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.
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.
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.
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.
Diabetic foot infection (DFI) is a serious, difficult-to-treat infection, especially when caused by methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin has been the standard treatment for MRSA infection, but lower response rates in MRSA skin infections have been reported. This analysis assessed the outcome and safety of daptomycin therapy in patients with a DFI caused by MRSA.
Using the Cubicin Outcomes Registry and Experience and the European Cubicin Outcomes Registry and Experience (2006–2009), 79 patients with MRSA DFI were identified and included in this analysis.
In the 74 evaluable patients, daptomycin was administered at a median dose of 4.8 mg/kg primarily every 24 hours (85.1%) and for a median of 15.0 days. Overall, 77.0% of the patients (57 of 74) received initial therapy with activity against MRSA; however, of patients receiving daptomycin as second-line therapy (n = 31), only 45.2% were treated with an antibiotic agent active against MRSA. The overall clinical success and treatment failure rates were 89.2% and 10.8%, respectively. Success with daptomycin therapy was higher in patients who had surgery and in those whose initial therapy was daptomycin. Eleven patients had 14 adverse events, two of which were possibly related to daptomycin use and led to discontinuation.
In a large real-world cohort of patients with MRSA DFI, daptomycin therapy was shown to be generally well tolerated and effective. The use of an anti-MRSA antibiotic agent should be considered when implementing first-line antibiotic drug therapy for DFI in countries where MRSA is common to avoid inappropriate empirical treatment and potential negative effects on outcomes.