From the Guidelines
Linezolid is a recommended antibiotic for the treatment of skin and soft tissue infections, particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA), due to its effectiveness and favorable safety profile, as evidenced by a recent study published in 2024 1.
Key Points About Linezolid
- Linezolid belongs to the oxazolidinone class of antibiotics, primarily used to treat serious infections caused by Gram-positive bacteria, including MRSA and vancomycin-resistant Enterococcus (VRE) 1.
- The standard adult dosage is 600 mg administered orally or intravenously every 12 hours, typically for 10-14 days depending on the infection type, though treatment may extend to 28 days for certain conditions 1.
- Linezolid works by inhibiting bacterial protein synthesis through binding to the 23S ribosomal RNA of the 50S subunit, preventing the formation of the 70S initiation complex 1.
- Common side effects include headache, nausea, diarrhea, and potential myelosuppression with prolonged use, particularly thrombocytopenia, as reported in a study comparing linezolid with vancomycin 1.
- Patients should avoid tyramine-rich foods and medications with serotonergic properties due to the risk of serotonin syndrome, and regular blood count monitoring is recommended for treatments exceeding 14 days 1.
- Linezolid offers excellent bioavailability when taken orally, allowing for convenient transition from IV to oral therapy without dosage adjustment, making it a preferred option for outpatient treatment 1.
Efficacy of Linezolid
- A Cochrane meta-analysis included all randomized controlled trials comparing linezolid with vancomycin in the treatment of skin and soft tissue infections, and found that linezolid was associated with a significantly better clinical and microbiological cure rate in adults 1.
- For infections caused by MRSA, linezolid was significantly more effective than vancomycin in clinical and microbiological cure rates, as reported in a study published in 2018 1.
Safety and Tolerability
- Linezolid has been shown to be well tolerated, with adverse events similar to its established safety profile, and the daily cost of outpatient therapy was less with oral linezolid than with intravenous vancomycin 1.
- Although inpatient treatment with linezolid cost more than inpatient treatment with vancomycin per day, the median length of hospital stay was 3 days shorter with linezolid, as reported in a study comparing the two treatments 1.
From the FDA Drug Label
Linezolid is a synthetic antibacterial agent of a new class of antibiotics, the oxazolidinones, which has clinical utility in the treatment of infections caused by aerobic Gram-positive bacteria. The in vitro spectrum of activity of linezolid also includes certain Gram-negative bacteria and anaerobic bacteria Linezolid inhibits bacterial protein synthesis through a mechanism of action different from that of other antibacterial agents; therefore, cross-resistance between linezolid and other classes of antibiotics is unlikely Linezolid binds to a site on the bacterial 23S ribosomal RNA of the 50S subunit and prevents the formation of a functional 70S initiation complex, which is an essential component of the bacterial translation process.
Key Information about Linezolid:
- Mechanism of Action: Linezolid inhibits bacterial protein synthesis by binding to the 23S ribosomal RNA of the 50S subunit.
- Spectrum of Activity: Linezolid is effective against aerobic Gram-positive bacteria, certain Gram-negative bacteria, and anaerobic bacteria.
- Resistance: Resistance to linezolid can occur through point mutations in the 23S rRNA.
- Clinical Use: Linezolid is used to treat infections caused by susceptible microorganisms, including vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus, and Streptococcus pneumoniae 2.
- Formulations: Linezolid is available as an intravenous injection, tablets, and oral suspension 2.
From the Research
Overview of Linezolid
- Linezolid, also known as Zyvox, is an oxazolidinone antimicrobial agent effective against gram-positive bacteria, including penicillin-, cephalosporin-, and vancomycin-resistant species 3.
- It inhibits bacterial protein synthesis via binding to the 50S ribosomal subunit to prevent translation, and lacks cross-resistance with other antimicrobials 3, 4.
Clinical Efficacy
- Linezolid is effective in the treatment of vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus (MRSA) infections, nosocomial and community-acquired pneumonia, and skin and skin-structure infections due to susceptible organisms 3, 5, 6.
- It has been shown to be effective in children with MRSA infections, with a clinical cure rate of 92.3% in the outpatient trial and 94.1% in the inpatient trial 6.
Pharmacokinetics and Dosage
- Linezolid is primarily excreted renally as unchanged drug, with a plasma half-life of four to five hours, allowing for twice-daily administration for all indicated infections 3.
- The recommended dosage is 600 mg i.v. or p.o. twice daily for all indications except uncomplicated skin and skin-structure infections (400 mg twice daily) 3.
- Adjustments for mild to moderate renal or hepatic impairment are not necessary 3.
Safety and Tolerability
- Linezolid has a well-defined safety profile, with diarrhea, headache, and nausea being the most frequently reported adverse effects 3, 5, 4.
- Reversible myelosuppression has been observed in a few patients, and clinically important interactions with monoamine oxidase inhibitors have not been observed 3.
- In children, linezolid has been shown to be well-tolerated, with few adverse events or drug-related adverse events reported 6.
Comparison with Other Antibiotics
- Linezolid has been compared to other antibiotics, including vancomycin, teicoplanin, quinupristin-dalfopristin, daptomycin, tigecycline, and others, for the treatment of complicated skin and skin structure infections and MRSA 7.
- It has been shown to be effective against MRSA and vancomycin-resistant enterococci, with a similar efficacy profile to vancomycin 7.