Dose optimisation based on pharmacokinetic/pharmacodynamic target of tigecycline

Tigecycline, a new first-in-class glycylcycline antibiotic, has shown promising efficacy against a broad range of micro-organisms. It is widely prescribed for various infections, with most prescriptions being considered for off-label use. However, only a few years after its approval by the US Food and Drug Administration (FDA), tigecycline is suspected of increasing all-cause mortality. Some clinicians have suggested such unfavourable outcomes correlate with inadequate drug exposure at the infection site. The pharmacokinetic/pharmacodynamic (PK/PD) profile of a drug plays an important role in predicting its antibiotic effect, which for tigecycline is determined as the ratio of area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC). In this study, PK/PD targets based on infection sites, bacterial isolates and patient populations are discussed. Generally, a higher dosage of tigecycline for the treatment of serious infections has been recommended in previous reports. However, the latest finding of tigecycline's atypical protein binding property requires consideration when recommending further use. In addition, combination therapy with other antibiotics provides another option by potentially lowering the MICs of multidrug-resistant bacteria. (C) 2021 The Authors. Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.