Clinical Pharmacokinetics and Pharmacodynamics of Oxazolidinones

Abstract

Oxazolidinones are a class of synthetic antimicrobial agents with potent activity against a wide range of multidrug-resistant Gram-positive pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. Oxazolidinones exhibit their antibacterial effects by inhibiting protein synthesis acting on the ribosomal 50S subunit of the bacteria and thus preventing formation of a functional 70S initiation complex. Currently, two oxazolidinones have been approved by the US Food and Drug Administration: linezolid and more recently tedizolid. Other oxazolidinones are currently under investigation in clinical trials. These antimicrobial agents exhibit a favourable pharmacokinetic profile with an excellent bioavailability and a good tissue and organ penetration. In-vitro susceptibility studies have shown that oxazolidinones are bacteriostatic against enterococci and staphylococci, and bactericidal for the majority of strains of streptococci. In the context of emergence of resistance to glycopeptides, oxazolidinones have become an effective alternative to vancomycin treatment frequently associated with nephrotoxicity. However, oxazolidinones, and linezolid in particular, are associated with significant adverse events, myelosuppression representing the main unfavourable side effect. More recently, tedizolid has been shown to effectively treat acute bacterial skin and skin structure infections. This newer oxazolidinone offers the advantages of once-daily dosing and a better safety profile in healthy volunteer studies (fewer gastrointestinal and haematological side effects). The potential use of tedizolid for other infections that could require longer therapy warrants further studies for positioning this new oxazolidinone in the available antimicrobial armamentarium. Moreover, other oxazolidinones are currently under active investigation.

Using old antibiotics to treat ancient bacterium—β-lactams for Bacillus anthracis meningitis

“…An experts' committee convened by the CDC drafted recommendations for treating systemic anthrax in the presence and absence of indications for CNS infection [19]. These recommendations include carbapenems and Linezolid (oxazolidinone), relatively new antibiotic classes that are efficient in treating other common resistant bacterial infections [20]. Though never used to treat anthrax in humans, these substances were recommended in combination with a fluoroquinolone, for the treatment of anthrax, mainly in the late meningeal stages of the disease [18].…”

Linezolid‐induced rare triad of hypoglycaemia, bone marrow suppression and hyponatraemia in elderly

“…Linezolid, a member of the oxazolidinone class of antibacterial drugs, is approved by the US Food and Drug Administration (FDA) for the treatment of vancomycin‐resistant Enterococcus faecium infections, nosocomial and community‐acquired pneumonia, as a part of antitubercular regimen and complicated and uncomplicated skin and skin structure infections, including diabetic foot infections . Linezolid has potential adverse effects including bone marrow suppression, peripheral neuropathy and hyponatraemia .…”

Multidrug-Resistant Orthopaedic Surgical Site Infections Treated with Linezolid in Four Dogs

“…Linezolid is a synthetic oxazolidinone antimicrobial agent that inhibits protein synthesis by binding to ribosomal 50S subunits, which leads to inhibition of 70S subunit initiation and messenger ribonucleic acid translation. 1 Linezolid is an effective antimicrobial against multidrug-resistant Gram-positive bacteria, including methicillin-resistant Staphylococcus (MRS) and vancomycin-resistant Enterococcus species. 2 The use of linezolid has been reported in dogs for the treatment of MRS infections such as discospondylitis and deep pyoderma.…”