Tedizolid Phosphate vs Linezolid for Treatment of Acute Bacterial Skin and Skin Structure Infections

Abstract

NTIMICROBIALS AVAILABLE FOR treatment of complicated skin and skin structure infections (SSSIs) are generally efficacious, but antimicrobial resistance 1-7 and adverse effects limit their use. 1,8,9 Linezolid, an oxazolidinone, is the only drug approved for complicated SSSI caused by methicillinresistant Staphylococcus aureus (MRSA). Sporadic outbreaks of linezolidresistant strains of MRSA and enterococci, including those carrying a plasmid-borne cfr gene encoding the chloramphenicol/florfenicol resistance protein, have been reported. 10 Significant safety concerns with linezolid have emerged since it was approved in 2000 by the US Food and Drug Administration (FDA). 11 In 2010, the FDA issued a draft guidance for the development of systemic drugs to treat acute bacterial SSSIs (ABSSSIs) with recommendations for clinical response criteria and noninferiority trial design. 12,13 Given the time required to develop and obtain approval for a new chemical entity, trials demonstrating noninferiority to currently approved antimicrobials allow the development of new agents in advance of the selection of resistant pathogens in hospitals or in the community. Even within the same class of For editorial comment see p 609.

Hospitalist Perspective on the Treatment of Skin and Soft Tissue Infections

“…97 Tedizolid was reported to be statistically noninferior to linezolid in patients with ABSSSIs at early clinical response evaluated 48 to 72 hours after initiating therapy. 98 Dalbavancin and oritavancin have the potential to be dosed less frequently. Dalbavancin has a prolonged halflife of 6 to 10 days and can potentially be administered as 2 doses 1 week apart.…”

New Antibiotics in the Therapy of Osteomyelitis

“…The molecule inhibits translation by binding to the bacterial 23S ribosome initiation complex [100] . Its spectrum covers Grampositive pathogens, including linezolid-resistant S. aureus [101] . It has been shown to be efficient, safe and well-tolerated in phase 3 studies and a post-hoc analysis for Latino patients [101][102][103] .…”

“…Its spectrum covers Grampositive pathogens, including linezolid-resistant S. aureus [101] . It has been shown to be efficient, safe and well-tolerated in phase 3 studies and a post-hoc analysis for Latino patients [101][102][103] . Its efficiency has been studied in rat foreign-body osteomyelitis, but no data for human osteomyelitis exists [104] .…”

Tedizolid in skin and skin structure infections: brave new world?

“…This specific molecule interacts with the bacterial 23S ribosome initiation complex to inhibit translation. The efficacy and safety of this new antibacterial agent have been studied in the Efficacy and Safety of 6-day Oral Tedizolid in Acute Bacterial Skin and Skin Structure Infections vs. 10-day Oral Linezolid Therapy-1 (ESTABLISH-1) trial, whereby a 6-day oral tedizolid regimen was compared with a 10-day oral linezolid therapy in ABSSSIs [8]. Tedizolid was statistically noninferior to linezolid in early clinical response at 48-72 h after initiating therapy [8].…”

“…The efficacy and safety of this new antibacterial agent have been studied in the Efficacy and Safety of 6-day Oral Tedizolid in Acute Bacterial Skin and Skin Structure Infections vs. 10-day Oral Linezolid Therapy-1 (ESTABLISH-1) trial, whereby a 6-day oral tedizolid regimen was compared with a 10-day oral linezolid therapy in ABSSSIs [8]. Tedizolid was statistically noninferior to linezolid in early clinical response at 48-72 h after initiating therapy [8]. A further trial, Efficacy and Safety of 6-day Oral Tedizolid in Acute Bacterial Skin and Skin Structure Infections vs. 10-day Oral Linezolid Therapy-2 (ESTABLISH-2), randomized patients to either intravenous tedizolid phosphate 200 mg once daily for 6 days or intravenous linezolid 600 mg twice daily for 10 days, with optional oral step-down [9].…”