Safety of aerosol tobramycin administration for 3 months to patients with cystic fibrosis

Abstract

To determine the potential toxicity of prolonged aerosol tobramycin administration, 22 patients with cystic fibrosis were monitored while receiving inhaled tobramycin three times a day for 12 weeks. Prior to, four times during administration and approximately 6 weeks after discontinuation of treatment, we assessed pulmonary function, weight, height, body temperature, eighth cranial nerve function, serum creatinine, blood urea nitrogen, urinary creatinine clearance, plasma iothalamate clearance, urinary beta-2 microglobulin concentration, and Pseudomonas aeruginosa density in sputum. There was no detectable laboratory evidence of nephrotoxicity. Neither a decrease in auditory acuity (range 250-20,000 Hz) nor vestibular dysfunction was detected. Pulmonary function tests significantly improved during the first month in all subjects (P less than 0.05) but returned to enrollment values by the end of the 12th week of administration of tobramycin aerosol. Sputum P. aeruginosa density initially decreased from a mean of 10(7) cfu/gm to a mean of 10(4) cfu/gm after 2 weeks of aerosol tobramycin administration and remained significantly below the enrollment value throughout. Coincident with the reduced bacterial density, a reduction in cough frequency and sputum production, as well as a weight gain was observed. Seventy-three percent of the patients with sputum P. aeruginosa isolates susceptible to tobramycin on enrollment yielded resistant organisms during aerosol administration. However, 1 year later all sputum P. aeruginosa isolates obtained from patients were susceptible to tobramycin. We conclude that thrice daily aerosol tobramycin administration for 3 months is not associated with detectable eighth cranial nerve or renal toxicity. Transient emergence of tobramycin resistant P. aeruginosa may occur.

A phase 2 study of aztreonam lysine for inhalation to treat patients with cystic fibrosis and Pseudomonas aeruginosa infection

“…22,23 Median sputum aztreonam concentrations 10 min after the first dose of 75 and 225 mg AZLI were above the parenteral breakpoint for aztreonam and well in excess of the baseline MIC 50 and MIC 90 values for these patients. Observed sputum concentrations demonstrate that no significant dose accumulation occurred after 1 week of treatment, this is consistent with results of the previous Phase 1b study.…”

Bronchial Hyperreactivity Related to Inhalation Therapy in Cystic Fibrosis Patients

“…Some authors did not report on or did not find airway narrowing, [77][78][79][80]83,[86][87] or did not specify whether airway narrowing itself was one of the observed 'adverse events' [90]. Airway narrowing within 30 minutes post-inhalation of the preservative-free solution was transient and similar to that observed after inhalation of placebo [77].…”

Pediatric Aerosol Therapy: New Devices and New Drugs

“…Nevertheless, antimicrobial resistance continues to increase and is time dependent; but resistance will reverse if the drug is stopped for a sufficiently long duration. 19 Although the risk of renal dysfunction and hearing loss are decreased, these are not eliminated by aerosol administration. 20 Patients who receive inhaled gentamicin have nephrotoxicity related to the cumulative dose.…”