By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
A new oxazolidinone-class antibacterial has been approved for the treatment of acute bacterial skin and skin structure infections. Tedizolid was designated a Qualified Infectious Disease Product (QIDPS). Tedizolid is chemically similar to linezolid and is marketed by Cubist Pharmaceuticals as Sivextro.
INDICATIONS
Tedizolid is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible Gram-positive bacteria.1 These include Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant strains), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group, and Enterococcus faecalis.
DOSAGE
The recommended dose is 200 mg orally or intravenously (infused over 1 hour) once daily for 6 days.1 Tedizolid is available as 200 mg tablets and as powder for injection.
POTENTIAL ADVANTAGES
Tedizolid is more active than linezolid against species of Staphylococcus, Streptococcus, and Enterococcus, including vancomycin-resistant enterococci and linezolid resistant genotypes.2
POTENTIAL DISADVANTAGES
The antibacterial activity decreases in the absence of granulocytes.1 Alternative therapy should be considered in neutropenic patients.
COMMENTS
The efficacy and safety of tedizolid were evaluated in two randomized, double-blind, double-dummy, non-inferiority trials with linezolid as the active comparator.1,3,4 Subjects had FDA-defined clinical syndrome for ABSSSI (cellulitis/erysipelas, wound infections, and major cutaneous abscess). They were randomized to receive tedizolid (200 mg x 6 days) or linezolid (1200 mg x 10 days). In one study, subjects could receive oral tedizolid after a minimum of 1 day of the intravenous drug. The primary endpoint, determined at 48 to 72 hours after treatment initiation was no increase in lesion surface area from baseline and oral temperature of ≤ 37.6° C, confirmed by a second temperature reading within 24 hours or at least a 20% decrease from baseline in lesion area. In the second trial the same endpoint was evaluated in patients randomized to tedizolid or linezolid.1 A secondary endpoint was investigator-assessed clinical response post therapy (EOT) (7-14 days after the last dose). Response rates for the first endpoint were 79.5% vs 79.4% for study 1 and 86.1% vs 84.1% for study 2. For the other endpoint, rates were 78% vs 76.1% and 85.2% vs 82.6%, respectively. EOT success rates were similar. The efficacy endpoint met the predetermined condition for non-inferiority to linezolid. Adverse events profiles were generally similar with a lower frequency of gastrointestinal disorders (e.g., nausea and vomiting) and platelet counts below the lower limit of normal (< 150,000 cells/mm3).3
CLINICAL IMPLICATIONS
Tedizolid provides another option for the treatment of ABSSSI, particularly with multi-drug-resistant pathogen. The current Infectious Diseases Society of America guidelines on skin and soft tissue infections recommend treatment according to infection type (purulent [e.g. abscess] vs nonpurulent [e.g. cellulitis]) and suspected bacterial pathogen.5 Vancomycin and linezolid are currently the preferred antibacterials for methicillin-resistant Staphylococcus aureus (MRSA) infections. The wholesale cost for a course of treatment is $3037 for linezolid and $1770 for tedizolid.
REFERENCES
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Sivextro Prescribing Information. Cubist Pharmaceuticals. March 2015.
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Zhanel GG, et al. Tedizolid: A novel oxazolidinone with potent activity against multi-drug-resistant gram-positive pathogens. Drugs 2015;75:253-270.
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Shorr AF, et al. Analysis of the phase 3 ESTABLISH trials of tedizolid vs linezolid in acute bacterial skin and skin structure infections. Antimicrob Agents Chemother 2015;59:864-871.
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Prokocimer P, et al. Tedizolid phosphate vs linezolid for treatment of acute bacterial skin and skin structure infections: The ESTABLISH-1 randomized trial. JAMA 2013;309:559-569.
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Stevens DL, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis 2014;59:e10-52. Erratum in Clin Infect Dis 2015 Feb26 [Epub ahead of print].
