Comparison of Operative Outcomes Between Monopolar and Bipolar Coagulation in Hepatectomy: A Propensity Score-Matched Analysis in a Single Center

Background: Various hemostatic devices have been utilized to reduce blood loss during hepatectomy. Nonetheless, a comparison between monopolar and bipolar coagulation, particularly their usefulness or inferiority, has been poorly documented. The aim of this study is to reveal the characteristics of these hemostatic devices.Methods: A total of 264 patients who underwent open hepatectomy at our institution from January 2009 to December 2018 were included. Monopolar and bipolar hemostatic devices were used in 160 (monopolar group) and 104 (bipolar group) cases, respectively. Operative outcomes and thermal damage to the resected specimens were compared between these groups using propensity score matching according to background factors. Multivariate logistic regression analysis was performed to identify predictive factors for postoperative complications.Results: After propensity score matching, 73 patients per group were enrolled. The monopolar group had significantly lower total operative time (239 vs. 275 min; P=0.013) and intraoperative blood loss (487 vs. 790 mL; P<0.001). However, the incidence rates of ascites (27.4% vs. 8.2%; P=0.002) and grade ≥3 intra-abdominal infection (12.3% vs. 2.7%; P=0.028) were significantly higher in the monopolar group. Thermal damage to the resected specimens was significantly longer in the monopolar group (4.6 vs. 1.2 mm; P<0.001). Use of monopolar hemostatic device was an independent risk factor for ascites (odds ratio, 5.626, 95% confidence interval 1.881–16.827; P=0.002) and severe intra-abdominal infection (odds ratio, 5.905, 95% confidence interval 1.096–31.825; P=0.039).Conclusions: Although monopolar devices have an excellent hemostatic ability, they might damage the remnant liver. The use of monopolar devices can be one of the factors that increase the frequency of complications.

1154. Safety and Efficacy of Ceftolozane/Tazobactam Plus Metronidazole Versus Meropenem in Pediatric Participants With Complicated Intra-abdominal Infection: A Phase 2, Randomized Clinical Trial

Background Ceftolozane/tazobactam (C/T), a cephalosporin–β-lactamase inhibitor combination, is approved for treatment of complicated urinary tract infections, complicated intra-abdominal infections (cIAI), and nosocomial pneumonia in adults. Safety and efficacy of C/T in pediatric participants with cIAI was assessed. Methods This phase 2 study (NCT03217136) compared C/T + metronidazole (MTZ) with meropenem (MEM) for treatment of cIAI. Age- and weight-adjusted dosing is summarized in Table 1. The primary objective was to evaluate the safety and tolerability of C/T + MTZ compared with MEM. A key secondary endpoint was clinical cure at end of treatment (EOT) and test of cure (TOC). Table 1. Summary of Dosing and Pharmacokinetic Sampling Schedule by Age Cohort Results A total of 94 participants were randomized 3:1; 91 were treated with C/T + MTZ (n=70) or MEM (n=21) comprising the modified intent-to-treat (MITT) population. The clinically evaluable population included 78 participants at EOT (C/T + MTZ, n=59; MEM, n=19) and 77 participants at TOC (C/T + MTZ, n=58; MEM, n=19). The most common diagnosis and pathogen in the MITT population were complicated appendicitis (C/T + MTZ, 91.4%; MEM, 100%) and Escherichia coli (C/T + MTZ, 67.1%; MEM, 61.9%). The mean (SD) intravenous therapy/overall treatment duration was 6.4 (2.8)/9.3 (3.6) days and 5.8 (1.8)/9.0 (3.2) days for C/T + MTZ and MEM, respectively. In total, ≥1 adverse events (AE) occurred in 80.0% and 61.9% of participants receiving C/T + MTZ and MEM, respectively (Table 2), of which 18.6% and 14.3% were considered drug related. Serious AE occurred in 11.4% (8/70) and 0% (0/21) of participants receiving C/T + MTZ and MEM, respectively; none were considered drug related. No drug-related study drug discontinuations occurred. In the MITT population, rates of clinical cure for C/T + MTZ and MEM at EOT were 80.0% and 95.2%, and at TOC were 80.0% and 100%, respectively (Figure 1); 6 of the 14 failures for C/T + MTZ were indeterminate responses scored as endpoint failures per protocol. In the clinically evaluable (CE) population, rates of clinical cure for C/T + MTZ and MEM were 89.8% and 100% at EOT, and 89.7% and 100% at TOC, respectively (Figure 1). Conclusion C/T + MTZ was well tolerated in pediatric participants with cIAI, and rates of clinical success were high with C/T treatment. C/T is a promising new treatment option for children with cIAI. Disclosures Carl-Christian A. Jackson, MD, Merck & Co. Inc. (Shareholder) Julia Lonchar, MSc, Merck Sharp & Dohme Corp. (Employee, Shareholder) Feng-Hsiu Su, MPH, MBA, Merck Sharp & Dohme Corp. (Employee, Shareholder) Jennifer A. Huntington, PharmD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee) Mekki Bensaci, PhD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee) Myra W. Popejoy, PharmD, Merck Sharp & Dohme Corp. (Employee) Matthew G. Johnson, MD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee) Carisa S. De Anda, PharmD, Merck Sharp & Dohme Corp. (Employee, Shareholder) Elizabeth G. Rhee, MD, Merck Sharp & Dohme Corp (Employee, Shareholder) Christopher Bruno, MD, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Employee)

Analysis of six tonB gene homologs in Bacteroides fragilis revealed that tonB3 is essential for survival in experimental intestinal colonization and intra-abdominal infection

The opportunistic, anaerobic pathogen and commensal of the human large intestinal tract, Bacteroides fragilis strain 638R, contains six predicted TonB proteins, termed TonB1-6, four ExbBs orthologs, ExbB1-4, and five ExbDs orthologs, ExbD1-5. The inner membrane TonB/ExbB/ExbD complex harvests energy from the proton motive force (Δp) and the TonB C-terminal domain interacts with and transduces energy to outer membrane TonB-dependent transporters (TBDTs). However, TonB’s role in activating nearly one hundred TBDTs for nutrient acquisition in B. fragilis during intestinal colonization and extraintestinal infection has not been established. In this study, we show that growth was abolished in the ΔtonB3 mutant when heme, vitamin B12, Fe(III)-ferrichrome, starch, mucin-glycans, or N-linked glycans were used as a substrate for growth in vitro . Genetic complementation of the ΔtonB3 mutant with the tonB3 gene restored growth on these substrates. The ΔtonB1 , ΔtonB2 , ΔtonB4, ΔtonB5, and ΔtonB6 single mutants did not show a growth defect. This indicates that there was no functional compensation for the lack of TonB3, and it demonstrates that TonB3, alone, drives the TBDTs involved in the transport of essential nutrients. The ΔtonB3 mutant had a severe growth defect in a mouse model of intestinal colonization compared to the parent strain. This intestinal growth defect was enhanced in the ΔtonB3 ΔtonB6 double mutant strain which completely lost its ability to colonize the mouse intestinal tract compared to the parent strain. The ΔtonB1 , ΔtonB2 , ΔtonB4, and ΔtonB5 mutants did not significantly affect intestinal colonization. Moreover, the survival of the ΔtonB3 mutant strain was completely eradicated in a rat model of intra-abdominal infection. Taken together, these findings show that TonB3 was essential for survival in vivo . The genetic organization of tonB1 , tonB2 , tonB4, tonB5, and tonB6 gene orthologs indicates that they may interact with periplasmic and nonreceptor outer membrane proteins, but the physiological relevance of this has not been defined. Because anaerobic fermentation metabolism yields a lower Δp than aerobic respiration and B. fragilis has a reduced redox state in its periplasmic space - in contrast to an oxidative environment in aerobes - it remains to be determined if the diverse system of TonB/ExbB/ExbD orthologs encoded by B. fragilis have an increased sensitivity to PMF (relative to aerobic bacteria) to allow for the harvesting of energy under anaerobic conditions.

Progressive Development of Cefiderocol Resistance in Escherichia coli During Therapy Is Associated with Increased blaNDM-5 Copy Number and Gene Expression

Background As cefiderocol is increasingly being prescribed in clinical practice, it is critical that we understand key mechanisms contributing to acquired resistance to this agent. Methods We report the case of a patient with acute lymphoblastic leukemia with an NDM-5 producing Escherichia coli intra-abdominal infection where resistance to cefiderocol evolved approximately 2 weeks after initiating cefiderocol therapy. Through WGS investigations, mRNA expression studies, and EDTA inhibition analysis, we investigate the role of increased NDM-5 production and genetic mutations contributing to the development of cefiderocol resistance using 5 sequential clinical E. coli isolates obtained from the patient. Results blaNDM-5 genes were identified in all 5 isolates. Cefiderocol MICs were 2, 4, and &gt;32 mcg/mL for isolates 1-2, 3, 4-5, respectively. WGS showed that isolates 1-3 contained a single copy of the blaNDM-5 gene, whereas isolates 4 and 5 had 5 copies and 10 copies of the blaNDM-5 gene on an IncFIA/FIB/IncFII plasmid, respectively. These findings correlated with NDM-5 mRNA expression analysis in which isolates 4 and 5 expressed NDM 1.7x and 2.8x greater than isolate 1. Synergy testing with the combination of ceftazidime-avibactam and aztreonam demonstrated expansion of the zone of inhibition between the disks for all isolates. The patient was eventually successfully treated with this combination and remained infection free 10 months later. Conclusions Our patient’s case suggests that increased copy numbers of bla NDM genes through translocation events is used by Enterobacterales to evade cefiderocol-mediated cell death. The frequency of increased NDM expression in contributing to cefiderocol resistance needs investigation.

Ceftolozane-tazobactam: When, how and why using it?

Ceftolozane-tazobactam is currently the most active antipseudomonal agent, including multidrug-resistant extensively drug-resistant strains. Tazobactam provides additional activity against many extended-spectrum beta-lactamases Enterobacterales. Ceftolozane-tazobactam is formally approved for complicated urinary tract infection, complicated intra-abdominal infection, and hospital-acquired and ventilator-associated bacterial pneumonia. The clinical and microbiological success is over 70-80% in many series. However, resistant mutants to ceftolozane-tazobactam have been already described. Combination therapies with colistin or meropenem could be among the strategies to avoid the resistance emergence.

Predictors of relaparotomy for persisting intra abdominal infection in secondary peritonitis

Background: Peritonitis is one of the commonest causes of acute abdomen in Ethiopia. One of the causes of high morbidity and mortality is persistent intraabdominal infection. The two essential approaches for managing post-op collection are laparotomy on-demand and planned Relaparotomy. Despite multiple studies, both have comparative mortality. This study aimed to identify clinical variables that are predictive of persistent intraabdominal infection. Methods: A retrospective study was conducted on patients who were operated on from Sept 2018 to April 2020 at two affiliated referral hospitals of AAU, college of Medicine; Yekatit 12 hospital Medical College and Minilik II referral Hospital. All of the patients were cases of secondary peritonitis. Clinical progress of the patients from admission to discharge/death was documented. Multiple preoperative and intraoperative variables were analyzed to develop the predictive clinical model. Results: Out of 172 laparotomy cases for secondary peritonitis, 40 (23.3%) required relaparotomy for postop collection. From Patients who developed postop collection, 45% of them were diagnosed after pus/Gi content leaked through the surgical wound. The mortality rate of patients who develop postop collection and undergone relaparotomy was 27.5 % and 4.5% for those without postop collection. Logistic regression identified 4 variables as having significant predictive value: Duration of illness more than 5 days, Systolic BP 1000 ml, and small bowel as a source of contamination. Overall prediction successes of the above model is 88.4% (sensitivity 53.3%, specificity 96.8%). Conclusion: Management of persistent intra-abdominal infection is challenging. We have identified 4 clinical variables that predict persistent intraabdominal infection requiring relaparotomy. These sets of variables can be a milestone for future validation study before being inserted in today to day clinical practice.

Is percutaneous radiologic gastrostomy safer than percutaneous endoscopic gastrostomy?

Objectives: The objectives of the study were to compare the indications, adverse events, removal rates, and mortality of percutaneous endoscopic gastrostomy (PEG) and percutaneous radiologic gastrostomy (PRG) techniques at our tertiary care institution from 2014 to 2019. Material and Methods: We undertook a 5-year retrospective review of patients who underwent either PEG or PRG at our institution from 2014 to 2019. Common adverse events include tube clogs, leaks, minor bleeds, and wound infections, while more rare major complications include peritonitis, intra-abdominal infection, and major hemorrhage. The procedures were all performed with either conscious sedation or general anesthesia. A total of 789 patients were reviewed, of whom 519 (65.8%) had a PRG and 270 (34.2%) had a PEG. PRGs were more likely to be placed for head-and-neck cancer (P < 0.0001) and amyotrophic lateral sclerosis (P < 0.0001), while PEGs were more likely to be placed for gastric outlet obstruction (GOO) (P <.0001) and malnutrition (P < 0.0001). Results: The rate of major adverse events was similar between the two groups (P = 0.938). GI placed gastrostomy tubes were more likely to have a minor adverse event (P < 0.0001), however, this was secondary to a significant increase in tube clog in the PEG/J group as compared to PEG (P < 0.0001). Conclusion: The decision to place a PEG or PRG should be individualized to the patient’s specific condition and indication. Both procedures have favorable safety profiles, and it is likely that institutional expertise and procedural access will be the primary determinants of the procedural technique chosen for minimally invasive gastrostomy.

413 The Clinical Efficacy of Intra-Operative Peritoneal Fluid Sampling in Abdominal infections

Aim To uncover the practical efficacy of intra-operative peritoneal fluid sampling and the impact on antibiotic prescription and clinical outcomes in patients undergoing emergency surgery due to intra-abdominal infections. Method Our retrospective study included all patients undergoing emergency surgery for intra-abdominal infections at Southend University Hospital over 6 months (January – July 2019). Data was collected from electronic patient records, case notes and microbiology reports and included the following information: patient age demographics; type of infection; peritoneal fluid sampling indication; samples taken; details of swab culture report including organisms grown and antibiotic sensitivity; clinical course and incidence of subsequent intra-abdominal infection to include readmission and/or further procedures; the type, duration and route of antibiotic prescribed and duration of hospital stay. This audit was approved by the Departmental Audit Lead. Results 441 patients undergoing emergency surgery for intra-abdominal infection were identified. After exclusions, intra-operative peritoneal fluid samples were indicated in 77 patients (mean age 39.4 years). Of these only 3 had samples taken (3.9%). The most common organisms isolated were mixed anaerobes followed by Streptococcus angiosus. The most common antibiotic sensitivity was Metronidazole and Penicillin. One readmission occurred due to an intra-abdominal tubo-ovarian abscess. Conclusions The study shows that the current practice in our hospital regarding intra-operative peritoneal fluid sampling in intra-abdominal infections reflects the present widely held attitudes regarding its reduced practical utility. Abandoning routine sampling had no significant impact on the clinical course and may be more cost-effective. The study may help surgeons reflect on changing perspectives on this traditional practice.