Efficacy and Safety of Tedizolid and Linezolid for the Treatment of Acute Bacterial Skin and Skin Structure Infections in Injection Drug Users: Analysis of Two Clinical Trials

Abstract

Introduction: Injection drug users (IDUs) often develop acute bacterial skin and skin structure infections (ABSSSI) and use emergency departments as their primary source for medical care.

Methods: A post hoc subgroup analysis of two randomized trials examined the efficacy and safety of tedizolid in the treatment of ABSSSI in IDUs. IDUs (n = 389) were identified from two pooled phase 3 trials (NCT01170221, NCT01421511) in patients with ABSSSI (n = 1333). Patients were randomly assigned to tedizolid phosphate (200 mg once daily, 6 days) or linezolid (600 mg twice daily, 10 days). Primary endpoint was ≥ 20% reduction in lesion area from baseline at 48 -72 h. Secondary endpoints included investigator-assessed clinical and microbiological response at the post-therapy evaluation (PTE).

Results: Wound infection was more common in IDUs (52.2%), while cellulitis/erysipelas was more common in non-IDUs (55.9%). Most infections were due to Staphylococcus aureus (IDUs, 75.2%; non-IDUs, 85.6%), while oral pathogens were more prevalent in IDUs. Early clinical success rates for tedizolid and linezolid were 82.5% and 79.6% in IDUs and 81.3% and 79.3% for non-IDUs, respectively; responses at PTE were similar. Microbiological response per pathogen was similar between treatment groups. Rates of treatment-emergent adverse events (AEs) in IDUs were comparable between tedizolid (46.2%) and linezolid (47.8%) arms, while lower incidence of gastrointestinal AEs was observed with tedizolid (20.3%) than with linezolid (25.1%).

Conclusion: Efficacy and safety of tedizolid and linezolid in the treatment of ABSSSI was similar in IDUs and non-IDUs, supporting the use of oxazolidinones in treating ABSSSIs in IDUs.

Funding: Merck & Co., Inc., Kenilworth, NJ, USA.

Keywords: ABSSSI; Injection drug user; Linezolid; Tedizolid.

Fig. 1

Early clinical response at the 48- to 72-h visits by injection drug use in the intent-to-treat population. Early clinical response was defined as ≥ 20% reduction in lesion size. Early clinical response rates for the tedizolid and linezolid treatment groups were similar in IDUs and non-IDUs. IDUs injection drug users, non-IDUs non-injection drug users

Fig. 2

Clinical success rates at the PTE by injection drug use in the a ITT population and the b CE-PTE population. No differences in clinical response rates at the PTE were observed between tedizolid and linezolid treatment or between IDUs and non-IDUs in the ITT or CE-PTE population. CE clinically evaluable, IDUs injection drug users, ITT intent-to-treat, non-IDUs non-injection drug users, PTE post-therapy evaluation

Fig. 3

Favorable microbiological response by injection drug use. a EOT evaluation for the MITT population. b EOT evaluation for the ME-EOT population. c PTE for the MITT population. d PTE evaluation for the ME-PTE population. No difference in favorable microbiological response was observed between tedizolid and linezolid treatment in IDUs and non-IDUs in these populations. EOT end-of-therapy, IDUs injection drug users, ME microbiologically evaluable, MITT microbiological intent-to-treat, non-IDUs non-injection drug users, PTE post-therapy evaluation