Program Schedule

269
Comparison of the Hematologic Safety of Tedizolid and Linezolid: Pooled Results from Two Phase 3 Trials in Acute Bacterial Skin and Skin Structure Infections

Session: Poster Abstract Session: Antimicrobial Resistance: Novel Agents and Approaches to Gram-positive Infections
Thursday, October 9, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC

Background: Tedizolid (TZD) is a novel oxazolidinone antibacterial with a favorable tolerability profile and potent activity against a wide range of Gram-positive pathogens, including resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. In two randomized, double-blind, Phase 3 trials in patients with acute bacterial skin and skin structure infections (ABSSSI), 6 days of TZD 200 mg once daily was noninferior to 10 days of linezolid (LZD) 600 mg twice daily. Oxazolidinones are known to inhibit mitochondrial protein synthesis, which may have an effect on hematologic parameters. Differences in pharmacokinetics and dosing characteristics between LZD and TZD may lead to a reduced potential for mitochondrial toxicity with TZD.

Methods: We compared the hematologic profiles of TZD and LZD using pooled data from the 2 trials (safety population, N=1324). The incidence of abnormal values (<lower limit of normal [LLN]) and  substantially abnormal (SA) values (for absolute neutrophil count [ANC]: <50% LLN if normal value at baseline or <50% of LLN and <50% of baseline if abnormal value at baseline; for platelets and hemoglobin: <75% LLN if normal value at baseline or <50% of LLN and <75% of baseline if abnormal value at baseline) were determined on study days 7-9, 11-13, on day of last active dose, and for the entire treatment period.

Results: At all time points, the incidence of platelet counts <LLN was lower in the TZD group (3%-6%) than in the linezolid group (6%-11%), and over the entire treatment period was 6% versus 13% (Figure 1). SA platelet counts ranged from 0.8% to 1.2% with TZD and from 0.8% to 1.9% with LZD. Incidence of ANC <LLN was lower with TZD (<2%) than with LZD (<4%) at each time point, with rates of 1.9% and 4.7%, respectively, over the entire treatment period. SA ANC were reported in <1% in both groups at all time points. Hemoglobin changes were similar in the TZD and LZD groups.

Conclusion: Although the clinical relevance is not known, this pooled data analysis suggests that TZD 200 mg daily for 6 days may have a lower potential for adverse hematologic outcomes versus LZD 600 mg twice daily for 10 days when treating patients with ABSSSI.

 

Figure 1. Incidence of platelet counts (A) and ANC (B) less than the lower limit of normal with TZD or LZD in two Phase 3 studies in ABSSSI

Edward Fang, Carisa De Anda, Sonia Minassian, Shawn Flanagan and Philippe Prokocimer, Cubist, San Diego, CA

Disclosures:

E. Fang, Trius/Cubist: Employee, Salary

C. De Anda, Cubit: Employee and Shareholder, Salary

S. Minassian, Cubist: Consultant, Consulting fee

S. Flanagan, Cubist: Employee and Shareholder, Salary

P. Prokocimer, Cubist: Employee and Shareholder, Salary

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