Pharmacokinetic and pharmacodynamic evaluation of tigecycline.

As the spread of multidrug-resistant (MDR) and extensive drug-resistant (XDR) organisms constitutes a real threat for patients, new antimicrobials are needed. Tigecycline, the first-in-class glycylcycline, possesses an extended spectrum of antimicrobial activity including MDR and XDR organisms, which holds promise as a treatment option beyond currently approved indications and deserves expanded evaluation of its pharmacokinetics/pharmacodynamics (PK/PD). This review highlights the areas where our knowledge on PK/PD of tigecycline has been both strengthened and questioned during the recent years. New information has become available on the PK of tigecycline in patients with complicated skin and skin structure infections, complicated intra-abdominal infection, community- and nosocomial-acquired pneumonia. Human PD data from clinical trials linking tigecycline drug exposure to clinical, microbiological and toxicological outcomes are also of great interest. Tigecycline remains one of our last resorts against MDR pathogens; its clear role has to be re-defined through intense PK/PD applications; dose escalation and exploration of combinations with other antibiotics seem to be the first step towards an expansion of its currently approved indications. The lung remains the most controversial and challenging site regarding the PK/PD standpoint due to the predominance of Acinetobacter baumannii and carbapenemase-producing Klebsiella pneumoniae among ventilator-associated pneumonia infections, for which tigecycline is mostly used off-label.