Cephalosporins have traditionally been one of the most commonly used antibacterial classes for the treatment of respiratory tract infections. In recent years, drug development within this class has been limited owing to competitiveness, the lack of novel candidates, and high development costs relative to return. Cephalosporins differ widely in their spectrum of activity, susceptibility to β-lactamases produced by bacteria, and serum half-life. Dong-A pharmaceuticals in South Korea is developing DA-7101, indicated for the potential treatment of respiratory and urinary tract infections.
Ketolides: Cethromycin
Ketolides are a new class of antibacterials specially designed to combat respiratory tract pathogens that have acquired resistance to macrolides. The ketolides are derivatives of the macrolide erythromycin A.
Streptogramins
Streptogramins are produced by streptomycetes and are classified as A or B compounds, based on their mechanism of action as outlined below. As a class, streptogramin A and B compounds are bacteriostatic when used separately.
Peptide Deformylase Inhibitors
Peptide deformylase is an essential bacterial metalloenzyme required for protein synthesis and thus represents a good target for antibacterial therapy. Peptide deformylase inhibitors act on the peptide deformylase enzyme, disrupting protein maturation and inhibiting protein synthesis.
Dihydrofolate Reductase Inhibitors
The dihydrofolate reductase (DHFR) inhibitors target bacterial DHFR, an enzyme involved in the folic acid pathway, thereby disrupting bacterial replication. DHFR inhibitors target both gram-positive and gram negative-bacteria and hence could serve as broad-spectrum antibacterials.
Glycopeptides
Glycopeptides are used for the treatment of severe or life-threatening infections that are caused by gram-positive organisms such as streptococci and staphylococci. In acute exacerbations of chronic bronchitis , they are used rarely.
Tetracyclines
Tetracyclines are the prototypical broad-spectrum antibiotic and are occasionally used as first-line agents in some markets (e.g., Germany) for the treatment of mild acute exacerbations of chronic bronchitis, particularly when cost, penicillin hypersensitivity, and β-lactam resistance are of concern. The widespread use of tetracyclines has resulted in a steady increase in the prevalence of resistance to these agents. Therefore, empiric use of tetracyclines is usually restricted to regions where resistance levels remain low or when other appropriate antibiotics are contraindicated.
Fluoroquinolones
Fluoroquinolones are broad-spectrum antibacterials that have experienced an upsurge in use in recent years. Because of their broad-spectrum activity, high efficacy, favorable dosing, and availability in oral and IV form, these agents are indicated for a range of bacterial infections, including respiratory, GI, and urinary tract infections. Earlier generations of fluoroquinolones (e.g., ofloxacin) had limited activity against some respiratory pathogens, such as S. pneumoniae. However, more recent fluoroquinolone agents (so-called third-generation agents or the “respiratory fluoroquinolones”) are active against a broad spectrum of gram-positive and gram-negative bacteria, including atypical organisms.
Moxifloxacin
Moxifloxacin displays excellent activity against a broad spectrum of bacteria, including penicillin- and macrolide-resistant S. pneumoniae.
Ketolides
Ketolides are a new class of macrolide derivatives designed specifically to combat macro fide-resistant respiratory tract pathogens. The ketolides are semisynthetic derivatives of the macrolide erythromycin A, with a keto group replacing the 1-cladinose group at position 3 of the macrolactone ring. The ketolides exhibit good activity against gram-positive and some gram-negative organisms, and have excellent activity against drug-resistant S. pneumoniae, including macrolide-resistant strains.