Tygacil (tigecycline)

Author: Claudio Faria, PharmD; Carolyn Soo, PharmD; and Nina Patel

More than 160 million antibiotic prescriptions are written each year in the United States. Approximately 235 million antibiotic doses are used annually, with 20% to 50% taken unnecessarily.1 Moreover, roughly 70% of bacteria causing hospital-acquired infections are resistant to one or more commonly used agents.2 The increase in bacterial resistance over the years has prompted an array of antibiotic products. Tygacil, manufactured by Wyeth Pharmaceuticals Inc, has been approved for use as monotherapy of complicated skin and skin structure infections (cSSSIs) and complicated intra-abdominal infections (cIAIs) in adults.3

Pharmacology

Tygacil, derived from the tetracycline family, is part of a new class known as glycylcyclines. It has activity against gram-positive, gram-negative, and anaerobic microorganisms, as well as methicillin-resistant Staphylococcus aureus. Tygacil exerts its actions via inhibition of protein translation in bacteria by binding to the 30S ribosomal subunit and blocking the entry of amino-acyl tRNA molecules into the A site of the ribosome.3,4

Clinical Trials

Two randomized, double-blind, multinational studies evaluated tigecycline in adults for the treatment of cSSSIs.4-6 Tigecycline at an initial dose of 100 mg intravenous (IV), followed by subsequent doses of 50 mg every 12 hours, was compared with vancomycin 1 g and aztreonam 2 g every 12 hours for 5 to 14 days.4 The study included patients with a known or suspected diagnosis of cSSSI, who were expected to require IV antibiotic therapy for at least 5 days, and who had one or more prespecified indicators of infection. Patients were excluded from the study if they received more than 2 doses of nonstudy antibacterial therapy after the original cure was obtained and before the study drug was administered.6

The results were summarized into 2 categories: the clinically evaluable (CE) and the clinically modified intent-totreat (c-mITT) populations. A favorable clinical response was observed in the North American trial for both the CE and the c-mITT categories, for the tigecycline and the vancomycin-aztreonam treatment groups, respectively.4 Favorable responses also were observed in a global trial for the CE and for the cmITT categories, respectively.4,6

In addition, tigecycline was evaluated in patients with a cIAI. Two randomized, double-blind, active-controlled, multinational studies compared tigecycline at an initial dose of 100 mg IV, followed by 50 mg every 12 hours, and imipenem/cilastatin at a dose of 500 mg IV every 6 hours for a total of 5 to 14 days.4,7,8 Inclusion criteria comprised a known or suspected diagnosis of cIAI and previous consideration for or a previous laparotomy, laparoscopy, or percutaneous drainage of an intra-abdominal abscess.8 Patients were excluded from participation if more than one dose of nonstudy antibacterial therapy was administered, after the original culture and before the study drug.7

The results were divided into 2 groups: those for patients who exhibited a clinical and microbiological response (ME) and those for the microbiologically modified intent-to-treat (m-mITT) group. A favorable response was observed in the first trial in both the ME and the m-mITT groups, with tigecycline and imipenem/cilastatin, respectively.7 In a second trial, a similar favorable clinical response was observed in both the ME and the mmITT groups, respectively.4,8

Safety

The most common adverse events reported with the use of tigecycline were nausea and vomiting. Tygacil is in pregnancy category D and is not advised for pregnant or breast-feeding women. Generally, Tygacil does not require any renal adjustments. Patients with severe hepatic impairment (Child-Pugh Class C), however, should receive an initial dose of 100 mg followed by 25 mg every 12 hours.3,4

Outlook

Tygacil is supplied as 50-mg lyophilized powder for reconstitution in single-dose 5-mL glass vials. The recommended initial dose is 100 mg, followed by subsequent doses of 50 mg IV administered over 30 to 60 minutes every 12 hours for 5 to 14 days. Tygacil appears to be a safe and favorable antimicrobial option.4

Drs. Faria and Soo are both senior research pharmacists with the Investigational Drug Service at Brigham and Women's Hospital, Boston, Mass. Dr. Faria also is a senior human research specialist with Partners HealthCare System. Nina Patel is a sixth-year PharmD candidate from Northeastern University currently on clinical clerkship in the Investigational Drug Service at Brigham and Women's Hospital.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Stahl, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: astahl@ascendmedia.com.