Clinical perspective on aztreonam lysine for inhalation in patients with cystic fibrosis.

Progressive obstructive lung disease is a characteristic component of cystic fibrosis (CF). It is the pulmonary manifestations, including obstruction and endobronchial infection, which directly contribute to the premature mortality of patients affected with CF. Due to the devastating effects on the pulmonary system, interest abounds in ways to improve antimicrobial delivery to the lungs and to impact clinical patient outcomes positively, whilst minimizing systemic toxicities. Recently, aztreonam lysine for inhalation solution, a new monobactam formulation, was approved by the US Food and Drug Administration for use in a subgroup of CF patients with Pseudomonas aeruginosa to improve respiratory symptoms. The purpose of this review is to present a summary of relevant pharmacologic, microbiologic, and clinical data related to the use of aztreonam lysine for inhalation in patients with CF.

Tobramycin solution for inhalation in cystic fibrosis patients: a review of the literature.

Cystic fibrosis patients suffer increased sputum production and a notable decline in respiratory function throughout the progression of their disease. Patients are left vulnerable to respiratory colonization/infection from a number of pathogens, including Pseudomonas aeruginosa. At present, the only antibiotic formulation that is FDA approved for aerosolized delivery is tobramycin solution for inhalation (TSI). TSI allows for targeted antibiotic delivery to the lungs and is indicated for maintenance therapy in cystic fibrosis patients infected with P. aeruginosa. Studies demonstrate that cyclical treatment with TSI is associated with an increase in respiratory function and a decrease in sputum density in cystic fibrosis patients. Additional benefits include fewer hospitalizations and a decreased need for systemic antibiotics. However, because of the need for chronic administration, issues such as emergence of resistant organisms and toxicity are a potential concern and have also been evaluated. This review details the pharmacology of TSI and literature involving its use in cystic fibrosis patients.

Aerosolised antibiotics: a critical appraisal of their use.

Aerosolised antimicrobial agents have been used in clinical practice since the 1950s. The main advantage of this route of administration is the targeted drug delivery to the site of infection in the lung. Exploitation of this targeted delivery can yield high concentrations at the site of infection/colonisation while minimising systemic toxicities. It is important to note that the ability of a drug to reach the target area in the lung effectively is dependent on a number of variables, including the nebuliser, patient technique, host anatomy and disease-specific factors. The most convincing data to support the use of aerosolised antimicrobials has been generated with tobramycin solution for inhalation (TOBI, Chiron Corp.) for maintenance treatment in patients with cystic fibrosis. In addition to cystic fibrosis, the use of aerosolised antimicrobials has also been studied for the treatment or prevention of a number of additional disease states including non-cystic fibrosis bronchiectasis, ventilator-associated pneumonia and prophylaxis against pulmonary fungal infections. Key studies evaluating the benefits and shortcomings of aerosolised antimicrobial agents in these areas are reviewed. Although the theory behind aerosolised administration of antibiotics seems to be sound, there are limited data available to support the routine use of this modality. Owing to the gaps still existing in our knowledge base regarding the routine use of aerosolised antibiotics, caution should be exercised when attempting to administer antimicrobials via this route in situations falling outside clearly established indications such as the treatment of patients with cystic fibrosis or Pneumocystis pneumonia.