Author: Brian Holtry

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 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.

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 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 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 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 displays excellent activity against a broad spectrum of bacteria, including penicillin- and macrolide-resistant S. pneumoniae.

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.

Macrolides inhibit bacterial protein synthesis. They demonstrate excellent activity against atypical organisms (Mycoplasma, Chlamydia, and Legionella species), but their activity against typical pathogens (H. influenzae and S. pneumoniae) is variable. Macrolides are indicated for use in acute exacerbations of chronic bronchitis and are typically used as first- and second-line agents for this indication.

Carbapenems are penicillin derivatives that have good activity against gram-positive and gram-negative aerobic and anaerobic bacteria. They are highly resistant to β-lactamase and have a very favorable spectrum of activity. A drawback of these agents is that they are available in IV form only.