with permanent disability resulting. As mentioned in the question, there are hereditary syndromes and certain genetic mutations that increase susceptibility, but ototoxicity can occur without them.

In summary, ototoxicity is a common, irreversible, unpredictable, and severe side effect of aminoglycoside use.

Goodman & Gilman's The Pharmacologic Basis of Therapeutics provides a good overview of aminoglycosides, with a detailed section on ototoxicity.

Topical use doesn't eliminate systemic absorption

Topical preparations of aminoglycosides are approved in the U.S. for certain eye and skin infections. Topical use reduces, but does not eliminate absorption and systemic distribution these antibiotics (Goodman & Gilman Ch. 54). This is not surprising, as infection and the associated inflammation compromise the barrier function of the skin. Absorption can be substantial in the presence of blistering or denuded skin. In the ear, specifically, while tympanic membrane perforation increases the risk of ototoxicity, there is detectable absorption without perforation.

  • 1
    OK big thanks, De Novo. I am going to ask a couple of local doctors for their rationale too, though for some reason it is hard to get them to talk openly around here, and update this answer with comments. I am skeptical and suspect local incompetence but on the other hand I am loathe to outright dismiss practical experience. They might have some experience-based reason. – Frank Jan 9 at 10:17
0

Why is Tobramycin prescribed for ear infections?

It doesn't seem to be recommended as eardrops for home use.

Tobramycin has spectrum of activity limited to gram negative bacilli and is indicated for Pseudomonas aeruginosa, a hospital-acquired infection. Fluoroquinolones (for example), while also effective and not ototoxic, have (in some cases) been withdrawn from the US market.

In a hospital setting, with patient monitoring, and the development of multidrug resistance by P. aeruginosa, it might be indicated after careful consideration of risk factors, other options, and patient examination. It can also be used for most staphylococci.

An accurate diagnosis to determine colonization versus infection might involve a delay. If the bacteria was contracted during bathing it may be expected to be gone once the ears are dry. Horizontal gene transfer prevention from P. aeruginosa is another consideration. Topical Gentamicin would normally only be used for a couple of days while awaiting bacterial cultures to determine what specific antibiotics the infection is sensitive to.

Antibiotics Spectrum Source: Wikipedia: "Broad-spectrum antibiotic".

  • I'm sorry, I'm not sure why you insist on disagreeing here. I'm trying to help. Tobramycin's spectrum of activity includes gram positive cocci. Though it is often administered in combination with a cell wall active antibiotic for synergistic effect, it is perfectly fine on it's own for, e.g. MSSA. Wikipedia is generally a bad reference for clinical medicine, though at least in your linked reference for broad spectrum antibiotics it gets something right. Aminoglycisides are the first antibiotic listed under the examples of broad spectrum antibiotics – De Novo Jan 9 at 5:59
  • 1
    Is that diagram correct? AFAIK the aminoglycosides are effective on MRSA and MSSA – Frank Jan 9 at 10:19
  • @Frank, Another user repeatedly pinging me caused me to miss providing you with a quicker reply. As one can see some of the sources are Merck; no one source was relied upon, nor am I aware of complaints made against these sources being accepted by said sources. --- To your question, one source: "Today Methicillin-Resistant Staphylococcus aureus (MRSA) have acquired multiple resistance to a wide range of antibiotics including aminoglycosides." URL: sciencedirect.com/science/article/pii/S1607551X17301341 – Rob Jan 11 at 20:33

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.