Understanding When Did Linezolid Come Out?: The History of the Oxazolidinone Antibiotic

October 7, 2025 •

3 min read

In 2000, linezolid (trade name Zyvox) became the first in a new class of antibiotics, the oxazolidinones, to be approved in over 35 years. Understanding when did linezolid come out reveals a story of innovative drug development aimed at tackling the growing threat of resistant Gram-positive bacterial infections.

Quick Summary

Linezolid, marketed as Zyvox, received its initial FDA approval on April 18, 2000, as the first oxazolidinone antibiotic developed to combat serious resistant Gram-positive infections.

Key Points

FDA Approval in 2000: Linezolid (Zyvox) received US Food and Drug Administration approval on April 18, 2000, as the first oxazolidinone antibiotic.
Response to Rising Resistance: The drug was developed by Pharmacia & Upjohn (now Pfizer) in the 1990s specifically to address the growing threat of antibiotic-resistant Gram-positive bacteria, including MRSA and VRE.
Unique Mechanism of Action: Linezolid inhibits bacterial protein synthesis by blocking the ribosomal initiation complex, a mechanism distinct from other antibiotics that helps prevent cross-resistance.
High Oral Bioavailability: Unlike many comparable antibiotics such as vancomycin, linezolid offers 100% oral bioavailability, providing an advantage for patients transitioning from intravenous to oral therapy.
Broad Spectrum for Gram-Positive Infections: It is indicated for a range of serious Gram-positive infections, including pneumonia and complicated skin and soft tissue infections.
Inspiration for Future Drugs: Linezolid's success inspired further research and development in the oxazolidinone class, leading to the later approval of other drugs like tedizolid.

The Emergence of the Oxazolidinone Class

The development of linezolid addressed a significant need in the late 20th century due to the rise of bacterial resistance to existing antibiotics. Research into oxazolidinone compounds by DuPont in the 1970s and 80s was initially halted due to toxicity concerns. However, Upjohn (later Pharmacia & Upjohn and then Pfizer) revived this research in the 1990s, aiming to find an oxazolidinone with strong antibacterial action and a favorable safety profile.

The Selection of Linezolid for Clinical Trials

Through extensive research, eperezolid and linezolid were identified as promising candidates. Both showed similar preclinical results, but linezolid demonstrated superior pharmacokinetics in human trials, allowing for a twice-daily dosing regimen compared to eperezolid's thrice-daily requirement. This practical advantage led to linezolid being chosen for further clinical development.

Official FDA Approval and Commercial Launch

The U.S. Food and Drug Administration (FDA) approved linezolid on April 18, 2000, marking its official entry into the market. Launched as Zyvox in May 2000, it was the first antibiotic from a new class to be approved in over three decades.

Initial approved uses for linezolid included certain types of pneumonia and complicated skin and skin structure infections caused by susceptible bacteria, as well as infections from vancomycin-resistant Enterococcus faecium. Following its U.S. approval, Zyvox quickly gained regulatory approval and was launched in several other countries, including Brazil, the UK, Canada, and across Europe and Japan, throughout 2000 and 2001.

The Unique Mechanism of Action

Linezolid's effectiveness, particularly against resistant bacteria like MRSA and VRE, lies in its distinct mechanism of action. It inhibits bacterial protein synthesis by binding to the 23S ribosomal RNA on the 50S subunit and blocking the formation of the 70S initiation complex. This unique approach prevents the bacteria from starting the protein synthesis process, thereby hindering their ability to function and reproduce. This mechanism also helps to minimize cross-resistance with other existing antibiotic classes.

Linezolid vs. Vancomycin: A Comparison

Linezolid became an important alternative, particularly for serious Gram-positive infections, offering advantages over existing treatments like vancomycin. Below is a comparison of key features:


Feature	Linezolid (Zyvox)	Vancomycin
Drug Class	Oxazolidinone	Glycopeptide
Mechanism	Inhibits initiation of protein synthesis.	Inhibits cell wall synthesis.
Resistance Issues	Mechanisms exist (e.g., G2576T mutation, cfr gene).	Widespread resistance, particularly VRE.
Administration	Oral and intravenous options.	Primarily intravenous for systemic infections.
Oral Option	Yes, excellent bioavailability.	No, poor oral absorption for systemic infections.
Cost	Initially higher cost	Generally lower cost, available as generic.

Conclusion

Linezolid's FDA approval in April 2000 marked a significant step in the fight against antibiotic-resistant bacteria. As the first oxazolidinone antibiotic, its unique mechanism and availability in an oral form provided a valuable new treatment option for serious Gram-positive infections, including those caused by MRSA and VRE. Its development highlighted the critical need for continuous innovation in antimicrobial drug discovery to combat evolving resistance. The legacy of linezolid continues to influence research in this field and contributed to the subsequent development of other oxazolidinones.

Ongoing Monitoring and Successors

The emergence of antibiotic resistance remains a challenge, leading to global monitoring programs for linezolid resistance and the development of newer oxazolidinones. Building on linezolid's success, tedizolid, a second-generation oxazolidinone, was approved by the FDA in 2014 for treating acute bacterial skin and skin structure infections, illustrating the continued progress in this class of antibiotics.

Frequently Asked Questions

Linezolid (trade name Zyvox) is a synthetic antibiotic belonging to the oxazolidinone class, the first new class of antibiotics introduced in over 35 years when it was approved by the FDA in 2000.

The US Food and Drug Administration (FDA) approved linezolid for commercial use on April 18, 2000.

Linezolid was developed by researchers at the Upjohn Company, which became part of Pharmacia & Upjohn and later Pfizer.

Linezolid was crucial because it offered a new treatment option against serious Gram-positive infections, including those caused by difficult-to-treat pathogens like methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE).

Linezolid inhibits bacterial protein synthesis by uniquely binding to the 50S ribosomal subunit and preventing the formation of the 70S initiation complex. This mechanism helps avoid cross-resistance with older antibiotics.

Yes, one of linezolid's significant advantages is its 100% oral bioavailability, meaning it can be administered effectively both orally and intravenously.

Yes. Following linezolid's groundbreaking introduction, other oxazolidinone antibiotics have been developed. For example, tedizolid phosphate was approved by the FDA in 2014.