2025 Southeastern Residency Conference

Title: Evaluation of the Necessity of Gram-negative Coverage in Skin and Soft Tissue Infections (SSTIs) 


Authors: Blake Wannarat, Rachel Langenderfer, Ryan Lally, Matthew Timmons, Brittany NeSmith, Eve Woodum, Olivia Whitworth, Michael Shaw


Background: Skin and soft tissue infections (SSTIs) range from mild to severe, involving microbial invasion of the skin and soft tissues. Most SSTIs are caused by gram-positive pathogens, including Staphylococcus aureus and beta-hemolytic streptococci. The Infectious Diseases Society of America (IDSA) guidelines recommend classifying SSTIs as purulent or non-purulent and by severity to guide targeted antimicrobial therapy, emphasizing S. aureus in purulent and streptococci in non-purulent cases. The objective of this study was to evaluate the necessity of empiric broad-spectrum gram-negative coverage in uncomplicated SSTIs at a community hospital in the southeast of the United States.  


Methods: This was a single center, retrospective cohort study. The electronic medical record system was utilized to identify hospitalized adults ≥18 years of age that were diagnosed with SSTI and received ≥3 days of vancomycin therapy between April 30, 2024 and October 30, 2024. The gram-positive group was defined as receiving ≥3 days of vancomycin therapy with or without ≤24 hours of gram-negative antimicrobial therapy. The gram-negative group was defined as receiving ≥3 days of vancomycin therapy plus broad-spectrum gram-negative antibiotics for >24 hours (i.e., 3^rd and 4^th generation cephalosporins, fluoroquinolones, piperacillin/tazobactam, and carbapenems). The primary outcome was the requirement of additional intervention, including escalation of antimicrobial therapy, antibiotics reordered for an additional course, or prolongation of inpatient antimicrobial therapy secondary to the index infection. The secondary outcomes were 90-day Clostridioides difficile infection occurrence, total duration of inpatient antimicrobial therapy for the index infection, and development of a resistant pathogen 90-days following index antimicrobial therapy. 


Results: A total of 66 patients were included in this study from a medical record review of 291 patients hospitalized with SSTI. Additional intervention was required in 2 of 10 (20%) patients in the gram-positive group and 13 of 56 (23.2%) patients in the gram-negative group. No patients in the gram-positive group required escalation of therapy or additional antibiotic courses; however, 2 (20%) patients experienced prolongation of inpatient antimicrobial therapy. In contrast, among patients in the gram-negative group, 1 (1.8%) patient required escalation of antimicrobial therapy, 1 (1.8%) patient had antibiotics reordered for an additional course, and 13 (23.2%) patients experienced prolongation of inpatient antimicrobial therapy. Patients in the gram-negative group had a numerically longer mean duration of inpatient antibiotic therapy (6.1 days) compared to those in the gram-positive group (5.1 days). Additionally, 1 patient in the gram-negative group developed a resistant pathogen 90-days following the index infection. Neither group experienced Clostridioides difficile infection within 90 days. 


Conclusion: Empiric broad-spectrum gram-negative coverage in uncomplicated SSTIs was associated with a higher likelihood of prolonged inpatient antibiotic therapy and extended treatment duration, without a clear clinical benefit over gram-positive coverage alone. These findings suggest that targeted gram-positive therapy is sufficient for most uncomplicated SSTIs and that empiric broad-spectrum gram-negative coverage may contribute to unnecessary antibiotic exposure. Furthermore, these results align with IDSA SSTI guidelines, reinforcing the recommendation for gram-positive coverage for most uncomplicated SSTIs and highlighting the potential risks of gram-negative broad-spectrum antibiotic use.