Linezolid is one of the more recently developed antibiotics, and it is gaining increasing use in the treatment of infections caused by multiply resistant gram-positive organisms. An important, often underappreciated, feature of linezolid is its action as a weak, reversible inhibitor of monoamine oxidase. Lack of recognition of the possibility of significant MAOI-based interactions has led to unfortunate results in hospitalized patients.

To review briefly, the enzyme monoamine oxidase is critically important in the metabolism of the monoamines, which include all of the catecholamines deriving from tyrosine (epinephrine, norepinephrine, and dopamine) as well as serotonin. Inhibition of monoamine oxidase via pharmacologic agents can result in greatly increased catecholamine levels. Co-administration of an MAOI with a sympathomimetic agent, or with any medication that increases the activity or availability of catecholamines, creates the danger of a hypertensive crisis. Similarly, combining MAOIs with serotonergically active compounds may lead to a central serotonin syndrome, characterized by flushing, diarrhea, myoclonus, fever, delirium, seizures, and possibly autonomic collapse and death. Patients who take MAOIs must also adhere to a tyramine-free diet (no aged cheeses, aged or fermented meats, broad bean pods, chianti wine, sauerkraut, or most soybean products) in order to avoid a potential hypertensive crisis.

The most commonly prescribed monoamine oxidase inhibitors (MAOIs) are the antidepressant medications phenelzine (Nardil) and tranylcypromine (Parnate), both potent and irreversible inhibitors of monoamine oxidase. These drugs have been in clinical use for decades and are generally readily recognized by anesthesia providers. Clinical practice concerning the administration of phenelzine and tranylcypromine in the perioperative period has undergone some evolution over the years—generally, most practitioners do not withhold these drugs in the perioperative period, but in order to minimize the danger of a hypertensive crisis instead advocate careful and titrated administration of sympathomimetics.

Because linezolid is a reversible and less potent inhibitor of monoamine oxidase than phenelzine or tranylcypromine, it was hoped that the same pharmacodynamic interactions would not be seen. Unfortunately, such has not been the case. Since its introduction, there have been numerous reports of central serotonin syndrome when linezolid has been combined with selective serotonin reuptake inhibitors. There has also been one report of intractable intraoperative hypertension occurring in a patient on a combination of linezolid and bupropion (an antidepressant that inhibits the reuptake of both norepinephrine and dopamine).