Ototoxicity tobramycin

Which of the following complaints by a patient taking tobramycin would be most indicative the patient is experiencing ototoxicity ... 

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. 

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. 

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. 

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). 

In rats, ototoxicity caused by gentamicin or tobramycin was amehorated by melatonin, which did not interfere with the antibiotic action of the aminoglycosides (70). The free radical scavenging agent alpha-lipoic acid has previously been shown to protect against the cochlear adverse effects of systemically administered aminoglycoside antibiotics, and in a recent animal study it also prevented cochlear toxicity after the administration of neomycin 5% directly to the round window membrane over 7 days (71). 

The pharmacokinetics of once-daily intravenous tobramycin have been investigated in seven children with cystic fibrosis (162). All responded well. There was one case of transient ototoxicity but no nephrotoxicity. 

Bolus intraperitoneal gentamicin or tobramycin (5 mg/kg ideal body weight) is safe, achieves therapeutic blood concentrations for extended intervals, causes no clinical ototoxicity or vestibular toxicity, is cost-effective, and is convenient for patients and nurses (170). 

Histological examination of the temporal bones from two individuals with ototoxicity due to tobramycin showed reductions in the numbers of both ganglion cells and hair cells (21). Spiral ganglion cell loss was not necessarily subadjacent to areas of hair cell loss in cases of aminoglycoside ototoxicity. Instead, there may be a reduction in the number of ganglion cells in segments of the cochlea with normal-appearing hair cells. 

During multiple daily dosing peak serum concentrations of tobramycin over 5-7 pg/ml are associated with improved survival in patients with septicemia and pneumonia caused by Gram-negative bacteria (52,53). On the other hand, excessive peak concentrations (over 10-12 pg/ml) and trough concentrations (over 2 pg/ml) of tobramycin increase the risk of ototoxicity and nephrotoxicity (54). 

With aminoglycosides, systemic therapy is associated with a risk of ototoxicity and nephrotoxicity. However, no toxicity has been reported in several well-controlled trials of inhaled tobramycin in which subjects received repetitive courses [31,32]. 

In hypercalcemia, excessive volume depletion, hyponatremia, and hypotension are major risks associated with the use of loop diuretics, and the side effects of hypokalemia, hyperuricemia, and hyperglycemia are always present. Loop diuretics should not be used concurrently with ototoxic aminoglycoside antibiotics (i.e., streptomycin, gentamicin, kanamycin, tobramycin). 

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