SAN DIEGO, CA—Renal impairment does not appear to affect the safety or clinical efficacy of tedizolid compared to linezolid among adults treated for skin and skin structure infections (ABSSSI), according to a post-hoc analysis of data from two randomized, controlled phase 3 clinical trials, reported at IDWeek 2015.
“There were no differences in clinical response between patients randomized to tedizolid and those randomized to linezolid, regardless of renal status,” reported Pamela Moise, PharmD, and coauthors at Merck & Company, Inc., Kenilworth, New Jersey.
However, patients who received tedizolid had a lower incidence of platelet counts below the lower limit of normal (<LLN: <150,000 cells/mm3) at end of therapy. Additional studies are needed to confirm the findings, Moise added.
Patients with renal disease face elevated risks for linezolid-associated thrombocytopenia, Moise noted. The study authors sought to determine how renal impairment affects the safety and efficacy of tedizolid vs. linezolid for treating acute bacterial ABSSSI, conducting a post-hoc analysis of data from two Phase 3 trials of adults with ABSSSI. Patients in the clinical trials had received either tedizolid (200mg once daily for 6 days) or linezolid (600mg twice daily for 10 days).
“At baseline, 1077, 172, and 50 patients had normal renal function (GFR≥90 mL/min/1.73m2), Stage 2 (GFR 60–89) or Stage 3–4 (GFR 15–59) chronic kidney disease (CKD),” Moise reported. “No patients had Stage 5 CKD.”
The primary endpoint was clinical response at 48–72 hours. Clinical response rates at 48–72 hours were:
82.9% vs. 80.0% for patients receiving tedizolid vs. linezolid for normal renal function
79.8% vs. 83.6% for Stage 2 CKD patients receiving tedizolid vs linezolid, respectively
75.0% vs. 76.76% for tedizolid vs. linezolid among patients with Stage 3–4 CKD
No bleeding-related adverse events were reported.
“For patients with normal renal function, differences in reduced platelet counts (<LLN) at end of treatment were lower with tedizolid (3.4%) than linezolid (9.0%; P=0.0001),” Moise reported. “Similar trends were seen with reduced platelet counts (<LLN) at end of treatment among patients with Stage 2 CKD (3.0% vs. 9.6% for tedizolid and linezolid, respectively) and 3–4 CKD (0 vs. 16.7%).”
“Similar trends were also seen during the post-baseline period through the last day of active drug [therapy],” she said.