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Tigecycline (GAR-936) is the first glycylcycline antibiotic to be approved by the US Food and Drug Administration (FDA). The drug overcomes the 2 major resistance mechansisms of tetracycline: drug-specific efflux pump acquisition and ribosomal protection. Tigecycline is active against many gram-positive and -negative organisms, including methicillin-resistant Staphylococcus aureus, vancomycin-intermediate and -resistant enterococci, and extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae. It is also active against many anaerobic bacteria, as well as atypical pathogens, including rapidly growing, nontuberculous mycobacteria. Tigecycline is concentrated in cells and is eliminated primarily via biliary excretion. Diminished renal function does not significantly alter its systemic clearance. Furthermore, tigecycline does not interfere with common cytochrome P450 enzymes, making pharmacokinetic drug interactions uncommon. It provides parenteral therapy for complicated skin/skin-structure and intra-abdominal infections. The only prominent adverse effects are associated with tolerability, most notably nausea and vomiting. Tigecycline will be most useful as empirical therapy for polymicrobial infections, especially in cases in which deep tissue penetration is needed or in which multidrug-resistant pathogens are suspected.