New indication: Tigecycline (Tygacil), a tetracycline-class antibiotic, was approved on March 20, 2009, for the treatment of community-acquired bacterial pneumonia
Tigecycline is a glycylcycline antibiotic that exerts its antibacterial effects by inhibiting protein translation in bacteria. Tigecycline was approved on March 20, 2009, for the treatment of community-acquired bacterial pneumonia caused by Streptococcus pneumoniae (penicillin-susceptible isolates), including cases with concurrent bacteremia, Haemophilus influenzae (beta-lactamase-negative isolates), and Legionella pneumophila.
Efficacy. The efficacy of tigecycline for the treatment of community-acquired bacterial pneumonia was evaluated in 2 randomized, double-blind, active-controlled, multinational, multicenter studies that compared intravenous (IV) tigecycline 100 mg as an initial dose followed by 50 mg every 12 hours with IV levofloxacin 500 mg every 12 or 24 hours. In 1 of the studies, a switch to oral levofloxacin (500 mg/d) was permitted for both treatment arms after ≥3 days of IV therapy. In both studies, patients were treated for 7 to 14 days. The primary efficacy end point in both studies was clinical response at test of cure (TOC) visit in the clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations. Tigecycline-treated patients in the CE population demonstrated a clinical cure rate of 90.6% in the first study and 88.9% in the second study compared with 87.2% and 85.3% of levofloxacin-treated patients (first study treatment difference, 95% CI, –4.4 to 11.2; second study treatment difference, 95% CI, –5.0 to 12.2). In the c-mITT population, tigecycline-treated patients demonstrated a cure rate of 78% in the first study and 83.7% in the second study versus 77.8% and 81.5% in levofloxacin-treated patients (first study treatment difference, 95% CI, –8.5 to 8.9; second study treatment difference, 95% CI, –5.6 to 10.1). Cure rates for patients infected with H influenzae, L pneumophila, or S pneumoniae (penicillin-suspectible) were the same or better in tigecycline-treated patients compared with the cure rates in levofloxacin-treated patients.
Safety. With all antibacterial agents, including tigecycline, there is a risk of anaphylaxis that may be life-threatening. As tigecycline is structurally similar to tetracycline-class antibiotics, this agent should be administered with caution in patients who have known hypersensitivity to tetracycline-class agents. Patients treated with tigecycline have demonstrated increases in total bilirubin concentration, prothrombin time, and transaminases. Rarely, cases of significant hepatic dysfunction and hepatic failure have been reported in patients treated with tigecycline. Tigecycline may cause fetal harm in pregnant women. The use of this agent during tooth development may cause permanent discoloration of the teeth. Patients treated with antibacterial agents, including tigecycline, are at risk of developing Clostridium difficile-associated diarrhea, which can range in severity from mild diarrhea to fatal colitis. Tigecycline may be associated with adverse effects similar to those observed with tetracycline-class antibiotics, including photosensitivity, pseudotumor cerebri, and antianabolic action. Pancreatitis has also been associated with the use of tigecycline. Use of antibacterial drugs may result in the overgrowth of nonsusceptible organisms. The most common adverse events associated with tigecycline treatment include nausea, vomiting, diarrhea, infection, headache, and abdominal pain.