Oxazolidinone

A class of synthetic antibiotics used to treat infections caused by Gram-positive bacteria

Oxazolidinones are a class of synthetic antibiotics that are particularly effective against Gram-positive bacteria, including resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). They are characterized by a unique mechanism of action that involves the inhibition of bacterial protein synthesis.

History

The development of oxazolidinones began in the 1980s, with the first clinically approved drug, Linezolid, being introduced in 2000. This marked a significant advancement in the treatment of infections caused by resistant Gram-positive bacteria.

Mechanism of Action

Oxazolidinones inhibit bacterial protein synthesis by binding to the 50S subunit of the bacterial ribosome. This action prevents the formation of the initiation complex necessary for translation, thereby halting protein synthesis and bacterial growth. Unlike many other antibiotics, oxazolidinones do not affect the 30S subunit, which contributes to their unique mechanism.

Pharmacokinetics

Oxazolidinones are well absorbed orally, with bioavailability often exceeding 90%. They are also available in intravenous formulations. The drugs are metabolized in the liver and excreted primarily in the urine. The half-life of oxazolidinones allows for twice-daily dosing, which is convenient for patients.

Clinical Uses

Oxazolidinones are primarily used to treat infections caused by Gram-positive bacteria, including:

• Pneumonia
• Skin and soft tissue infections
• Bacteremia
• Endocarditis

Resistance

Resistance to oxazolidinones is relatively rare but has been documented. It typically arises from mutations in the 23S rRNA of the bacterial ribosome, which reduces the binding affinity of the drug. Resistance can also occur through the acquisition of the cfr gene, which methylates the ribosomal RNA and prevents drug binding.

Side Effects

Common side effects of oxazolidinones include:

• Gastrointestinal disturbances (nausea, diarrhea)
• Headache
• Thrombocytopenia (low platelet count)

Long-term use can lead to more serious side effects such as:

• Peripheral neuropathy
• Optic neuropathy
• Lactic acidosis

Examples of Oxazolidinones

• Linezolid
• Tedizolid

Also see

• Antibiotic resistance
• Gram-positive bacteria
• Protein synthesis inhibitors
• Methicillin-resistant Staphylococcus aureus
• Vancomycin-resistant Enterococcus