Hearing loss with Tobi® inhalation

Question

Dear expert team,

about a week ago, I (26 years old, CF) had acute hearing loss. During its treatment phase, several hearing tests were done. My hearing loss was reversible, but it was detected in this context that I suffer from hearing loss in the high-frequency range. I have been inhaling once a day with Tobi® (tobramycin) for many years (perhaps even since its approval), though I have only had one i.v. therapy with tobramycin and gentamicin so far (6 years ago). Through my job as a pharmacist, I immediately thought of Tobi®. Also, according to the product specifications for Tobi®, hearing loss can be one potential side effect of inhalation, initially in the high-frequency range. There is hardly any information on the issue of hearing loss with Tobi® inhalation. However, I would not like to either become deaf over time or get Pseudomonas. I would now like to have my tobramycin level checked after an inhalation. When is the peak level reached, and is there a certain tobramycin level at all that has been proven to cause hearing loss with daily inhalation?

Kind regards and many thanks for your effort.

Answer

Dear questioner,

hearing loss can be a great burden in daily life. Acute hearing loss is a sudden loss of hearing that usually occurs within 24 hours and mostly one-sided, and whose causes cannot be determined by definition. It is frequently accompanied by tinnitus and less commonly also by dizziness. It has a relatively high rate of spontaneous recovery and the prevalent therapy measures are usually not conclusively scientifically proven. During a follow-up after acute hearing loss, you were diagnosed with hardness of hearing in the high-frequency range and are now afraid that this may be linked to an antibiotics therapy against Pseudomonas with tobramycin and/or gentamycin.

Intensive use of antibiotics has been one of the key pillars that have contributed to improved progression in cystic fibrosis. It prevents or significantly reduces lung damage caused by problem germs such as Pseudomonas aeruginosa. That said, antibiotics therapy can have unwanted side effects. The possibility of damage of the auditory canal due to systemic application of so-called amino glycoside antibiotics (tobramycin, gentamycin) has been well known since this group of agents has been introduced more than 30 years ago. The risk of hearing impairment depends partly on the dosage, the form of application, and the duration of the therapy. However, there are also other factors of each individual patient’s sensitivity that we do not know conclusively. In Tübingen, Germany (Koitschev et al. HNO, 2005), 108 CF patients underwent a hearing test in the context of a cross-sectional study. 12% were found to have hearing impairment of the inner ear, which, like in your case, typically affects the high frequency range that is not required for understanding speech. All of the patients had been treated with systemic intravenous amino glycosides (as infusion).

Inhalative antibiotics therapy in particular has the advantage that usually no critical impact levels are reached in the blood and hence in the hearing organ, though very well the highest possible antibiotics concentrations in the sputum. An inhalative tobramycin dosage of 2x 300 mg/day (TOBI® or Bramitob®) can lead to measurable amino glycoside blood levels that usually peak at just about the uncritical low level range and are below 2 mg/l.

Earlier studies on tobramycin’s drug safety and effectiveness report of 148 patients who inhaled on/off with TOBI® for 24 weeks. None of these patients suffered from hearing impairment. In the meantime, however, there are also reports about problems in the hearing organ during/after inhalation therapy. When inhaling with newer, highly effective nebulizers (iNeb® Akita®), it is important to adjust the dosage and to be careful with dumping the amount of anitibiotics remaining in the eFlow® so that it is nebulized as well. Otherwise the result may be blood levels that can also cause systemic side effects. In case of renal insufficiency, the decomposition of amino glycosides can be disturbed, which can lead to increased agent levels in the blood and ear as well as to kidney damage. It is therefore important to adjust the dosage with the inhalation methods mentioned above or in case of renal insufficiency.

Your anamnesis with only a one-time i.v. therapy with amino glycosides but long-term inhalation of the antibiotic and development of high-range hearing impairment is unusual. A link between the application of antibiotics and your acute hearing loss cannot be ruled out reliably. However, the prevention of life-restricting lung damage by problem germs will weigh more strongly than the burden of a relatively rare form of side effects. It is therefore important to follow the precautionary measures mentioned above, but to not do without vitally important therapy.

Kind regards,
Jochen Mainz

27.02.2012