Oxazolidinone antibiotics
Oxazolidinone antibiotics are a class of medications that function by disrupting the synthesis of proteins in bacteria, thereby inhibiting their growth and reproduction. The first oxazolidinone used for human medicine was cycloserine in 1956, primarily for treating tuberculosis. In 2000, linezolid (Zyvox) emerged as the first new class of antibiotic introduced in two decades, demonstrating effectiveness against multidrug-resistant bacterial infections. Newer oxazolidinones, such as torezolid, posizolid, and radezolid, are currently undergoing clinical trials.
These antibiotics primarily target gram-positive bacteria and are utilized in treating various infections, particularly those caused by resistant strains like methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. While they are effective, oxazolidinones can also cause side effects, particularly with long-term use, including bone marrow suppression and peripheral neuropathy, linked to their impact on mitochondrial ribosomes. Despite low resistance rates, increased use of these antibiotics may elevate resistance levels in the future, making careful management essential.
Oxazolidinone antibiotics
Definition
Oxazolidinone antibiotics disrupt the synthesis of new proteins. In doing so, they inhibit bacterial growth and reproduction.
History
The first oxazolidinone antibiotic used in human medicine was cycloserine, which was introduced in 1956 as a second-line drug against Mycobacterium tuberculosis, the bacterium that causes tuberculosis. In 2000, the company Amersham Pharmacia (now Pfizer) introduced to the market an oxazolidinone called linezolid (Zyvox). Linezolid was the first new class of antibiotic to pass clinical trials successfully in twenty years. It has proven to be extremely effective against multidrug-resistant bacteria. Tedizolid (Sivextro), another oxazolidinone antibiotic, was approved for use in the United States in 2014.
Mechanisms of Action and Bacterial Resistance
Cells synthesize proteins on large protein-ribonucleic acid (RNA) complexes called ribosomes. Oxazolidinone antibiotics bind to ribosomes and disrupt the synthesis of new proteins, inhibiting bacterial growth and reproduction. Because frequent use of oxazolidinone antibiotics increases resistance, they should be used only to treat severe infections caused by MDR Gram-positive bacteria.
Side Effects
Inside human cells are vesicles called mitochondria that make the chemical energy for the cell. Mitochondria possess their own deoxyribonucleic acid (DNA) chromosomes and ribosomes that synthesize some of their proteins. Mitochondrial ribosomes have many similarities to bacterial ribosomes, and these structural resemblances render mitochondrial ribosomes susceptible to inhibition by linezolid.
When used for a short time, linezolid causes headache, nausea, vomiting, and rash in a small minority of persons. It can also cause the overgrowth of various bodily surfaces with yeast (antibiotic candidiasis); a few persons show signs of liver damage. Long-term use of linezolid (more than fourteen days), however, can cause bone marrow suppression, peripheral and optical neuropathy, and the accumulation of lactic acid in the blood (lactic acidosis). All of these side effects directly result from the inhibition of mitochondrial ribosomes. Long-term use of tedizolid has been shown to be more effective and less likely to cause bone marrow suppression. Side effects include headache, rash, dizziness, blurred vision, and chest tightness.
Impact
Linezolid has provided new treatment options for some infectious diseases that have, because of bacterial drug resistance, exhausted all previous antibiotic treatment regimes. It is largely active against gram-positive bacteria; gram-positive bacteria have thick cell walls, and gram-negative bacteria have thin cell walls in addition to an outer membrane.
Physicians use linezolid to treat skin and respiratory tract infections caused by methicillin-resistant Staphylococcus aureus and Streptococcus strains. Linezolid is also effective against vancomycin-resistant bacterial meningitis and vancomycin-resistant strains of Enterococcus faecium, which can cause a variety of infections that are difficult to treat. In combination with other drugs, linezolid also has been used to treat multidrug-resistant tuberculosis.
Bibliography
Brenciani, Andrea, et al. "Oxazolidinones: Mechanisms of Resistance and Mobile Genetic Elements Involved." Journal of Antimicrobial Chemotherapy, vol. 77, no. 10, Oct. 2022, pp. 2596-2621, doi.org/10.1093/jac/dkac263. Accessed 4 Feb. 2025.
Gallagher, Jason. Antibiotics Simplified. Sudbury, Mass.: Jones and Bartlett, 2008.
Goldsmith, Connie. Superbugs Strike Back: When Antibiotics Fail. Breckenridge, Colo.: Twenty-First Century Books, 2006.
Walsh, Christopher. Antibiotics: Actions, Origins, Resistance. Washington, D.C.: ASM Press, 2003.