Aminoglycoside induced ototoxicity in patients with cystic fibrosis

Mulherin, D.; Fahy, John V.; Grant, Wendy J.; Keogan, M.; Kavanagh, Brian P.; FitzGerald, M. X.

doi:10.1007/bf02961666

Cited by 39 publications

(23 citation statements)

References 11 publications

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“…Testing was carried out in standard soundproof rooms of hospital audiology departments or in quiet rooms. These locations satisfied the criteria for ambient noise levels during audiometric testing (30,44). In cases of marked unilateral hearing loss, narrow-band masking noise was delivered to the contralateral ear (i.e., threshold at a test frequency of Ն40 dB greater than the threshold level in the contralateral ear) (7).…”

Section: Methodsmentioning

confidence: 94%

“…The effects of repeated AG therapy on auditory function in CF has been reported in a number of studies (13,24,29,30,33,39,45). Using similar audiometric methods and criteria to those used in single-course studies, the incidence of cochleotoxicity in adult CF patients ranged from 0% (33,39,45) In pediatric CF patients, who would generally be expected to have had fewer courses, this range was 0 to 6% (13,24,29).…”

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confidence: 91%

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Occurrence and Risk of Cochleotoxicity in Cystic Fibrosis Patients Receiving Repeated High-Dose Aminoglycoside Therapy

Mulheran

Degg

Burr

et al. 2001

Antimicrob Agents Chemother

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Cystic fibrosis (CF) patients receive repeated courses of aminoglycoside therapy. These patients would consequently be expected to be more susceptible to cochleotoxicity, a recognized side effect with single courses of aminoglycoside therapy. The primary aim of this retrospective study was to establish the incidence and severity of auditory deficit in CF patients. Standard (0.25-to 8-kHz) and high-frequency (10-to 16-kHz) pure-tone audiometry was carried out in 70 CF patients, and the results were compared with the results from 91 control subjects. These subjects were further divided into pediatric and adult groups. Of 70 CF patients, 12 (1 pediatric) displayed hearing loss considered to be caused by repeated exposure to aminoglycosides. There was a nonlinear relationship between the courses of therapy received and the incidence of hearing loss. The severity of the loss did not appear to be related to the number of courses received. Assuming the risk of loss to be independent for each course, preliminary estimates of per course risk of hearing loss were less than 2%. Upon comparison with previous clinical studies and experimental work, these findings suggest that the incidence of cochleotoxicity in CF patients is considerably lower than would be expected, suggesting that the CF condition may confer protection against aminoglycoside cochleotoxicity.

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Section: Methodsmentioning

confidence: 94%

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confidence: 91%

Occurrence and Risk of Cochleotoxicity in Cystic Fibrosis Patients Receiving Repeated High-Dose Aminoglycoside Therapy

Mulheran

Degg

Burr

et al. 2001

Antimicrob Agents Chemother

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“…With an increasing life expectancy of this group, the ototoxic side effects are becoming an important quality-of-life issue. Bilateral hearing impairment in this population has been documented at 16% [Mulherin et al, 1991]. Postmortem studies on cystic fibrosis patients with signs of ototoxicity confirmed loss of hair cells in the lower cochlear turns and degeneration of spiral ganglion cells [Sone et al, 1998].…”

Section: Emerging Patient Populations At Riskmentioning

confidence: 99%

Aminoglycoside Antibiotics

Forge

Schacht²

2000

Audiol Neurotol

593

504

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In the 50 years since their discovery, the aminoglycoside antibiotics have seen unprecedented use. Discovered in the 1940s, they were the long-sought remedy for tuberculosis and other serious bacterial infections. The side effects of renal and auditory toxicity, however, led to a decline of their use in most countries in the 1970s and 1980s. Nevertheless, today the aminoglycosides are still the most commonly used antibiotics worldwide thanks to the combination of their high efficacy with low cost. This review first summarizes the history, chemistry, antibacterial actions and acute side effects of the drugs. It then details the pathophysiology of aminoglycoside ototoxicity including experimental and clinical observations, risk factors and incidence. Pharmacokinetics, cellular actions and our current understanding of the underlying molecular mechanisms of ototoxicity are discussed at length. The review concludes with recent advances towards therapeutic intervention to prevent aminoglycoside ototoxicity.

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“…Aminoglycoside antibiotics such as gentamicin (GM) are widely used in underdeveloped countries to treat gram-negative bacterial infections and tuberculosis and they are also employed in the treatment of Duchenne muscular dystrophy and cystic fibrosis (Barton-Davis et al, 1999;Mulherin et al, 1991). Aminoglycoside antibiotics bind to the 30S ribosomal RNA and inhibit protein synthesis (Yoshizawa et al, 1998).…”

Section: Introductionmentioning

confidence: 99%