Outcomes and Predictors of Fungal Necrotizing Soft Tissue Infections

Authors:
Anahita Jalilvand, Bradley Butsch, Courtney Collins, George Abboud, Jonathan Wisler, Patrick Quinn, Shachi Srivatsa

Body of Abstract:
Background: The treatment of necrotizing soft tissue infections (NSTIs) relies heavily on early antibiotic initiation and surgical debridement. While rare, fungal NSTIs are often difficult to diagnose. We sought to better understand outcomes, treatment patterns, and predictors in fungal necrotizing soft tissue infections.

Methods: Retrospective analysis of institutional data for patients diagnosed with NSTIs was performed (n = 634; 2011-2023). Patients were stratified by the presence of fungi in the wound culture. Abstracted patient characteristics included demographics, comorbidities, treatments received, and hospitalization outcomes. Primary outcomes included mortality, length of stay, intensive care requirements, acute kidney injury, and 30-day readmission. Logistic regression was used to identify potential predictors of fungal infection.

Results: Of 634 patients, 110 (17.4%) had fungal-positive wound cultures and 524 (82.6%) did not. Patients with fungal NSTIs were more likely to have type two diabetes mellitus (74.5% vs. 61.6%, p=0.014). There was no difference between cohorts in the incidence of sepsis, APACHE II score, or SOFA score. Of those with positive fungal cultures, candida albicans was the most common (47.3%) followed by the grouping of other candida types including galbrata, parapsilosis, and auris (44.5%). The most common antifungal antibiotics used were fluconazole (35.5%) and caspofungin (32.7%). The median time from wound culture to therapy administration was 3 (IQR 2, 5) days and the median time from wound culture to culture result was 2 (IQR 2,5) days. Only 12 patients (10.9%) received empiric antifungal therapy. Regarding hospital course, patients with positive fungal wound cultures were more likely to require two or more operative debridement (p < 0.001), had a higher total length of stay (19 vs. 12 days, p < 0.001), require mechanical ventilation (p < 0.001), and had higher 30-day (9.9% vs 18.2%, p = 0.01) and 90-day mortality (12% vs 20%, p = 0.038). Patients with polymicrobial cultures positive for fungi and clostridial species had the highest 90-day mortality rate (38%). Diabetes mellitus was an independent predictor of developing a fungal NSTI (odds ratio 2.11, 95% CI 1.27 – 3.49, p = 0.004). Conclusion: Fungal NSTI infections were associated with higher rates of 30-day and 90-day mortality with more complex hospital courses than those without fungi. Diabetes mellitus was an independent predictor for fungal NSTI. Very few patients received empiric anti-fungal therapy and on average anti-fungal therapy was not initiated until three days after fungal infection was present. Our data suggests that empiric anti-fungal therapy should be considered in patients who are critically ill with an NSTI, especially those with known diabetes. The high incidence of azole-resistant candida species (galbrata, parapsilosis/auris) in our patients suggests that caspofungin is a more appropriate empiric therapy than fluconazole.