Establishing the Role of Tigecycline in an era of Antimicrobial Resistance

*Following a 30-min intravenous infusion.
^‡Following a 60-min intravenous infusion.
^§One 100 mg dose.
^¶100-mg dose initially, followed by 50 mg every 12 h.
AUC = Area under the curve concentration; Cl = Clearance; C_max = Maximum serum concentration; Vss = Steady-state volume of distribution.
Adapted from ^[2].

*Methicillin-resistant Staphyloccocus aureus: 43.5%; ^‡Methicillin-resistant CoNS = 85%.
AMK = Amikacin; Cipro = Ciprofloxacin; CoNS = Coagulase-negative Staphylococcus; CPM = Cefepime; Dap = Daptomycin; IMP = Imipenem; Lev = Levofloxacin; LZD = Linezolid; P/T = Piperacillin/tazobactam; Q/D = Quinupristin/dalfopristin; TGC = Tigecycline; Van = Vancomycin.
Adapted from ^[12].

*Vancomcyin plus aztreonam.
^‡Imipenem-cilastatin.
ALT = Alanine aminotransferase; aPTT = Activated partial thromboplastin time; AST = Aspartate aminotransferase; cIAI = Complicated intra-abdominal infection; cSSI = Complicated skin/skin-structure infection; PT = Prothrombin time.
Adapted from ^[42,43]

Authors and Disclosures

Jason J. Schafer, UPMC St Margaret Hospital, Department of Pharmacy, 815 Freeport Road, Pittsburgh, PA 15215, USA.

Debra A. Goff, The Ohio State University Medical Center, Department of Pharmacy, 368 Doan Hall, Columbus, OH 43215, USA.

E-mail: Jason J. Schafer - schaferjj@upmc.edu ; Debra A. Goff - debbie.goff@osumc.edu

Disclosure: Debra A. Goff has received grant funds from Wyeth. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Sidebar: Key Issues

Mechanism of Action:

• Tigecycline exerts bacteriostatic activity through high-affinity reversible binding to 30S bacterial ribosomal subunits.

• This mechanism inhibits bacterial protein translation by interrupting amino-acyl tRNA entrance into the A site of the ribosome, which prevents completion of intracellular peptides.

Pharmacokinetic Properties:

• Tigecycline exhibits a large volume of distribution and penetrates several tissues, including pulmonary, skin and intra-abdominal sites.

• The agent follows linear pharmacokinetics, is not extensively metabolized and is eliminated primarily unchanged in bile and feces. Additional elimination of the active drug occurs in the urine (<30%).

Clinical Efficacy:

• The efficacy of tigecycline for complicated intra-abdominal, complicated skin and skin-structure infections and hospitalized patients with community-acquired pneumonia has been demonstrated in clinical trials.

• Aside from approved indications, limited experience is reported for the treatment of infections due to drug-resistant pathogens.

Safety and Tolerability:

• Gastrointestinal upsets, including nausea and vomiting, were the most commonly reported adverse events from clinical trial data.

• Side effects common to tetracycline antibiotics may also occur with tigecycline.

Drug Interactions:

• The concurrent administration of tigecycline and warfarin may result in higher concentrations of warfarin isomers. It is recommended to monitor international normalized ratio values in patients receiving these agents concurrently.

Dosage and Administration:

• Tigecycline is available for intravenous administration and is recommended to be given with a 100-mg loading dose followed by maintenance dosing 50 mg every 12 h.

• Dosing adjustments are not required in patients with renal insufficiency or end-stage renal disease. In patients with severe hepatic dysfunction (Child Pugh class C), systemic clearance of tigecycline is prolonged and a dosage adjustment is required (100-mg loading dose followed by 25 mg every 12 h).

• There is no dosage adjustment required in patients with mild-to-moderate liver dysfunction or in patients receiving hemodialysis, since tigecycline is not significantly removed.