Effect of Linezolid Compared to Clindamycin for Necrotizing Soft Tissue Infections

Clindamycin is commonly employed for empiric necrotizing soft tissue infection (NSTI) treatment to inhibit streptococcal toxin production. Group A Streptococcus resistance and risk of clostridial infection are driving a shift in therapy. Linezolid inhibits bacterial protein synthesis, is bactericidal against most streptococcal isolates and suppresses toxin production. There are limited studies comparing the efficacy of linezolid versus clindamycin. The purpose of this study is to evaluate the effect of linezolid versus clindamycin on hospital length of stay (LOS) in patients with NSTI.

This was a retrospective, single-centered cohort study conducted at a large academic medical center (1/2021 - 11/2025). Adult patients who were admitted received clindamycin or linezolid for treatment of NSTIs were eligible for inclusion. Patients who were diagnosed with a non-NSTI or received one dose of either antibiotic were excluded. The primary outcome was risk of hospital LOS greater than 14 days. Secondary outcomes included limb loss, LOS, serotonin syndrome, and thrombocytopenia. Student’s t-test was used for normally distributed data; Mann-Whitney U test was applied to non-normally distributed data. Categorical data were compared using Fisher’s exact test. Time-to-event analysis was performed using Cox univariable regression to estimate the hazard ratio (HR) and 95% confidence intervals (CI).

There were 211 patients who met inclusion criteria for the study period. There were 36 patients in each cohort included in the final analysis with 83 patients excluded for receiving one dose of antibiotics and 56 patients excluded for non-NSTI. The average age was 55, and 70.8% were male. After censoring mortality, there was no significant difference in hospital LOS greater than 14 days (0.67 vs 0.5; HR 1.97 [95% CI 0.9-4.3] p=0.0.0893). There were no differences between limb loss after excluding patients with Fournier gangrene (0.28 vs 0.09; OR 3.68 [0.83-15.63] p=0.0855). There were no cases of serotonin syndrome, one case of thrombocytopenia, and one case of clostridial infection.

Despite a higher incidence, there was no statistically significant difference in hospital LOS greater than 14 days and incidence of limb loss between patients treated with clindamycin or linezolid for NSTI. Linezolid may be a reasonable alternative to clindamycin for NSTI empiric treatment.