Linezolid is an antibiotic from the oxazolidinone class of drugs. The drug is used as a reserve antibiotic.
What is linezolid?
Currently, linezolid is the only MRSA-active antibiotic available for both oral and intravenous use. The drug linezolid belongs to the fairly new group of oxazolidinones. Oxazolidinones have saturated heterocyclic compounds. They inhibit protein biosynthesis in bacteria. However, unlike other antibiotics such as tetracyclines, macrolides and lincosamides, they already inhibit the onset of synthesis. Linezolid is an antibiotic used primarily for infections with vancomycin-resistant pathogens. Linezolid is particularly effective in infections with Gram-positive bacteria. It is currently the only MRSA-active antibiotic available for both oral and intravenous use. MRSA refers to strains of the bacterium Staphylococcus aureus that are resistant to all ß-lactam antibiotics, such as penicillin. Typically, these pathogens are multidrug resistant and also have resistance to antibiotics such as quinolones, tetracyclines, erythromycin, sulfonamide and vancomycin. Linezolid has approvals for the treatment of nosocomial pneumonia and severe skin and soft tissue infections.
Pharmacologic Action
The antibiotic linezolid inhibits protein synthesis in bacteria. In protein biosynthesis, living organisms produce proteins (albumin) by translation. Protein biosynthesis is essential for the formation of new proteins in cells. Without the production of proteins, gene expression is not possible. This also means that without protein biosynthesis, cells cannot continue to proliferate. They also cannot continue to grow. Linezolid inhibits the protein biosynthesis of the bacteria right at the beginning. To do this, the drug binds to the 50S subunits of the ribosomes. Protein biosynthesis takes place in the ribosomes. However, linezolid prevents protein synthesis by forming a so-called initiation complex. However, only Gram-positive pathogens are affected by this bacteriostatic effect. Gram-negative pathogens are resistant to linezolid.
Medical application and use
Linezolid became an important reserve antibiotic, relative to Gram-positive bacteria, shortly after its development. Reserve antibiotics may be administered only under restrictions. Strict indications exist. One reason for this restriction is the severe side effects of the agents. In addition, the targeted use of reserve antibiotics is intended to prevent further resistance. Normally, vancomycin is the standard MRSA antibiotic. However, there are now more and more germs that are also resistant to vancomycin. In these cases, linezolid is used. It plays a role particularly in the treatment of severe MRSA infections in hospitals and in the therapy of multidrug-resistant tuberculosis. Staphylococci including methicillin-resistant strains (MRSA), enterococci including vancomycin-resistant strains (VRE) and streptococci including penicillin-resistant strains are sensitive to linezolid. The drug is approved for the treatment of nosocomial or community-acquired pneumonia. Linezolid is also used for severe skin or soft tissue infections. Before treatment, however, microbiologic testing should be performed to determine whether the infection is caused by linezolid-susceptible gram-positive bacteria.
Risks and side effects
A serious side effect of linezolid is bone marrow suppression. Because blood formation occurs in the bone marrow, changes in the blood count occur. In pancytopenia, all blood cells in the blood are severely decreased, so anemia, leukopenia, and thrombocytopenia exist at the same time. However, neutropenia and thrombocytopenia can also occur solitarily. In neutropenia, neutrophil granulocytes are decreased. Because the immune system is directly affected, severe bacterial infections with fever and chills may develop. Affected individuals feel very ill and suffer from mucosal necrosis of the mouth, throat, neck, and genitals. In thrombocytopenia, blood clotting is impaired. Patients suffer hematomas more quickly or have increased nose and/or gum bleeding.Another side effect of linezelide is high blood pressure (hypertension). In addition, inhibition of monoaminooxidase-A and monoaminooxidase-B may occur. This can negatively affect the nervous system. Furthermore, patients taking linezolid report headaches and irritation of the gastrointestinal tract. Linezolid should not be administered in the presence of a known intolerance. Pregnancy and lactation are also contraindications due to the serious side effects. Furthermore, linezolid must not be used with concomitant use of MAO inhibitors. MAO inhibitors are drugs from the group of antidepressants. They are prescribed for Parkinson’s disease and depression, among others. It should also be noted that linezolid also affects serotonin levels in the central nervous system (CNS) via inhibition of monoamine oxidase. When the drug is administered with other medications that increase serotonin levels in the blood, a life-threatening serotonin syndrome can result. Characteristic of the disorder, which results from an accumulation of the neurotransmitter serotonin, are neuromotor and cognitive symptoms. Affected individuals suffer from restlessness, involuntary muscle twitching, chills, tremors, sweating, and increased reflexes.
