Intra-abdominal Infections Research Articles

Development and validation of a nomogram to predict postsurgical intra-abdominal infection in blunt abdominal trauma patients: A multicenter retrospective study

BackgroundIntra-abdominal infection is a common complication of blunt abdominal trauma. Early detection and intervention can reduce the incidence of intra-abdominal infection and improve patients’ prognoses. This study aims to construct a clinical model predicting postsurgical intra-abdominal infection after blunt abdominal trauma. MethodsThis study is a retrospective analysis of 553 patients with blunt abdominal trauma from the Department of General Surgery of 7 medical centers (2011–2021). A 7:3 ratio was used to assign patients to the derivation and validation cohorts. Patients were divided into 2 groups based on whether intra-abdominal infection occurred after blunt abdominal trauma. Multivariate logistic regression and least absolute shrinkage and selection operator regression were used to select variables to establish a nomogram. The nomogram was evaluated, and the validity of the model was further evaluated by the validation cohort. ResultsA total of 113 were diagnosed with intra-abdominal infection (20.4%). Age, prehospital time, C-reactive protein, injury severity score, operation duration, intestinal injury, neutrophils, and antibiotic use were independent risk factors for intra-abdominal infection in blunt abdominal trauma patients (P < .05). The area under the receiver operating curve (area under the curve) of derivation cohort and validation cohort was 0.852 (95% confidence interval, 0.784–0.912) and 0.814 (95% confidence interval, 0.751–0.902). The P value for the Hosmer-Lemeshow test was .135 and .891 in the 2 cohorts. The calibration curve demonstrated that the nomogram had a high consistency between prediction and practical observation. The decision curve analysis also showed that the nomogram had a better potential for clinical application. To facilitate clinical application, we have developed an online at https://nomogramcgz.shinyapps.io/IAIrisk/. ConclusionThe nomogram is helpful in predicting the risk of postoperative intra-abdominal infection in patients with blunt abdominal trauma and provides guidance for clinical decision-making and treatment.

Study of utilization of antimicrobial drugs and its resistance pattern in patients with septicemia at a tertiary care hospital

Background: Many types of bacteria can produce septicemia. The most common infections that lead to septicemia are urinary tract infections, pneumonia, nephritis and abdominal infections. Methods: The study aims to assess the pattern of antimicrobial drugs used in septicemia and to assess the etiological organisms and their drug sensitivity and resistance pattern. Study participants admitted to tertiary health care centre and who are having septicemia were included in this prospective observational study. Blood culture, bronchial secretions were subjected to microbiological analysis. The etiological organisms, their drug sensitivity and resistance pattern and the outcome of drug therapy were recorded. The clinical course of the study participants was monitored till cure either the resolution of pneumonia. Qualitative data were analyzed using the chi-square test or Fischer's exact test and quantitative data using the independent t test. Results: Mean duration of hospital stay in all patients 13.22±0.45 days and in resistance cases it was found 19.22±0.45 days. Mean duration of ICU stay in all patients was 4.34±0.45 days and in resistant cases mean duration of ICU stay was 8.18±0.45 days. Clinical outcome in overall admitted patients recovered was 97 patients (80.83%) death was 16 patients (13.33%). Clinical outcome in resistant patients recovered 16 patients (13.33%) and death 26 patients (21.66%). Conclusions: The organisms had a varied sensitivity and resistance pattern. The clinical outcome was multifactorial.

Risk factors of acute respiratory distress syndrome in sepsis caused by intra-abdominal infections: A retrospective study

BackgroundIntra-abdominal infections are frequently associated with acute respiratory distress syndrome, which significantly affects patient prognosis. However, little is known about the specific risk factors of acute respiratory distress syndrome in sepsis caused by intra-abdominal infections. MethodsThis retrospective study included adult patients with intra-abdominal sepsis admitted to the intensive care unit of a tertiary teaching hospital in China between June 2017 and June 2022. Patients were categorized based on the presence or absence of acute respiratory distress syndrome. Data, including vital signs, laboratory values, and severity scores collected within 24 hours of sepsis diagnosis, as well as outcomes within 90 days, were analyzed. Multivariable logistic regression was used to identify independent risk factors associated with acute respiratory distress syndrome. ResultsA total of 738 patients were included, of whom 218 (29.5%) developed acute respiratory distress syndrome. Patients with acute respiratory distress syndrome were younger, had a higher body mass index and disease severity scores, and exhibited higher proportions of septic shock and hospital-acquired intra-abdominal infections. The mortalities in the intensive care unit and at 28 and 90 days were higher in the acute respiratory distress syndrome group. In the multivariate logistic regression model, age under 65 years (odds ratio [95% confidence interval]: 1.571 [1.093–2.259]), elevated body mass index (2.070 [1.382–3.101] for overweight, 6.994 [3.207–15.255]) for obesity, septic shock (2.043 [1.400–2.980]), procalcitonin (1.009 [1.004–1.015]), hospital-acquired intra-abdominal infections (2.528[1.373–4.657]), and source of intra-abdominal infections (2.170 [1.140–4.128] for biliary tract infection, 0.443 [0.217–0.904] for gastroduodenal perforation) were independently associated with acute respiratory distress syndrome. ConclusionIn patients with intra-abdominal sepsis, age under 65 years, higher body mass index and procalcitonin, septic shock, hospital-acquired intra-abdominal infections, and biliary tract infection were risk factors for acute respiratory distress syndrome.

Real-world experience with meropenem/vaborbactam for the treatment of infections caused by ESBL-producing Enterobacterales and carbapenem-resistant Klebsiella pneumoniae.

Real-world experience with meropenem/vaborbactam (M/V) is limited. Our aim is to report a clinical experience of M/V in the treatment of resistant Gram-negative bacilli. This is a prospective observational study including patients hospitalized in the University Hospital of Pisa (March 2021-Jan 2023) with infections by both extended-spectrum β-lactamases (ESBL)-producing Enterobacterales and carbapenem-resistant Klebsiella pneumoniae (Kp) treated with M/V. The primary outcome measure was clinical success, defined as a composite of survival, resolution of signs and symptoms and absence of microbiological failure at day 30 from infection onset. A multivariable regression analysis was performed to identify factors associated with clinical failure. Odds ratio (OR) with 95% confidence intervals (CI) was calculated. A total of 104 patients who received M/V were included: 24/104 (23.1%) infections were caused by ESBL non-hypervirulent Enterobacterales, 17/104 (16.3%) by ESBL-producing hypervirulent Klebsiella pneumoniae (hvKp) and 63/104 (60.6%) by CRE. The most common infections were bloodstream infections, followed by urinary tract infections, hospital-acquired pneumonia, intra-abdominal infections and others. Septic shock occurred in 16/104 (15.4%) patients. Clinical success was achieved in 77% of patients, and 30-day mortality rate was 15.4%. In patients with KPC-producing Kp infections, clinical success and 30-day mortality rates were 82% and 11.5%, respectively. On multivariable analysis, SOFA score (OR 1.32, 95% CI 1.02-1.7, p=0.032) was independently associated with clinical failure, while source control (OR 0.16, 95% CI 0.03-0.89, p=0.036) was protective. M/V is a promising therapeutic option against infections caused by difficult-to-treat ESBL-producing Enterobacterales and CR-Kp.

Possibilities of local effect the healing of small bowel sutures in a rat model of acute intra-abdominal infection

Aims: Investigate the regeneration of the small bowel suture line regeneration after suturing with a material with antioxidant properties. Methodology: 7 intact rats, 63 with simulated intra-abdominal infection (IAI). A laparotomy was performed in 12 h after simulating. The small bowel was cut and sutured in 56 rats (2 groups of 28) after an abdominal lavage. Standard Kapron was used in the control group (CG). Kapron impregnated with a 5% solution of ethylmethylhydroxypyridine succinate was used in the research group (RG). Sections of the small bowel were collected from a total of 21 rats (7 intact rats, 7 rats with intra-abdominal infection (IAI) models, and 7 rats at different time points (1, 3, 5, and 7 days) post suturing) for subsequent histological examination. The preparations were stained with hematoxylin-eosin and by Mikel Calvo. The R/B coefficient (R/BC) was determined. The experiment's time duration was 7.5 days in December 2022. Results: R/BC increased (p&lt;0.05) in the connective tissue fibers of the small bowel submucosal base in 12 h after the simulating of IAI. R/BC increased (p&lt;0.05) in both groups in 1 day after suturing. R/BC increased in CG, decreased (p&lt;0.05) in RG in 3 days. Fibrin was found between the ligature’s fibers in RG. R/BC decreased (p&lt;0.05) in both groups in 5 days, indicators were smaller (p&lt;0.01) in RG. Fibrin was found between the ligature’s fibers in CG, granulation tissue was in RG. R/BC decreased in both groups in 7 days, but indicators were smaller in RG (p&lt;0.01). Unfilled areas in the granulation tissue between the ligature fibers were in CG. Conclusion: 1. The use of ligatures impregnated with the 5% ethylmethylhydroxypyridine succinate solution for suturing the small bowel in rats with intra-abdominal infection models is associated with the significant decrease in the activity of local proteins oxidation and the significant acceleration of local regeneration processes. 2. The creation of a suture material with antioxidant properties may be a promising direction for the prevention of suture leakage

Improving the antibiotic duration of therapy with the implementation of antimicrobial lanyard cards and education in a regional hospital

AbstractBackgroundThere is increasing evidence to support reducing antibiotic duration of therapy (DoT). The Therapeutic Guidelines: Antibiotic (version 16 [TG]) have been updated accordingly. However, these recommendations are not consistently followed.AimThe project aimed to reduce antibiotic DoT for common infections using antimicrobial lanyard cards and education.MethodA retrospective pre‐ and post‐implementation audit was undertaken to examine whether antimicrobial stewardship education and lanyard cards defined DoT per infection and severity in accordance with the TG improved antibiotic DoT for common respiratory, urinary, abdominal, and skin infections. Cards were distributed to doctors and pharmacists, with education delivered by an antimicrobial stewardship (AMS) pharmacist. This project was exempt due to the local policy requirements that constitute research by the Darling Downs Hospital and Health Service Human Research Ethics Committee (Reference no: EX/2022/QTDD/86644). The justification for this ethics exemption was as follows: the study conformed with the National Health and Medical Research Council (NHMRC) Ethical considerations in quality assurance and evaluation activities; education was incorporated as part of routine, scheduled sessions ran at Toowoomba hospital and staff were provided with information on the project as part of the education; consent was not required from staff to attend the education nor for using the lanyard cards; the research did not include any assessment of the education program, use of lanyard cards, or involvement of staff.ResultsFor all patients an improvement was found in the percentage of antibiotics prescribed per the TG (55–72%, p = 0.0095). This included statistically significant differences for respiratory (42–89%, p = 0.0002), but not for urinary (87–91%, p = 0.99), skin (58–77%, p = 0.3039), or abdominal infections (48–44%, p = 0.6990). The mean total excess treatment days decreased across all infections from 1.86 to 0.95 days (p = 0.0036, 95% confidence interval = −1.52 to −0.30).ConclusionThe introduction of antibiotic DoT cards, with AMS education, can improve antimicrobial prescribing in line with the TG in a regional hospital.

Use of pus metagenomic next-generation sequencing for efficient identification of pathogens in patients with sepsis

The positive detection rate of blood metagenomic next-generation sequencing (mNGS) was still too low to meet clinical needs, while pus from the site of primary infection may be advantageous for identification of pathogens. To assess the value of mNGS using pus in patients with sepsis, thirty-five samples were collected. Pathogen identification and mixed infection diagnosis obtained by use of mNGS or cultivation methods were compared. Fifty-three aerobic or facultative anaerobes, 59 obligate anaerobes and 7 fungi were identified by the two methods. mNGS increased the accuracy rate of diagnosing aerobic or facultative anaerobic infections from 44.4% to 94.4%; mNGS also increased the sensitivity of diagnosing obligate anaerobic infections from 52.9% to 100.0%; however, mNGS did not show any advantage in terms of fungal infections. Culture and mNGS identified 1 and 24 patients with mixed infection, respectively. For obligate anaerobes, source of microorganisms was analyzed. The odontogenic bacteria all caused empyema (n = 7) or skin and soft tissue infections (n = 5), whereas the gut-derived microbes all caused intra-abdominal infections (n = 7). We also compared the clinical characteristics of non-obligate anaerobic and obligate anaerobic infection groups. The SOFA score [9.0 (7.5, 14.3) vs. 5.0 (3.0, 8.0), P = 0.005], procalcitonin value [4.7 (1.8, 39.9) vs. 2.50 (0.7, 8.0), P = 0.035], the proportion of septic shock (66.7% vs. 35.3%, P = 0.044) and acute liver injury (66.7% vs. 23.5%, P = 0.018) in the non-obligate anaerobic infection group were significantly higher than those in the obligate anaerobic infection group. In patients with sepsis caused by purulent infection, mNGS using pus from the primary lesion may yield more valuable microbiological information.

To treat or not to treat: Assessing the role of anti-enterococcal therapy for intra-abdominal infections in patients with cancer.

The clinical significance of enterococci in intra-abdominal infections, particularly those caused by multiple organisms, remains unclear. There are no definitive guidelines regarding the use of empiric therapy with antimicrobial agents targeting enterococci. In this study, we evaluated the impact of the initial antimicrobial therapy administration of anti-enterococcal agents on the treatment of intra-abdominal infections in patients with cancer in whom enterococci were isolated from ascitic fluid cultures. This retrospective study was conducted at Shizuoka Cancer Center between January 1, 2014, and December 31, 2020, on all adult patients with cancer with enterococci in their ascitic fluid cultures. The primary outcome was all-cause mortality, and the secondary outcomes were composite outcomes consisting of three components (mortality, recurrence, and treatment failure) and the risk factors associated with all-cause mortality and composite outcomes. In total, 103 patients were included: 61 received treatment covering enterococci, and 42 did not. The mortality rates did not differ significantly between the treated and untreated groups (treated: 8/61 [13.1%]; untreated: 5/42 [11.9%]; p = 1.00). Additionally, no significant difference was observed between the groups in terms of composite outcomes (treated group: 11/61 [18.0%]; untreated group: 9/42 [21.4%]; p = 0.80). Multivariate analysis showed that performance status (PS2-4; p < 0.0001) was an independent risk factor for mortality. The composite outcome was also significantly higher for PS2-4 (p = 0.007). Anti-enterococcal treatment was not associated with mortality or the composite outcome. In patients with cancer and intra-abdominal infections caused by enterococci, anti-enterococcal therapy was not associated with prognosis, whereas PS2 or higher was associated with prognosis. The results of this study suggest that the initial routine administration of anti-enterococcal agents for intra-abdominal infections may not be essential for all patients with cancer. To substantiate these findings, validation by a prospective randomized trial is warranted.

Long-term outcomes of stapled closure of the aortic stump with axillo-bifemoral bypass grafting for abdominal aortic infection

ObjectivesThe stapled suture is used to close the aortic stump during surgery for abdominal aortic infection. The current study aimed to investigate the short- and long-term outcomes of stapled closure of the aortic stump with axillo-bifemoral (AxBF) bypass grafting. MethodsThe short- and long-term outcomes of 11 patients who underwent surgery for abdominal aortic infection were retrospectively analyzed. ResultsOf 11 patients, 7 underwent stapled closure of the aortic stump with AxBF bypass grafting, and four underwent other reconstructive procedures with no aortic stump. Four patients (three who underwent stapled closure of the aortic stump and one who underwent other reconstructive procedures without the aortic stump) had operative death. However, none of the patients had aortic stump blow-out during the same hospitalization for surgery. The 1- and 5-year survival rates of the patients who underwent stapled closure of the aortic stump with AxBF bypass grafting were 57% and 29%, respectively. One patient developed aorto-duodenal fistula at 32 months after surgery. The patient survived for 12 months until bleeding in the recurrent aorto-enteric fistula occurred. ConclusionStapled closure of the aortic stump is durable. The use of a linear stapler is a useful technique for reinforcing the aortic stump in patients who underwent excision of an infected abdominal aortic aneurysm or an infected abdominal graft.

Estimates of antibiotic resistance in Italy and Western Europe in 2019: a MICROBE-based comparative analysis.

antimicrobial resistance (AMR) will cause 10 million deaths per year worldwide by 2050, with economic costs of up to 100 trillion dollars. Antibiotic resistance (ABR) constitutes the majority of this health threat. Globally, 1.27 million people died in 2019 as a direct result of ABR. One in 5 deaths occurred in children under five, and 6 bacterial pathogens accounted for more than 70% of ABR-associated deaths. to compare ABR estimates in terms of death and disability-adjusted life-years (DALYs) in 2019 in Italy and in Western Europe (WE) by grading the infectious syndromes and the bacterial pathogens involved, with the aim to identify the most urgent healthcare needs in Italy. the estimates of the burden of ABR in 2019 in WE and Italy, extracted from the Measuring Infectious Causes and Resistance Outcomes for Burden Estimation (MICROBE) tool by the Institute for Health Metrics and Evaluation (IHME; Seattle, USA), reported deaths and DALYs associated with 33 bacterial pathogens across 12 infectious syndromes, as well as deaths and DALYs associated with and attributable to ABR for 23 bacteria and 86 pathogen-drug combinations. The comparison between WE and Italy was performed in steps. First, among the 12 groups of infectious syndromes from the Global Burden of Diseases (GBD) study 2019, the most impacting in terms of deaths and DALYs were ranked based on the magnitude of rates, and the corresponding ABR-associated burden was reported. Then, the burden of the leading pathogens (bacteria, viruses, fungi, and polymicrobial infections) for all infectious syndromes was compared between the two areas. Death and DALY rates associated with ABR were reported for each bacterium, together with the percentage of ABR-attributable burden. Although it is known that Italy is one of the WE countries with the largest share of elderly, crude rates were reported instead of age-standardized rates, in order to quantify the actual burden of ABR in the two areas. Italy and Western Europe. death and DALYs rates per 100,000 inhabitants. the largest difference between ABR-associated death rates in the two areas was found for bloodstream infections (25.2 and 18.8 per 100,000 in Italy and WE, respectively), followed by peritoneal and abdominal infections (15.1 and 12.2 in Italy and WE, respectively). However, the percentages of deaths and DALYs attributable to ABR were always higher in Italy for all the infections considered. Regarding pathogens, Escherichia coli accounted for the greatest burden associated to ABR, in terms of both deaths and DALYs, in both areas. The highest ABR-attributable percentage of deaths was found for Acinetobacter baumannii (28.4% in WE and 31.9% in Italy), accounting also for the highest percentage of ABR-attributable DALYs (28.4% in WE and 31.7% in Italy). The pathogen-drug combination with the highest burden associated with AMR was Escherichia coli-Aminopenicillin, while the greatest AMR-attributable burden was found for Staphylococcus aureus-Methicillin (MRSA). On average, 55.4% of Escherichia coli was resistant to Aminopenicillin in WE, with Italy ranking third (67.6%). Nordic countries showed smaller values, with Sweden in last place (32.8%). The average percentage of MRSA in WE was 16%, with Italy exceeding it by more than 13 pointsConclusions: despite similar sepsis mortality rates in Italy and other WE countries, the proportion of ABR-associated and attributable deaths was higher in Italy. Targeted strategies aimed at reducing the circulation of bacteria and resistant microorganisms together with other interventions could lead to an overall reduction in deaths associated with ABR.

Evaluation of the results of laparoscopic appendectomy for appendicitis peritonitis treatment

Objectives: To evaluate the results of laparoscopic appendectomy for appendicitis peritonitis treatment. Methods: Prospective study, including 37 patients diagnosed with appendicitis peritonitis based on clinical and subclinical symptoms and determined during surgery to have peritonitis due to ruptured appendix and treated with laparoscopic surgery from April 2022 to June 2023 at the Department of Digestive Surgery, Hue University of Medicine and Pharmacy Hospital. Results: Patients with appendicitis peritonitis had an average age of 54.9 years. The females accounted for 58.6%. Normal BMI accounted for the highest rate at 56.8%, the rate of overweight and obesity was up to 29.7%; there were 62.2% of patients were assessed to have ASA index 2 or 3. The average time from onset to hospital admission was 30.8 ± 29.1 hours. Generalized peritonitis accounts for 24.3%. The average surgical time was 60.5 ± 17.2 minutes. Peritoneal drainage was placed in 45.9% of cases. There were no cases of complications during surgery or conversion to open surgery. The average time to return to fart after surgery was 20.2 ± 12 hours, the average time to use analgesic after surgery was 1.53 ± 0.7 hours. The average postoperative hospital stay was 5.3 ± 1.3 days. There were 2.7% of patients had complication of abdominal drainage site infection. Evaluating treatment results, there were 97.3% of patients achieved good results. There was no 30-day mortality. Conclusions: Laparoscopic surgery to treat appendicitis peritonitis is a safe and effective method. Patients can recover well in a short time. Key words: appendicitis peritonitis, laparoscopic appendectomy, acute appendicitis, abdominal drainage.

Ceftolozane/Tazobactam for the Treatment of Complicated Infections in Hospital Settings-A French Real-world Study.

This study describes the conditions of use of ceftolozane/tazobactam (C/T) and associated outcomes in French hospital settings. This was a prospective, multicenter, French observational study. Patients who received at least 1 dose of C/T were included and followed up as per routine clinical practice, until stop of C/T. A total of 260 patients were enrolled between October 2018 and December 2019 in 30 centers across France. Of these, 177 (68.0%) received C/T as per indication of usage following the results of the antibiogram (documented cases). Among documented patients, the mean age was 61.8 years, 73.4% were males, and 93.8% presented with multidrug-resistant (MDR) bacteria at inclusion. C/T was most frequently prescribed for pneumonia (48.6%), bacteremia (14.7%), complicated intra-abdominal infections (13.0%), or complicated urinary tract infections (9.6%). Pseudomonas aeruginosa was the species most frequently isolated with 212 strains from 155 patients, and 96.2% of these strains were susceptible to C/T. The median duration of C/T treatment was 16.1 days (1-115, n = 176). Complete or partial cure was achieved in 71.7% of patients, C/T was discontinued upon adaptation to microbiology results in 11.3% of patients for the following reasons: treatment failure in 2.8%, death in 4.0%, adverse events in 1.7%, and other in 8.5%. This is the first prospective observational study of C/T utilization in a health care setting enrolling many patients in France. C/T demonstrated a high rate of clinical effectiveness in MDR infections, confirming it as an effective treatment option for complicated infections in a high-risk population.

Attributable mortality of infections caused by carbapenem-resistant Enterobacterales: results from a prospective, multinational case-control-control matched cohorts study (EURECA)

ObjectivesTo assess the mortality attributable to infections caused by carbapenem-resistant Enterobacterales (CRE) and to investigate the effect of clinical management on differences in observed outcomes in a multinational matched cohort study. MethodsA prospective matched-cohorts study (NCT02709408) was performed in 50 European hospitals from March 2016 to November 2018. The main outcome was 30-day mortality with an active post-discharge follow-up when applied. The CRE cohort included patients with complicated urinary tract infections, complicated intra-abdominal infections, pneumonia, or bacteraemia from other sources because of CRE. Two control cohorts were selected: patients with infection caused by carbapenem-susceptible Enterobacterales (CSE) and patients without infection. Matching criteria included type of infection for the CSE group, hospital ward of CRE detection, and duration of hospital admission up to CRE detection. Multivariable and stratified Cox regression was applied. ResultsThe cohorts included 235 patients with CRE infection, 235 patients with CSE infection, and 705 non-infected patients. The 30-day mortality (95% CI) was 23.8% (18.8–29.6), 10.6% (7.2–15.2), and 8.4% (6.5–10.6), respectively. The difference in 30-day mortality rates between patients with CRE infection when compared with patients with CSE infection was 13.2% (95% CI, 6.3–20.0), (HR, 2.57; 95% CI, 1.55–4.26; p < 0.001), and 15.4% (95% CI, 10.5–20.2) when compared with non-infected patients (HR, 3.85; 95% CI, 2.57–5.77; p < 0.001). The population attributable fraction for 30-day mortality for CRE vs. CSE was 19.28%, and for CRE vs. non-infected patients was 9.61%. After adjustment for baseline variables, the HRs for mortality were 1.87 (95% CI, 0.99–3.50; p 0.06) and 3.65 (95% CI, 2.29–5.82; p < 0.001), respectively. However, when treatment-related time-dependent variables were added, the HR of CRE vs. CSE reduced to 1.44 (95% CI, 0.78–2.67; p 0.24). DiscussionCRE infections are associated with significant attributable mortality and increased adjusted hazard of mortality when compared with CSE infections or patients without infection. Underlying patient characteristics and a delay in appropriate treatment play an important role in the CRE mortality.

Impact of collagen matrix on reconstructive material selection and postoperative complications in endoscopic endonasal skull base surgery.

The aim of this study was to investigate the impact of collagen matrix on reconstructive material selection and postoperative complications in endoscopic endonasal skull base surgery. The authors retrospectively reviewed the data of consecutive patients who underwent purely endoscopic endonasal skull base surgery from January 2015 to March 2023. Intraoperative CSF leakage was classified according to the Esposito grade, and skull base repair was tailored to the leakage grade. The patients were divided into two groups: before (group A) and after (group B) collagen matrix implementation. The rates of autologous graft harvesting (fat, fascia, and nasoseptal flap), postoperative CSF leakage, and donor-site complications were compared between the two groups. In total, 270 patients were included. Group A included 159 patients and group B included 111 patients. There were no differences in patient characteristics, including age, pathology, and Esposito grade, between the two groups. The overall fat usage rate was significantly higher in group A (63.5%) than in group B (39.6%) (p = 0.0001), and the fascia usage rate was also significantly higher in group A (25.8%) than in group B (4.5%) (p < 0.0001). The nasoseptal flap usage rate did not differ between group A (32.7%) and group B (30.6%) (p = 0.79). Postoperative CSF leakage was similar between the two groups (0.63% in group A vs 1.8% in group B, p = 0.57), and the overall rate of CSF leakage was 1.1%. Donor-site complications occurred in 3 patients in group A, including 1 abdominal hematoma, 1 delayed abdominal infection, and 1 fluid collection after fascia lata harvesting. Collagen matrix implementation significantly decreased autologous graft harvesting without increasing postoperative CSF leakage, contributing to less invasive surgery.

Novel nitroxoline derivative combating resistant bacterial infections through outer membrane disruption and competitive NDM-1 inhibition

ABSTRACT New Delhi metallo-β-lactamase-1 (NDM-1) has rapidly disseminated worldwide, leading to multidrug resistance and worse clinical prognosis. Designing and developing effective NDM-1 inhibitors is a critical and urgent challenge. In this study, we constructed a library of long-lasting nitroxoline derivatives and identified ASN-1733 as a promising dual-functional antibiotic. ASN-1733 can effectively compete for Ca2+ on the bacterial surface, causing the detachment of lipopolysaccharides (LPS), thereby compromising the outer membrane integrity and permeability and exhibiting broad-spectrum bactericidal activity. Moreover, ASN-1733 demonstrated wider therapeutic applications than nitroxoline in mouse sepsis, thigh and mild abdominal infections. Furthermore, ASN-1733 can effectively inhibit the hydrolytic capability of NDM-1 and exhibits synergistic killing effects in combination with meropenem against NDM-1 positive bacteria. Mechanistic studies using enzymatic experiments and computer simulations revealed that ASN-1733 can bind to key residues on Loop10 of NDM-1, hindering substrate entry into the enzyme's active site and achieving potent inhibitory activity (Ki = 0.22 µM), even in the presence of excessive Zn2+. These findings elucidate the antibacterial mechanism of nitroxoline and its derivatives, expand their potential application in the field of antibacterial agents and provide new insights into the development of novel NDM-1 inhibitors.

P239 Characteristics and outcomes of portal vein thrombosis in patients with Inflammatory Bowel Disease in Korea

Abstract Background Portal vein thrombosis (PVT) is known to occur frequently in patients with inflammatory bowel disease (IBD), particularly when compounded by factors such as abdominal infection, IBD flares, or intra-abdominal surgery. However, PVT can lead to diverse complications, causing acute issues like intestinal ischemia or necrosis and long-term problems such as portal hypertension, varices, and ascites. Nevertheless, there is a significant shortage of research regarding the characteristics and prognosis of PVT in the context of IBD. Particularly, with the rising prevalence of IBD patients in Asia, the authors conducted an evaluation of clinical presentation and prognosis of PVT in IBD patients at a large tertiary hospital in South Korea. Methods This study is a retrospective study conducted at a single tertiary center in South Korea. It examined patients aged 18 and above diagnosed with inflammatory bowel disease (IBD) who had confirmed portal vein thrombosis (PVT) between June 1, 1989, and December 15, 2021. The study focused on investigating patient characteristics, PVT characteristics, treatment methods, and outcomes. The diagnosis and resolution of PVT were confirmed using enhanced CT imaging. Results A total of 78 patients met the inclusion criteria for this study. Only 21% (16/78) received oral anticoagulants, yet nearly all patients (96%; 75/78) achieved Complete Radiologic Resolution (CRR). When comparing baseline characteristics between the anticoagulation use group and the non-use group, a trend was observed with a higher utilization of anticoagulants in cases where the main portal vein was involved rather than only the left or right portal vein (p-value 0.006). However, when conducting multivariable analysis, no factors significantly influenced CRR, especially anticoagulant use and surgery status. Conclusion PVT concomitant with IBD demonstrated favorable outcomes regardless of anticoagulation use.

Preoperative Exclusive Enteral Nutrition Is Associated With Reduced Skin and Soft Tissue and Intra-abdominal Infections in Patients With Crohn's Disease Undergoing Intestinal Surgery: Results from a Meta-Analysis.

Malnutrition is an independent risk factor for adverse postoperative outcomes and is common among patients with Crohn's disease (CD). The objective of this meta-analysis was to precisely quantify the association of preoperative exclusive enteral nutrition (EEN) and total parenteral nutrition (TPN) with surgical outcomes in patients undergoing intestinal surgery for CD. PubMed, Embase, and Scopus were queried for comparative studies evaluating the impact of preoperative nutritional support on postoperative outcomes in patients undergoing surgery for CD. Random effects modeling was used to compute pooled estimates of risk difference. Heterogeneity was assessed using I2. Fourteen studies, all nonrandomized cohort studies, met inclusion criteria for studying EEN. After pooling data from 14 studies (874 EEN treated and 1044 control patients), the relative risk of intra-abdominal septic complications was decreased 2.1-fold in patients receiving preoperative EEN (relative risk 0.47, 95% confidence interval [CI], 0.35-0.63, I2 = 0.0%). After pooling data from 9 studies (638 EEN treated and 819 control patients), the risk of skin and soft tissue infection was decreased 1.6-fold (relative risk 0.63; 95% CI, 0.42-0.94, I2 = 42.7%). No significant differences were identified in duration of surgery, length of bowel resected, or operative blood loss. Among the 9 studies investigating TPN, no significant differences were identified in infectious outcomes. Preoperative nutritional optimization with EEN was associated with reduced risk of infectious complications in CD patients undergoing intestinal surgery. Preoperative nutritional support with EEN should be considered for optimizing outcomes in CD patients requiring bowel resection surgery.

Perspectives on the use of ceftolozane/tazobactam: a review of clinical trial data and real-world evidence.

Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) are common healthcare-associated infections linked to high morbidity and mortality. Gram-negative pathogens, such as Pseudomonasaeruginosa, exhibit multidrug resistance and are recognized as major public health concerns, particularly among critically ill patients with HABP/VABP. Ceftolozane/tazobactam is a novel combination antibacterial agent comprising ceftolozane (a potent antipseudomonal cephalosporin) and tazobactam (a β-lactamase inhibitor). Phase III trials have demonstrated non-inferiority of ceftolozane/tazobactam to comparators, leading to the approval of ceftolozane/tazobactam for the treatment of complicated urinary tract infections, complicated intra-abdominal infections, and nosocomial pneumonia. In this article, we review the clinical trial evidence and key real-world effectiveness data of ceftolozane/tazobactam for the treatment of serious healthcare-associated Gram-negative infections, focusing on patients with HABP/VABP.

Results of a prospective phase II study of total neoadjuvant therapy for locally advanced rectal cancer.

147 Background: Total neoadjuvant therapy is further accepted for the treatment of locally advanced rectal cancer, which is more valuable for patients with high-risk factors. Optimal schedule of radiotherapy and chemotherapy remains unknown and needs further exploration. Methods: We conducted a multicenter, randomized, phase II trial (ClinicalTrials.gov No.: NCT04543695). Patients aged 18-75 years with initial stage II / III rectal adenocarcinoma (At least one of high-risk factors should be included: mesorectal fascia involvement, T4, N2, positive lateral lymph node, or extramural vessel invasion) were assigned into three groups, 1) Chemoradiotherapy (50 Gy of radiation combined with oral capecitabine) followed by consolidation chemotherapy using six cycles of XELOX(CNCT group), 2) Induction chemotherapy before chemoradiotherapy (INCT group), or 3) Chemoradiotherapy alone (Control group). Then enrolled patients were required to undergo radical surgery after neoadjuvant therapy. Patients in Control group need six cycles of XELOX after surgery. The primary end point was proportion of yp0-II, and watch-and-wait strategy after complete clinical response (cCR) was allowed. Results: Of the 257 patients enrolled, 255 patients were evaluable (Control: CNCT: INCT= 84: 86: 85). Neoadjuvant treatment related grade 3 or 4 toxicity was higher in TNT approach (7.1%, 23.3% and 32.9% in Control, CNCT and INCT, respectively), of with myelosuppression being most common. Compliance of chemoradiotherapy was lower in INCT group (98.8%, 100% and 90.6% in Control, CNCT and INCT, respectively). As to CNCT and INCT, 60.0% and 74.1% of patients completed six cycles of chemotherapy, with 76.7% and 83.5% completing four cycles of chemotherapy, respectively. Proportions of downstage (yp0-II + sustained cCR) were achieved 75.6% in CNCT group and 74.1% in INCT group, respectively, compared to 56.0% in Control group. CR rates (pCR + sustained cCR) were achieved 43.0% in CNCT group and 38.8% in INCT group, respectively, compared to 20.2% in Control group. Both TNT approaches did not increase the incidence of surgical complications (6.0%, 8.1% and 10.9% in Control, CNCT and INCT, respectively), with anastomotic fistula and abdominal infection being of most common. Conclusions: Both TNT approaches increased the probability of ≥ G3 acute toxicities, but most patients could tolerate 4 cycles of neoadjuvant chemotherapy. Both TNT approaches could achieve a higher proportion of downstage and CR rate. Clinical trial information: NCT04543695 .

Animal Models in Regulatory Breakpoint Determination: Review of New Drug Applications of Approved Antibiotics from 2014-2022.

We sought to better understand the utility and role of animal models of infection for Food and Drug Administration (FDA)-approved antibiotics for the indications of community-, hospital-acquired-, and ventilator-associated bacterial pneumonia (CABP, HABP, VABP), complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), and acute bacterial skin and structural infections (ABSSSIs). We reviewed relevant documents from new drug applications (NDA) of FDA-approved antibiotics from 2014-2019 for the above indications. Murine neutropenic thigh infection models supported the choice of a pharmacokinetic-pharmacodynamic (PKPD) target in 11/12 NDAs reviewed. PKPD targets associated with at least a 1-log bacterial decrease were commonly considered ideal (10/12 NDAs) to support breakpoints. Plasma PK, as opposed to organ specific PK, was generally considered most reliable for PKPD correlation. Breakpoint determination was multi-disciplinary, accounting at minimum for epidemiologic cutoffs, non-clinical PKPD, clinical exposure-response and clinical efficacy. Non-clinical PKPD targets in combination with probability of target attainment (PTA) analyses generated breakpoints that were consistent with epidemiologic cutoffs and clinically derived breakpoints. In 6/12 NDAs, there was limited data to support clinically derived breakpoints, and hence the non-clinical PKPD targets in combination with PTA analyses played a heightened role in the final breakpoint determination. Sponsor and FDA breakpoint decisions were in general agreement. Disagreement may have arisen from differences in the definition of the optimal PKPD index or the ability to extrapolate protein binding from animals to humans. Overall, murine neutropenic thigh infection models supported the reviewed NDAs by providing evidence of pre-clinical efficacy and PKPD target determination, and played, in combination with PTA analysis, a significant role in breakpoint determination for labeling purposes.