Tigecycline, a derivative of the tetracycline minocycline, is the first available glycylcycline antibiotic. Tigecycline inhibits protein synthesis by binding to the 30S ribosomal subunit. It is bacteriostatic.
Pharmacokinetics
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, blood levels are low, so tigecycline is probably not a good choice for patients with bacteremia especially those with intravascular sources of infection.
Most of the drug is excreted in bile and feces. No dosing adjustment is required in patients who have renal insufficiency.
Indications for Tigecycline
Tigecycline is effective against many resistant bacteria, including those with resistance to tetracyclines. Tigecycline has in vitro activity against the following:
Many gram-positive bacteria, including methicillin-susceptible and methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae that are penicillin-susceptible, and vancomycin-susceptible Enterococcus faecalis
Many gram-negative bacteria, such as multidrug-resistant Acinetobacter baumannii, Stenotrophomonas maltophilia, beta-lactamase–negative Haemophilus influenzae, and most Enterobacterales (formerly Enterobacteriaceae; including some strains that produce extended-spectrum beta-lactamases [ESBLs] and other strains that were carbapenem-resistant based on production of a carbapenemase or metallo-beta-lactamase)
Many atypical respiratory pathogens (chlamydiae, Mycoplasma species), Mycobacterium abscessus, M. fortuitum, and anaerobes, including Bacteroides fragilis, Clostridium perfringens, and Clostridioides difficile (formerly Clostridium difficile)
It is not effective against Pseudomonas aeruginosa, Providencia species, Morganella morganii, or Proteus species.
Tigecycline is indicated for
Complicated skin and soft-tissue infections
Complicated intra-abdominal infections
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 U.S. Food and Drug Administration. 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.
Contraindications to Tigecycline
Tigecycline is contraindicated in patients who have had an allergic reaction to it and in children < 8 years of age.
Tigecycline has a black box warning because it increases the risk of mortality and so should be reserved for situations where there are no suitable alternatives.
Use During Pregnancy and Breastfeeding
Tigecycline, like tetracyclines, can affect fetal bones and teeth. If a pregnant woman takes it during the 2nd or 3rd trimester, it may cause permanent discoloration of the fetus's teeth.
Whether tigecycline enters breast milk and is safe to use during breastfeeding is unknown; however, it has limited oral bioavailability.
Adverse Effects of Tigecycline
Adverse effects of tigecycline include
Nausea, vomiting, and diarrhea
Photosensitivity
Hepatotoxicity
Nausea and vomiting are common. Increases in serum amylase, total bilirubin concentration, prothrombin time, 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).
Dosing Considerations for Tigecycline
Dose is adjusted in patients with hepatic dysfunction but not in those with renal dysfunction.
Serum levels of warfarin may increase, but international normalized ratio does not appear to increase.