Introduction

The inhalation of antimicrobial agents to treat infections in the lung has been of interest for decades [1]. As early as the 1950s, extemporaneously prepared antimicrobial agents were aerosolized to treat pneumonia. These preparations were often crude and not well tolerated by patients. Dosage, formulation procedures, and stability assessment in these early reports were not consistent. Although some successes were reported, the potential benefit of this route of administration was not fully appreciated until the 1980s.

A number of antibiotics have been used as aerosol therapies. Examples include beta lactam agents, polymycin antimicrobials, neomycin, gentamicin, and tobramycin. Many of the early efforts were reported as case studies, and observations and data regarding safety and efficacy were lacking. Controlled clinical trials were not conducted until the middle of the 1980s. More recent evaluations have focused on the role of inhaled tobramycin used as suppressive therapy for cystic fibrosis patients colonized with Pseudomonas aeruginosa.

Currently, there is a paucity of antimicrobial products delivered by aerosolization. Pentamidine and tobramycin are the only two agents approved for use in the United States as aerosolized antimicrobial therapies. However, interest in using the lung as a site of delivery of therapeutic agents has continued to evolve, and several therapies are under investigation for both local and systemic effects [2].

The delivery of antibiotics to the lower airway through aerosolization offers several theoretical advantages over systemically administered therapy [3,4]. It allows for direct deposition at the site of infection, resulting in high concentrations that may be beneficial in eradicating bacteria. The risk of adverse or toxic effects may be lower as a result of this method of administration.

Much of the interest in aerosol therapy has focused on the management of patients with cystic fibrosis and has extended beyond the use of aerosolized antibiotics to various proteins and biotechnological therapies. The use of these therapies is discussed elsewhere in this publication (see Chs. 16, 17). Recent advances in the use of antibiotics directed against bacterial infections and technologic improvements of delivery systems has spurred additional research into the use of antifungal and antiviral therapies as well [5].

Although antimicrobial therapies have been delivered by aerosolization for over five decades, much is still unknown or not well understood. For example, there are few data to help guide dosing of these therapies. For optimal benefit, an understanding of the clinical utility, as well as the physiologic, physical, chemical, and delivery considerations is essential [6].

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