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Tedizolid and Linezolid for Treatment of Acute Bacterial Skin and Skin Structure Infections of the Lower Extremity versus Non–Lower-Extremity Infections

Pooled Analysis of Two Phase 3 Trials

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  • 1 Roxborough Memorial Hospital, Philadelphia, PA.
  • | 2 Merck & Co, Inc, Kenilworth, NJ.
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Background:

Tedizolid phosphate, the prodrug of the oxazolidinone tedizolid, has been approved in a number of countries, including the United States, those in the European Union, and Canada, for treatment of patients with acute bacterial skin and skin structure infections (ABSSSI). Two phase 3 trials demonstrated the noninferior efficacy of tedizolid (200 mg once daily for 6 days) to linezolid (600 mg twice daily for 10 days) in patients with ABSSSI. Because of the challenges of treating lower-extremity ABSSSI, the efficacy and safety of tedizolid and linezolid for treating lower-extremity versus non–lower-extremity infections were compared.

Methods:

This was a post hoc analysis of pooled data from patients with lower-extremity infections enrolled in two phase 3 studies, ESTABLISH-1 (NCT01170221) and ESTABLISH-2 (NCT01421511), comparing tedizolid to linezolid in patients with ABSSSI.

Results:

Lower-extremity ABSSSI were present in 40.7% of tedizolid-treated and 42.2% of linezolid-treated patients. Methicillin-resistant Staphylococcus aureus (MRSA) was present in 34.7% of all patients with a baseline causative pathogen. Early clinical responses at 48 to 72 hours and investigator-assessed responses at the post-therapy evaluation were similar between tedizolid and linezolid, regardless of ABSSSI type. With both treatments, the early clinical response was slightly higher in patients with non–lower-extremity infection than in those with lower-extremity ABSSSI (tedizolid, 84.8% versus 77.0%; linezolid, 81.4% versus 76.6%, respectively); however, by the post-therapy evaluation visit, response rates were similar (tedizolid, 87.1% versus 86.3%; linezolid, 86.6% versus 87.2%, respectively). Gastrointestinal adverse events and low platelet counts were observed more frequently with linezolid treatment.

Conclusions:

Post-therapy evaluations showed that the clinical response of lower-extremity ABSSSI to tedizolid and linezolid was comparable to that of ABSSSI in other locations. A short 6-day course of once-daily tedizolid was as effective as a 10-day course of twice-daily linezolid in treating patients with lower-extremity ABSSSI.

Corresponding author: Warren S. Joseph, DPM, 1109 Old Ford Road, Huntington Valley, PA 19006. (E-mail: wsjoseph@comcast.net)