Makindo Medical Notes

Linezolid is a synthetic antibiotic from the oxazolidinone class, alongside tedizolid. It is used for serious Gram-positive infections — particularly where resistance to β-lactams, glycopeptides, or macrolides limits alternatives. Linezolid is unique in offering 100% oral bioavailability, allowing seamless IV-to-oral switch — an advantage in OPAT and step-down therapy. Always 🔗 check the BNF entry here for up-to-date dosing and cautions.

🧠 Mode of Action

• Linezolid binds to the 50S ribosomal subunit (at the 23S rRNA site) and prevents the formation of the 70S initiation complex — a crucial step in bacterial protein synthesis.
• Unlike most other protein synthesis inhibitors, linezolid acts at the initiation phase, not elongation — hence active even against strains resistant to macrolides or clindamycin.
• Bacteriostatic against staphylococci and enterococci; bactericidal against most streptococci.

📋 Indications & Typical Dosing

• Resistant Gram-positive infections — particularly when MRSA or VRE (vancomycin-resistant enterococci) are suspected or confirmed.
• Nosocomial pneumonia: 600 mg every 12 hours (IV or oral) for 10–14 days.
• Community-acquired pneumonia: 600 mg every 12 hours (IV or oral) for 10–14 days.
• Complicated skin and soft tissue infections: 600 mg every 12 hours for 10–14 days.
• Other off-label uses (specialist-led): bone/joint infections, prosthetic device infections, CNS infections by MRSA/VRE, multi-drug resistant tuberculosis (MDR-TB).
• Max duration: 28 days (due to myelosuppression and neuropathy risk).
• IV to oral switch: safe and effective due to equivalent exposure (bioavailability ~100%).

🔬 Spectrum of Activity

• 🦠 Active against: Gram-positive organisms — MRSA, MSSA, VRE, Streptococcus pneumoniae (including penicillin-resistant strains), coagulase-negative staphylococci.
• ❌ Not active against: Gram-negative organisms (e.g. Pseudomonas, Enterobacterales, Neisseria) — must be combined if mixed flora suspected.

⚠️ Interactions (Mechanism-based)

• Reversible MAO inhibitor → risk of serotonin syndrome with serotonergic agents (SSRIs, SNRIs, TCAs, triptans, tramadol, pethidine, linezolid + citalopram = ⚠️ avoid unless essential).
• Concurrent use with adrenergic or dopaminergic agents (e.g., pseudoephedrine, dopamine, noradrenaline) may cause hypertension.
• Contraindicated with recent (<14 days) or concurrent MAOIs (e.g., phenelzine, isocarboxazid, selegiline).
• Check the BNF for full interaction list before prescribing.

🚧 Cautions

• Not active against Gram-negative bacteria — must be combined with Gram-negative coverage (e.g., piperacillin–tazobactam or meropenem) if polymicrobial infection suspected.
• Use with caution in uncontrolled hypertension, phaeochromocytoma, carcinoid syndrome, hyperthyroidism, or bipolar affective disorder (risk of catecholamine or serotonin excess).
• Monitor FBC weekly during therapy >10 days due to myelosuppression risk.
• Use with caution in renal or hepatic impairment — metabolites may accumulate (though dose adjustment not usually required).

⛔ Contraindications

• Concurrent or recent (within 14 days) use of MAO inhibitors.
• Uncontrolled hypertension, phaeochromocytoma, thyrotoxicosis.
• Carcinoid syndrome, acute confusional states, bipolar depression, or schizophrenia (serotonergic excess risk).
• Pregnancy and breastfeeding — only if benefits outweigh risks (limited safety data).

🩸 Side Effects & Toxicities

• Myelosuppression (anaemia, leucopenia, thrombocytopenia) — usually reversible on stopping; risk ↑ after 10–14 days or in renal impairment.
• Peripheral and optic neuropathy (with prolonged use >28 days): may be irreversible — monitor for visual changes.
• Lactic acidosis — due to mitochondrial protein synthesis inhibition; presents with unexplained acidosis or raised lactate, fatigue, or dyspnoea.
• Gastrointestinal: diarrhoea, nausea, vomiting, taste disturbance, glossitis.
• Other: rash, candidiasis, headache, dizziness, transient transaminitis.

🧪 Monitoring (Specialist Use)

• FBC: baseline and weekly during therapy, particularly beyond 10 days.
• Lactate: if unexplained metabolic acidosis, tachypnoea, or malaise develops.
• Visual symptoms: counsel to report blurred vision or colour changes — prompt ophthalmic review if suspected optic neuropathy.
• Blood pressure: if on adrenergic agents or history of hypertension.

💡 Practical/Clinical Pearls

• Excellent oral step-down for MRSA pneumonia or deep SSTI where vancomycin cannot be continued (renal toxicity, IV line issues).
• Always add Gram-negative cover for broad-spectrum empiric regimens until sensitivities known.
• Do not exceed 28 days — risk of cumulative mitochondrial toxicity (neuropathy, lactic acidosis).
• If ongoing therapy needed (e.g. bone infection): specialist infectious diseases/microbiology input mandatory.
• Beware serotonin syndrome — agitation, confusion, myoclonus, hyperreflexia, fever; stop serotonergic drug or linezolid as clinically appropriate.
• In OPAT settings: ensure weekly FBC, review for neuropathic or visual symptoms, and monitor adherence carefully.

📚 References

• BNF: Linezolid
• Public Health England (now UKHSA): Management of MRSA and GRE infections, 2024.
• NICE NG15: Antimicrobial stewardship — systems and processes for effective antimicrobial medicine use.
• British Society for Antimicrobial Chemotherapy (BSAC) OPAT Guidelines, 2023.