Tetracyclines: Doxycycline
Overview
Tetracyclines are the prototypical broad-spectrum antibiotics and are occasionally used as first-line agents in some markets (e.g., Germany) for the treatment of mild community-acquired pneumonia, particularly when cost, penicillin hypersensitivity, and β-lactam resistance are concerns.
The widespread use of tetracyclines has resulted in a steady increase in the prevalence of resistance to these agents. Therefore, empiric use of tetracycline is usually restricted to regions where resistance levels remain low or to cases where other appropriate antibiotics are contraindicated. Although some tetracyclines have very low activity against S. pneumoniae, doxycycline maintains good antipneumococcal activity and is the tetracycline most commonly used for treatment of bacterial community-acquired pneumonia.
Tetracyclines are also sometimes used to treat community-acquired pneumonia caused by atypical pathogens. Minocycline (Wyeth’s Minocin, generics) is another widely available tetracycline also used for RTIs, but this agent will not be discussed further owing to its limited use in community-acquired pneumonia. All tetracyclines have important adverse reactions with respect to bones and teeth (i.e., bone deposition and permanent teeth staining), and they are contraindicated during pregnancy and for children younger than age eight. Adverse events most commonly reported include stomach upset, diarrhea, nausea, headache, and vomiting. Additionally, phototoxicity, dizziness, and vertigo may also occur.
Mechanism Of Action
Tetracyclines bind to receptors on the 30S subunit of bacterial ribosomes and prevent the attachment of transfer RNA (tRNA) to the ribosomal complex. Binding to the 30S subunit effectively prevents the addition of new amino acids to the growing polypeptide chain, thus halting the process of protein synthesis. Tetracyclines are usually bacteriostatic, but in some organisms, their effect can be bactericidal at high doses.
Doxycycline
Doxycycline (Pfizer’s Vibramycin, generics) is a broad-spectrum antibiotic derived from oxytetracycline that has been used since the 1960s to treat both gram-negative and gram-positive bacterial infections. It is currently available in oral suspension, capsule, syrup, and IV formulations and has an improved pharmacokinetic profile that includes higher oral bioavailability, greater distribution volume, and longer serum half-life, compared with earlier tetracyclines.
Doxycycline inhibits bacterial protein synthesis by binding to the 30S subunit of the bacterial ribosome and subsequently preventing the addition of new amino acids to the growing polypeptide chain. In a double-blind, multicenter Phase III study, doxycycline (200 mg once daily) was compared with roxithromycin (150 mg twice daily) in 305 patients with lower respiratory tract infections.
The clinical effectiveness of doxycycline was 84%, compared with 83% for roxithromycin. Adverse events most commonly associated with doxycycline include stomach upset, diarrhea, nausea, headache, and vomiting; however, phototoxicity, dizziness, and vertigo can also occur. Doxycyline has been associated with esophagitis and esophageal injury.