Linezolid and its derivatives: the promising therapeutic challenge to multidrug-resistant pathogens

Linezolid is the main drug representative of the oxazolidinones, widely used in the clinical practice to treat severe Gram-positive infections for some decades. The uniquely particular mechanism of action of Linezolid, with a block of ribosomal assembling before the initiation of bacterial protein synthesis has been studied in various bacteria and linked mainly to mutations in the ribosomal 50S subunit. Over the years, a large amount of clinical and pharmacokinetic data have been accumulated, relating to linezolid use in different patient groups (obesity, enteral feeding, renal failure, neonates, and paediatrics) and in different clinical conditions (sepsis syndrome, skin and soft tissue infection, diabetic foot infection, pneumonia, bone and joint infection, infection of the central nervous system, eye infection, and neutropenic sepsis). In 2001 Linezolid resistance started emerging in Staphylococcus aureus and Enterococcus faecium clinical isolates and once again the attention of researchers has been caught looking for new antimicrobials with improved efficacy and reduced toxicity, therefore, subsequent studies have been designed to modify the oxazolidinone structure in order to improve safety profile, to extend spectrum of antibacterial activity and to obtain reliable activity against strains resistant to Linezolid. A better understanding of the molecular mechanisms of Linezolid’s derivatives should contribute to the development of new tools to predict therapeutic failures in high-risk patients. Meanwhile, pharmacological strategies such as the use of Linezolid or its derivatives and also combination regimens may serve as valuable approaches to increase and/or preserve Linezolid’s activity against multidrug-resistant pathogens