Distinct Appendiceal Microbiota Profiles in Perforated Versus Nonperforated Appendicitis: A Prospective Cohort Study

Authors:
Yasmin Arda, John Jachimiak, Riley Brackin, Jason Brocker, Katherine Albutt, Michael DeWane, Joshua Ng-Kamstra, Jonathan Parks, Casey Luckhurst, John Hwabejire, Matthew Bartek, Haytham Kaafarani, Adam Hensley, Eran Brauner, Erica Rangel, George Velmahos, Charudutt Paranjape

Body of Abstract:
Background: The role of the appendiceal microbiota in the pathogenesis of appendicitis has been widely studied, yet microbial differences between perforated and nonperforated appendicitis and their relevance in clinical practice remain poorly defined. This study aimed to characterize the appendiceal microbiota in adult patients with perforated versus nonperforated appendicitis.

Methods: We conducted a multicenter prospective cohort study of patients ≥18 years with acute appendicitis undergoing appendectomy across three regional medical centers. The distal tip of the appendix lumen was cultured intraoperatively. Patients were stratified into perforated and nonperforated appendicitis based on the operative report. Patients with previous antibiotic treatment for appendicitis were excluded. Multivariable logistic regression adjusting for demographics, comorbidities, symptom duration, and time to surgery was used to compare microbiota profiles between perforated and nonperforated appendicitis. Bacterial diversity was assessed using Rao’s quadratic diversity index. Antibiotic resistance patterns were also evaluated.

Results: A total of 110 patients were included, of which 29 (26%) had perforated appendicitis. The median age was 42 years, and the median time to surgery was 11 hours. On univariate analysis, Bacteroides species were more frequently isolated in perforated compared to nonperforated cases (35% vs. 22%, P=0.02). On multivariable analyses, perforation was independently associated with higher odds of isolating Bacteroides species (aOR 3.58, 95% CI 1.19-5.74) and mixed anaerobes (aOR 2.72, 95% CI 1.02-3.08), as well as greater total bacterial diversity (aOR 1.72, 95% CI 1.11-2.66). In the overall cohort, the most commonly prescribed antibiotics were ceftriaxone (48.6%) and piperacillin-tazobactam (36.4%), with higher ceftriaxone resistance in perforated cases and higher piperacillin-tazobactam resistance in nonperforated cases, though not statistically significant (Figure 1).

Conclusions: Perforated appendicitis is associated with greater appendiceal bacterial diversity and higher prevalence of Bacteroides species and mixed anaerobes compared to nonperforated cases. These findings support a microbiota-driven model of appendicitis clinical variability and suggest that distinct microbial profiles may contribute to perforation, highlighting the role of tailored antibiotic strategies in patients with perforated appendicitis.