Tobramycin toxicity

With combined inhalational and intravenous tobramycin, toxic serum drug concentrations can occur (48). 

A prospective, single-centre study assessing once daily intravenous tobramycin dosing to treat pulmonary exacerbations of CF noted two cases (8%) of transient vestibular disturbance, without any significant nephrotoxicity. Vestibular disturbance appeared to be an early indicator of tobramycin toxicity [18 ]. Cessation of therapy or dose reduction with careful monitoring should be considered in patients experiencing vestibular symptoms. 

The answer is a. (Hardman, pp 1105-1108.) The activity of streptomycin is bactericidal for the tubercle bacillus organism. Other aminoglycosides (e.g., gentamicin, tobramycin, neomycin, amikacin, and kanamycin) have activity against this organism but are seldom used clinically because of toxicity or development of resistance. 

Monitoring In patients with normal renal function, serum tobramycin concentrations are approximately 1 mcg/mL 1 hour after dose administration. Monitoring of serum concentrations in patients with renal dysfunction or patients treated with concomitant parenteral tobramycin may reduce the risk of toxicity. 

Renal toxicity - Renal toxicity may be characterized by decreased creatinine clearance, cells or casts in the urine, decreased urine specific gravity, oliguria, proteinuria, or evidence of nitrogen retention. Renal damage is usually reversible. The relative nephrotoxicity of these agents is estimated to be Kanamycin = Amikacin = Gentamicin = Tobramycin Streptomycin. 

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. 

Aminoglycosides are a group of bactericidal antibiotics originally obtained from various streptomyces species and sharing chemical, antimicrobial, pharmacologic, and toxic characteristics. The group includes streptomycin, neomycin, kanamycin, amikacin, gentamicin, tobramycin, sisomicin, netilmicin, and others. 

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. 

As with gentamicin, toxic psychoses can occur with tobramycin (622). 

Side effects produced by topical gentamicin or tobramycin are imcommon but can include corneal and conjunctival toxicity. Punctate epithelial erosions, delayed reepithelialization, and corneal ulceration characterize this corneal toxicity, whereas chemosis, hyperemia, and necrosis characterize conjimctival toxicity. Allergic reactions to topical gentamicin occur infrequently, but approximately 50% of patients who are allergic to neomycin are also allergic to gentamicin. 

Associated toxic epithelial keratitis should respond to blepharitis treatment. Topical steroids are generally not required imless the cornea is significantly involved or a phlyctenule is present. In this case prednisolone 0.12% used two or three times a day for a few days may be used. Combination steroid-antibiotic ointments, such as tobramycin-dexamethasone or the topical combination drop tobramycin-loteprednol, may prove to be useful for those patients complaining of excessive itching and burning. Steroids control the hypersensitivity component that is often present and reduce the congestion and irritation that often provoke the patient to rub the eye and aggravate the blepharitis. 

Initial treatment of bacterial ophthalmia neonatorum should be directed by the results of conjimctival smears. Broad-spectrum antibiotics with low toxicity should be used. Topical erythromycin or tetracycline ointment can be used four to six times daily fc>r gram-positive organisms, and gentamicin or tobramycin solution four to six times daily can be started if gram-negative organisms are isolated. Trimethoprim-polymyxin B (Polytrim) has... 

Topical uses. Neomycin and framycetin, whilst too toxic for systemic use, are effective for topical treatment of infections of the conjunctiva or external ear. They are sometimes used in antimicrobial combinations selectively to decontaminate the bowel of patients who are to receive intense immunosuppressive therapy. Tobramycin is given by inhalation for therapy of infective exacerbations of cystic fibrosis. 

Gentamicin and tobramycin ophthalmic preparations are commonly used to treat difficult ear infections. The latter is less toxic than gentamicin, and its activity against Pseudomonas is higher. These antibacterial... 

After administration of the recommended doses of amikacin for 10 days, renal damage probably occurs in less than 10% of cases. Limited data support the view that amikacin is less nephrotoxic than other aminoglycosides, possibly because of lower binding affinity to proximal tubular cells or reduced potential to cause phospholipidosis (SEDA-20,236). In several prospective randomized studies the liability of amikacin to cause nephrotoxicity was no greater than that of gentamicin or tobramycin (6-8). In a prospective study there was significantly lower nephrotoxicity with amikacin 15 mg/kg/day (4% toxicity) compared with netilmicin 7 mg/kg/day (12%) (9). As with other aminoglycosides, renal toxicity is reversible in most cases (10). 

In 40 patients tobramycin had little effect on audiometric thresholds, but produced a change in the amplitude of the distortion products, currently considered an objective method for rapidly evaluating the functional status of the cochlea (17). In one case, tobramycin caused bilateral high-frequency vestibular toxicity, which subsequently showed clinical and objective evidence of functional recovery (18). 

There are interesting differences in the toxicity patterns of aminoglycosides in animals. Gentamicin and tobramycin affect the cochlear and vestibular systems to a similar extent, while amikacin, kanamycin, and neomycin preferentially damage the cochlear and streptomycin the vestibular system. Netilmicin appears to be the least toxic (26,27). 

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). 

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