Tigecycline, a derivative of the tetracycline minocycline, is the first available glycylcycline. Tigecycline inhibits protein synthesis by binding to the 30S ribosomal subunit. It is bacteriostatic.
Tigecycline is given IV. Tigecycline has a large volume of distribution (> 12 L/kg), penetrating well into bone, lung, liver, and kidney tissues. However, because of its extensive distribution into tissue, high blood levels are not maintained, so tigecycline is probably not a good choice for patients with bacteremia.
A half-life of 36 h facilitates once/day dosing.
Most of the drug is excreted in bile and feces.
Tigecycline is effective against many resistant bacteria, including those with resistance to tetracyclines. Tigecycline is active against
Many gram-positive bacteria, including methicillin-susceptible and methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae with reduced penicillin sensitivity, vancomycin-sensitive Enterococcus faecalis, vancomycin-resistant E. faecium,and Listeria sp
Many gram-negative bacteria, such as multidrug-resistant Acinetobacter baumannii, Stenotrophomonas maltophilia, Haemophilus influenzae, and most Enterobacteriaceae (including some strains that produce extended-spectrum β-lactamases [ESBLs] and other strains that were carbapenem-resistant based on production of a carbapenemase or metallo-β-lactamase)
Many atypical respiratory pathogens (chlamydiae, Mycoplasma sp), Mycobacterium abscessus, M. fortuitum, and anaerobes, including Bacteroides fragilis, Clostridium perfringens, and C. difficile
It is not effective against Pseudomonas aeruginosa, Providencia sp, Morganella morganii, or Proteus sp.
Tigecycline is indicated for
However, a recent meta-analysis showed that patients treated with tigecycline (particularly those treated for ventilator-associated pneumonia) had a higher mortality than those given other antibiotics, resulting in a black box warning from the FDA. In general, tigecycline should be reserved for infections with multidrug-resistant (MDR) organisms when other treatment options are more toxic or less effective. Because of its parenteral activity against C. difficile, tigecycline may be a useful antibiotic when a patient requires concurrent treatment of an MDR infection and a C. difficile infection.
Tigecycline is in pregnancy category D (there is evidence of human risk, but clinical benefits may outweigh risk); it, like tetracyclines, can affect fetal bones and teeth.
Whether tigecycline enters breast milk and is safe to use during breastfeeding is unknown; however, it has limited oral bioavailability.
Adverse effects include
Nausea and vomiting are common. Increases in serum amylase, total bilirubin concentration, PT, and transaminases can occur in patients treated with tigecycline. Isolated cases of significant hepatic dysfunction and hepatic failure have been reported in patients being treated with tigecycline. Many of tigecycline’s adverse effects are similar to those of tetracyclines (eg, photosensitivity).