Ototoxicity gentamicin

In man, differences in the ototoxic risks of the currently used aminoglycosides are difficult to evaluate (20). There have been no prospective comparisons of more than two drugs using the same criteria in similar patient populations. However, several controlled comparisons of two aminoglycosides are available and provide some information. A survey of 24 such trials showed the following mean frequencies of ototoxicity gentamicin 7.7%, tobramycin 9.7%, amikacin 13.8%, netilmicin 2.3% (28). There was also a lower incidence of netilmicin-induced inner ear damage compared with tobramycin in two studies (29,30). 

The risk of ototoxicity from gentamicin in children is probably less than in adults. In many studies of serious neonatal infections treated with gentamicin there have been very few cases that have provided unequivocal evidence of gentamicin-induced ototoxicity. Gentamicin can be an excellent drug in neonatal sepsis, and its potential toxicity should not preclude its use when it is needed. 

T. Finitzo-Hieber, G. McCracken, R. Roeser. D. Allen. D. Chrane. and J. Morrow, Ototoxicity in neonates treated with gentamicin and kanamycin Results of a four year controlled follow-up study. Pediatrics, 63, 445 (1979). 

Stockwell M Gentamicin ear drops and ototoxicity Update. CMAJ 2001 164 93-94. 

Gentamicin is an aminoglycoside. All aminoglycosides tend to be nephrotoxic and ototoxic. The dose must be reduced and serum concentrations must be monitored in patients with impaired renal function. Concomitant administration of aminoglycosides and other nephrotoxic drugs, such as certain diuretics, ciclosporin, teicoplanin and vancomycin should be avoided. 

Ototoxicity with both auditory and vestibulatory effects is the most serious of the adverse reactions of aminogycosides as it is mostly irreversible. Vestibular involvement manifests itself by dizziness, nystagmus, vertigo and ataxia. Cochlear toxicity results initially in high-frequency hearing loss. Amikacin more often causes cochlear damage than vestibular problems, while gentamicin and tobramycin are associated more frequently with vestibular symptoms. 

Adverse effects include skin rash, ototoxicity, nephrotoxicity, phlebitis, nausea, vomiting, urticaria and headache. Ototoxicity and nephrotoxicity is lower than gentamicin. 

Like other aminoglycosides, tobramycin is ototoxic and nephrotoxic. Nephrotoxicity of tobramycin may be slightly less than that of gentamicin, but the difference is clinically inconsequential. 

Neomycin is particularly ototoxic and nephrotoxic when given parenterally. As with gentamicin and kanamycin, the nephrotoxicity may be reversible but the ototoxicity is usually irreversible and deafness may occur following oral administration, instillation into cavities, or topical use. It may block neuromuscular action and respiratory depression has been reported. Local treatments may cause hypersensitivity, rashes, pruritus, and anaphylaxis. Neomycin is not geno-toxic. 

Sisomicin (Figure 8.28) is a dehydro analogue of gentamicin C-ia, and is produced by cultures of Micromonospora inyoensis. It is used medicinally in the form of the semi-synthetic A/-ethyl derivative netilmicin (Figure 8.28), which has a similar activity to gentamicin, but causes less ototoxicity. 

Topical application of neomycin rarely results in detectable serum concentrations. However, in the case of gentamicin, serum concentrations of 1-18 g/mL are possible if the drug is applied in a water-miscible preparation to large areas of denuded skin, as in burned patients. Both drugs are water-soluble and are excreted primarily in the urine. Renal failure may permit the accumulation of these antibiotics, with possible nephrotoxicity, neurotoxicity, and ototoxicity. 

It is important to monitor peak and trough plasma levels (see p. 20) of gentamicin, tobramycin, netilmicin, and amikacin to avoid concentrations that cause dose-related toxicities (Figure 31.7). [Note Peak levels are defined as those obtained 1/2 to 1 hour after infusion. Trough levels are obtained immediately before the next dose.] Patient factors, such as old age, previous exposure to aminoglycosides, gender, and liver disease, tend to predispose patients to adverse reactions. The elderly are particularly susceptible to nephrotoxicity and ototoxicity. 

Conlee, J. W., Gill, S. S., McCandless, P. T., and Creel, D. J., Differential susceptibility to gentamicin ototoxicity between albino and pigmented guinea pigs. Hearing Res., 41, 43,1989. 

LOOP DIURETICS AMINOGLYCOSIDES t risk of ototoxicity and possible deafness as a result of concomitant use of furosemide and gentamicin Both furosemide and gentamicin are associated with ototoxicity this risk is t if they are used together If used concurrently patients should be monitored for any hearing impairment... 

The same spectrum of toxicity (ototoxicity and nephrotoxicity) is shared by all members of the group, The more important and frequent interactions are pharmacodynamic. Streptomycin and gentamicin produce predominantly vestibular effects, whereas amikacin, kanamycin and neomycin primarily affect auditory function. All are rapidly excreted by the kidney,... 

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