Linezolid-induced lactic acidosis: the thin line between bacterial and mitochondrial ribosomes

ABSTRACT

Introduction: Linezolid inhibits bacterial growth by targeting bacterial ribosomes and by interfering with bacterial protein synthesis. Lactic acidosis is a rare, but potentially lethal, side effect of linezolid.

Areas covered: The pathogenesis of linezolid-induced lactic acidosis is reviewed with special emphasis on aspects relevant to the recognition, prevention and treatment of the syndrome.

Expert opinion: Linezolid-induced lactic acidosis reflects the untoward interaction between the drug and mitochondrial ribosomes. The inhibition of mitochondrial protein synthesis diminishes the respiratory chain enzyme content and thus limits aerobic energy production. As a result, anaerobic glycolysis and lactate generation accelerate independently from tissue hypoxia.

In the absence of any confirmatory test, linezolid-induced lactic acidosis should be suspected only after exclusion of other, more common, causes of lactic acidosis such as hypoxemia, anemia or low cardiac output. Normal-to-high whole-body oxygen delivery, high venous oxygen saturation and lack of response to interventions that effectively increase tissue oxygen provision all suggest a primary defect in oxygen use at the mitochondrial level.

During prolonged therapy with linezolid, blood drug and lactate levels should be regularly monitored. The current standard-of-care treatment of linezolid-induced lactic acidosis consists of drug withdrawal to reverse mitochondrial intoxication and intercurrent life support.

KEYWORDS:

• Linezolid
• oxazolidinones
• mitochondria
• lactic acidosis
• oxygen

Article highlights

• Linezolid exerts its therapeutic effects by targeting bacterial ribosomes and by interfering with bacterial protein synthesis

• Linezolid-induced lactic acidosis reflects the untoward interaction between the drug and mitochondrial ribosomes

• Lactic acidosis should be attributed to linezolid only after exclusion or correction of other, more common, causes

• High (>80%) central venous oxygen saturation is consistent with linezolid-induced lactic acidosis

• In high-risk subjects, including those undergoing prolonged therapy, blood linezolid and lactate levels should be regularly monitored

• The current standard-of-care treatment of linezolid-induced lactic acidosis consists of drug withdrawal and life support

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.