A novel oxazolidinone antibiotic, Linezolid is effective against all Gram-positive infections, but is considered with reservation only for resistant Gram-positive organisms, especially vancomycin-resistant Enterococcus (VRE) and Methicillin-resistant Staphylococcus aureus (MRSA). Being orally available, it is sometimes considered if outpatient treatment with oral medicines is required.
Linezolid acts by inhibiting the bacterial translation process by binding to the 23S peptidyltransferase of the 50S subunit, preventing the formation of a functional 70S initiation complex, an essential step in the bacterial translational process. This prevents the bacteria from multiplying.
Cross-resistance with other antimicrobial agents is rare because of its unique mode of action.
Plus + Plus = Minus?
Despite its numerous plus points, what makes its administration a decisive game? Side-effect of any drug become its limiting factor.
In this case, the most significant side-effect is myelosuppression, causing thrombocytopenia, neutropenia, and anemia. Any of these untoward effects should be considered seriously and Linezolid stopped, if unavoidable. Linezolid-induced thrombocytopenia is fortunately reversible with withdrawal of the drug. The rate of thrombocytopenia in patients receiving Linezolid for more than 10 days is as high as 47%, which is much higher than was seen in Phase III trials, which was found to be 2.4%. This is alarming, and hence, caution must be taken during patient selection for this antibiotic.
Linezolid should not be administered in those receiving drugs with monoamine oxidase inhibitor (MAOI) activity, such as selective serotonin reuptake inhibitors (SSRIs).
Linezolid-induced Myelosuppression: What now?
Stop Linezolid if mylesuppression develops. This usually stops the myelosuppression. Gram-positive cover should be achieved with some alternative agents.
- Quinupristin-dalfopristin: A streptogramin antibiotic approved in 1999, is effective against both methicillin- and vancomycin-resistant S. aureus. However, due to rapid development of resistance, it is less reliable than Linezolid. It is also inactive against vancomycin-resistant Enterococcus faecalis.
- Daptomycin: A cyclic lipopeptide, and the only in its class, was approved in 2003 for its Gram-positive coverage which includes vancomycin-resistant enterococcus (VRE), methicillin-resistant staphylococcus aureus (MRSA), and vancomycin-resistant staphylococcus aureus (VRSA).
- Tigecycline: Approved in 2005, it has extended spectrum coverage including all Gram positives and resistant Gram positives. It also has activity against anaerobes and Gram negatives, including extended-spectrum beta-lactamases.