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Inhaled Antibiotics: Why TOBI and Other Aminoglycosides Have Such Clinical Importance

Newhouse MT, Labiris R, Freitag A.

RDD Europe 2009. Volume 1, 2009: 35-48.

Abstract:

Aminoglycosides (Ags) have long been used for treating a variety of infections. However, this class of antibiotics has become most closely associated with the therapy of pulmonary pseudomonas aeruginosa (Psa) infection in cystic fibrosis (CF) where it remains the single most important component of a treatment program that, in the past 20 years, has greatly increased life expectancy and quality of life (QOL). Since about 1980, parenteral aminoglycosides (initially gentamicin, later tobramycin and amikacin) have also been administered by inhalation. For the past decade, a preservative-free, tobramycin (TOBI®) solution has replaced the phenol preservative-containing IV dosage form to become the standard of care in the USA. In the past two decades, regularly scheduled intermittent IV and more recently, inhaled aminoglycosides, have been administered to CF patients with chronic Psa infection resulting in fewer exacerbations requiring hospitalization, and increased survival. This led to attempts at Psa eradication of early infection to prevent severe and irreversible lung damage and to minimize antibiotic resistance due to mucoid-type Psa biofilms. Innovative small volume wet nebulizers (e.g., vibrating mesh) and dry powder inhalers (DPIs) have considerably improved aerosol delivery efficiency and speed of administration, making aerosol antibiotics more effective and convenient, thus probably improving adherence. Adverse effects have been virtually eliminated since serum Ags levels are minimal, whereas airway mucosal concentrations may be as much as 10-12 times the sputum levels achieved by systemic administration and about 10 times the minimum inhibitory concentration for resistant Psa. Early Psa eradication therapy with small molecule and eventually with new peptide antibiotics are likely to further increase longevity and quality of life for CF patients.