General Information

Tygacil (tigecycline) is a tetracycline-class antibacterial indicated for the treatment of infections caused by susceptible isolates of the designated microorganisms. Tygacil is specifically indicated for the following conditions:

Complicated skin and skin structure infections caused by Escherichia coli, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus agalactiae, Streptococcus anginosus grp. (includes S. anginosus, S. intermedius and S. constellatus), Streptococcus pyogenes, Enterobacter cloacae, Klebsiella pneumoniae and Bacteroides fragilis.
Complicated intra-abdominal infections caused by Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens and Peptostreptococcus micros.
Community-acquired bacterial pneumonia caused by Streptococcus pneumoniae (penicillin-susceptible isolates), including cases with concurrent bacteremia, Haemophilus influenzae (betalactamase negative isolates) and Legionella pneumophila.

Mechanism of Action

Tygacil 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. Tigecycline carries a glycylamido moiety attached to the 9-position of minocycline. The substitution pattern is not present in any naturally occurring or semisynthetic tetracycline and imparts certain microbiologic properties to tigecycline. In general, tigecycline is considered bacteriostatic; however, it has demonstrated bactericidal activity against isolates of S. pneumoniae and L. pneumophila.

Side Effects

Adverse events associated with the use of Tygacil may include, but are not limited to, the following:

• nausea
• vomiting
• diarrhea
• infection
• abdominal pain
• headache

Dosing/Administration

Tygacil is supplied as a lyophilized powder for reconstitution to intravenous infusions. The recommended initial dose is 100 mg, followed by 50 mg every 12 hours. Intravenous infusions of Tygacil should be administered over approximately 30 to 60 minutes every 12 hours.
Duration of treatment
The recommended duration of treatment with Tygacil for complicated skin and skin structure infections or for complicated intra-abdominal infections is five to 14 days. The recommended duration of treatment with Tygacil for community-acquired bacterial pneumonia is seven to 14 days. The duration of therapy should be guided by the severity and site of the infection and the patient's clinical and bacteriological progress.

Clinical Trial Results

The FDA approval of Tygacil for complicated skin and skin structure infections was based on two randomized, double-blind, active-controlled, multinational, multicenter studies (studies 300 and 305). These studies compared Tygacil (100 mg intravenous initial dose followed by 50 mg every 12 hours) with vancomycin (1 g intravenous every 12 hours)/aztreonam (2 g intravenous every 12 hours) for five to 14 days. The primary efficacy endpoint was the clinical response at the test of cure visit (5-14 days after therapy) in the co-primary populations of the clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) patients. The clinical cure rates (percent of cured) were as follows:
Study 300: CE population: 82.9 percent for Tygacil; 82.3 percent for Vancomycin/Aztreonam. c-mITT population: 75.5 percent for Tygacil; 76.9 percent for Vancomycin/Aztreonam.
Study 305: CE population: 89.7 percent for Tygacil; 94.4 percent for Vancomycin/Aztreonam. c-mITT population: 84.3 percent for Tygacil; 86.9 percent for Vancomycin/Aztreonam.

The FDA approval of Tygacil for complicated intra-abdominal infections was based on two randomized, double-blind, active-controlled, multinational, multicenter studies (studies 301 and 306). These studies compared Tygacil (100 mg intravenous initial dose followed by 50 mg every 12 hours) with imipenem/cilastatin (500 mg intravenous every 6 hours) for 5 to 14 days. The primary efficacy endpoint was the clinical response (percent responding) at the test-of-cure visit for the microbiologically evaluable (ME) and the microbiologic modified intent-to-treat (m-mITT) co-primary populations. Study 301 ME: 80.6 percent versus imipenem/cilastatin: 82.4 percent; m-mITT: 73.5 percent versus imipenem/cilastatin: 78.2 percent. Study 306 ME: 91.3 percent versus imipenem/cilastatin: 89.9 percent; m-mITT: 86.6 percent versus imipenem/cilastatin: 84.6 percent.

The FDA approval of Tygacil for community-acquired pneumonia was based on two randomized, double-blind, active-controlled, multinational, multicenter studies (dtudies 308 and 313). These studies compared Tygacil (100 mg intravenous initial dose followed by 50 mg every 12 hours) with levofloxacin (500 mg intravenous every 12 or 24 hours). In study 308, after at least three days of intravenous therapy, a switch to oral levofloxacin (500 mg daily) was permitted for both treatment arms. Total therapy was seven to 14 days. The primary endpoint was clinical response at the test of cure (TOC) visit in the co-primary populations of the clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT). The clinical cure rates (percent of cured) were as follows:
Study 308: CE population: 90.6 percent for Tygacil; 87.2 percent for Levofloxacin c-mITT population: 78 percent for Tygacil; 77.8 percent for Levofloxacin
Study 313: CE population: 88.9 percent for Tygacil; 85.3 percent for Levofloxacinc-mITT population: 83.7 percent for Tygacil; 81.5 percent for Levofloxacin.