Long‐term tobramycin aerosol therapy in cystic fibrosis

Abstract

The long-term efficacy and safety of aminoglycoside aerosol therapy for Pseudomonas aeruginosa colonization/infection in cystic fibrosis has not been fully investigated. In the present study, 14 patients with cystic fibrosis, ages 8-19 years (mean: 13.3 years), received tobramycin aerosol therapy for a mean duration of 20 months. Eighty milligrams of a tobramycin solution were inhaled twice daily after physiotherapy via a jet nebulizer. After 1 year, weight for height increased significantly by 2.9% of the predicted normal, and the Kraemer clinical score increased by 2.1 points (P less than 0.05). The frequency of hospital admissions decreased from 2.0 to 1.3 per patient, respectively, during the years before and after the study onset. The antibody response to P. aeruginosa elastase, exotoxin A, and alkaline phosphatase showed a reduction in serum titers against one or more enzymes in eight patients. The best long-term results after 12-38 months of treatment were obtained in moderately ill children. No evidence of ototoxicity or renal damage was observed. Although intermittent bacterial resistance occurred in five patients after 10-21 months of tobramycin inhalation, this was not associated with clinical deterioration. The study demonstrates the safety and clinical efficacy of long-term tobramycin aerosol therapy. Double-blind studies with larger patient cohorts are required to determine the value of aminoglycoside inhalation as an adjunct to the established therapeutic regimens.

Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus

“…The emergence of resistant micro-organisms does not necessarily lead to a poor response to repeated treatment [41,44,47,50,51]. Nevertheless, the emergence of multiresistant P. aeruginosa strains from CF patients is well known.…”

“…Several studies using aerosolized antibiotics in CF patients have been performed often with variable results [33,45,50,51,141,143,144]. Besides aminoglycosides (gentamicin [144], tobramycin [33, 44, 45, 47, 51] and b-lactam antibiotics (ceftazidime [50] carbenicillin [143]), combinations of both classes have been used [50,60].…”

“…Despite these methodological difficulties, most of the studies showed improved lung function [33,45,47,50,143,144] or slowing of the deterioration of lung function [33,44,51] in the active treatment group compared to placebo. Additionally, most studies report a reduction in the number of hospital admissions [50,51,143,144] and some report on a reduction of P. aeruginosa numbers [47,145]. Only one study demonstrated a decrease in inflammation by treatment with aerosolized antibiotics [51].…”

“…Additionally, most studies report a reduction in the number of hospital admissions [50,51,143,144] and some report on a reduction of P. aeruginosa numbers [47,145]. Only one study demonstrated a decrease in inflammation by treatment with aerosolized antibiotics [51]. A review of five randomized controlled trials [33, 43, 50, 143] showed benefit for nebulized antipseudomonal antibiotic therapy with no demonstrable adverse effects [147].…”

“…In general, the distribution of a drug in the CF lung is not homogenous, but focal in the larger central lung areas [164,174,175]. Hence, it is quite conceivable that CF patients with mild disease and low sputum production improve the most from aerosol antibiotic therapy [51], suggesting that early antipseudomonal treatment with aerosolized antibiotics is most effective. Consequently, it has also been suggested that antibiotic aerosolization should be preceded by physiotherapy, bronchodilators [176], mucolytic agents [177,178], 1% N-acetylcysteine [179] or recombinant human deoxyribonuclease (rhDNase) [180].…”