Use of Aerosolized Antibiotics in Patients With Cystic Fibrosis: Safety of Aerosolized Preservative-Free 300-mg Dose of Tobramycin
Nephrotoxicity: Nephrotoxicity has been documented with IV use of tobramycin. Nephrotoxicity has been evaluated in several studies of aerosolized tobramycin using several parameters to assess renal function (Table 2); to our knowledge, no studies have documented nephrotoxicity.
Ototoxicity: Ototoxicity has been documented with IV use of tobramycin. The study by Ramsey et al, using 600 mg of aerosolized tobramycin three times a day, assessed vestibular function and hearing. The dynamic E test did not document vestibular toxicity and audiograms performed between 500 and 8,000 Hz did not document hearing loss as defined by a > 20-dB increase in threshold after enrollment. Likewise, Smith et al did not detect a change in auditory threshold up to 20,000 Hz or in performance of the dynamic E test.
Bronchospasm: Bronchospasm occurs in some asthmatic patients with inhalation of sulfites. Pretreatment with (3-agonists decreases this side effect. Antioxidants such as sodium bisulfite and preservatives such as phenol are contained in commercial preparations of tobramycin for parenteral use. Thus, a preservative-free preparation has been developed for aerosol use in CF patients. this
Safety of Aerosolized Preservative-Free 300-mg Dose of Tobramycin
The phase III preservative-free tobramycin trials are the most comprehensive examination of the safety of aerosolized tobramycin. The nonmicrobio-logical risks of aerosolized tobramycin include those related to systemic exposure and local airway effects.
Tinnitus was experienced by 8 of 258 (3%) tobramycin-treated patients and in none of the patients who received placebo. All of the episodes were transient and characterized as mild or moderate in severity. In these patients, results of audiology testing were normal, although not always performed during tinnitus, and none of the patients discontinued tobramycin treatments. None of the remaining patients had evidence of ototoxicity. Nephrotoxicity as determined by BUN and creatinine values was not seen in treated patients.
The only adverse event related to aerosol delivery was voice alteration that occurred in 30 of 258 (12%) of patients receiving aerosolized 300 mg of preservative-free tobramycin. Most episodes were characterized as mild in severity. Spirometry obtained immediately before and 30 min after the nebulized dose detected that 62 of 258 (24%) patients in the treatment group experienced a > 10% decrease in FEV1 30 min after study drug administration. All but four of these patients had been prescribed broncho-dilators prior to baseline, suggesting a history of bronchospasm.
Table 2—E-valuation of the Effect of Aerosolized Tobramycin on Renal Function
|Source||No. of Patients||Duration (Dosage)||Parameter of Renal Function Assessed||Findings*|
|Smith et al||22||12 wk (666 mg tid)||BUN, Cr,t urine2 microglobulin urine analysis, Cr clearance, plasma/renal iothalamate CI||No changes|
|Ramsey et al||71||4 wk (600 mg tid)||BUN, Cr||No difference|
|MacLusky et al||27||32 mo (mean 80 mg tid)||BUN, Cr||No changes|
|Steinkamp et al||14||20 mo (mean 80 mg tid)||Cr, N-acetyl-p-D-glucosaminase||No changes|
|Ramsey et al||249||6 mo (300 mg bid)||Cr||No difference|