Antibiotic, Antifungal, Antiviral Drugs

The penicillins comprise several subgroups of agents with a wide range of bacterial coverage and efficacy. Each penicillin molecule contains a basic β-lactam structure fused to a five-membered ring. Because of their broad spectrum of activity and availability in oral form, the penicillins are commonly used in the treatment of acute exacerbations of chronic bronchitis and have become the drugs of choice in treating many common infections. The penicillins are further divided into the following groups: natural penicillins, aminopenicillins, and the extended-spectrum penicillins.

The product is available in immediate-release tablets, extra-strength and extended-release tablets, oral suspension, chewable tablets, and parenteral form (in Europe only). GlaxoSmithKline is attempting to retain sales of its amoxicillin/clavulanate franchise with the branded Augmentin XR and ES formulations, following the market entry of generic competitors to Augmentin in 2002.

TABLE: Pharmacological Management of Underlying Disease During an Acute Exacerbation of Chronic Bronchitis summarizes the general pharmacological agents and classes used to manage acute exacerbations of chronic bronchitis. The primary therapies used in acute exacerbations of chronic bronchitis treat the causative infection (antibiotics), relieve symptoms (bronchodilators), and treat the underlying inflammation (corticosteroids). TABLE: Current Therapies Used for Acute Exacerbations of Chronic Bronchitis summarizes the leading antibiotic therapies used to treat the infection.

Comparisons of clinical efficacy across major classes of antibacterials suggest that many compounds achieve comparable clinical efficacy in resolving infection. Indeed, most clinical trials demonstrate clinical equivalence rather than superiority of one agent over another.

Infection associated with acute exacerbations of chronic bronchitis is usually localized to the pulmonary mucosa. Most bacteria that infect the bronchial tree either reside as commensal organisms in the nasopharynx (e.g., H. influenzae) or act as opportunistic pathogens invading hosts with suppressed immune systems (e.g., P. aeruginosa). Mucosal infections are usually superficial, and most bacteria reside in the lumen, associating with mucus or other secretions. Some pathogenic bacteria adhere to the epithelial surface, particularly in areas of epithelial damage, while others infiltrate the mucosa.

The abundance of neutrophils in sputum collected from chronic bronchitis or acute exacerbations of chronic obstructive pulmonary disease patients during an exacerbation suggests a primary or secondary bacterial infection. Increases in bacterial flora without increases in neutrophil cell count are more suggestive of a bacterial colonization rather than an acute exacerbation. As such, an increase in cough/sputum production alone in chronic bronchitis or acute exacerbations of chronic obstructive pulmonary disease patients is not indicative of an infectious exacerbation.

The increase in antibiotic-resistant organisms has compromised the empiric use of certain antibiotics in the management of acute exacerbations of chronic bronchitis. Studies have shown that resistance in the community of the main causative pathogens in acute exacerbations of chronic bronchitis — H. influenzae, M. catarrhalis, and S. pneumoniae — has increased significantly over time. Patients with severe lung disease are more likely to harbor pathogens (e.g., P. aeruginosa) that are resistant to first-line antibiotics and therefore may be more likely to fail such therapy.

Acute exacerbations of chronic bronchitis is a disease that occurs in patients who suffer from chronic underlying airway disease, typically related to tobacco smoking. It does not commonly occur among healthy children or adults.

Chronic Underlying Airway Disease Acute exacerbations of chronic obstructive pulmonary disease is an umbrella term that includes the entities of chronic bronchitis and emphysema when they are associated with airflow limitation. Ordinarily, asthma, cystic fibrosis, bronchiectasis, and bronchiolitis obliterans (other bronchitic syndromes) are excluded from this definition.

Among episodes of infectious etiology, aerobic gram-positive and gram-negative bacteria (50-75%), atypical pathogens (1-10%), and respiratory viruses (30%) are the primary pathogens associated with acute exacerbations of chronic bronchitis. The relative contribution of these pathogens differs depending on the severity of the underlying airway disease. Approximately 30% of all acute exacerbations are precipitated by respiratory viruses.