Antimicrobials · Linezolid
The facts most likely to be tested
Press 1–5 to rate · ↑↓ to navigate
Linezolid is the primary agent in the oxazolidinone class used to treat Vancomycin-resistant Enterococcus (VRE) and Methicillin-resistant Staphylococcus aureus (MRSA).
The mechanism of action involves inhibiting bacterial protein synthesis by binding to the 50S ribosomal subunit, preventing the formation of the 70S initiation complex.
Bone marrow suppression, specifically thrombocytopenia, is the most significant dose-limiting side effect during prolonged therapy.
Linezolid acts as a non-selective monoamine oxidase inhibitor (MAOI), posing a high risk for serotonin syndrome when combined with SSRIs or other serotonergic agents.
Peripheral neuropathy and optic neuritis are classic adverse effects associated with long-term administration of linezolid.
Oxazolidinones are bacteriostatic against staphylococci and enterococci but exhibit bactericidal activity against most strains of Streptococcus pneumoniae.
Lactic acidosis is a rare but serious metabolic complication associated with mitochondrial toxicity resulting from prolonged linezolid use.
Vignette unlocked
A 62-year-old male with a history of chronic wounds is admitted for a persistent Vancomycin-resistant Enterococcus (VRE) infection. He is started on an intravenous antibiotic that inhibits the 50S ribosomal subunit. After 14 days of therapy, he develops petechiae and laboratory results reveal a platelet count of 45,000/µL. He is also currently taking sertraline for depression and reports mild tremors and diaphoresis.
Which medication is the most likely cause of this patient's clinical presentation?
Linezolid
The patient is experiencing thrombocytopenia (bone marrow suppression) and symptoms of serotonin syndrome due to the MAOI activity of linezolid, which is the standard treatment for VRE.
Full handout
High yield triage
Classification
Oxazolidinones are bacteriostatic protein synthesis inhibitors targeting the 50S ribosomal subunit.
Indications
Primary use is MRSA and VRE infections, specifically hospital-acquired pneumonia and skin/soft tissue infections.
Mechanism of Action
Binds to the 23S ribosomal RNA of the 50S subunit, preventing formation of the 70S initiation complex.
Side Effects
Common: diarrhea, nausea. Myelosuppression (thrombocytopenia) and serotonin syndrome.
Contraindications / Monitoring
MAO inhibitor use is contraindicated. Monitor complete blood count (CBC) weekly for thrombocytopenia.
Full handout
Mechanism of Action
These agents bind to the 23S ribosomal RNA site on the 50S subunit. This unique binding site prevents the formation of the 70S initiation complex, effectively halting bacterial protein synthesis. Because they bind to a site distinct from other classes, they exhibit no cross-resistance with other protein synthesis inhibitors.
Unique Properties
Linezolid is the prototype, while Tedizolid offers a once-daily dosing schedule and a potentially improved safety profile. Both drugs possess excellent bioavailability, allowing for seamless transition from intravenous to oral therapy.
Indications
Indicated for serious infections caused by Gram-positive organisms, including MRSA and VRE. They are frequently utilized for hospital-acquired pneumonia and complicated skin and soft tissue infections where resistance is suspected.
Pharmacokinetics
These drugs are primarily metabolized by the liver via non-enzymatic oxidation, meaning they have minimal CYP450 interactions. They are widely distributed into tissues, including the cerebrospinal fluid, making them useful for central nervous system infections.
Side Effects & Adverse Events
Common adverse effects include headache and gastrointestinal distress. Long-term use (>2 weeks) is associated with myelosuppression, specifically thrombocytopenia. Additionally, they act as weak non-selective MAO inhibitors, posing a risk for serotonin syndrome when combined with serotonergic agents.
Contraindications
MAO inhibitor use within the last 14 days is strictly contraindicated due to the risk of hypertensive crisis and serotonin syndrome. Use caution in patients with pre-existing bone marrow suppression.
Monitoring
Perform a complete blood count (CBC) at least weekly to monitor for thrombocytopenia and anemia. Assess for signs of peripheral neuropathy or optic neuritis during prolonged therapy.
Clinical Pearls
Boards love the Linezolid-induced thrombocytopenia trap; always check the duration of therapy. Remember that these are the drugs of choice for VRE (Vancomycin-resistant Enterococcus) infections. Watch for the serotonin syndrome interaction if the patient is on an SSRI.