902. Renal Impairment and Clinical Outcomes of Tedizolid and Linezolid in Two Randomized Trials
Session: Poster Abstract Session: Clinical Trials
Friday, October 9, 2015
Room: Poster Hall
Posters
  • 150100692 RenalPooledPh3_L5a.pdf (340.9 kB)
  • Background: Patients with renal disease have increased risk for linezolid associated thrombocytopenia. We determined the effect of renal impairment on the safety and efficacy of tedizolid compared to linezolid when used as treatment of acute bacterial skin and skin structure infections (ABSSSI).

    Methods: This is a post hoc analysis of two randomized controlled Phase 3 studies that enrolled adults with ABSSSI. Patients received either tedizolid 200 mg q.d. for 6 days or linezolid 600 mg b.i.d. for 10 days. Efficacy and safety was evaluated. Platelet counts were evaluated by prespecified thresholds: less than lower limit of normal (<LLN; <150K cells/mm3), <75% LLN (<112K), and a commonly accepted clinical threshold (<100K).

    Results: At baseline, 1077, 172, and 50 patients had normal renal function (GFR ≥90 ml/min/1.73m2), stage 2 (60-89) or stage 3-4 (15-59) chronic kidney disease (CKD). No patients had stage 5 CKD. Clinical responses at 48-72 h (primary endpoint) were 82.9% vs 80.0%, 79.8% vs 83.6%, and 75.0% vs 76.7% for tedizolid vs linezolid for normal renal function, stage 2, and stage 3-4 CKD groups, respectively. For patients with normal renal function, differences in reduced platelet counts (<LLN) at EOT were lower with tedizolid (3.4%) than linezolid (9.0%) (P=0.0001). Similar trends were seen with reduced platelet counts (<LLN) at EOT among patients with stage 2 CKD and 3-4 CKD (see Table). Similar trends were also seen during the post-baseline period through the last day of active drug. No patient experienced bleeding-related adverse events.

    Renal Function at Baseline

    Platelet Count Outcome at EOT

    Tedizolid
    200 mg QD

    Linezolid
    600 mg BID

     Normal

     

    N=533

    N=544

     

     <150,000, <LLN

    18 (3.4%)

    49 (9.0%)

     

     <112,000, <75% LLN

    6 (1.1%)

    15 (2.8%)

     

     <100,000

    6 (1.1%)

    12 (2.2%)

     Stage 2 CKD

     

    N=99

    N=73

     

     <150,000, <LLN

    3 (3.0%)

    7 (9.6%)

     

     <112,000, <75% LLN

    1 (1.0%)

    5 (6.8%)

     

     <100,000

    1 (1.0%)

    3 (4.1%)

     Stage 3-4 CKD

     

    N=20

    N=30

     

     <150,000, <LLN

    0%

    5 (16.7%)

     

     <112,000, <75% LLN

    0%

    1 (3.3%)

     

     <100,000

    0%

    0%

     Conclusion: There were no differences in clinical response between patients randomized to tedizolid and those randomized to linezolid, regardless of renal status. Patients who received tedizolid had a lower incidence of platelet counts <LLN at EOT. Further studies are needed to confirm these findings.

    Pamela Moise, PharmD, Natasha Broyde, MS, Steven Anuskiewicz, MS, Benjamin Miller, PharmD, Taylor Sandison, MD and Philippe Prokocimer, MD, Merck & Co., Inc., Kenilworth, NJ

    Disclosures:

    P. Moise, Merck & Co., Inc.: Employee , Salary

    N. Broyde, Merck & Co., Inc.: Employee , Salary

    S. Anuskiewicz, Merck & Co., Inc.: Employee , Salary

    B. Miller, Merck & Co., Inc.: Employee , Salary

    T. Sandison, Merck & Co., Inc.: Employee , Salary

    P. Prokocimer, Merck & Co., Inc.: Employee , Salary

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