Mechanism of Action
Tigecycline inhibits protein translation in bacteria by binding to the 30S ribosomal subunit and blocking entry of amino-acyl tRNA molecules into the A site of the ribosome. This prevents incorporation of amino acid residues into elongating peptide chains. In general, tigecycline is considered bacteriostatic; however, TYGACIL has demonstrated bactericidal activity against isolates of S. pneumoniae and L. pneumophila.
Resistance
To date there has been no cross-resistance observed between tigecycline and other antibacterial drugs. Tigecycline is less affected by the two major tetracycline-resistance mechanisms, ribosomal protection and efflux. Additionally, tigecycline is not affected by resistance mechanisms such as beta-lactamases (including extended spectrum beta-lactamases), target-site modifications, macrolide efflux pumps or enzyme target changes (e.g., gyrase/topoisomerases). However, some ESBL-producing isolates may confer resistance to tigecycline via other resistance mechanisms. Tigecycline resistance in some bacteria (e.g., Acinetobacter calcoaceticus-Acinetobacter baumannii complex) is associated with multi-drug resistant (MDR) efflux pumps.
Interaction with Other Antimicrobials
In vitro studies have not demonstrated antagonism between tigecycline and other commonly used antibacterial drugs.
Antimicrobial Activity
Tigecycline has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections [see Indications and Usage (1)].
Gram-positive bacteria
Enterococcus faecalis (vancomycin-susceptible isolates)
Staphylococcus aureus (methicillin-susceptible and -resistant isolates)
Streptococcus agalactiae
Streptococcus anginosus group (includes S. anginosus, S. intermedius, and S. constellatus)
Streptococcus pneumoniae (penicillin-susceptible isolates)
Streptococcus pyogenes
Gram-negative bacteria
Citrobacter freundii
Enterobacter cloacae
Escherichia coli
Haemophilus influenzae
Klebsiella oxytoca
Klebsiella pneumoniae
Legionella pneumophila
Anaerobic bacteria
Bacteroides fragilis
Bacteroides thetaiotaomicron
Bacteroides uniformis
Bacteroides vulgatus
Clostridium perfringens
Peptostreptococcus micros
The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for tigecycline against isolates of similar genus or organism group. However, the efficacy of tigecycline in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled clinical trials.
Gram-positive bacteria
Enterococcus avium
Enterococcus casseliflavus
Enterococcus faecalis (vancomycin-resistant isolates)
Enterococcus faecium (vancomycin-susceptible and -resistant isolates)
Enterococcus gallinarum
Listeria monocytogenes
Staphylococcus epidermidis (methicillin-susceptible and -resistant isolates)
Staphylococcus haemolyticus
Gram-negative bacteria
Acinetobacter baumannii1
Aeromonas hydrophila
Citrobacter koseri
Enterobacter aerogenes
Haemophilus influenzae (ampicillin-resistant)
Haemophilus parainfluenzae
Pasteurella multocida
Serratia marcescens
Stenotrophomonas maltophilia
Anaerobic bacteria
Bacteroides distasonis
Bacteroides ovatus
Peptostreptococcus spp.
Porphyromonas spp.
Prevotella spp.
Other bacteria
Mycobacterium abscessus
Mycobacterium fortuitum
Susceptibility Testing
For specific information regarding susceptibility test interpretive criteria, and associated test methods and quality control standards recognized by FDA for this drug, please see https://www.fda.gov/STIC.