Real World Comparison of the Safety and Efficacy of Linezolid Versus Adjunctive Clindamycin for the Treatment of Necrotizing Skin and Soft Tissue Infections

Abstract

Purpose:

Bacterial exotoxins play a crucial role in the pathogenicity of necrotizing skin and soft tissue infections (NSTI). Clindamycin has historically been utilized as an adjunctive antitoxin in empiric therapy along with broad-spectrum antibiotics, commonly vancomycin. However, due to toxicity concerns associated with this combination, and the similar mechanism of action, linezolid’s role as a toxin suppressing agent has gained interest in recent years. The objective of this study was to assess the safety and efficacy of linezolid versus adjunctive clindamycin in the empiric treatment of NSTI.

Methods:

This multicenter retrospective cohort study included 144 adults admitted from April 2022 to December 2024 with a diagnosis of NSTI who received either linezolid or adjunctive clindamycin for at least 48 hours. The primary outcome was 30-day mortality. Secondary outcomes measured 60- and 90-day mortality, as well as hospital readmission, infection recurrence, and incidence of acute kidney injury (AKI), Clostridioides difficile infection (CDI), suspected serotonin syndrome, and new onset of thrombocytopenia.

Results:

There were no patients in the linezolid cohort that met the primary outcome (0% vs 4.4%; P = .12). The incidence of AKI was significantly higher among patients treated with adjunctive clindamycin (9.4% vs 33.0%; P = .001).

Conclusion:

There were no differences in mortality, hospital readmission, or infection recurrence between the linezolid and adjunctive clindamycin cohorts. The lower incidence of AKI observed in patients treated with linezolid suggests it may be considered a reasonable antitoxin alternative to adjunctive clindamycin in the empiric treatment of NSTI.