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Tigecycline Injection (Tygacil™)
By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Associate Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationships to this field of study.
The FDA has approved tigecycline, the first of a new class of antimicrobial agents. The drug is a novel parenteral antibiotic that is chemically similar to minocycline. It is active against a wide variety of bacteria that cause complicated intra-abdominal and complicated skin and skin structure infections including methicillin-resistant Staphylococcus aureus (MRSA). Tigecycline is marketed by Wyeth as Tygacil™.
Tigecycline is indicated for the treatment of complicated intra-abdominal infections (cIAIs) caused by Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterobacter faecalis (vancomycin-susceptible isolates only), Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens, and Peptostreptococcus micros.1
Tigecycline is also indicated for the treatment of complicated skin and skin structure infections (cSSSIs) caused by E. coli, Enterococcus faecalis (vancomycin-susceptible isolates only), S. aureus (methicillin-susceptible and resistant isolates), Streptococcus agalactiae, Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Streptococcus pyogenes, and Bacteroides fragilis.1
The recommended dose is 100 mg initially followed by 50 mg every 12 hours. The dose should be given by intravenous infusion over 30-60 minutes. The recommended duration of treatment is 5-14 days depending on the severity, site of infection, and patient response. No dosage adjustment is required for mild-to-moderate hepatic dysfunction, renal impairment, age, gender, or race. For patients with severe hepatic dysfunction, the maintenance dose should be reduced to 25 mg every 12 hours.1
Tigecycline is supplied as a 50 mg single-dose vial.
In vitro data indicate that tigecycline is generally not affected by resistance mechanisms associated with methicillin resistant staphylococcus, glycopeptide-inter-mediate and resistant S. aureus, vancomycin-resistant enterococci, penicillin-resistant pneumococci, and b lactamase producing pathogens.2
Nausea and vomiting are the most common side effects, occurring in nearly 30% and 20% of patients respectively.1
Tigecycline is the first member of the glycycline class of antimicrobial agents. Its bacteriostatic action is based on binding to bacterial 30S-ribosome. This is similar to, but more effective than, the tetracyclines, including tetracycline-resistant ribosomes.2 It has demonstrated in vitro activity against the most prevalent bacteria that cause cSSSIs and cIAIs.3 In phase III studies tigecycline monotherapy was found to be similar to vancomycin/aztreonam in cSSSIs and to imipenem/cilastatin in cIAIs.4,5 In cSSSIs studies, patients were treated with tigecycline (100 mg, followed by 50 mg twice daily) or vancomycin/aztreonam (1 g and 2 g twice daily). Duration of treatment was up to 14 days. Clinical response based on clinical modified intent-to-treat was 79.7% for tigecycline and 81.9% for vancomycin/aztreonam (P = 0.42) (n = 1057). Microbiologically evaluable clinical response was 86.4% and 88.5% respectively (P = 0.54) (n = 540). For the treatment of cIAIs, tigecycline (100 mg followed by 50 mg) was compared to imipenem/cilastatin (500 mg/50 0 mg every 6 hours). The treatment duration was 12-42 days. Clinical cure based on clinical modified intent-to-treat was 79.8% for tigecycline and 82.0% for imipenem/aztreonam (P = 0.29) (n = 1601). Microbiologically evaluable clinical response was 86.1% and 86.2% respectively (P = 1.0) (n = 1026). Tigecycline appeared to be well tolerated with gastrointestinal symptoms (nausea, vomiting, anorexia, diarrhea, dyspepsia) as the most common adverse events. In vitro data indicate that tigecycline is active against glycoprotein-immediately resistant S. aureus, resistant strains of E. faecalis and E. faecium, penicillin-resistant S. pneumoniae. Tigecycline appears to be generally unaffected by the commonly prevalent resistant phenotypes.2,6 Comparative clinical trials with other antibiotics are lacking (eg, vs daptomycin or linezolid in cSSSIs). The cost for a 10-day course of therapy is about $10,000.
Tigecycline is a member of a new class of antimicrobials. It appears to be an important addition as an agent against pathogens resistant to other antimicrobials. Judicious use of this new agent is paramount in order to minimized future development of resistant pathogens.
1. Tygacil Product Information. Wyeth Pharmaceutical, Inc., June 2005.
2. Rubinstein E, Vaughan D. Tigecycline: a novel glycylcycline. Drugs. 2005;65:1317-1336.
3. Bradford PA, et al. In vitro activity of tigecycline against isolates from patients enrolled in phase 3 clinical trials of treatment for complicated skin and skin-structure infections and complicated intra-abdominal infections. Clin Infect Dis. 2005;41(Suppl 5):S315-S332.
4. Babinchak T, et al. The efficacy and safety of tigecycline for the treatment of complicated intra-abdominal infections: analysis of pooled clinical trial data. Clin Infect Dis. 2005;41(Suppl 5):S354-S367.
5. Ellis-Grosse EJ, et al. The efficacy and safety of tigecycline in the treatment of skin and skin-structure infections: results of 2 double-blind phase 3 comparison studies with vancomycin-aztreonam. Clin Infect Dis. 2005;41(Suppl 5):S341-S353.
6. Petersen PJ, et al. In vitro and in vivo activities of tigecycline (GAR-936), daptomycin, and comparative antimicrobial agents against glycopeptide-intermediate Staphylococcus aureus and other resistant gram-positive pathogens. Antimicrob Agents Chemother. 2002;46:2595-2601.