Definition
Oxazolidinones are a class of synthetic, bacteriostatic antibiotics that function by inhibiting bacterial protein synthesis at an early stage of ribosomal activity. These antibiotics are active against Gram-positive bacteria, including multidrug-resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and penicillin-resistant Streptococcus pneumoniae. Their clinical utility lies predominantly in the management of serious Gram-positive infections, including skin and soft tissue infections, pneumonia, and infections caused by resistant pathogens.
Key agents within this class include:
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Linezolid
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Tedizolid
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Investigational agents: Radezolid, Torezolid, and Contezolid
Oxazolidinones were first introduced in the early 2000s, with linezolid becoming the first agent in this class to receive FDA approval in 2000.
1. Mechanism of Action
Oxazolidinones exert their antibacterial effect by selectively binding to the 50S ribosomal subunit of bacterial ribosomes. They inhibit the formation of the 70S initiation complex, a critical early step in bacterial protein translation. Unlike other antibiotics that act on protein synthesis (e.g., macrolides, aminoglycosides), oxazolidinones act very early in the translation process, preventing initiation rather than elongation or termination.
This unique mechanism of action:
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Does not overlap with other antibiotic classes
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Reduces the risk of cross-resistance
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Makes them effective against resistant Gram-positive pathogens
2. Agents in This Class
| Drug Name | Brand Name | Approval | Spectrum | Key Notes |
|---|---|---|---|---|
| Linezolid | Zyvox | FDA 2000 | Broad Gram-positive | First-in-class; oral & IV forms; used in serious MDR infections |
| Tedizolid | Sivextro | FDA 2014 | Broad Gram-positive | More potent than linezolid; once-daily dosing; lower myelosuppression risk |
| Contezolid | Youxitai | NMPA (China) 2021 | Gram-positive | Investigational in U.S.; better safety profile than linezolid |
| Radezolid | (Investigational) | Not yet approved | Gram-positive | Under clinical development; improved oral bioavailability |
3. Spectrum of Activity
Oxazolidinones are primarily effective against aerobic Gram-positive bacteria, including:
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Staphylococcus aureus (including MRSA)
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Streptococcus pneumoniae (including PRSP)
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Enterococcus faecalis and Enterococcus faecium (including VRE)
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Streptococcus pyogenes
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Listeria monocytogenes
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Corynebacterium spp.
No significant activity against:
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Gram-negative bacteria (due to efflux and outer membrane impermeability)
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Anaerobes (limited activity)
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Mycobacteria (some activity reported in investigational use)
4. Clinical Indications
| Condition | Drugs Used | Notes |
|---|---|---|
| Skin and soft tissue infections (SSTIs) | Linezolid, Tedizolid | Including complicated SSTIs caused by MRSA/VRE |
| Pneumonia (community- or hospital-acquired) | Linezolid | Particularly useful for MRSA pneumonia |
| Bacteremia (off-label) | Linezolid | Especially when MRSA or VRE is involved |
| Bone and joint infections (off-label) | Linezolid | Penetrates bone; used in osteomyelitis |
| Endocarditis (off-label) | Linezolid | As part of combination therapy for resistant organisms |
| Tuberculosis (investigational/off-label) | Linezolid | Used in MDR-TB regimens |
5. Pharmacokinetics
| Property | Linezolid | Tedizolid |
|---|---|---|
| Bioavailability | ~100% (oral = IV) | ~90% |
| Half-life | ~5–7 hours | ~12 hours |
| Protein Binding | ~30% | ~80% |
| Metabolism | Non-CYP (oxidation) | Phosphate prodrug (hepatic) |
| Excretion | Renal and hepatic | Primarily hepatic |
| Dosing | 600 mg q12h (Linezolid) | 200 mg q24h (Tedizolid) |
6. Adverse Effects
| System | Linezolid | Tedizolid |
|---|---|---|
| Hematologic | Thrombocytopenia (esp. >2 weeks), anemia | Lower incidence of myelosuppression |
| Neurologic | Peripheral and optic neuropathy (long-term use) | Rare; lower risk |
| GI | Diarrhea, nausea, vomiting | Milder GI profile |
| Lactic acidosis | Reported with prolonged therapy | Not commonly reported |
| Serotonin syndrome | Risk when combined with SSRIs/SNRIs | Risk exists, but lower than linezolid |
7. Contraindications
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Known hypersensitivity to oxazolidinones
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Concomitant use with monoamine oxidase inhibitors (MAOIs)
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Uncontrolled hypertension or tyramine-rich diet (linezolid acts as a weak MAO inhibitor)
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Caution in patients with serotonergic agents (risk of serotonin syndrome)
8. Drug Interactions
| Interacting Agent | Effect |
|---|---|
| SSRIs/SNRIs/TCAs | Risk of serotonin syndrome |
| MAOIs | Additive sympathomimetic and serotonergic effects |
| Adrenergic agents (e.g., pseudoephedrine) | Hypertensive crisis risk |
| Tyramine-containing foods | Risk of hypertensive reactions (especially with linezolid) |
9. Resistance Mechanisms
Although resistance is relatively rare, documented mechanisms include:
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Mutations in 23S rRNA (G2576T) → prevents drug binding to ribosome
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cfr gene → methylates ribosomal RNA
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optrA/poxtA genes → encode efflux pumps and protection proteins
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Resistance is more common in Enterococcus faecium than S. aureus
Ongoing surveillance is critical due to increasing oxazolidinone resistance, especially in VRE and coagulase-negative staphylococci.
10. Monitoring Recommendations
| Parameter | Recommended Monitoring |
|---|---|
| Complete blood count (CBC) | Baseline and weekly during prolonged use |
| Visual symptoms | Monitor for optic neuropathy |
| Peripheral neuropathy signs | Especially beyond 28 days of therapy |
| Serotonin syndrome symptoms | If combined with serotonergic drugs |
11. Comparison Table: Linezolid vs. Tedizolid
| Feature | Linezolid | Tedizolid |
|---|---|---|
| Dosing Frequency | Twice daily | Once daily |
| Duration Approved | Up to 28 days | 6 days |
| Myelosuppression | Common (>14 days) | Rare |
| Peripheral Neuropathy | Reported (esp. long-term) | Rare |
| Serotonin Syndrome Risk | Higher | Lower |
| Spectrum | Broad Gram-positive | Similar |
| Cost | Moderate-high | High (newer agent) |
12. Use in Special Populations
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Renal impairment: No dosage adjustment needed; caution with accumulation of metabolites.
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Hepatic impairment: No major dose changes required.
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Pediatrics: Linezolid approved for children ≥ birth (adjusted dosing); tedizolid not routinely recommended.
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Pregnancy: Category C (linezolid); use only if clearly needed.
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Elderly: No specific dose adjustment, but monitor for hematologic toxicity.
13. Investigational and Emerging Agents
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Radezolid: Dual-acting oxazolidinone; being studied for MRSA, VRE, and Mycobacterium tuberculosis
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Contezolid (MRX-I): Approved in China for skin infections; shown reduced hematological toxicity
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Delpazolid: Promising for resistant TB; under phase 2 trials
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Cadazolid: Designed for Clostridioides difficile infections (discontinued after phase 3 failure)
14. Clinical Practice Guidelines
| Condition | Guideline Recommendation |
|---|---|
| MRSA pneumonia | IDSA recommends linezolid or vancomycin |
| SSTI with MRSA | Linezolid preferred when oral therapy is needed |
| VRE bacteremia | Linezolid often used when daptomycin resistance is present |
| TB (drug-resistant) | Linezolid used as part of WHO Group A regimen for MDR-TB |
15. Storage and Handling
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Linezolid oral suspension: Refrigerate; protect from light
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Tablets and IV formulations: Store at room temperature
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Tedizolid: Tablets stored at room temperature; IV reconstitution required
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