Tigecycline, the first member of the glycylcyclines, has been approved for complicated skin and soft tissue infections' (cSSTIs) and complicated intra-abdominal infections (cIAIs). It has a wide range of activity against Gram-positive and Gram-negative bacteria, including anaerobes. Since its approval, the worldwide clinical use of tigecycline has been heterogeneous, either as a monotherapy or as a part of combination therapy, almost exclusively at the standard dosage, in patients with community-acquired (CA) infections as well as health-care associated (HCA) or nosocomial infections (HA), including infections caused by multidrug-resistant (MDR) bacteria. In recent years, issues and warnings of an increased mortality in these heterogeneous patients treated with tigecycline have been raised by meta-analyses and by regulatory agencies. Re-defining tigecycline therapy is a proposal, based on epidemiological, clinical, microbiological and pharmacological considerations, to distinguish patients who may be treated with monotherapy, according to the official indications and dosages, from those treated with combination treatment, mostly with high dosages in the setting of nosocomial IAIs, possibly caused by MDR bacteria or as a carbapenem-sparing strategy. Whilst available clinical data and guidelines suggest caution with monotherapy in severe infections, experience worldwide indicates that combination treatment with high-dosage tigecycline is increasingly used.
