Tigecycline (Tygacil): the first in the glycylcycline class of antibiotics

Tigecycline is the first drug in the glycylcycline class of antibiotics. Although it is structurally related to minocycline, alterations to the molecule resulted in its expanded spectrum of activity and decreased susceptibility to the development of resistance when compared with other tetracycline antibiotics. Tigecycline has a broad spectrum of activity, including activity against drug-resistant gram-positive organisms. Randomized trials have shown tigecycline to be efficacious for the treatment of complicated intraabdominal infections and complicated skin and skin structure infections. The dose of tigecycline is 50 mg intravenously every 12 hours after a 100-mg loading dose. Nausea, vomiting, and diarrhea were the most common adverse events reported with tigecycline therapy and may result in discontinuation of therapy. Resistant organisms remain a concern in hospitalized patients and are becoming an increased concern in community-acquired infections. Gram-positive organisms continue to increase in resistance, and very few agents are available to treat these infections. Available options include vancomycin, linezolid, daptomycin, and quinupristin/ dalfopristin. These antimicrobials have improved treatment of resistant gram-positive organisms but may have adverse events that require discontinuation. For this reason, new antimicrobials are needed to treat resistant organisms without sacrificing safety. Tetracyclines are broad-spectrum antibiotics that have been available since the mid-1900s, but use in recent years has been limited by widespread resistance to these agents. Resistance generally occurs by alterations in tetracycline efflux or ribosomal protection. The glycylcyclines were developed to help overcome these resistance mechanisms. Tigecycline, approved by the Food and Drug Administration (FDA) on June 15, 2005, is the first drug in this class of antimicrobials. Alterations to the tetracycline structure allow tigecycline to maintain activity against tetracycline-resistant organisms, including resistant gram-positive organisms such as penicillin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE), and vancomycin-resistant Enterococcus (VRE) species. Tigecycline is approved for the treatment of complicated skin and skin structure infections (cSSSI) and complicated intraabdominal infections caused by susceptible organisms (1). Tigecycline is a glycylcycline antimicrobial structurally related to minocycline. Like minocycline, tigecycline binds to the bacterial 30S ribosome, blocking the entry of transfer RNA. This ultimately prevents protein synthesis by halting the incorporation of amino acids into peptide chains and thus limits bacterial growth (1–3). However, the addition of an N,N,-dimethylglycylamido group at the 9 position of the minocycline molecule increases the affinity of tigecycline for the ribosomal target up to 5 times when compared with minocycline or tetracycline (4). This allows for an expanded spectrum of activity and decreased susceptibility to the development of resistance (1, 2, 5).