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

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

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

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?

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

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

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.

Dose-Dependent Effects of Whole Blood Transfusion on Associated Infection Risk in Trauma

Dose-Dependent Effects of Whole Blood Transfusion on Associated Infection Risk in Trauma

Authors:
Hadi Hamdan, Ahmad El Nouiri, Camden Gardner, Drishti Lall, Kurt Kralovich, Jeffrey Johnson

Body of Abstract:
Background: Whole blood (WB) transfusion has emerged in trauma resuscitation as a method associated with improved survival over component therapy (CT), largely attributed to reduced hemorrhagic deaths. However, WB is a biologically complex fluid with distinct immunologic and volume-expanding properties that may affect infection risk differently than CT. Although infections have often been secondary outcomes in transfusion studies, their direct relationship with WB use remains unclear. We hypothesized that a higher WB-to-total-transfusion ratio would be associated with lower rates of nosocomial infection in a dose-dependent manner.

Methods: Adult trauma patients from the 2020–2023 national TQIP database who received transfusion were included. The WB ratio was defined as the proportion of total transfused volume given as WB. Outcomes were examined across the full ratio range (0–1), with extremes (CT-only vs WB-only) analyzed separately to confirm consistency. Variables significant on univariate analysis were entered into multivariable logistic regression models evaluating associations between WB ratio and infection outcomes: severe sepsis, surgical site infections, catheter-associated urinary tract infection (CAUTI), and central-line associated bloodstream infection (CLABSI). Models adjusted for demographics, physiology, injury severity, comorbidities, transfusion volume, and hospital characteristics. A subanalysis of ventilated ICU patients assessed ventilator-associated pneumonia (VAP), additionally adjusting for ICU stay and ventilator days.

Results: Among 221,142 transfused patients, 79.8% received CT only, 8.7% WB only, and 11.5% both. Increasing WB ratio was associated with lower odds of severe sepsis (aOR 0.82, p = 0.006), superficial SSI (aOR 0.79, p = 0.020), and CAUTI (aOR 0.73, p = 0.012). At the extremes, WB-only versus CT-only showed similar reductions in severe sepsis (aOR 0.74, p = 0.001), superficial SSI (aOR 0.73, p = 0.008), deep SSI (aOR 0.79, p = 0.028), organ/space SSI (aOR 0.65, p < 0.001), and CAUTI (aOR 0.73, p = 0.021), with no difference in CLABSI. In the ventilated ICU subanalysis (n = 94,206), higher WB ratio was associated with increased odds of VAP (aOR 1.21, p < 0.001), and this persisted when comparing WB-only to CT-only. Across models, older age, higher ISS, diabetes, steroid use, chemotherapy, and longer hospitalization remained independent infection predictors. Conclusion: Our findings demonstrate a consistent, dose-dependent protective association between increasing WB ratio and several nosocomial infections in trauma patients, an effect that remained stable at the extremes of transfusion practice (WB-only vs CT-only). However, this trend did not extend to ventilator-associated pneumonia, which increased with higher WB exposure. These results highlight a potentially heterogeneous effect of WB transfusion across infection types and support further study into the mechanisms and optimal transfusion balance.

Early Bronchoscopy for the Prevention of Pneumonia in Trauma Patients Undergoing Emergent Intubation: An Interim Analysis

Early Bronchoscopy for the Prevention of Pneumonia in Trauma Patients Undergoing Emergent Intubation: An Interim Analysis

Authors:
Michelle Lippincott, Louis Perkins, Laura Haines, Jessica Weaver

Body of Abstract:
Background: Patients who are intubated emergently are at increased risk for developing ventilator associated pneumonia. This risk is theoretically further increased in trauma patients who often undergo prolonged noninvasive ventilation with altered mental status in the prehospital setting. We hypothesized that early bronchoscopy in these patients reduces the risk of pneumonia by decreasing airway bacterial burden and removing inflammatory gastric acid and digestive enzymes. Methods: After implementation of an early bronchoscopy protocol at a Level 1 Trauma center, a retrospective cohort study was performed on all patients intubated in the prehospital setting or within 1 hour of arrival to the hospital. Patients were excluded if they died or were extubated within 24 hours of arrival or they were transferred to another ICU service. Patients who underwent bronchoscopy within 24 hours of admission (early bronchoscopy) were compared to those who did not receive a bronchoscopy within 24 hours (control group). The primary outcome was diagnosis of pneumonia during the same hospitalization. Secondary outcomes included ICU length of stay (LOS), ventilator days, hospital LOS, and mortality. Results: Among the 59 patients included in our interim analysis, 7 (11.9%) underwent bronchoscopy within 24 hours of admission. No patients in the early bronchoscopy group developed pneumonia, compared to 28.8% in the control group. There was no difference in median ventilator days (3 vs 4 days, p=0.41), median ICU LOS (4 vs 6.5 days, p=0.49), hospital LOS (median 10 vs 11 days, p=0.93), or mortality (28.6% vs 21.2%, p=0.64). In the early bronchoscopy group, a bronchial alveolar lavage culture was sent in three patients and 100% were positive for organisms, though none of these patients developed a clinical pneumonia. One patient that received early bronchoscopy received antibiotics for prophylaxis against aspiration pneumonia, while 71% of patients received antibiotics for any indication. Conclusions: In this preliminary analysis, for trauma patients intubated in the pre-hospital setting or within 1 hour of arrival, early bronchoscopy was not associated with a statistically-significant difference in pneumonia rates, hospital LOS, ICU LOS, ventilator days or mortality. However, no patients developed pneumonia in the early bronchoscopy group. Continued data collection for a larger sample size is necessary to demonstrate if there is any benefit in these patients.

Ehrlichiosis and Anaplasmosis Infections in Solid Organ Transplant Recipients: A Single-Center Series

Ehrlichiosis and Anaplasmosis Infections in Solid Organ Transplant Recipients: A Single-Center Series

Authors:
Benjamin Fisher, Pravin Meshram, Michael Megaly, Rubeena Naaz, Anmol Nigam, Anna Sachdeva, Jo-Anne Young, Michael Park, Raja Kandaswamy, James Harmon

Body of Abstract:
Introduction

Ehrlichiosis and anaplasmosis are emerging tick-borne rickettsial infections in the bacterial family of Anaplasmataceae. This series describes three cases of ehrlichiosis and four cases of anaplasmosis after organ transplantation at a single center. We report the time between transplant and infection diagnosis, laboratory values, and comorbidities.

Methods

We conducted a 13-year (2011-2024) retrospective cohort study using data from our institutional database. Demographic characteristics, transplant history, comorbidities, medications, and laboratory data were analyzed using R. Relevant laboratory measures and antibiotic usage were identified using pattern-based searches chronologically to characterize trends for each recipient. 

Results

We identified a total of 727 patients who were diagnosed with ehrlichiosis or anaplasmosis at our center. The median age was 66 years and 65% of these patients were male. Seven infections occurred in solid organ transplant (SOT) recipients. The median age of the 7 recipients was 65 years, and all were white. Six of 7 were male, and outdoor hobbies and occupations will be assessed with a later chart review. The dates of organ transplantation ranged from 1982 to 2022. Ehrlichiosis was diagnosed in 3 patients following kidney transplantation. Anaplasmosis was diagnosed in 4 recipients, 3 of whom were heart transplant recipients, and 1 of whom was a liver transplant recipient. One patient was diagnosed using cell-free DNA testing. Three of 7 were diagnosed during a hospital stay. Infections were diagnosed between June and November, consistent with the typical exposure season. The median time between transplant and diagnosis of ehrlichiosis was 4 years (range, 2-5), and anaplasmosis was 8 years (range, 2-31). The liver transplant recipient died 5 months after anaplasmosis infection. All recipients were chronically immunosuppressed with agents including tacrolimus, mycophenolate mofetil, everolimus, cyclosporine, and/or azathioprine. Recipient comorbidities included systemic hypertension in 7, chronic kidney disease in 6, coronary artery disease in 5, heart failure in 2, and diabetes in 1. CRP was elevated in all recipients in whom it was measured (4 out of 7, ehrlichiosis 3, anaplasmosis 1). Leukopenia, anemia, thrombocytopenia (5 out of 7, all less than 100,000), hyponatremia, and elevated creatinine were noted in 5 out of 7 transplant recipients. Aspartate aminotransferase was elevated in 5 of 7 recipients (range, 46-920; upper limit normal 33 U/L), and total bilirubin was elevated in 1 recipient. All recipients were treated with 100mg Doxycycline BID for 9-15 days.

Conclusion

We report 7 transplant recipients who were diagnosed with ehrlichiosis or anaplasmosis at a single center. Immune-suppressed transplant recipients are typically at increased risk of poor outcomes following infection. Our report highlights the features of ehrlichiosis and anaplasmosis infection in SOT recipients.

Evaluation of ASEPSIS Score as a Secondary Endpoint in the Phase 3 SHIELD II Trial of D-PLEX100 in Colorectal Surgery

Evaluation of ASEPSIS Score as a Secondary Endpoint in the Phase 3 SHIELD II Trial of D-PLEX100 in Colorectal Surgery

Authors:
Robert Sawyer, Livnat Levy, Elena Zafirovikj

Body of Abstract:
Background: D-PLEX100 is a novel extended-release doxycycline delivery system applied as a single dose to the surgical site prior to incision closure. D-PLEX100 was evaluated in SHIELD II, a randomized, double-blind, controlled trial in patients undergoing abdominal colorectal surgery. The study met its primary endpoint, demonstrating a significantly lower rate of treatment failure (defined as occurrence of any of the following: surgical site infection (SSI) in the target incision, re-intervention, or death) in the D-PLEX100 arm compared with standard of care (SoC). ASEPSIS score was used as a post-operative wound surveillance tool to standardize the assessment and grading of surgical site infections based on observable clinical criteria. The score is determined based on the following characteristics: Additional treatment, Serous discharge, Erythema, Purulent exudate, Separation of deep tissue, Isolation of bacteria, Stay duration as inpatient. It provides an objective and standardized approach to wound assessment, offering a quantitative measure of SSI severity derived from specific, predefined clinical findings. Herein, we report on key secondary endpoints related to ASEPSIS scoring.     

Methods: Abdominal colorectal surgery patients were randomized to receive D-PLEX100 plus SoC systemic antibiotics or SoC alone. The primary outcome was treatment failure defined as a composite of any one of the following: adjudicated incision SSI, re-intervention at the target incision site, and mortality. One of the three key secondary endpoints was determining ASEPSIS scores at each study visit as part of the surgical site assessment. Number of subjects with at least one ASEPSIS score of >20 within 30 days post abdominal (index) surgery were compared between both study arms in the intention-to-treat (ITT) population. The averages of cumulative ASEPSIS assessment scores were also reported for those who experienced adjudicated SSI within 30 days post index surgery. 

Results: SHIELD II had 798 subjects [n = 405 (D-PLEX arm) n = 393 (SOC arm)] in the ITT population. There was a 38% relative risk reduction in the primary outcome in the D-PLEX100 arm compared to SoC [44 (10.9%) vs 71 (18.1%); difference -7.2 (95% CI, -12.1 to -2.3), p = 0.0039]. The proportion of subjects with at least one ASEPSIS score >20 was lower in the D-PLEX100 arm [8/391 (2.0%)] compared to the SoC arm [21/377 (5.6%)]. The stratified risk difference was -3.5 (95% CI -6.2 to ‑0.8; p = 0.0103). The median cumulative ASEPSIS score was 175 in the D-PLEX arm and 216.25 in the SoC arm. The median cumulative ASEPSIS score within the SSI period was 110 in the D-PLEX arm and 160 in the SoC arm. 

Conclusions: The use of D-PLEX100 resulted in improved outcomes for abdominal colorectal surgery patients, specifically demonstrating reduction in treatment failures compared to SoC antibiotics. D-PLEX100 was also associated with lower rates of wound infections as determined by ASEPSIS scoring.