Evaluating length of antimicrobial therapy for necrotizing soft tissue infections

Introduction: Necrotizing soft tissue infections (NSTI) result in severe tissue destruction. Mainstay of treatment is surgical debridement and antimicrobial therapy. There are no definitive recommendations regarding the duration of antibiotics for NSTI. This study aims to evaluate length of antimicrobial therapy following optimal source control. Methods: This was a retrospective medical chat review in a five-hospital system. Patients treated for an NSTI (January 2015 to December 2021) were identified. Adult patients who received treatment for a diagnosed NSTI with >1 debridement and concomitant antimicrobials were included. Patients who received a short (≤12 days) duration of antimicrobial therapy following source control were compared to long (>12 days) duration. Primary efficacy endpoint was the Necrotizing Infection Clinical Composite Endpoint (NICCE), defined as patients alive at day 28, receiving < 3 debridements before day 14 and no amputations beyond the first debridement, and mSOFA < 1 at day 14. Results: 969 patients were identified via ICD codes with 52 patients meeting inclusion criteria. Median age was 52.5 years (IQR 45.8-62.3) with 32 patients (61.5%) having diabetes mellitus. Patients in the short-duration group were older with lower incidence of immunocompromising conditions and more likely to have lower limb infections. The median antibiotic durations were 7.0 (IQR 5.5-9.0) and 30.0 (IQR 20.0-40.0) days. The most common antimicrobials initiated were vancomycin (94.2%), piperacillin-tazobactam (76.9%), and clindamycin (65.4%), with a median number of antimicrobials of 5 (IQR 5-6) vs. 5 (IQR 4-6.3) for the short and long-duration groups, respectively. A smaller proportion of patients achieved the NICCE endpoint in the short-duration group (40.0% vs. 56.8%). The short duration of antibiotics was associated with a lower incidence of achieving clinical cure, defined as resolution of fever and leukocytosis, on day 14 (46.7% vs. 67.6%) and increased number of wound debridements after hospital discharge (40.0% vs. 13.5%). There was no major difference in ICU admissions, ICU and hospital lengths of stay, 90-day inpatient readmissions or time between readmissions. Conclusions: This study provides a descriptive report for characteristics associated with more extended antibiotic regimens for NSTI.