Linezolid

Linezolid (INN, /lɪˈnɛzəlɪd/ li-NEZ-ə-lid) is a synthetic antibiotic developed by a team at Pharmacia and Upjohn Company. It is used for the treatment of serious infections caused by Gram-positive bacteria that are resistant to several other antibiotics.

A member of the oxazolidinone class of drugs, linezolid is active against most Gram-positive bacteria that cause disease, including streptococci, vancomycin-resistant enterococci (VRE), and methicillin-resistant Staphylococcus aureus (MRSA). The main indications of linezolid are infections of the skin and soft tissues and pneumonia (particularly hospital-acquired pneumonia), although off-label use for a variety of other infections is becoming popular. Linezolid is marketed by Pfizer under the trade names Zyvox (in the United States, United Kingdom, Australia, and several other countries), Zyvoxid (in Europe), and Zyvoxam (in Canada and Mexico). Generics are also available, such as Linospan (in India, by Cipla) and Arlin (in Bangladesh, by Beximco).

Discovered in the 1990s and first approved for use in 2000, linezolid was the first commercially available 1,3-oxazolidinone antibiotic. As of 2009, it is the only marketed oxazolidinone, although others are in development. As a protein synthesis inhibitor, it stops the growth of bacteria by disrupting their production of proteins. Although many antibiotics work this way, the exact mechanism of action of linezolid appears to be unique in that it blocks the initiation of protein production, and not one of the later steps. Bacterial resistance to linezolid has remained very low since it was first detected in 1999, although it may be increasing.

When administered for short periods, linezolid is a relatively safe drug; it can be used in patients of all ages and in people with liver disease or poor kidney function. Common adverse effects of short-term use include headache, diarrhea, and nausea. Long-term use, however, has been associated with serious adverse effects; linezolid can cause bone marrow suppression and low platelet counts, particularly when used for more than two weeks. If used for longer periods still, it may cause peripheral neuropathy (which can be irreversible), optic nerve damage, and lactic acidosis (a buildup of lactic acid in the body), all most likely due to mitochondrial toxicity.

In the United States, linezolid costs approximately 115 U.S. dollars per pill, compared to generic vancomycin which can cost fifteen dollars per day of treatment. Nonetheless, it appears to be more cost-effective than comparable antibiotics, mostly because of the possibility of switching from intravenous to oral administration as soon as patients are stable enough, without the need for dose adjustments.