Improving cefazolin use for surgical antimicrobial prophylaxis in patients with penicillin allergy labels

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Improving cefazolin use for surgical antimicrobial prophylaxis in patients with penicillin allergy labels

Authors:
Sara Ausman, Jason Beckermann, Christopher Huiras, FNU Shweta, Sarah Lessard

Body of Abstract:
Background

Use of beta-lactam (BL) antibiotics for surgical antibiotic prophylaxis (SAP) has been linked to better surgical outcomes, including reduced surgical site infections and less safety events like acute kidney injury. Patients with documented reactions to penicillin or cephalosporin antibiotics often receive non-BL antibiotics which are linked to more adverse events and delays in administration.  Implementation of a new protocol supporting safety of cefazolin in patients with penicillin allergy labels (PwPALs) improves BL use in surgical and procedural prophylaxis.

 

Methods

A retrospective, pre-post analysis of SAP for PwPALs was performed in a multi-region healthcare system in Wisconsin.  Adult and pediatric PwPALs were included if antibiotics were administered as surgical prophylaxis. Patients without documented penicillin allergy labels or antibiotic doses administered were excluded. Interventions were undertaken in a step-wise approach between January 2021 and December 2023 including electronic health record allergy module enhancements, algorithm development, and point-of-care guidance to surgical clinicians. The pre-intervention (Pre-I) group reflects antibiotic doses documented in 2020 while antibiotic administrations in 2024 were included in the post-intervention (Post-I) group. A secondary analysis of PwPALs documented as anaphylaxis was also completed.

 

Results

Overall, cefazolin use improved in PwPALs from 72.9% to 91.1% between 2020 and 2024 (844/1157 doses and 1362/1495 doses, respectively).  Improvement in cefazolin prescribing was seen regardless of procedure category – clean versus clean-contaminated (Table 1).   A corresponding decrease in vancomycin prescribing for PwPALs was observed across all procedure types from 8% (74/1157) of patients receiving in 2020 compared to 0.6% (9/1495) in 2024.  Secondary analysis of PwPALs documented as anaphylaxis showed cefazolin use improved significantly from 36.2% (34/94 doses) pre-intervention to 88.2% (85/93 doses) post-intervention for all procedure types.  Similar reduction in vancomycin doses was seen in the PwPAL documented as anaphylaxis (Pre-I: 27.7%, 26/94 doses vs. Post-I 2.2%, 2/93 doses). All post-intervention changes were statistically significant (Table 1). No difference in new cefazolin allergies added to EHR or anaphylaxis surrogate markers, including administration of rescue medications or tryptase orders, were observed in the Post-I cohort. 

 

Conclusions

Use of cefazolin for surgical antimicrobial prophylaxis in patients with penicillin allergy labels, including reported anaphylaxis, is safe. Developing institutional protocols improves appropriate SAP choice in PwPALs.

Complex And Simple Appendicitis: REstrictive or Liberal postoperative Antibiotic eXposure (CASA RELAX) using Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR): a multicenter Bayesian randomized controlled trial

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Complex And Simple Appendicitis: REstrictive or Liberal postoperative Antibiotic eXposure (CASA RELAX) using Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR): a multicenter Bayesian randomized controlled trial

Authors:
D. Dante Yeh, Gabrielle Hatton, Claudia Pedroza, Rafael Torres Fajardo, Sean Thomas Dieffenbaugher, Gerd Daniel Pust, Luciana Tito Bustillos, Diedra Turnacliff, Erin Fitzgerald, Jesse Victory, Lucy Z. Kornblith, Caitlin Collins, Genna Beattie, William G. Cheadle, Nicholas Caminiti, Alonso Andrade, Susan F. McLean, Andrew Bernard, Matthew Ray, Lillian Kao

Body of Abstract:
Background: The optimal duration of antibiotics (abx) after appendectomy for simple or complicated (gangrenous or perforated) appendicitis is unknown. We performed a randomized trial to compare a restrictive to a liberal antibiotic strategy on a composite, patient-centered outcome, the Desirability of Outcome Ranking (DOOR).

Methods: Adults with appendicitis undergoing appendectomy at 9 sites were randomized 1:1 to either a Restrictive (no postop abx for simple, up to 1 day of postop abx for complicated) or Liberal (up to 1 day of postop abx for simple, 4 days of postop abx for complicated) strategy. The primary endpoint was based on DOOR, an ordinal scale of mutually exclusive clinical complications with within-category rankings determined by duration of antibiotic exposure.

Randomization was stratified by age >65 and site. Bayesian cumulative logistic models using a neutral prior were used to assess the probability of benefit with a Restrictive strategy. Posterior probabilities of benefit of Restrictive strategy were generated. Type of appendicitis (simple vs complicated) was assessed as an interaction.

Results: A total of 346 subjects (182 Restrictive, 164 Liberal) enrolled from 9 sites were included in the final analysis. Baseline demographics between groups were similar. There were 265 simple and 81 complicated (11 gangrenous) appendicitis cases. The DOOR category outcomes were similar between groups (Figure). The majority experienced the best possible outcome, DOOR 1 (Cure; no adverse effects), and no patient experienced death (DOOR 7). The Restrictive strategy had a cumulative odds ratio of 0.84 (95% CrI 0.42-1.72) for each sequential DOOR category.   This correlated with a 68% probability that Restrictive strategy reduces (improves) DOOR category. However, this finding was driven by patients with complicated appendicitis, resulting in a DOOR OR 0.69 (95% CrI 0.27-1.68), which correlates with a 79% probability that the Restrictive strategy reduces DOOR. In contrast, the Restrictive strategy with simple appendicitis resulted in a DOOR OR 1.17 (95% CrI 0.47-3.0), which correlates with a 37% probability that the Restrictive strategy reduces DOOR.

Conclusions: A Restrictive postoperative antibiotic strategy in acute appendicitis resulted in similar to mildly improved clinical outcomes, when compared to a Liberal strategy overall. The patients who benefitted most from a Restrictive strategy were patients with complicated appendicitis. Given the well-established risks of prolonged antibiotic exposure in the absence of clinical benefits, we suggest that a restrictive postoperative antibiotic strategy be adopted for patients with complicated appendicitis.

Infection Type and Class: Exploring Thrombotic and Renal Complications in a SICU Cohort

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Infection Type and Class: Exploring Thrombotic and Renal Complications in a SICU Cohort

Authors:
Ioannis Karikis, Yasmin Arda, John O. Hwabejire, Michael P. DeWane, Casey M. Luckhurst, Lydia Maurer, Joshua S. Ng-Kamstra, Haytham M. Kaafarani, George C. Velmahos, Galit H. Frydman

Body of Abstract:
Background:
 Infection-related thrombosis and organ injury are increasingly recognized in critically ill patients. Surgical ICU (SICU) patients may be particularly vulnerable because they combine severe physiological stress, complex operations, and high rates of invasive devices and broad-spectrum antimicrobials. We aimed to examine how pathogen burden and diversity relate to clinically significant adverse events in SICU patients with suspected infection. 

Methods:
 We conducted a single-center retrospective study of 137 SICU patients with suspected infection and available microbiologic data, who underwent longitudinal microbiologic sampling from 2020-2024. Organisms were grouped into four pathogen classes (Gram-positive bacteria, Gram-negative bacteria, fungi, and viruses). For each patient, we derived (1) the number of pathogen classes involved (0–4), (2) the number of distinct bacterial isolates (0, 1, 2–3, ≥4), and (3) combinations of bacteria, fungi, and viruses. The primary outcome was a major thrombotic event (deep venous thrombosis, pulmonary embolism, line thrombosis, myocardial infarction, or stroke). Secondary outcomes were AKI and hospital LOS. Associations were evaluated descriptively with univariate analysis.

Results:
 Median age was 63 (51–73) years and median hospital LOS 12 (6–25) days. Overall, 22/137 patients (16%) developed an MTE and 41/132 (31%) developed AKI. Across pathogen-class strata (N=132 with complete data), MTE rates rose from 1/44 (2.3%) with no detected class to 5/15 (33.3%) with three classes and 4/5 (80.0%) with all four classes involved (p<0.001); AKI showed a similar pattern (13.6%, 19.5%, 51.9%, 60.0%, and 80.0%, respectively; p<0.001). Median LOS increased from 12 (5.5–22.5) days with no pathogen class to 23.5 (11–30) days with three classes and 60 (50–96.5) days with all four classes (p=0.003). When stratified by bacterial isolates, MTE rose from 4/80 (5.0%) with no bacterial growth to 6/20 (30.0%) with ≥4 isolates, and AKI from 14/80 (17.5%) to 8/15 (53.3%) (both p<0.001), with LOS increasing from 8.5 (5–18) to 29 (14–54) days (p=0.002). The highest rates of MTE and AKI were observed in a small subgroup with concurrent bacteria, fungi, and viruses (57.1% and 85.7%, respectively). Conclusions:  In this SICU cohort, increasing pathogen burden and diversity were associated with higher rates of clinically significant adverse events, including major thrombotic events, AKI, and prolonged hospitalization in a graded fashion. A plausible explanation for these patterns is an underlying immunothrombotic process linking infection, thrombosis, and organ injury. These hypothesis-generating findings support larger studies to clarify causal pathways and to test strategies to prevent complications in high-risk surgical ICU patients, such as combinatorial and/or amplifying inflammatory pathways secondary to multimodal infectious stimuli.

Critical review of a series of Acinetobacter spp surgical and blood stream infections at a rural hospital in the Appalachian region

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Critical review of a series of Acinetobacter spp surgical and blood stream infections at a rural hospital in the Appalachian region

Authors:
Saron Araya, Pathya Kunthy, Sridha Gona, Aaron George, Hugo Bonatti

Body of Abstract:
Background: Acinetobacter spp are opportunistic non-fermentative Gram-negative rods, which are found in soil and water. The organisms are associated with surgical, urinary tract, respiratory tract and blood stream infections, which may be difficult to treat due to natural resistance against many antibiotics.

Methods: Our institutional database was searched for all infections caused by Acinetobacter spp during a 4-year period.

Results: In total 64 isolates in 58 patients were identified. Median age of the 38 males and 26 females was 62.6 (11.3-88.2) years. Rates of comorbid conditions were DM 33%, hypertension 38%, hyperlipidemia 31%, COPD 10%, CAD 16%, and malignancies 7%. 37% of individuals were obese and 29% active smokers. Acinetobacter baumannii was isolated in 69%, lwoffii in 17%, radioresistens 6%, ursinglis 3% and calcoaceticus, junii and species 2% each. Demographic, clinical, and microbiology data are shown in table 1. Bacterial growth pattern based on streak appearance for surgical specimens was reported light in 48%, moderate in 7% and heavy in 45%; 72% of infections were polymicrobial with staphylococci in 32%, streptococci in 13%, Gram-negative rods in 34%, anaerobes in 19% and yeast in 1% as co-pathogens. Blood cultures accounted for 34%, drainage fluids/tissue specimens for 31% and wound cultures for 33% of specimens, 12% came from drained abscesses. Lower extremity soft tissue infections were the most common manifestation with 55%, the trunk was involved in 10% and upper extremities in 2%; in 9% intraabdominal infections were diagnosed. The majority of blood cultures were sent by emergency department and 50% of the surgical specimens were submitted by podiatry. Treatment for surgical infection included incision and drainage, debridement and amputation as indicated together with antibiotics according to sensitivity testing considering the high rate of mixed infections. 

Conclusion: Acinetobacter spp infections in our rural setting were caused by a surprising variety of different strains. Clinically, one third of cases included bacteremia. The most common infection in this series was diabetic foot syndrome. The majority of these infections were treated successfully and 91% of patients were alive after a 2 year follow up.

Infectious Complications After Surgical Stabilization of Rib Fractures: A National Analysis

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Infectious Complications After Surgical Stabilization of Rib Fractures: A National Analysis

Authors:
Hadi Hamdan, Ahmad El Nouiri, Camden Gardner, Tarek Araji, Michael Bock, Jeffrey Johnson

Body of Abstract:
Background: Surgical stabilization of rib fractures (SSRF) has gained increasing traction for the management of severe chest wall injuries. Prior national studies have focused on mortality and pulmonary outcomes, while infectious complications are only reported as secondary endpoints. Thus, the relationship between SSRF and nosocomial infections are poorly understood. We aimed to evaluate the association between SSRF and major hospital-acquired infections using a contemporary national trauma cohort.

Methods: A retrospective analysis of adult trauma patients with ≥1 rib fracture was conducted using ACS-TQIP (2019–2023). ICD-10 diagnosis and procedure codes identified rib fractures and SSRF cases. Patients were categorized as to whether they underwent SSRF vs. non-operative management (NOM). Multivariable logistic regression evaluated associations of both interventions with severe sepsis, catheter-associated urinary tract infection (CAUTI), and central line–associated bloodstream infection (CLABSI). Adjustment for demographics, comorbidities, physiology, injury severity (ISS, GCS, shock index), antibiotic therapy, hospital length of stay, ICU length of stay, ventilator days, and hospital characteristics was done. A planned sub-analysis—restricted to mechanically ventilated, ICU-admitted patients—assessed ventilator-associated pneumonia (VAP).

Results: Among 595,375 eligible patients, 18,140 (3.0%) underwent SSRF. Median time to surgery was 4 days (IQR 3–8). SSRF patients had greater critical-care exposure, including longer ICU stay (7 days, IQR 4–13 vs. 4 days, IQR 2–7) and ventilator duration (7 days, IQR 3–13 vs. 4 days, IQR 2–10). Unadjusted rates of severe sepsis (1.66% vs. 0.53%), CAUTI (0.41% vs. 0.21%), CLABSI (0.14% vs. 0.06%), and VAP (3.34% vs. 0.86%) were all higher among SSRF patients. After full adjustment, SSRF remained independently associated with severe sepsis (aOR 1.87, p<0.001). SSRF was not independently associated with CAUTI (aOR 1.25, p=0.067) or CLABSI (aOR 1.50, p=0.063). In the ventilated ICU sub-analysis (94,842 patients), SSRF remained independently associated with increased VAP risk (aOR 1.44, p<0.001) after adjustment. Conclusion: In a large national cohort, SSRF was associated with increased odds of severe sepsis and VAP despite adjustment for comorbidities, physiology, injury severity, and critical-care exposure. SSRF was not independently associated with an increase in CAUTI or CLABSI risk. The persistence of the VAP association suggests that factors intrinsic to patients selected for SSRF—such as injury complexity or clinical trajectory—may contribute to this elevated vulnerability. Further work is needed to clarify whether these risks reflect operative factors, patient selection, or underlying injury patterns.

Cross-Platform Metabolomic Profiling Uncovers Prognostic Serum Biomarkers of Sepsis Risk in Burn Patients

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Cross-Platform Metabolomic Profiling Uncovers Prognostic Serum Biomarkers of Sepsis Risk in Burn Patients

Authors:
Fadi Khalaf, Ana Stanciu, Diana Julia Tedesco, Philip Britz-Mckibbin, Marc Jeschke

Body of Abstract:
Background: Sepsis remains a major cause of mortality in burn patients, yet early diagnosis is hindered by its rapid progression, patient heterogeneity, and the confounding metabolic effects of burn injury. Existing clinical biomarkers are inconsistent and fail to reliably predict sepsis onset. To address this gap, we move beyond traditional markers and directly profile the metabolic disturbances underlying burn sepsis. Through comparative metabolomic and lipidomic analysis across multiple time points, we aim to identify novel circulating metabolites with strong diagnostic and prognostic potential, offering mechanistic insight and a more accurate framework for predicting sepsis in burn patients.

Methods: Serum samples from septic (n=39) and non-septic (n=37) burn patients were collected at 0–3, 4–10, 11–18, and >20 days post-injury (DPI). Untargeted analysis of serum metabolites and lipids was performed. A total of 91 metabolites and 84 lipids were annotated. Supervised orthogonal partial least squares-discriminant analysis (OPLS-DA) and receiver operating characteristic (ROC) curves were used to identify and classify discriminative metabolic signatures between septic and non-septic patients. Age, sex, DPI, and comorbidities were adjusted for. 

Results: Established clinical markers—including creatinine, lactic acid, and CRP—showed no differences between septic and non-septic patients, underscoring the need for better biomarkers. Using all available time points, we identified several metabolites with strong diagnostic potential for burn sepsis, including the amino-acid–related metabolites S-methylcysteine, 3-methyl-2-oxovaleric acid, and N-methyllysine, as well as the bioactive lipids LPE 20:4 and PE 36:4 (p<0.001). The valerylcarnitine/crotonobetaine ratio demonstrated the strongest discriminative performance (AUC=0.83, p<0.0001). Using only early timepoints, we identified several metabolites with significant prognostic value for burn sepsis, including the amino acids arginine and isoleucine, and the methylated osmolytes/gut-derived metabolites betaine and crotonobetaine (all p< 0.001). The valerylcarnitine/crotonobetaine ratio demonstrated the strongest prognostic performance (AUC=0.88, p<0.0001). Lastly, enrichment analysis of the early time points identified methylhistidine metabolism as the most significantly altered metabolic pathway for distinguishing patients who later developed sepsis from those who did not. Conclusions: In summary, this is the first study to apply comprehensive serum metabolomics to burn sepsis, revealing diagnostic and prognostic biomarkers that outperform traditional clinical indicators and identifying early metabolic pathways linked to sepsis progression. These findings establish a foundation for timely, metabolically informed sepsis detection and have the potential to significantly improve clinical decision-making and outcomes in burn critical care.

Inflammatory Dysregulation and Persistent Epigenetic Modifications of A20 in Necrotizing Enterocolitis

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Inflammatory Dysregulation and Persistent Epigenetic Modifications of A20 in Necrotizing Enterocolitis

Authors:
Heather Grubbs, Christopher Luschen, Catherine Hunter

Body of Abstract:
Background

The pathogenesis of necrotizing enterocolitis (NEC) centers on dysregulation of inflammation, intestinal barrier function, and cell death. A20 is an inflammatory cascade-suppressing protein which we hypothesize is decreased in active NEC. Additionally, we hypothesize that decreased expression is maintained following recovery due to epigenetic modifications of the TNFAIP3 gene promoter region which encodes for A20. 

 

Methods

Intestinal tissue from neonates with active NEC, following NEC recovery, or without NEC was snap frozen. RNA was extracted for RT-qPCR analysis of TNFAIP3 expression. DNA was also extracted and underwent bisulfite conversion followed by PCR amplification of the TNFAIP3 promoter region and sanger sequencing. Site-specific methylation percentage was then calculated in the TNFAIP3 promoter region. Statistical significance was determined with ANOVA.   

 

Results

            Intestinal tissue from patients with no history of NEC had elevated A20 expression compared to active and recovered tissue (p=0.0039 and p=0.0009, respectively). Additionally, there was no difference in expression between expression in active and recovered tissue (p=0.9063). Three methylation sites were identified in the TNFAIP3 promoter region at positions -115, -26, and -5 from gene start with higher percent methylation in active and recovered NEC compared to controls (p=0.0006 and p=0.0005, respectively). No difference was found between active and recovered NEC percent methylation (p=0.9755).

 

Conclusions

            The inflammatory regulator A20 was found to have decreased expression in NEC and recovered NEC tissue compared to control, emphasizing the dysregulated inflammatory response seen in NEC. Additionally, the promoter region of the TNFAIP3 gene was found to have significantly higher percent methylation at three sites in recovered and active NEC tissue compared to control. Therefore, epigenetic modifications seen in both active and recovered NEC tissue may be associated with decreased transcription of A20 and therefore impaired inflammatory regulation in NEC which persists following recovery.

Differential Expressions of Fever: Is Hyperthermia Really a Clue?

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Differential Expressions of Fever: Is Hyperthermia Really a Clue?

Authors:
Mikayla Moody, Robert Sawyer, Tjasa Hranjec

Body of Abstract:
Introduction: Fever in the ICU often prompts an investigation for infectious causes. However, differential expression of fever, when accompanied by clinical signs of infection, could offer insight into a patient’s focus of infection or causative pathogen. Our hypothesis is that infection without fever will be associated with specific sites of infection and pathogens, potentially suggesting adjustment of empiric antimicrobial coverage.

 

Methods: From 1996-2023, data were prospectively collected from 3 surgical intensive care units (ICUs) using thrice-weekly chart review by a single investigator. ICU-acquired infections were identified using CDC criteria. Temperature maximum (Tmax) data within 24 hours of diagnosis were stratified into low-grade (<38.5°C) versus high-grade fever (≥38.5°C), and infections were categorized by infectious organism and site of infection. Data were analyzed using univariate analysis; categorical variables were evaluated using Chi square analysis test with significance set at p<0.05.   Results:  Retrospective data review revealed a total of 4661 infections; 3069 were from a single site.  High-grade fever was recorded in 1684 (54.8%)  infections.  Compared to all  infectious sites, lung (62.3%) and blood (60.6%) were more likely to be associated with high-grade fever (p<0.05), unlike patients with abdomen (42.9%), urine (44.3%), surgical site (43.4%), and colon (27.5%) as their source of infection.  Pathogens (Table 1) including Methicillin-sensitive Staphylococcus aureus, S. epidermidis, Escherichia coli, and Enterobacter cloacaeinfections were associated with high-grade fever, whereas Candida albicans and Enterococcus faeciuminfections more commonly presented without fever.   Conclusion: Patients with clinical signs of infection but low-grade or no fever warrant evaluation forintra-abdominal urinary, surgical site, and/or colonic (principally Clostridioides difficile) sources. Depending on the clinical context, adjunctive anti-fungal, anti-enterococcal, or anti-C. difficile therapy may be appropriate alongside standard empiric coverage.

Intraoperative Particulate Matter Exposure and Surgical Site Infection Risk in Cardiac Surgery: A Prospective Feasibility Study

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Intraoperative Particulate Matter Exposure and Surgical Site Infection Risk in Cardiac Surgery: A Prospective Feasibility Study

Authors:
Oluwaseun Adeyemi, Divya Kewalramani, Justin Benton, Gediminas Mainelis, Philip Barie, Mayur Narayan

Body of Abstract:
Despite decades of investment in operating room ventilation systems, surgical site infections (SSIs) remain a major source of morbidity in clean cardiac procedures. While bacterial contamination of surgical wounds correlates with airborne particle concentrations, the relationship between quantified intraoperative particulate matter (PM) exposure and clinical SSI development remains uncharacterized. We hypothesized that patients who develop SSI following cardiac surgery encounter higher proportions of high-risk PM thresholds compared to patients without SSI, with phase-specific exposure patterns distinguishing infected from non-infected cases.

Methods: We prospectively enrolled 31 CABG patients with continuous intraoperative PM monitoring and 30-day SSI surveillance. PM was quantified by number concentration (NC: 0.3–0.5, 0.5–1.0, 1.0–2.5 µm) and mass (PM1.0, PM2.5). Operative phases were baseline (procedure start to cardiopulmonary bypass [CPB] initiation), prolonged electrocautery (CPB period), and closure (CPB termination to procedure end). High-risk PM exposure was defined as ≥2 standard deviations above baseline mean. We calculated the proportion of each phase exceeding high-risk thresholds and compared exposure patterns between SSI and non-SSI cohorts.

Results: Among 31 enrolled patients (mean age 65.5 ± 9.7 years, 90.3% male, mean BMI 29.1 ± 5.2 kg/m²), one patient (3.2%) developed deep sternal wound SSI requiring surgical debridement and prolonged antibiotic therapy. Median operative duration was 4.2 hours (IQR 3.8–4.9), with baseline, electrocautery, and closure phases comprising 18%, 64%, and 18% of total operative time, respectively. During the closure phase, the SSI case exhibited elevated PM exposure across all size fractions compared to non-SSI patients: PM2.5 exceeded high-risk thresholds for 8.3% versus 0.3% of phase duration (27.7-fold difference), PM1.0 for 8.0% versus 0.3% (26.7-fold), NC1.0–2.5 for 1.4% versus 0.1% (14-fold), NC0.5–1.0 for 8.3% versus 0.6% (13.8-fold), and NC0.3–0.5 for 8.3% versus 0.01% (830-fold). Mass-based PM metrics demonstrated more pronounced divergence than number concentrations, with PM2.5 and PM1.0 showing the largest absolute differences. During the prolonged electrocautery phase, the SSI case exhibited elevated exposure primarily in fine particle fractions: NC0.5–1.0 exceeded thresholds for 2.9% versus 0.2% of phase duration (14.5-fold difference) and NC0.3–0.5 for 3.0% versus 0.2% (15-fold). Temporal analysis revealed that 89% of high-risk PM excursions during closure occurred within 15 minutes preceding final skin approximation

Conclusion: This preliminary evidence demonstrates phase-specific PM exposure patterns distinguishing SSI from non-SSI cases, with closure phase exhibiting the strongest divergence. These findings establish technical feasibility for continuous, size-resolved PM monitoring and justify larger prospective studies examining PM exposure thresholds as modifiable SSI risk factors.

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

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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.