Acute Portal Vein, Superior Mesenteric Vein and Splenic Vein Thrombosis Secondary to JAK2 V617 Mutation- A Case Report

Portal vein thrombosis (PVT) is a rare finding which usually occurs in association with local factors such as cirrhosis, malignancy, pancreatitis, intraabdominal infections or systemic hypercoagulable states. It may present acutely as abdominal pain, ascites, fever or exist in a chronic state which is generally asymptomatic and an incidental finding. With advancement in Imaging and laboratory studies, PVT cases are diagnosed more frequently along with its predisposing factors. The invention of JAK2 mutation and it’s addition to the WHO criteria for Myeloproliferative neoplasm (MPN) diagnosis, has increased the number of MPN cases which were previously labelled idiopathic. We present a case of 54 year old female diagnosed with unprovoked PVT with bowel ischemia and JAK 2 mutation positive, managed surgically and with long term anticoagulation.

1274. Activity of Ceftolozane/Tazobactam, Imipenem/Relebactam, and Comparators Against Pseudomonas aeruginosa Isolates from Patients with Bloodstream and Other Infection Types—SMART United States/Canada 2018-2019

Background Ceftolozane/tazobactam (C/T), an antipseudomonal cephalosporin combined with a β-lactamase inhibitor, was approved for treatment of complicated urinary tract (cUTI) and intraabdominal infections (cIAI), and hospital-acquired/ventilator-associated bacterial pneumonia (HAP/VAP). Imipenem/relebactam (IMI/REL) is a combination of imipenem/cilastatin with relebactam, an inhibitor of class A and C β-lactamases. IMI/REL was approved for HAP/VAP and for infections due to aerobic gram-negative organisms in adults with limited treatment options (e.g., cUTI, cIAI). We compared the activity of C/T and IMI/REL against P. aeruginosa from bloodstream infections (BSI) to those from other infection types. Methods As part of the SMART program, 24 hospitals in the US and 8 in Canada each collected up to 250 consecutive gram-negative isolates per year in 2018-2019 from patients with BSI, lower respiratory tract infections (LRTI), IAI, and UTI. A total of 2351 Pa isolates were collected. MICs were determined using CLSI broth microdilution and breakpoints. Results Pa isolates from BSI tended to show higher susceptibility than IAI, UTI, and especially LRTI isolates (Table). Susceptibility to the tested comparator β-lactams was 11-12 percentage points lower among LRTI than BSI isolates, while C/T and IMI/REL susceptibility was only 2-5% lower. Even among BSI isolates, the comparator β-lactams were active against only 75-88% of isolates, while C/T and IMI/REL were active against >95%. Only amikacin showed higher activity. Analyzing coverage by either C/T or IMI/REL, 98.7% of Pa isolates from BSI were susceptible to one or both agents. C/T and IMI/REL maintained activity against 89% and 69% of meropenem-nonsusceptible (MEM-NS) Pa isolates from BSI (n=36), respectively, and 87% and 76% of piperacillin/tazobactam (P/T)-NS Pa (n=38). Results Table Conclusion Even among BSI isolates, which were generally more susceptible than those from other infection types, Pa susceptibility to commonly used β-lactams like MEM and P/T was < 90%, 7-23% lower than C/T and IMI/REL. Given the desirability of β-lactams among clinicians and the >98% coverage by either C/T or IMI/REL of Pa isolates from BSI, both agents represent important options in the treatment of patients with BSI. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Kelly Harris, PharmD, BCPS, Merck & Co. Inc (Employee) Katherine Young, MS, Merck (Employee) Mary Motyl, PhD, Merck & Co., Inc. (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

1080. Relebactam Increases Imipenem Activity Against Imipenem-Nonsusceptible and -Susceptible Pseudomonas aeruginosa and Enterobacterales: Assessment of Isolates from RESTORE-IMI 2

Background Relebactam (REL) inhibits class A and C β-lactamases (BLs) and is approved in the US in the combination imipenem/cilastatin/REL (IMI/REL) for hospital acquired bacterial pneumonia (HABP) and ventilator associated bacterial pneumonia (VABP), and also in patients with limited treatment options for complicated urinary tract infections and complicated intraabdominal infections. The objective of this study was to evaluate the potentiation of imipenem (IMI) by REL in baseline respiratory isolates from the recently completed Phase 3 RESTORE-IMI 2 study that demonstrated efficacy and safety of IMI/REL in the treatment of patients with HABP/VABP. Methods Baseline lower respiratory tract (LRT) isolates were evaluated for IMI MICs in the presence and absence of REL using broth microdilution and CLSI interpretive criteria. All Pseudomonas aeruginosa and Enterobacterales for which IMI/REL is either indicated or the MIC90 is less than or equal to the susceptibility breakpoint were evaluated. Results Summary statistics and the MIC distribution for P. aeruginosa are shown in the figure. For P. aeruginosa, REL reduces the IMI mode MIC of IMI-nonsusceptible (IMI-NS) (MIC >2) isolates ≥8-fold (from 16-32 to 2 µg/mL) and that of IMI-susceptible (IMI-S) (MIC ≤2) isolates ≥2-fold (from 1 to ≤0.5 µg/mL). Among Enterobacterales, the IMI mode MIC of IMI-NS (MIC >1) isolates was reduced ≥4-fold (from 2 to ≤0.5 µg/mL). REL enhanced the activity of IMI among IMI-S isolates (MIC ≤1), most notably observed in Enterobacterales species that produce a chromosomal AmpC, increasing the proportion with MIC ≤0.5 µg/mL from 76% to 98%. MIC Distribution and Summary Statistics of RESTORE IMI-2 Isolates Conclusion Among baseline LRT isolates from RESTORE-IMI 2 the potentiation of IMI by REL results in the restoration of susceptibility among IMI-NS P. aeruginosa and Enterobacterales and enhanced IMI activity among IMI-S isolates. This enhanced activity among IMI-S Enterobacterales is most notable among species with reported chromosomal expression of AmpC. This lowering of IMI MICs upon addition of REL contributes to the high probability of target attainment (≥90%) observed following administration of IMI/REL 1.25g every 6 hours, further supporting the IMI/REL efficacy data observed in RESTORE-IMI 2. Disclosures David W. Hilbert, PhD, Merck (Employee) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Maria C. Losada, BA, Merck (Employee) Pamela Moise, PharmD, Merck (Employee) Luke F. Chen, MBBS MPH MBA FRACP FSHEA FIDSA, Merck (Employee) Katherine Young, MS, Merck (Employee)

1295. Susceptibility to Ceftolozane/Tazobactam and Comparators Among Pseudomonas aeruginosa Isolates Collected from Patients in Hospitals in Latin America – SMART 2017-2019

Background Ceftolozane is a cephalosporin specifically developed to have enhanced antibacterial activity against P. aeruginosa. Combined with tazobactam, it was approved by FDA and EMA for complicated urinary tract and intraabdominal infections, as well as hospital-acquired/ventilator-associated bacterial pneumonia. We evaluated the activity of ceftolozane/tazobactam (C/T) against P. aeruginosa isolates collected as part of the global SMART surveillance program in 10 countries in Latin America. Methods In 2017-2019, 41 clinical labs each collected up to 250 consecutive gram-negative pathogens per year from various infection sources. A total of 21,864 isolates were collected, of which 3,335 (15.3%) were P. aeruginosa. MICs were determined using CLSI broth microdilution and breakpoints. C/T-nonsusceptible (NS) P. aeruginosa isolates were screened for genes encoding β-lactamases. Results The table shows the antimicrobial susceptibility of P. aeruginosa and β-lactam-NS subsets. C/T was active against 85.9% of all collected P. aeruginosa, with lowest activity against isolates collected in Chile and Venezuela, where 28.0% and 23.2% of isolates, respectively, carried carbapenemases, and highest activity against isolates from Ecuador and Guatemala, where 2.2% and 4.2%, respectively, were carbapenemase-positive. Substantial variability in the activity of C/T and comparators was observed among β-lactam-NS subsets. In aggregate, however, C/T remained active against 59.9% of all meropenem-NS P. aeruginosa isolates from Latin America (n=1,101), 57.3% of piperacillin/tazobactam-NS isolates (n=1054), 48.9% of cefepime-NS isolates (n=895), and 50.3% of ceftazidime-NS isolates (n=937). Conversely, other common β-lactams (meropenem, cefepime, ceftazidime, and piperacillin/tazobactam) remained active against 8-38% of these resistant isolates. Results Table Conclusion C/T showed the highest activity against P. aeruginosa among the tested β-lactam antibiotics. While amikacin showed similar or better activity in vitro, its toxicities severely limit its clinical use. Given the desirability of β-lactams among clinicians, C/T represents an important option in the treatment of infections caused by P. aeruginosa in Latin America. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Jacquleine Pavía, MSc, Merck & Co, Inc (Employee) Fakhar Siddiqui, PhD, Merck & Co, Inc (Employee) Katherine Young, MS, Merck (Employee) Mary Motyl, PhD, Merck & Co., Inc. (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

Lesson learned from the pandemic: Isolation and hygiene measures for COVID-19 could reduce the nosocomial infection rates in oncology wards

Introduction It was previously demonstrated that seasonal influenza incidence was significantly decreased during the COVID-19 pandemic, possibly due to respiratory and hygiene precautions. From this point, we hypothesized that the COVID-19 precautions could lead to a decrease in nosocomial infection rates in oncology inpatient wards. Methods We evaluated the nosocomial infection rates in an inpatient palliative oncology ward in the first 3 months of the COVID-19 pandemic in our country and compared this rate with the same time frame of the previous year in our institution. Results The percentage of nosocomial infections complicating the hospitalization episodes were significantly reduced in the first 3 months of the pandemic compared to the previous year (43 vs. 55 nosocomial infection episodes; 18.6% vs. 32.2%, p = 0.002). The decrease in the nosocomial infections was consistent in the different types of infections, namely pneumonia (4.8% vs. 7.6%), urinary tract infection (5.2% vs. 7.6%), bacteremia (5.2% vs. 7%) and intraabdominal infections (2.6% vs. 3.5%). The median monthly disinfectant use was significantly increased to 98 liters (interquartile range: 82 – 114) in 2020 compared to 72 L (interquartile range: 36 – 72) in 2019 ( p = 0.046). Conclusion The continuation of the simple and feasible hygiene and distancing measures for healthcare workers and patient relatives and adaptations for earlier discharge could be beneficial for preventing nosocomial infections in oncology wards. These measures could be implemented routinely even after the COVID-19 pandemic for patient safety, especially in settings with higher nosocomial infection rates like inpatients palliative care units.

Update of pancreas transplantation. Experience of the Hospital Doce de Octubre

Pancreas transplantation (PT) is considered as the only treatment that can convert a diabetic patient in a euglucemic state without the use of insulin or oral antidiabetic drugs. From 1996 to the end of 2016, more than 50,000 PT were performed in USA, and in Spain were performed 1.730 PT during the last 10 years. In this review we will perform an update of PT considering the introduction of several advances in the last years, adding our accumulated experience from the beginning of our program in the year 1995. The first PT was carried out in the Hospital of the University of Minnesota, and from that date several significant improvements have been introduced along the time due to advances in surgical technique in pancreas donors and recipients, perioperative management of patients, and introduction of more potent immunosuppressors able to reduce the rejection rate under 20%. Although PT is a therapy associated with a higher morbidity (pancreas graft thrombosis, systemic and intraabdominal infections, anastomotic leakages, etc.), currently most of the PT teams have obtained a rate of 93% of patient survival at 3-years, and between 78% and 83% of graft survival at 3-years. Additionally, the normal pancreas graft function is associated with an improvement of quality of life and most of complications related to diabetes, without the necessity to treat with antidiabetics drugs or insulin.

Characteristics of Pyogenic Liver Abscess

Objectives: Liver abscess can develop as a complication of hepatobiliary disease or other intraabdominal infections, but more recently it is associated with primary and secondary liver malignancies and their treatment. The goal of this study was to analyze the epidemiology, etiology and clinical characteristics of pyogenic liver abscess in Oman. The intention was to obtain the information needed for the adequate liver abscess empirical treatment. Methods: This retrospective study took place in a tertiary hospital. Consecutive patients treated for the liver abscess during the five years period, from January 2013 until the end of 2017, were enrolled. Their demographic and clinical data were used to study the characteristics of pyogenic liver abscess in Oman. Results: Fifty-three patients with pyogenic liver abscess were enrolled in the study. They were predominantly male and younger than 60 years. Klebsiella pneumoniae was the most usual bacteria causing the liver abscess. Clinical presentation was unspecific and the abdominal pain and high fever were the most usual symptoms. Conclusion: The majority of pyogenic liver abscesses are caused by K. pneumoniae so the empirical treatment should be started with antibiotic directed against it. Further studies are needed to establish the local role of anaerobic bacteria in pyogenic liver abscess as well as to monitor the presence of hypervirulent K. pneumoniae in Oman. Keywords: Pyogenic liver abscess; Etiology; Epidemiology; Klebsiella pneumoniae.

A67 DELAYED PRESENTATION AND SURGICAL MANAGEMENT OF PRIMARY PNEUMOCOCCAL PERITONITIS

Background S. pneumoniae intraabdominal infections are rare in healthy individuals, but the literature reveals a female dominance for primary peritonitis in the early post-partum period. Limited studies exist evaluating the timing of surgical management. Aims We present a case of primary pneumococcal peritonitis in which the presentation and surgical intervention was delayed. Methods A case chart review and literature review was conducted. Results A 41-year-old female with a spontaneous vaginal delivery 4 months prior presented with progressive abdominal pain, distention, and emesis over 10 days. She was septic with a firm, distended abdomen and rebound tenderness. A CT revealed significant panenteritis and ascites. She received intravenous fluids and was empirically started on ceftriaxone, vancomycin and metronidazole. The gastrointestinal virus panel, stool cultures and C. difficile toxin were negative. However, her blood cultures revealed Strep. pneumoniae and the purulent peritoneal fluid contained gram-positive cocci. Despite sensitivity to ceftriaxone, and several paracenteses, her ascites, pain and new fever continued. Twenty-eight days after admission, she underwent a laparoscopic abdominal lysis of adhesions and drainage of three intraabdominal abscess collections. Cultures of the purulent peritoneal fluid were negative. She was stepped down to amoxicillin-clavulanate and discharged six weeks after symptom onset. Despite the development of pneumococcal vaccines, worldwide S. pneumoniae is a common pathogen with high morbidity and mortality. It is a rare cause of intraabdominal infections; however, primary peritonitis has been widely recognized in children. Prior to antibiotics, the mortality of pneumococcal peritonitis was 31.5–100%. Secondary pneumococcal peritonitis is established in adult patients with cirrhosis, nephrotic syndrome and immunocompromised conditions. In healthy individuals, pneumococcal peritonitis often mimics appendicitis and is diagnosed with positive blood cultures. The majority of primary pneumococcal peritonitis cases occur in females, are associated with the early post-partum period (less than two months), IUD placement, and pelvic inflammatory disease. Theories of pathogenesis include direct hematogenous spread or translocation. Transient colonization of the genital tract after IUD placement or during the post-partum period may allow for ascension from the fallopian tubes into the peritoneum. The majority of cases undergo surgery within one week of symptom onset. While it has not been studied in randomized trials, early surgical intervention for source control may decrease morbidity and hospital stay. Conclusions Primary pneumococcal peritonitis has a female predominance and can occur later in the post-partum period than previously reported. Surgery should be considered early to achieve source control and improve patient outcomes. Funding Agencies None

Ceftazidimeavibactam use in children and adolescents

The increasing number of infections caused by multidrug-resistant gram-negative bacteria in children is a serious problem all over the world. Ceftazidim-avibactam is a promising antimicrobial drug recently approved in Russia for use in pediatric practice. This review provides information on the possible use of ceftazidime-avibactam in children with complicated intraabdominal infections (in combination with metronidazole); complicated urinary tract infections, including pyelonephritis; hospital-acquired pneumonia, including ventilator-associated pneumonia; infections caused by aerobic gram-negative microorganisms in patients with limited choice of antibacterial therapy. Based on the data on the in vitro activity of the drug, the results of clinical studies of pharmacokinetics, safety and efficacy of ceftazidimeavibactam for the treatment of infections in children the main clinical cases in which the use of ceftazidimeavibactam in pediatric practice is most justified and appropriate are identified.