Augmented Gentamicin Ototoxicity Induced by Vancomycin in Guinea Pigs

Brummett, Robert E.; Fox, Kaye E.; Jacobs, Frédéric; Kempton, Julie; Stokes, Zoë; Richmond, AlmaSue

doi:10.1001/archotol.1990.01870010065019

Cited by 47 publications

(28 citation statements)

References 31 publications

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“…This treatment was designed to extend the hair cell damage as far as possible into the apical (low-frequency) region. Previous studies have shown that treatment with a combination of ototoxic drugs and intense sound exposure causes larger hair cell lesions than either drugs or sound presentation alone (Bone and Ryan, 1978;Collins, 1988;Brummett et al, 1990Brummett et al, , 1992Pye and Collins, 1991). Treatment with only low-frequency sound exposure does not result in hair cell damage localized to the apical end of the basilar papilla Rubel, 1982, 1985;Cotanche et al, 1994;Woolley, unpublished observations).…”

Section: Methodsmentioning

confidence: 92%

High-Frequency Auditory Feedback Is Not Required for Adult Song Maintenance in Bengalese Finches

Woolley

Rubel

1999

J. Neurosci.

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Male Bengalese finches do not normally change their vocal patterns in adulthood; song is stereotyped and stable over time. Adult song maintenance requires auditory feedback. If adults are deafened, song will degrade within 1 week. We tested whether feedback of all sound frequencies is required for song maintenance. The avian basilar papilla is tonotopically organized; hair cells in the basal region encode high frequencies, and low frequencies are encoded in progressively apical regions. We restricted the spectral range of feedback available to a bird by killing either auditory hair cells encoding higher frequencies or those encoding both high and low frequencies and documented resultant changes in song. Birds were treated with either Amikacin alone to kill high-frequency hair cells or Amikacin and sound exposure to target hair cells across the entire papilla. During treatment, song was recorded from all birds weekly. After treatment and song recording, evokedpotential audiograms were evaluated on each bird, and papillas were evaluated by scanning electron microscopy. Results showed that hair cell damage over 46-63% of the basal papilla and the corresponding high-frequency hearing loss had no effect on song structure. In birds with hair cell damage extending further into the apical region of the papilla and corresponding low-frequency and high-frequency hearing loss, song degradation occurred within 1 week of beginning treatment and was comparable with degradation after surgical deafening. We conclude that either low-frequency spectral cues or temporal cues via feedback of the song amplitude envelope are sufficient for song maintenance in adult Bengalese finches.

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Section: Methodsmentioning

confidence: 92%

High-Frequency Auditory Feedback Is Not Required for Adult Song Maintenance in Bengalese Finches

Woolley

Rubel

1999

J. Neurosci.

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“…Using nor mal doses of V in guinea pigs, Brummett et al [3] found no evidence of ototoxicity either, but an enhancement of the ototoxic action of concurrently administered gen tamicin. This might explain many former cases of clini cal ototoxicity of V in which a combined therapy with aminoglycosides had been used.…”

Section: Discussionmentioning

confidence: 99%

“…Especially in the earlier literature of internal medicine [2] hearing impairment has been re ported in several cases during local and systemic treat ment with V. Unfortunately, complete audiometric doc umentation is only rarely available. Further reservation concerning the reliability of these reports may be war ranted due to the multimorbidity in these intensive-care patients and the interaction with other ototoxic drugs like aminoglycosides and loop diuretics [3,4], Interestingly, the active principle must be isolated from soil samples of the interior of Borneo, containing the actinomycète Slreptomyces orientalis. After im proved purification methods were developed in the last three decades, the ototoxic and nephrotoxic risks might have decreased.…”

Section: Introductionmentioning

confidence: 99%

Ototoxicity of Vancomycin: An Experimental Study in Guinea Pigs

Lutz

Lenarz

Weidauer

et al. 1991

ORL

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Vancomycin (V) – a polypeptide antibiotic – is the drug of choice in severe infections with multiresistant staphylococcus spp. Due to the multimorbidity of the patients receiving V, the interactions with known ototoxic agents and the lack of an audiometric documentation, earlier clinical reports of V-associated hearing loss must be carefully interpreted. To elucidate this topic, a controlled animal study considering nonspecific effects was performed. 40 albino guinea pigs with positive Preyer’s reflex and normal hearing were used. The hearing function was controlled by means of brainstem auditory evoked potentials before and after intraperitoneal administration of V (75, 150, 300 mg/kg b.w. for 11–17 days), gentamicin (60 mg/kg b.w. for 26 days), neomycin (100 mg/kg b.w. for 17 days) and sodium chloride solution. The cochleas were dissected for hair cell counting by the surface preparation technique. Additionally, the serum concentrations of V were measured. As a result there was no significant difference in hearing loss between the controls and the animals treated with 75 and 150 mg V; toxic doses of 300 mg V led to a certain threshold elevation after click stimuli, but not after trapezoid stimuli of 1, 4 and 8 kHz. On the other hand, the aminoglycosides as a positive control caused an obvious hearing loss after click and trapezoid stimuli, which was correlated to the amount of outer hair cell loss. Renal damage could be excluded by histological examination of the kidneys and estimation of creatinine in serum. Therefore, treatment with moderate doses of V comparable to clinical conditions does not exhibit a specific ototoxicity as compared to the aminoglycosides. However, serum levels of V should be controlled as a safety measure in older patients and in patients with impaired renal function.

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“…A review of the literature (Brummett and Fox 1989 ) concluded that the ototoxicity of vancomycin has been overrated, and that only a very few cases of true vancomycin ototoxicity have occurred. However, an animal study has demonstrated that vancomycin, though not ototoxic itself (Lutzet al 1991 ), enhances the ototoxicity of aminoglycosides (Brummett et al 1990 ), so vancomycin may be ototoxic when used with aminoglycosides, or possibly with other ototoxic agents.…”

Section: Toxicity Of Vancomycinmentioning

confidence: 99%

Glycopeptides

Gyssens

2013

Fundamentals of Antimicrobial Pharmacokinetics and Pharmacodynamics

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Glycopeptides are a class of antibiotic drugs that is composed of glycosylated cyclic or polycyclic nonribosomal peptides. Older molecules used in clinical practice are vancomycin and teicoplanin. Oritavancin, dalbavancin, and telavancin belong to the subclass of lipoglycopeptides. Glycopeptides inhibit bacterial cell wall peptoglycan synthesis of aerobic and anaerobic Gram-positive bacteria. Glyco (lipo)peptides are not absorbed orally and have to be administered intravenously. In this chapter, the pharmacokinetics (Pk) and the pharmacodynamics (Pd) of the glycopeptides are studied. Pk in serum as well as protein binding and elimination are reviewed. Pharmacodynamic data include MICs of Gram-positive bacteria, PK/Pd effects in in vitro systems, animal models and human studies. Adverse effects of glycopeptides on the host are concentration related nephro-and ototoxicity. In the past, because of fear of toxicity, the older glycopeptides have been underdosed in many settings. The implementation of Pk/Pd knowledge into clinical practice by e.g. administering higher doses of vancomycin and teicoplanin and using continuous infusion of vancomycin is urgently needed. This chapter contains clinical vignettes showing the benefi t of Therapeutic Drug Monitoring of glycopeptides.

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Augmented Gentamicin Ototoxicity Induced by Vancomycin in Guinea Pigs

Cited by 47 publications

References 31 publications

High-Frequency Auditory Feedback Is Not Required for Adult Song Maintenance in Bengalese Finches

High-Frequency Auditory Feedback Is Not Required for Adult Song Maintenance in Bengalese Finches

Ototoxicity of Vancomycin: An Experimental Study in Guinea Pigs

Glycopeptides

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