Can Linezolid (oxazolidinone antibiotic) cause metabolic acidosis, specifically lactic acidosis?

Linezolid and Metabolic Acidosis

Yes, linezolid can cause metabolic acidosis, specifically lactic acidosis, which is recognized as a serious adverse effect of this medication. 1

Mechanism of Linezolid-Induced Lactic Acidosis

Linezolid causes lactic acidosis through inhibition of mitochondrial protein synthesis. While the drug is designed to target bacterial ribosomes, it can also:

• Inhibit mitochondrial ribosomes due to structural similarities between bacterial and mitochondrial ribosomes 2
• Diminish respiratory chain enzyme content in mitochondria
• Limit aerobic energy production
• Accelerate anaerobic glycolysis and lactate generation independent of tissue hypoxia 2

Incidence and Risk Factors

The risk of linezolid-induced lactic acidosis increases with:

• Duration of therapy - particularly when used for more than 6 weeks 3
• ICU admission and mechanical ventilation - significantly increases risk (OR=32.67) 4
• Prolonged treatment courses, as commonly needed for MRSA, VRE, or multidrug-resistant TB infections 1

In pediatric patients, lactic acidosis appears to:

• Occur in approximately 16% of treated children
• Develop earlier than in adults (median 2 days; range 1-13 days) 4

Clinical Presentation

Linezolid-induced lactic acidosis may present with:

• Gastrointestinal symptoms (nausea, vomiting, abdominal pain)
• Lethargy and altered mental status
• Hypotension
• Elevated anion gap metabolic acidosis 5, 6

These symptoms can sometimes mimic other serious conditions, including neurological emergencies 6.

Monitoring Recommendations

For patients on linezolid therapy, especially those on prolonged courses:

• Monitor serum lactate levels regularly 3
• Check anion gap, particularly for patients on therapy >6 weeks 3
• Monitor for symptoms of metabolic acidosis (nausea, vomiting, abdominal pain, altered mental status)
• Consider more frequent monitoring in high-risk patients (ICU patients, mechanically ventilated patients, those on prolonged therapy) 4

Management of Linezolid-Induced Lactic Acidosis

When lactic acidosis is suspected:

1. Discontinue linezolid - this is the primary intervention 5
2. Provide supportive care while mitochondrial function recovers
3. Consider alternative antimicrobial therapy based on susceptibility testing
4. Rule out other common causes of lactic acidosis (hypoxemia, anemia, low cardiac output) 2

Other Important Considerations

Linezolid has several other potential serious adverse effects that should be monitored:

• Myelosuppression (weekly CBC monitoring recommended for the first 2 months) 1
• Peripheral and optic neuropathy (particularly with prolonged use) 1
• Serotonin syndrome (when used with serotonergic medications) 1

Clinical Pearls

• Linezolid-induced lactic acidosis may be overlooked as it can mimic other clinical conditions 6
• Normal-to-high whole-body oxygen delivery, high venous oxygen saturation, and lack of response to interventions that increase tissue oxygen provision suggest mitochondrial dysfunction 2
• In patients requiring long-term linezolid therapy (such as for MDR-TB), the benefits of treatment must be carefully weighed against the risk of lactic acidosis 1
• Therapeutic drug monitoring may help minimize toxicity in patients requiring prolonged therapy 1