Linezolid

Linezolid belongs to the oxazolidinone family, a class of synthetic antibiotics. It acts on the bacterial ribosome, the machine that builds the bacterium’s proteins. It binds to the 23S ribosomal RNA of the 50S subunit and prevents the assembly of the functional 70S initiation complex. Deprived of this starting point, the bacterium can no longer begin the synthesis of its proteins, and its multiplication stops.

This action does not always destroy the bacterium directly. Against staphylococci and enterococci, linezolid is bacteriostatic: it blocks growth without killing and lets the body’s defences finish the work. Against most streptococci, it is bactericidal, meaning it destroys the bacterium. This original mode of action explains why it remains active where other antibiotics have lost ground.

Linezolid is reserved for specific situations: infections caused by bacteria that have become resistant to the usual treatments. It targets in particular Enterococcus faecium enterococci resistant to vancomycin, often noted as VRE, against which few options remain. It also treats pneumonia due to methicillin-resistant Staphylococcus aureus, MRSA, whether contracted in hospital or in the community.

It is finally used in skin and soft tissue infections due to MRSA, both complicated and uncomplicated. This role as a fallback explains why it is not prescribed as a first choice for a common infection. The decision rests on identifying the organism and on its resistance profile, established by the doctor and the laboratory.

Linezolid comes as a tablet and in an injectable form. Its oral bioavailability approaches 100%, which means the tablet delivers the same amount of medicine as the infusion: the oral dose and the intravenous dose are identical, with no adjustment. Switching from the infusion to the tablet therefore happens without loss of effectiveness, an advantage for continuing treatment at home.

The medicine’s half-life is between 4.3 and 5.4 hours at steady state, which corresponds to two doses a day, twelve hours apart. It can be swallowed with or without food: food slows the rate of absorption but does not reduce the amount absorbed. You should keep to the schedule, follow the prescribed duration and not stop the treatment on your own, even when symptoms improve.

The most closely watched side effect involves the blood. Linezolid can slow the production of blood cells by the bone marrow, a phenomenon called myelosuppression: a fall in platelets (thrombocytopenia), red blood cells (anaemia), white blood cells (leukopenia), sometimes all three at once (pancytopenia). In adult trials, a marked fall in platelets affected 2.4% of patients; in hospitalised children, this figure reaches 12.9%.

This toxicity is partly due to the kinship between the bacterial ribosome and that of the mitochondria, the energy factories of our cells. By blocking the synthesis of mitochondrial proteins, linezolid hampers very active cells such as those of the marrow. This is why a full blood count is checked each week during treatment, in order to spot a fall early and adjust the course of action.

Two other effects appear above all during prolonged treatments. Neuropathies, damage to the peripheral nerves and the optic nerve, have been reported mainly beyond the maximum recommended duration of 28 days. They can show up as tingling, a loss of sensation or a decline in vision, and they do not always resolve: some damage is irreversible.

Lactic acidosis, that is, a build-up of lactic acid in the blood, has also been described. It stems from the same mitochondrial mechanism. Nausea, recurrent vomiting or a fall in bicarbonates should raise concern: if suspected, stopping the treatment is recommended and a medical assessment is required. These signs justify seeking care without delay.

Linezolid is a reversible and non-selective inhibitor of monoamine oxidase, the enzyme (MAO-A and MAO-B) that breaks down certain chemical messengers. Combined with medicines that increase serotonin, such as SSRI antidepressants, tricyclics, certain opioids and other serotonergic agents, it can trigger serotonin syndrome. Any combination of this kind must be known to the doctor, who decides on the course of action.

The same effect on MAO, in the gut and the liver, explains the caution towards foods rich in tyramine, detailed further down. On the nutrient side, the protective role of vitamin B6, pyridoxine, against blood toxicity remains debated: a prospective study showed no effect of pyridoxine on the frequency of myelosuppression during prolonged treatment. Monitoring rests above all on weekly surveillance of the blood count.