Abstract
Background:
Necrotizing soft tissue infections (NSTIs) and the associated exotoxins are associated with a high risk of mortality. Toxin coverage has been shown to decrease mortality but appropriate time to toxin coverage is unknown.

Aim:
The aim of this study is to evaluate whether starting early (<3 hours) toxin coverage improves outcomes compared to late (>3 hours) toxin coverage in relation to the initiation of broad-spectrum antibiotics.

Methods:
This retrospective, single-center, cohort study compared 30-day all-cause mortality in patients treated with early versus late toxin coverage for necrotizing skin infections. Adult patients admitted between January 2015 and December 2024 who had a diagnosis code of necrotizing fasciitis and were administered IV or PO clindamycin or linezolid within 72 hours of broad-spectrum antibiotics were included. The primary outcome was all-cause mortality at 30 days. Secondary outcomes included intensive care unit (ICU) length of stay (LOS), ICU-free days at 30 days, hospital LOS, acute kidney injury (AKI), Clostridioides difficile infection (CDI), serotonin syndrome and thrombocytopenia.

Results:
Baseline characteristics were similar between groups. Both groups had a similar number of ICU admissions (78.4% vs 75.6%), Charlson Comorbidity Index median of 3 (IQR 0-6 vs 0-7), and Quick Sequential Organ Failure Assessment median of 0 (IQR 0-2 vs 0-2). Lower extremity was the most common location of infection (29.7% vs 36.6%) and polymicrobial infections were the most common. Group A Streptococcus accounted for 3 infections in each group. There was no difference in all-cause mortality at 30 days (5.4% vs 14.6%, p=0.27). No differences were found in the secondary outcomes of ICU LOS, ICU-free days at 30 days, hospital LOS, rate of AKI and thrombocytopenia. There was no incidence of serotonin syndrome and a single incidence of CDI in the early toxin coverage group.

Conclusion:
In this retrospective study, there was no statistically significant difference between 30-day all-cause mortality in patients who received toxin coverage in <3 hours compared to >3 hours in relation to broad-spectrum antibiotics for the treatment of NSTIs. Further studies with a larger study population are needed to determine if the time to toxin coverage impacts mortality.

Key words: Antibiotics; Mortality; NSTI.