Aminoglycoside-induced hearing deficits – a review of cochlear ototoxicity

Figures & data

Table 1: Incidence of cochleotoxicity

Author	Year	Drug	Method	Participants	Incidence	Comments
Al-Malky et al^24	2011	Amikacin, tobramycin	Prospective high frequency pure tone audiometry	39	21%	Treatment for ±14 days
Black et al^25	1976	Amikacin	Prospective, pure tone audiometry	44	24%	Significant loss was defined as a reduction of ≥ 15 dB; 84% of participants who developed hearing loss were asymptomatic
De Jager et al^26	2002	Amikacin, kanamycin, streptomycin	Pure tone air conduction	110	18%	Treatment for > 14 days. Hearing loss was defined as a loss of 15 dB at two or more frequencies, or a minimum of 20 dB hearing loss of at least one frequency between 0.25 and 8.0 kHz
Duggal et al^27	2007	Amikacin, kanamycin, capreomycin	Pure tone air and bone conduction	64	25%	Treatment for 18–24 months
Fausti et al^28	1993	Aminoglycoside not specified	High frequency audiometry	94 ears	69%	Treatment for > 4 days
Fee et al^29	1980	Gentamicin, tobramycin	Prospective audiometry	113 participants, 138 courses	Gentamicin 16.4%	Hearing loss progressed after discontinued drug
Harris et al^19	2012	Kanamycin, streptomycin, capreomycin	Prospective, pure tone audiometry	153 participants with MDR-TB	57%	Monitored monthly for 3 months
Hotz et al^30	1994	Amikacin	Transient evoked otoacoustic emissions	10 ears	90%	Treatment for more than 12 days
Lerner et al^21	1979	Gentamicin, amikacin	Prospective, pure tone audiometry	54 participants for each drug	Gentamicin 7%; amikacin 9%	Cochlear toxicity defined as 15 dB decrease at two frequencies
Moore et al^31	1984	Amikacin	Prospective, pure tone air conduction	135	22.3%
Ramma et al^18	2012	Kanamycin, amikacin	Prospective, pure tone air and bone conduction	53	47%	Treatment between 1–18 months
Sturdy et al^32	2011	Amikacin, capreomycin, streptomycin	Retrospective, pure tone audiometry	50	28%	Treatment for > 2 weeks

Table 2: Intrinsic and extrinsic risk factors for cochleotoxicity

Intrinsic risk factors	Extrinsic risk factors
Previous treatment with ototoxic medication	Concomitant treatment with other ototoxic or nephrotoxic drugs
Prolonged exposure	Dosage in relation to weight
Renal impairment	Health practitioners’ knowledge of cochleotoxicity
Genetic susceptibility	Attitude of staff when symptoms are reported
Poor nutrition	Availability of diagnostic/monitoring services
Advanced age
Excessive noise exposure
Pre-existing hearing loss and vestibular dysfunction
HIV/AIDS

Table 3: Battery of tests for diagnosing/monitoring cochleotoxicity

Test	Aim of evaluation	Result if cochleotoxic	Notes
Case history	Establish complaints of hearing loss, tinnitus, dysequilibrium, nausea	Positive for presence of symptoms	Subjective hearing loss noted only once there is marked hearing loss, so poor method. Tinnitus should always prompt audiological investigation
Conventional pure tone audiometry from 250–8 000 Hz (air and bone conduction)	Quantifies presence and severity of hearing loss across the middle frequency range of human hearing	Progressive, initially high frequency sensorineural hearing loss, usually symmetrical in both ears	Will not detect hearing loss until there has been significant high frequency hearing loss, so a comparatively ‘late’ finding
			Can be done at bedside but easily contaminated by ambient noise and patient attending to the task
High frequency pure tone audiometry (including frequencies up to 20 000 Hz)	Quantifies presence and severity of hearing loss across the high frequency range of human hearing	Progressive, ultra-high frequency sensorineural hearing loss, usually symmetrical in both ears, will progress to middle frequency range and then be detected with conventional pure tone audiometry	Patient acts as own control. Detects hearing loss sooner than cPTA
			Requires more specialised equipment
			Again subject to patient’s ability to attend to task
Otoacoustic emissions	Measures outer hair cell function	Abnormal, i.e. either reduced or absent	Requires only passive cooperation from patient, suitable for moribund patients and can be done at bedside
			Reasonably resistant to ambient noise. Suitable for screening and diagnosis
			Screening/monitoring can be performed by audiological assistant
Auditory brainstem response	Measures integrity of VIII^th cranial nerve. Also used for threshold estimation but an indirect measure	Abnormal	Requires only passive cooperation from patient, suitable for moribund patients and can be done at bedside
			However, sensitive to both ambient noise and electrical interference
			Requires skilled interpretation by audiologist

Figure 1: Idealised scheme of professionals and services required for the management of a patient with cochleotoxicity

Al-Malky G, Suri R, Dawson SJ, et al. Aminoglycoside antibiotics cochleotoxicity in paediatric cystic fibrosis (CF) patients: a study using extended high-frequency audiometry and distortion product otoacoustic emissions. Int J Audiol 2011;50(2):112–22.10.3109/14992027.2010.524253

 PubMed Web of Science ®Google Scholar

Monsell EM, Teixido MT, Wilson MD, et al. Nonhereditary hearing loss: ototoxicity. In: Hughes GB, Pensak ML, editors. Clinical otology. 2nd ed. New York, NY: Thieme Medical Publishers, Inc.; 1997. p. 289–305.

 Google Scholar

De Jager P, van Altena R. Hearing loss and nephrotoxicity in long-term aminoglycoside treatment in patients with tuberculosis. Int J Tuberc Lung Dis. 2002;6(7):622–7.

 PubMed Web of Science ®Google Scholar

Duggal P, Sarkar M. Audiologic monitoring of multi-drug resistant tuberculosis patients on aminoglycoside treatment with long term follow-up. Biomed Central Ear Nose Throat Disorders. 2007;7(5):1–7.

 PubMedGoogle Scholar

Fausti SA, Frey RH, Henry JA, et al. High frequency testing techniques and instrumentation for early detection of ototoxicity. J Rehabil Res Dev. 1993;30(3):333–41.

 PubMed Web of Science ®Google Scholar

Fee WE. Aminoglycoside ototoxicity in the human. Laryngoscope. 1980;90(S24):1–19.10.1288/00005537-198010001-00001

 PubMed Web of Science ®Google Scholar

Harris T, Bardien S, Schaaf HS, et al. Aminoglycoside-induced hearing loss in HIV-positive and HIV-negative multidrug-resistant tuberculosis patients. S Afr Med J. 2012;102(6):363–6.

 PubMed Web of Science ®Google Scholar

Hotz M, Harris F, Probst R. Otoacoustic emissions: an approach for monitoring aminoglycoside-induced ototoxicity. Laryngoscope. 1994;104:1130–4.

 PubMed Web of Science ®Google Scholar

Lerner SA, Matz GJ. Suggestions for monitoring patients during treatment with aminoglycoside antibiotics. Otolaryngol Head Neck Surg. 1979;87:222–8.

 PubMed Web of Science ®Google Scholar

Moore RD, Smith CR, Lietman PS. Risk factors for the development of auditory toxicity in patients receiving aminoglycosides. J Infect Dis. 1984;149:22–30.

 Google Scholar

Ramma L, Ibekwe TS. Cochleo-vestibular clinical findings among drug resistant tuberculosis patients on therapy-a pilot study. Int Arch Med. 2012;5(1):1–5.

 PubMedGoogle Scholar

Sturdy A, Goodman A, Jose RJ, et al. Multidrug-resistant tuberculosis (MDR-TB) treatment in the UK: a study of injectable use and toxicity in practice. J Antimicrob Chemother. 2011;66(8):1815–20.10.1093/jac/dkr221

 PubMed Web of Science ®Google Scholar