Linezolid

Linezolid is an antibiotic used for the treatment of infections caused by Gram-positive bacteria that are resistant to other antibiotics. 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 uses are infections of the skin and pneumonia although it may be used for a variety of other infections including drug-resistant tuberculosis. It is used either by injection into a vein or by mouth. When given for short periods, linezolid is a relatively safe antibiotic. It can be used in people of all ages and in people with liver disease or poor kidney function. Common side effects with short-term use include headache, diarrhea, rash, and nausea. Serious side effects may include serotonin syndrome, bone marrow suppression, and high blood lactate levels, particularly when used for more than two weeks. If used for longer periods it may cause nerve damage, including optic nerve damage, which may be irreversible. As a protein synthesis inhibitor, linezolid works by suppressing bacterial protein production. This either stops growth or results in bacterial death. 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, rather than one of the later steps. As of 2014, bacterial resistance to linezolid has remained low. Linezolid is a member of the oxazolidinone class of medications. Linezolid was discovered in the mid 1990s, and was approved for commercial use in 2000. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Linezolid is available as a generic medication. The wholesale cost in the developing world is about US$2.90 per day, while that in the United States in 2016 was about US$13.79 per day. It appears to be more cost-effective than alternatives such as vancomycin, mostly because of the ability to switch from intravenous use to administration by mouth sooner. The main use of linezolid is the treatment of severe infections caused by aerobic Gram-positive bacteria that are resistant to other antibiotics; it should not be used against bacteria that are sensitive to drugs with a narrower spectrum of activity, such as penicillins and cephalosporins. In both the popular press and the scientific literature, linezolid has been called a 'reserve antibiotic'—one that should be used sparingly so that it will remain effective as a drug of last resort against potentially intractable infections. In the United States, the indications for linezolid use approved by the U.S. Food and Drug Administration (FDA) are the treatment of vancomycin-resistant Enterococcus faecium infections, with or without bacterial invasion of the bloodstream; nosocomial pneumonia (hospital-acquired) and community-acquired pneumonia caused by S. aureus or S. pneumoniae; complicated skin and skin structure infections (cSSSI) caused by susceptible bacteria, including diabetic foot infection, unless complicated by osteomyelitis (infection of the bone and bone marrow); and uncomplicated skin and soft tissue infections caused by S. pyogenes or S. aureus. The manufacturer advises against the use of linezolid for community-acquired pneumonia or uncomplicated skin and soft tissue infections caused by MRSA. In the United Kingdom, pneumonia and cSSSIs are the only indications noted in the product labeling. Linezolid appears to be as safe and effective for use in children and newborns as it is in adults. A large meta-analysis of randomized controlled trials found linezolid to be more effective than glycopeptide antibiotics (such as vancomycin and teicoplanin) and beta-lactam antibiotics in the treatment of skin and soft tissue infections (SSTIs) caused by Gram-positive bacteria, and smaller studies appear to confirm its superiority over teicoplanin in the treatment of all serious Gram-positive infections.