Linezolid is a beacon for treating infections, especially those resistant to multiple drugs.

However, beneath the surface of its clinical efficacy lies a rare but potentially treacherous adverse effect: linezolid-induced lactic acidosis (LILA).

A recent case study sheds light on this uncommon reaction, reminding healthcare professionals and patients alike of the importance of vigilance and awareness.

The Case That Brought LILA to Light

The spotlight on LILA was intensified by the case of a patient undergoing treatment for disseminated multidrug-resistant tuberculosis with linezolid.

The patient’s journey took a sudden detour when he presented symptoms that mirrored sepsis syndrome—vomiting, dyspnoea, hypotension, and high anion gap metabolic acidosis. With ketoacidosis and renal dysfunction ruled out and no evidence of toxin ingestion or infection, the medical team was left to navigate through murky waters.

The turning point came with the discontinuation of linezolid, leading to the resolution of lactic acidosis and a significant improvement in the patient’s condition. This course of action illuminated the diagnosis of LILA, a rare but real risk associated with linezolid therapy.

Understanding Lactic Acidosis

Lactic acidosis is a medical condition characterized by the buildup of lactate, mainly lactic acid, in the body, leading to an acidic environment in the bloodstream. It is a form of metabolic acidosis, where the body’s pH balance is disrupted due to increased acidity.

This condition can result from various causes, including increased lactate production, decreased lactate clearance, or a combination of both. Lactic acidosis is often categorized into two types based on its underlying cause:

Type A Lactic Acidosis

This occurs due to tissue hypoxia, where insufficient oxygen reaches the tissues, leading to anaerobic metabolism and the overproduction of lactate. Common causes include:

  • Severe infections (sepsis)
  • Cardiogenic shock (heart failure leading to poor blood circulation)
  • Hemorrhagic shock (severe blood loss)
  • Respiratory failure
  • Physical conditions that severely reduce oxygen delivery to tissues

Type B Lactic Acidosis

Type B is not directly related to tissue hypoxia but can be associated with various medical conditions, medications, or toxins. Causes include:

  • Liver disease affects the organ’s ability to clear lactate from the blood
  • Certain medications and toxins, such as metformin (especially in the context of renal failure), linezolid, and antiretroviral drugs
  • Inherited metabolic disorders
  • Diabetes
  • Malignancies that produce lactate


Symptoms of lactic acidosis can be nonspecific and may include:

  • Nausea and vomiting
  • Abdominal pain
  • Rapid breathing (tachypnea)
  • Weakness or fatigue
  • Confusion or altered mental status
  • Muscle cramps or pain

Diagnosis and Treatment

Diagnosis of lactic acidosis involves blood tests to measure lactate levels, blood pH, and other markers of acid-base balance. Identifying and treating the underlying cause of lactic acidosis is crucial. Treatment strategies may include:

  • Providing oxygen or mechanical ventilation for cases involving hypoxia
  • Fluid resuscitation and medications to support blood pressure in shock
  • Dialysis for cases involving renal failure or to remove toxins
  • Discontinuing or adjusting doses of medications known to cause lactic acidosis

Prompt recognition and treatment of lactic acidosis are essential, as the condition can rapidly progress and become life-threatening. Management focuses on correcting the acid-base imbalance and addressing the root cause to prevent further lactate accumulation.

How Does Linezolid Work?

How Does Linezolid Work - Safe Therapeutics

Linezolid is an antibiotic from a class of medications known as oxazolidinones. It is specifically designed to treat infections caused by Gram-positive bacteria, including resistant strains such as Methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-resistant Enterococcus (VRE).

Linezolid is effective against various bacterial infections, including skin infections, pneumonia, and other serious infections caused by susceptible bacteria.

Mechanism of Action

Linezolid works by inhibiting bacterial protein synthesis, a mechanism distinct from many other antibiotic classes. It achieves this by binding to a site on the bacterial 23S ribosomal RNA of the 50S subunit, a ribosome component responsible for protein synthesis.

By binding to this site, linezolid prevents the formation of a functional 70S initiation complex, which is an essential step in the translation process of proteins. As a result, linezolid effectively stops the bacteria from growing and reproducing by hindering their ability to produce proteins necessary for survival.

Key Features

  • Spectrum of Activity: Linezolid is primarily effective against Gram-positive bacteria, including multidrug-resistant strains such as MRSA and VRE. It is one of the antibiotics of choice when dealing with infections caused by these resistant bacteria.
  • Oral and Intravenous Administration: Linezolid can be administered both orally and intravenously, allowing flexibility in treatment based on the severity of the infection and patient needs. The bioavailability of oral linezolid is approximately 100%, meaning that its absorption is not significantly affected by food, and it can achieve similar blood concentrations to the intravenous form.
  • Resistance: Although linezolid is a powerful antibiotic, bacterial resistance can develop, particularly with prolonged use. Resistance mechanisms include mutations in the 23S rRNA and acquiring CFR genes that can methylate the ribosome, reducing linezolid’s binding affinity.
  • Side Effects: Like all medications, linezolid can cause side effects. Common ones include diarrhea, nausea, headache, and myelosuppression (which can lead to anemia, thrombocytopenia, and leukopenia). It can also interact with serotonergic medications, increasing the risk of serotonin syndrome, and prolonged use has been associated with peripheral and optic neuropathy.

The Dual Faces of Linezolid

Linezolid is a powerful ally in the fight against infections, particularly those caused by multidrug-resistant organisms.

However, its potential to induce lactic acidosis, though rare, reminds us of the delicate balance in antibiotic therapy. While thrombocytopenia and peripheral neuropathy are more commonly associated with prolonged linezolid use, LILA emerges as a silent threat that can easily be mistaken for other conditions, as seen in the case presented.

Navigating the Treatment Landscape

This case underscores the importance of considering LILA in patients exhibiting lactic acidosis symptoms while on linezolid, especially when other causes have been excluded.

The resolution of symptoms upon discontinuing the drug further emphasizes the need for healthcare professionals to remain alert to this possibility and to weigh the benefits of linezolid against its risks carefully.

A Call to Awareness

For patients and healthcare providers, the tale of LILA is a call to awareness. It highlights the need for careful monitoring of symptoms and open communication about the potential side effects of medications, no matter how rare.

Understanding the signs of lactic acidosis and the conditions under which they may arise can lead to prompt and effective interventions, ensuring that the scales of treatment remain balanced.


While linezolid continues to be a valuable tool in combating resistant infections, the shadow of linezolid-induced lactic acidosis looms, reminding us of the complexities and challenges in antibiotic therapy.

Through vigilance, awareness, and informed decision-making, we can navigate these waters safely, ensuring the well-being of patients embarking on their journey to recovery.