Studies of the compounds structure–activity relationships led to the development of several subclasses of oxazolidinone derivatives, with varying safety profiles and antimicrobial activity. Two compounds were considered drug candidates: eperezolid (codenamed PNU-100592) and linezolid (PNU-100766). In the preclinical stages of development, they were similar in safety and antibacterial activity, so they were taken to Phase I clinical trials to identify any difference in pharmacokinetics. Linezolid was found to have a pharmacokinetic advantage—requiring only twice-daily dosage, while eperezolid needed to be given three times a day to achieve similar exposure—and therefore proceeded to further trials. The U.S. Food and Drug Administration (FDA) approved linezolid on 18 April 2000. Approval followed in Brazil (June 2000), the United Kingdom (January 2001), Japan and Canada (April 2001), Europe (throughout 2001), and other countries in Latin America and Asia.As of 2009, linezolid was the only oxazolidinone antibiotic available. Other members of this class have entered development, such as posizolid (AZD2563), ranbezolid (RBx 7644), and radezolid (RX-1741). In 2014, the FDA approved tedizolid phosphate, a second-generation oxazolidinone derivative, for acute bacterial skin and skin structure infection. Society and culture
Economics
Linezolid was quite expensive in 2009; a course of treatment may cost one or two thousand U.S. dollars for the drug alone, not to mention other costs (such as those associated with hospital stay). With the medication becoming generic the price has decreased.
Low- to medium-quality evidence is also mounting for its use in bone and joint infections, including chronic osteomyelitis, although adverse effects are a significant concern when long-term use is necessary.In combination with other drugs, linezolid has been used to treat tuberculosis. The optimal dose for this purpose has not been established. In adults, daily and twice-daily dosing have been used to good effect. Many months of treatment are often required, and the rate of adverse effects is high regardless of dosage. There is not enough reliable evidence of efficacy and safety to support this indication as a routine use.Linezolid has been studied as an alternative to vancomycin in the treatment of febrile neutropenia in cancer patients when Gram-positive infection is suspected. It is also one of few antibiotics that diffuse into the vitreous humor, and may therefore be effective in treating endophthalmitis (inflammation of the inner linings and cavities of the eye) caused by susceptible bacteria. Again, there is little evidence for its use in this setting, as infectious endophthalmitis is treated widely and effectively with vancomycin injected directly into the eye. Infections of the central nervous system
In animal studies of meningitis caused by Streptococcus pneumoniae, linezolid was found to penetrate well into cerebrospinal fluid, but its effectiveness was inferior to that of other antibiotics. There does not appear to be enough high-quality evidence to support the routine use of linezolid to treat bacterial meningitis.