Tract InfectionsINTRODUCTION

In the U.S., community-acquired respiratory tract infections (RTIs), including acute bacterial sinusitis (ABS), community-acquired pneumonia (CAP), and acute exacerbations of chronic bronchitis (AECB), are prevalent conditions and constitute a substantial socioeconomic burden. Indeed, infections of the lower respiratory tract (i.e., CAP and AECB) represent a particular public health concern because of the morbidity and mortality associated with these infections.

The treatment of outpatient community-acquired RTIs is usually empirical, because the causative pathogen is rarely identified before the initiation of antibiotic therapy. Antibiotic therapies recommended by current treatment guidelines are therefore aimed at eradicating the key common causative pathogens, including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Antibiotic coverage of atypical organisms, such as Mycoplasma pneumoniae, Chlamy-dophila (Chlamydia) pneumoniae, and Legionella pneumophila (which is associated with significant morbidity and mortality), is also recommended, particularly in CAP and, to a lesser degree, in AECB.
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The development and spread of antibiotic resistance among respiratory pathogens, particularly S. pneumoniae, now represent a key challenge in the management of RTIs. For example, high levels of pneumococcal resistance to macrolide antibiotics have led to concerns over the continued clinical efficacy of these agents. Although increased concentrations of antibiotics may be able to overcome the effects of such resistance in vitro, the bioavailability and tolerability characteristics of current oral therapies generally prevent the use of higher doses of these agents in the outpatient setting. Furthermore, the intravenous (IV) route provides a means of administering high-dose to hospitalized patients, but the costs associated with IV therapy have resulted in a preference for moving patients to oral therapy as soon as they are clinically stable. Such factors highlight the need for new oral antibiotics with activity against key respiratory pathogens, in particular, strains of S. pneumoniae resistant to currently available agents.

In this article, we review the extent of the resistance problem in the U.S., assess the clinical and economic implications of such resistance, and provide an overview of the key characteristics of antibiotics currently available for the empirical treatment of outpatients with community-acquired RTIs, including newer classes of agents such as the respiratory fluoroquinolones and ketolides.