Tedizolid (Sivextro) for Acute Bacterial Skin and Skin Structure Infections
Tedizolid is administered at 200 mg once daily for 6 days, available in both oral and intravenous formulations, and represents a first-line option for treating ABSSSI when MRSA coverage is required. 1
FDA-Approved Indication and Dosing
The standard regimen is 200 mg once daily for exactly 6 days, regardless of route of administration. 1
Tedizolid is FDA-approved for adults and pediatric patients ≥12 years of age with ABSSSI caused by susceptible Gram-positive organisms including MRSA, MSSA, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus Group, and Enterococcus faecalis. 1
Oral administration can be taken with or without food, offering flexibility in dosing. 1
No dose adjustment is necessary when switching from IV to oral formulation, facilitating early hospital discharge and outpatient completion of therapy. 1
Route-Specific Administration
Intravenous Administration
Administer as a 1-hour infusion once daily; never give as IV push or bolus. 1
Reconstitute 200 mg vial with 4 mL Sterile Water for Injection, then dilute in 250 mL of 0.9% Sodium Chloride only. 1
Critical incompatibility: Do not use solutions containing divalent cations (Ca²⁺, Mg²⁺) such as Lactated Ringer's or Hartmann's Solution. 1
Total time from reconstitution to administration must not exceed 24 hours. 1
Oral Administration
- If a dose is missed, take it as soon as possible if more than 8 hours remain before the next scheduled dose; otherwise, skip and wait for the next dose. 1
Clinical Context and Guideline Recommendations
Tedizolid receives a 1A recommendation (highest level) for both oral and IV treatment of MRSA skin and soft tissue infections. 2
For purulent SSTIs with systemic signs (fever, tachycardia, abnormal WBC count) where MRSA is suspected or confirmed, tedizolid is a suitable first-line option. 3
For severe nonpurulent cellulitis/erysipelas in patients who have failed oral antibiotics, have systemic signs of infection, are immunocompromised, or show clinical signs of deeper infection, tedizolid should be considered. 3
Tedizolid offers advantages over vancomycin as an alternative for hospitalized patients requiring IV MRSA coverage, particularly with once-daily dosing and shorter treatment duration (6 days vs. 7-14 days). 2, 3
Comparative Efficacy Evidence
Tedizolid 200 mg once daily for 6 days demonstrated non-inferior efficacy to linezolid 600 mg twice daily for 10 days in Phase III trials. 3, 4
In the ESTABLISH-1 trial, early clinical response rates at 48-72 hours were 79.5% for tedizolid versus 79.4% for linezolid (treatment difference 0.1%, 95% CI -6.1% to 6.2%). 4
Investigator-assessed clinical success rates at post-therapy evaluation were 85.5% for tedizolid versus 86.0% for linezolid. 4
Efficacy was maintained in MRSA-infected patients and in challenging lower-extremity infections, with comparable response rates to non-lower-extremity sites by post-therapy evaluation (86.3% vs. 87.1%). 5
Key Advantages Over Linezolid
Tedizolid demonstrates superior tolerability with significantly fewer hematologic and gastrointestinal adverse effects compared to linezolid. 6
Shorter treatment duration (6 days vs. 10 days) improves adherence and reduces exposure-related toxicities. 7, 4
Lower incidence of thrombocytopenia and nausea compared to linezolid. 7, 6
Reduced risk of serotonin syndrome: Tedizolid is a weaker, reversible MAO inhibitor with no meaningful interactions in tyramine and pseudoephedrine challenge studies, making it safer in patients on SSRIs or MAOIs. 7, 6
Four- to eightfold greater in vitro potency against staphylococci, enterococci, and streptococci, including drug-resistant phenotypes. 6
Activity against certain linezolid-resistant strains harboring the cfr gene (in absence of specific ribosomal mutations). 6
Critical Clinical Considerations
No dose adjustment required for any degree of renal or hepatic dysfunction, as tedizolid is primarily excreted by the liver as an inactive sulfate conjugate. 6
High oral bioavailability (~90%) enables seamless transition from IV to oral therapy without dose modification. 6, 8
The 6-day fixed duration should not be extended beyond guideline recommendations (7-14 days for SSTI generally), as tedizolid trials specifically validated the 6-day regimen. 2, 4
When dual coverage for both streptococci and MRSA is needed for oral therapy and tedizolid is not used, alternative combinations include TMP-SMX or doxycycline plus a beta-lactam. 2