Which newer synthetic drug is used to treat MRSA and VRE?

October 10, 2025 •

3 min read

According to the World Health Organization, the rise of antimicrobial resistance poses a critical threat to human health, creating an urgent need for novel treatments against pathogens like Methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-resistant Enterococcus (VRE). In response, newer synthetic drugs have emerged to combat these superbugs, challenging older therapies and asking which newer synthetic drug is used to treat MRSA and VRE.

Quick Summary

This article explores newer synthetic drugs, including next-generation oxazolidinones, novel cephalosporins, and lipoglycopeptides, used to combat resistant MRSA and VRE infections.

Key Points

Tedizolid: A next-generation oxazolidinone with 4-8 times greater potency against MRSA and VRE than linezolid and a more convenient once-daily dosing.
Ceftaroline: A fifth-generation cephalosporin that uniquely binds to the PBP2a protein, making it effective against MRSA and some VRE (E. faecalis).
Dalbavancin and Oritavancin: Long-acting lipoglycopeptides that can be dosed infrequently (weekly or single dose), simplifying outpatient treatment for ABSSSI caused by MRSA and, for oritavancin, some VRE.
Diverse Mechanisms: These drugs utilize varied mechanisms, including inhibiting protein synthesis, disrupting cell walls, and altering cell membranes, to overcome existing resistance pathways.
Combatting Resistance: The development of newer synthetic drugs is a direct response to the increasing resistance seen with older antibiotics like vancomycin, offering alternatives for serious infections.
Future Challenges: While effective, the ongoing threat of resistance and potential side effects necessitates careful monitoring and prudent use of these advanced antibiotics to prolong their efficacy.

The emergence of antibiotic-resistant bacteria like MRSA and VRE has necessitated the development of new synthetic antimicrobial drugs. While vancomycin has long been a frontline treatment, issues such as increasing minimum inhibitory concentrations (MICs), poor tissue penetration in some areas, and outright resistance have spurred the search for more effective alternatives. A number of newer synthetic drugs offer advantages over traditional therapies, including greater potency, different mechanisms of action, and more convenient dosing regimens. These options are critical for addressing the growing public health challenge posed by multidrug-resistant pathogens.

Next-Generation Oxazolidinones: Tedizolid

Tedizolid (brand name Sivextro) is a next-generation oxazolidinone, a synthetic antimicrobial class that inhibits bacterial protein synthesis. Approved by the U.S. Food and Drug Administration (FDA) in 2014, it is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI). As a successor to the older oxazolidinone, linezolid, tedizolid offers several key advantages. Tedizolid is four to eight-fold more potent against many Gram-positive pathogens, including MRSA and VRE, and is effective against some linezolid-resistant strains. It allows for once-daily dosing for a shorter duration, which may lead to fewer side effects compared to linezolid. Tedizolid is available in intravenous and oral forms and is effective against MRSA, Enterococcus faecium, streptococci, and some linezolid-resistant strains.

Novel Cephalosporins: Ceftaroline

Ceftaroline (brand name Teflaro) is a fifth-generation cephalosporin notable for its activity against MRSA. Its anti-MRSA efficacy is due to its high affinity for penicillin-binding protein 2a (PBP2a), the protein causing methicillin resistance in Staphylococcus aureus. By binding to PBP2a, ceftaroline inhibits bacterial cell wall synthesis. Ceftaroline has a broad spectrum against Gram-positive and Gram-negative bacteria and is approved for ABSSSI and community-acquired bacterial pneumonia, including MRSA cases. It is active against vancomycin-resistant Enterococcus faecalis but has variable activity against E. faecium. Ceftaroline is administered intravenously with renal dose adjustments.

Long-Acting Lipoglycopeptides: Dalbavancin and Oritavancin

Dalbavancin (Dalvance) and oritavancin (Orbactiv) are newer lipoglycopeptides for treating ABSSSI. They inhibit cell wall synthesis like vancomycin but have a lipophilic tail extending their half-lives for infrequent dosing.

Dalbavancin: Has a long half-life allowing once-weekly dosing for two doses. It is active against MRSA but not vancomycin-resistant enterococci.
Oritavancin: Has an even longer half-life, enabling a single-dose treatment for ABSSSI. It inhibits cell wall synthesis and disrupts the bacterial cell membrane. Oritavancin is active against MRSA and VanA and VanB-type VRE.

These drugs' long half-lives can improve patient care by supporting outpatient treatment.

Comparing Newer Synthetic Drugs for MRSA and VRE


Drug	Class	Key Mechanism	Dosing Frequency	Key Indications (MRSA)	Key Indications (VRE)
Tedizolid	Oxazolidinone	Inhibits protein synthesis by binding to the 23S ribosomal RNA.	Once daily (6 days).	ABSSSI, some linezolid-resistant strains.	Yes, including some linezolid-resistant VRE.
Ceftaroline	Cephalosporin (5th-gen)	Inhibits cell wall synthesis by binding to penicillin-binding protein 2a (PBP2a).	Twice daily (IV).	ABSSSI, pneumonia, VISA, hVISA, VRSA.	Yes, but only E. faecalis; not active against E. faecium.
Dalbavancin	Lipoglycopeptide	Inhibits cell wall synthesis by binding to d-Ala-d-Ala and forms dimers.	Once weekly (2 doses).	ABSSSI, some VISA and hVISA.	No activity.
Oritavancin	Lipoglycopeptide	Inhibits cell wall synthesis; disrupts membrane integrity.	Single dose.	ABSSSI, some VRSA.	Yes, including VanA/B-type VRE.
Linezolid	Oxazolidinone	Inhibits protein synthesis by binding to the 50S ribosomal subunit.	Twice daily (IV/Oral).	ABSSSI, pneumonia.	Yes, but resistance can develop.

How newer drugs address resistance

Newer synthetic drugs overcome resistance by targeting different sites, circumventing efflux pumps, utilizing dual-action mechanisms, or binding to unique proteins like PBP2a.

Limitations and Future Outlook

Despite their benefits, these newer drugs face challenges. Resistance can still develop, as seen with linezolid. Careful monitoring and judicious use are essential to preserve their effectiveness. Additionally, some drugs have long half-lives that can prolong adverse effects, and the cost can be a barrier. Research continues to optimize their use and develop new strategies against evolving bacterial resistance.

Conclusion

Newer synthetic drugs like tedizolid, ceftaroline, dalbavancin, and oritavancin are important advances against MRSA and VRE. They offer advantages in potency, mechanism, and dosing compared to older drugs. However, the ongoing challenge of bacterial evolution requires continuous effort in research, clinical practice, and patient education to maintain their effectiveness.

Outbound link: Learn more about antimicrobial resistance from Baylor College of Medicine.

Frequently Asked Questions

Tedizolid is a newer oxazolidinone that is 4-8 times more potent than linezolid against many Gram-positive pathogens. It is also effective against some linezolid-resistant strains and has a more convenient once-daily dosing schedule for a shorter duration.

The main benefit is the ability for very infrequent dosing due to their long half-lives. This simplifies treatment for conditions like ABSSSI, potentially reducing the need for prolonged hospitalization and facilitating outpatient care.

No, ceftaroline has activity against vancomycin-resistant Enterococcus faecalis but not against E. faecium. Therefore, it is not effective for all types of VRE infections.

MRSA has developed various resistance mechanisms, including some isolates showing reduced susceptibility to vancomycin. The rise in vancomycin minimum inhibitory concentrations (MICs) and the emergence of VISA and VRSA strains make alternative therapies necessary for effective treatment.

No, while many are approved for skin and soft tissue infections (ABSSSI/SSTIs), some, like ceftaroline, are also used for pneumonia. Linezolid is indicated for pneumonia and VRE infections beyond skin infections.

Potential downsides include the high cost, the risk of resistance developing over time with continued use, and the long half-life of some drugs (like dalbavancin and oritavancin), which can prolong adverse effects if they occur.

They use novel strategies such as inhibiting protein synthesis at a different ribosomal site (tedizolid), binding to a unique protein that confers resistance (ceftaroline binding to PBP2a), or utilizing dual mechanisms of action (oritavancin).