Enterobacteriaceae In Patients Research Articles

Gut proinflammatory bacteria is associated with abnormal functional connectivity of hippocampus in unmedicated patients with major depressive disorder

Accumulating evidence has revealed the gut bacteria dysbiosis and brain hippocampal functional and structural alterations in major depressive disorder (MDD). However, the potential relationship between the gut microbiota and hippocampal function alterations in patients with MDD is still very limited. Data of resting-state functional magnetic resonance imaging were acquired from 44 unmedicated MDD patients and 42 demographically matched healthy controls (HCs). Severn pairs of hippocampus subregions (the bilateral cornu ammonis [CA1-CA3], dentate gyrus (DG), entorhinal cortex, hippocampal–amygdaloid transition area, and subiculum) were selected as the seeds in the functional connectivity (FC) analysis. Additionally, fecal samples of participants were collected and 16S rDNA amplicon sequencing was used to identify the altered relative abundance of gut microbiota. Then, association analysis was conducted to investigate the potential relationships between the abnormal hippocampal subregions FC and microbiome features. Also, the altered hippocampal subregion FC values and gut microbiota levels were used as features separately or together in the support vector machine models distinguishing the MDD patients and HCs. Compared with HCs, patients with MDD exhibited increased FC between the left hippocampus (CA2, CA3 and DG) and right hippocampus (CA2 and CA3), and decreased FC between the right hippocampal CA3 and bilateral posterior cingulate cortex. In addition, we found that the level of proinflammatory bacteria (i.e., Enterobacteriaceae) was significantly increased, whereas the level of short-chain fatty acids producing-bacteria (i.e., Prevotellaceae, Agathobacter and Clostridium) were significantly decreased in MDD patients. Furthermore, FC values of the left hippocampal CA3- right hippocampus (CA2 and CA3) was positively correlated with the relative abundance of Enterobacteriaceae in patients with MDD. Moreover, altered hippocampal FC patterns and gut microbiota level were considered in combination, the best discrimination was obtained (AUC = 0.92). These findings may provide insights into the potential role of gut microbiota in the underlying neuropathology of MDD patients.

Risk factors for the colonization of carbapenem-resistant Enterobacteriaceae in patients transferred to a small/medium-size hospital in Korea: a retrospective study

Purpose: This study aimed to identify the colonization rate of carbapenem-resistant Enterobacteriaceae (CRE), the characteristics of CRE isolates, and risk factors for CRE colonization in patients transferred to the general wards of a small/medium-sized hospital.Methods: This retrospective study was conducted on patients who underwent CRE culture tests within 24 hours of admission among patients transferred to a small/medium-sized hospital. Forty-seven patients confirmed as positive for CRE were classified as belonging to the patient group. For the control group, 235 patients (five times the number of the patient group) were matched by sex, age, and diagnosis, and then selected at random. Data were analyzed using descriptive analysis and multiple logistic regression analysis.Results: The CRE colonization rate was 5% (47 out of 933 patients), and Klebsiella pneumoniae (68.0%) was the most common isolate of CRE. The positivity rate of carbapenemase-producing Enterobacteriaceae was 61.7%. The risk factors for CRE colonization included renal disease (odds ratio [OR]=4.93; 95% confidence interval [CI], 1.49-16.31), heart disease (OR=3.86; 95% CI, 1.35-11.01), indwelling urinary catheters (OR=4.43; 95% CI, 1.59-12.36), and cephalosporin antibiotic use (OR=8.57; 95% CI, 1.23-59.60). Conclusion: Having a comorbid renal or cardiac disease, an indwelling urinary catheter, or a history of exposure to cephalosporin antibiotics could be classified as risk factors for CRE colonization in patients transferred to small and medium-size hospitals. It is necessary to perform active infection control through proactive CRE culture testing of patients with risk factors.

Risk factors and molecular epidemiology of fecal carriage of carbapenem resistant Enterobacteriaceae in patients with liver disease

BackgroundCarbapenem resistant Enterobacteriaceae (CRE) colonization is a risk factor for CRE infection. CRE infection results in an increase in mortality in patients with cirrhosis. However, minimal data regarding the prevalence and the risk factors of CRE colonization in patients with liver disease yet without liver transplantation are available. The present study aimed to investigate the prevalence, risk factors and molecular epidemiology characteristics of CRE fecal carriage among patients with liver disease.MethodsStool specimens from 574 adult inpatients with liver disease were collected from December 2020 to April 2021. CRE were screened using selective chromogenic agar medium and identified by the Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS). Antimicrobial susceptibility was determined using the broth microdilution method. Carbapenemase genes were characterized by polymerase chain reaction (PCR) and DNA sequencing. Multilocus sequence typing (MLST) was performed for Carbapenem Resistant Klebsiella pneumoniae (CR-KPN) isolates and Carbapenem Resistant Escherichia Coli (CR-ECO) isolates.ResultsThe total number of stool specimens (732) were collected from 574 patients with liver disease. 43 non-duplicated CRE strains were isolated from 39 patients with a carriage rate of 6.79% (39/574). The carriage rate was 15.60% (17/109) in patients with acute-on-chronic liver failure (ACLF). Multivariate analysis indicated that ACLF (P = 0.018), the history of pulmonary infection within past 3 months (P = 0.001) and the use of third generation cephalosporin/β-lactamases inhibitor within past 3 months (P = 0.000) were independent risk factors of CRE colonization in patients with liver disease. Klebsiella Pnuemoniae (KPN) (51.28%) and Escherichia coli (ECO) (30.77%) were main strains in these patients. All CRE strains showed high resistance to most antimicrobials except for polymyxin B and tigecycline. Most (83.72%, 36/43) of the CRE carried carbapenemase genes. blaKPC-2 was the major carbapenemase gene. The molecular epidemiology of KPN were dominated by ST11, while the STs of ECO were scattered.ConclusionsThe present study revealed that CRE fecal carriage rates were higher in patients with ACLF than in patients without liver failure. ACLF, the history of pulmonary infection within past 3 months and the use of third generation cephalosporin/β-lactamases inhibitor within past 3 months were independent risk factors of CRE colonization in patients with liver disease. Regular CRE screening for hospitalized patients with liver disease should be conducted to limit the spread of CRE strain.

Risk factors for extended-spectrum beta-lactamase- and carbapenem- resistant Enterobacteriaceae in patients with urinary tract infection from a tertiary care hospital

Background: Urinary tract infection (UTI) is a common health problem in both community and nosocomial settings. However, the predisposing factors which are responsible for production of extended spectrum beta-lactamase (ESBL) and carbapenem-resistant Enterobacteriaceae makes the treatment option narrow and cause multidrug resistance. Aim and Objectives: This study demonstrate various risk factors associated with multidrug resistance in Enterobacteriaceae from UTI at tertiary care center in Gujarat. Material and Methods: A retrospective observational study was conducted at a tertiary-care hospital. Urine samples were received from various departments and outpatient department (OPD). Organisms from Enterobacteriaceae group were isolated and identified by various biochemical methods. ESBL and Carbapenemase producing organisms were then processed for Antibiotic susceptibility test as per CLSI guideline. Results: A total of 196 Enterobacteriaceae organisms were isolated from processed urine samples of tertiary care Hospitals. The most prevalent in people aged 45–65 years (36%) followed by those aged 17–30 (22%) years. UTI due to ESBL and Carbapenemase producer are more isolated in female (28%, 11%) as compare to male (16%, 6%). Indoor patients had higher prevalence of ESBL (29%) and carbapenemases (10%) isolation compare to OPD patient (ESBL-15%, Carbapenemases-7%) and among them most common ward was medicine department. The most common predisposing factor was catheterization followed by diabetes mellitus and obstructive uropathy. Discussion: High prevalence of ESBL and Carbapenemase producing Enterobacteriaceae is found in Indoor patients than OPD patients. Most of these patients are from Medicine department. Catheterization is the most common risk factor associated with ESBL and carbapenemase producing organism.

The threat of carbapenem resistance in Eastern Europe in patients with decompensated cirrhosis admitted to intensive care unit.

Multidrug-resistant organisms are an increasing concern in patients with decompensated cirrhosis. We aimed to evaluate the prevalence of infections with carbapenem-resistant Enterobacteriaceae in patients with decompensated cirrhosis. Patients with decompensated cirrhosis admitted to ICU were included. The isolated Enterobacteriaceae strains were tested for carbapenemase-producing genes using the Roche LightMix® Modular VIM/IMP/NDM/GES/KPC/OXA48-carbapenemase detection kit. 48 culture-positive infections were registered in 75 patients with acutely decompensated cirrhosis. Thirty patients contracted a second infection. 46% of bacteria isolated at admission and 60% of bacteria responsible for infections identified during ICU-stay were multiresistant. ESBL+ Enterobacteriaceae were predominant at admission, while carbapenem-resistance was dominant in both Enterobacteriaceae and Non-Fermenting-Gram-Negative Bacteria responsible for infections diagnosed during hospitalisation. OXA 48 or KPC type carbapenemases were present in 30% of the analyzed Enterobacteriaceae and in 40% of the phenotypically carbapenem-resistant Klebsiella pneumoniae strains. The length of ICU stay was a risk-factor for a second infection (p=0.04). Previous carbapenem usage was associated with occurence of infections with carbapenem-resistant Gram-negative bacteria during hospitalization (p=0.03). The prevalence of infections with carbapenem-resistant Enterobacteriaceae is high in patients with decompensated cirrhosis admitted to ICU. Carbapenemase-producing genes in Enterobacteriaceae in our center are blaOXA-48 and blaKPC.

Adipose Tissue, Bile Acids, and Gut Microbiome Species Associated With Gallstones After Bariatric Surgery

Several risk factors are associated with gallstone disease after bariatric surgery, but the underlying pathophysiological mechanisms of gallstone formation are unclear. We hypothesize that gallstone formation after bariatric surgery is induced by different pathways compared with gallstone formation in the general population, since postoperative formation occurs rapidly in patients who did not develop gallstones in preceding years. To identify both pathophysiological and potentially protective mechanisms against postoperative gallstone formation, we compared the preoperative fasting metabolome, fecal microbiome, and liver and adipose tissue transcriptome obtained before or during bariatric surgery of obese patients with and without postoperative gallstones. In total, 88 patients were selected from the BARIA longitudinal cohort study. Within this group, 32 patients had postoperative gallstones within 2 years. Gut microbiota metagenomic analyses showed group differences in abundance of 41 bacterial species, particularly abundance of Lactobacillaceae and Enterobacteriaceae in patients without gallstones. Subcutaneous adipose tissue transcriptomic analyses revealed four genes that were suppressed in gallstone patients compared with patients without gallstones. These baseline gene expression and gut microbiota composition differences might relate to protective mechanisms against gallstone formation after bariatric surgery. Moreover, baseline fasting blood samples of patients with postoperative gallstones showed increased levels of several bile acids. Overall, we revealed different genes and bacteria associated with gallstones than those previously reported in the general population, supporting the hypothesis that gallstone formation after bariatric surgery follows a different trajectory. Further research is necessary to confirm the involvement of the bile acids, adipose tissue activity, and microbial species observed here.

Characteristics of Bacterial Colonization and Urinary Tract Infection after Indwelling of Double-J ureteral Stent and Percutaneous Nephrostomy Tube.

Introduction:Infections associated with catheter in the upper urinary tract (CUUT), which include the double-J stent and the percutaneous nephrostomy (PCN) tube, get particularly infected in patients with specific risk factors for developing an infection.Methods:A retrospective observational study was carried out by compiling data from the hospital information system of a tertiary care center from 2019 to 2021 to evaluate infections in patients with catheter in the upper urinary tract.Result:A total of 200 pus samples of double-J stent (96 pus samples) and PCN tube (104 pus samples) were included in our study. Among patients with nephrostomy tube, the most frequently isolated microorganisms were Escherichia coli, followed by Pseudomonas spp. In those with a double-J stent, Pseudomonas aeruginosa, followed by E. coli were the most commonly isolated microorganisms. We found 55.72% of cases of Enterobacteriaceae-producing carbapenemases in patients with a percutaneous catheter. 66.07% of Enterobacteriaceae in patients with double-J and nephrostomy stents are extended-spectrum beta-lactamase-producing bacteria. The percentage of cultures with multiple-drug resistance (MDR) microorganisms was 38.54% in patients with double-J stents and 37.75% in nephrostomy tubes. The presence of prior urinary tract infection (P = 0.010), presence of urinary catheter before admission (P = 0.005), increased time with single urinary catheter in-situ (P < 0.001), and increased length of hospital stay (P = 0.036) were risk factors for isolation of MDR microorganisms.Conclusion:Pseudomonas spp. and Pseudomonas aeruginosa are commonly infecting both the CUUT. E. coli infections are more commonly infecting the nephrostomy tubes. MDR microorganisms are frequent, mainly in patients with prior urinary tract infection, presence of urinary catheter before admission, and prolonged use of a single catheter.

Molecular Characterization of Clinical Carbapenem-Resistant Enterobacteriaceae Isolates from Sétif, Algeria

This study aimed to determine the incidence and the molecular mechanisms of carbapenem-resistant Enterobacteriaceae in patients from the Sétif University Hospital, Algeria. Nonduplicate clinical bacterial isolates recovered from patients attending the University Hospital of Sétif were collected between April and October 2018. Species identification was performed by MALDI-TOF/MS (matrix-assisted laser desorption ionization-time of flight mass spectrometry) method. The susceptibility of the isolates to carbapenems was determined using the disc diffusion method. The carbapenem resistant isolates were screened for the presence of common carbapenemase genes (blaKPC, blaOXA-48, blaVIM, blaIMP, and blaNDM) and extended-spectrum β-lactamase (blaCTX, blaTEM, and blaSHV) using PCR and sequencing technique. A total of 123 nonrepetitive Enterobacteriaceae isolates were obtained. Klebsiella pneumoniae (n = 52/42.28%), Escherichia coli (n = 24/19.51%), and Enterobacter cloacae (n = 19/15.45%) were the most prevalent species. The Carba-NP test showed that 6 out of 123 isolates carried carbapenemase enzymes. OXA-48 was found in five isolates (four K. pneumoniae and one E. coli) and NDM-5 in one E. cloacae isolate. We reported for the first time in Algeria the presence of NDM-5 carbapenemase enzyme in a clinical E. cloacae isolate.

Detection of blaTEM, blaSHV, and blaCTX-M genes among the Extended-Spectrum β-Lactamases (ESβLs) producing Enterobacteriaceae isolated from hospital-acquired infections and community in Egypt.

Abstract: Background: The spread of (ESβLs) representing a serious problem and threatening the ability to treat an infection. This study aimed to investigate ESβLs-producing Enterobacteriaceae sp. isolated from patients and healthy individuals and detect the resistant genes blaTEM, blaSHV, and blaCTX-M. Methods Two hundred bacterial isolates were recovered from patients and healthy individuals rectal swab samples. These isolates were screened for producing ESβLs and identified using both standard bacteriological methods and VITEK2 compact system). The antibiotics resistance of Enterobacteriaceae was assessed by the disk diffusion method and detection of blaTEM, blaSHV, and blaCTX-M genes by multiplex PCR. Results Two hundred Enterobacteriaceae screening for-producing ESβLs showed that 56% (112/200) produce ESβLs. One hundred and twelve ESβLs-Enterobacteriaceae identified as following, Klebsiella pneumonia 51.73% (58/112), Escherichia coli and 46.40% (52/112), and Enterobacter cloacae 1.80% (2/112). The antibiotic resistance patterns of Enterobacteriaceae showed high resistance to ciprofloxacin, levofloxacin, and amikacin with the ratio of (71.76%), (60.72%) and (60.72%), respectively. Furthermore, ESβLs Enterobacteriaceae harbored genes blaCTX-M (78.6%), blaTEM (73.2%) and blaSHV (68.75%). The blaTEM was found predominate gene in E. coli isolates 80.8%, while blaCTX-M in Klebsiella pneumonia 81%. Conclusion: The present study showed a significant distribution of multidrug-resistant ESβLs-producing Enterobacteriaceae in patients in hospital- and community-acquired rectal infection. ESβLs-producing Enterobacteriaceae species harboring co-existence resistant genes. .

The Influence of Antibiotics Usage on Extended-spectrum β-lactamase-producing Enterobacter Colonization among Intensive Care Unit Patients

BACKGROUND: The prevalence of extended-spectrum beta-lactamases (ESBLs)-producing Enterobacteriaceae has increased throughout the world and is a major cause of treatment failure in intensive care unit (ICU). ESBL-producing Enterobacteriaceae exhibit resistance to cephalosporins which is one of the most commonly used and effective group of antibiotics.&#x0D; AIM: The goal of this study was to identify the variables that influence the colonization of Enterobacteriaceae in patients treated at ICU.&#x0D; PATIENTS AND METHODS: A prospective study involving randomized 70 patients was conducted at ICU of Sanglah General Hospital from October 2018 to March 2019. Specimens were obtained from rectal swabs on admission to and discharged from ICU. Initial bivariate analysis was conducted using Pearson’s Chi-square and considered significant if p &lt;0.05. Adjusted relative risk ratio (RR) was used to estimate the influence of the variables to ESBL colonization.&#x0D; RESULTS: Respiratory system dysfunction (p = 0.012, RR = 2.828) and antibiotic prescription before ICU admission (p &lt; 0.001) influence ESBL-producing Enterobacteriaceae colonization on patient who was admitted to ICU. On discharged from ICU, ESBL colonization was associated to respiratory system dysfunction (p = 0.008, RR = 1.987), third-generation cephalosporin usage (p = 0.009, RR = 2.909), cefoperazone prescription (p &lt; 0.001, RR = 8.471), ceftriaxone prescription (p = 0.007, RR = 6.316), and antibiotics usage duration ≥3 days (p &lt; 0.001, RR = 7.071). The logistic regression results on influence of antibiotics usage and respiratory system dysfunction to ESBL colonization rate shows that both variables are independent risk factor to EBLS colonization both on admitted to and discharged from ICU.&#x0D; CONCLUSION: The antibiotics usage and respiratory system dysfunction are independent risk factors to EBLS colonization in ICU patients.

Current treatment options for infections caused by carbapenem-resistant Enterobacteriaceae in patients with hematological malignancies

Infections are a common complication in patients with hematological malignancies, especially during neutropenia. Recently, an increase in multidrug-resistant gram-negative pathogens has been observed in the etiology of infectious complications, including carbapenem-resistant Enterobacteriaceae. However, therapeutic options for treatment of these infections are limited. The review represents treatment options for infections caused by carbapenem-resistant Enterobacteriaceae, including the use of reserve drugs such as polymyxin, carbapenems, tigecycline, as well as a new antibiotic – ceftazidime-avibactam, which contains a new β-lactamase inhibitor with unique properties.

Active surveillance of the spread of mcr-1-positive E coli

Active surveillance of the spread of mcr-1-positive E coli

Different screening frequencies of carbapenem-resistant Enterobacteriaceae in patients undergoing hematopoietic stem cell transplantation: which one is better?

BackgroundA consensus has been reached that carbapenem-resistant Enterobacteriaceae (CRE) screening in immunosuppressed individuals can reduce the incidence of CRE bloodstream infection (BSI).MethodsWe retrospectively studied the clinical data of 395 consecutive HSCT patients from September 2017 to April 2019. From September 2017 to June 2018 (period 1), 200 patients received single CRE screening before transplantation. From July 2018 to April 2019 (period 2), 195 patients received continuous weekly CRE screening after admission. For patients colonized with CRE, targeted managements were received: (1) contact precautions and (2) preemptive CRE-targeted treatment if necessary.ResultsDuring period 1, 3 patients with CRE colonization were detected (1.5%). The CRE BSI rate was 2.0% (4 patients), and the related 30-day mortality was 50.0% (2 out of 4 patients). During period 2, 21 patients with CRE colonization were detected, and the detection rate was significantly higher than that in period 1 (P < 0.001). Of the 21 colonized patients, 4 (19.0%) patients were identified as positive for CRE at the first screening, 5 (23.8%) were identified at the second screening, and the remaining 12 (57.1%) were identified at the third or later screening. The CRE BSI rate decreased to 0.5% (1/195), and there were no CRE-related death.Fifteen colonized patients developed neutropenic fever. Thirteen colonizers were preemptively treated with tigecycline within 24 h of fever onset, and they achieved rapid temperature control. One colonizer received tigecycline later than 48 h after fever onset and ultimately survived due to the addition of polymyxin. The other received tigecycline later than 72 h after fever onset and died of septic shock.ConclusionThe increase in screening frequency contributed to the detection of patients with CRE colonization. Targeted managements for these colonized patients may contribute to reducing the incidence and mortality of CRE BSI, therefore improving the prognosis of patients.

Quantifying risk of disease due to extended-spectrum β-lactamase producing Enterobacteriaceae in patients who are colonized at ICU admission

BackgroundThe prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) has globally increased and spread to the community. No clinical score is available to select carriers in whom these organisms can be empirically targeted at ICU admission. MethodsWe prospectively assessed between 2009 and 2017 the prevalence of ESBL-PE infection in carriers at ICU admission. A logistic regression was used to determine independent risk factors associated with ESBL-PE infection, and to build a clinical risk score. ResultsOf the 8,061 admissions over the study 7-year period, 745 (9%) patients were ESBL-PE carriers at admission, of whom 395 had infections at ICU admission including 59 (15%) who had culture-proven ESBL-PE related infection. By multivariable analysis, age >60 years, cirrhosis, being on broad-spectrum antibiotics within the past three months, urinary or intra-abdominal source of infection, and the absence of chronic pulmonary disease, were the five independent factors associated with ESBL-PE infection in carriers. A clinical risk score ranging from 0 to 7 was built based on these variables, with an area under the receiver operating characteristic curve (ROC) of 0.82 (95% CI 0.78–0.86); p <0.001. The prevalence of ESBL-PE infection for clinical risk scores of 0–1, 2–3, 4–5, or 6–7 was 0%, 4%, 26%, and 49%, respectively. The negative predictive value when Mondor ESBL risk score is <4 was 97%. ConclusionESBL-PE related infection was not common in carriers at ICU admission. A clinical risk score may spare ESBL-PE carriers with lower risk of ESBL-PE infection at ICU admission unnecessary empiric carbapenem therapy.

Carbapenem-resistant Enterobacteriaceae in patients with bacteraemia at tertiary hospitals in South Africa, 2015 to 2018.

Enhanced surveillance for CREs was established at national sentinel sites in South Africa. We aimed to apply an epidemiological and microbiological approach to characterise CREs and to assess trends in antimicrobial resistance from patients admitted to tertiary academic hospitals. A retrospective analysis was conducted on patients of all ages with CRE bacteraemia admitted at any one of 12 tertiary academic hospitals in four provinces (Gauteng, KwaZulu-Natal, Western Cape and Free State) in South Africa. The study period was from July 2015 to December 2018. A case of CRE bacteraemia was defined as a patient admitted to one of the selected tertiary hospitals where any of the Enterobacteriaceae was isolated from a blood culture, and was resistant to the carbapenems (ertapenem, meropenem, imipenem and/or doripenem) or had a positive result for the Modified Hodge Test (MHT) according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. A positive blood culture result obtained after 21days of the last blood culture result was regarded as a new case. To distinguish hospital-acquired (HA) from the community-acquired (CA) bacteraemia, the following definitions were applied: the HA CRE bacteraemia was defined as a patient with CRE isolated from blood culture ≥ 72h of hospital admission or with any prior healthcare contact, within 1year prior to the current episode or referral from a healthcare facility where the patient was admitted before the current hospital. A case of the CA CRE bacteraemia was defined as a patient with CRE isolated from blood culture < 72h of hospital admission and with no prior healthcare contact. The majority of carbapenem-resistant Enterobacteriaceae (CRE) (70%) were hospital-acquired (HA) with Klebsiella pneumoniae being the predominant species (78%). In-hospital mortality rate was 38%. The commonest carbapenemase genes were bla-OXA-48 (52%) and bla-NDM (34%). The high mortality rate related to bacteraemia with CRE and the fact that most were hospital-acquired infections highlights the need to control the spread of these drug-resistant bacteria. Replacement with OXA-48 is the striking finding from this surveillance analysis. Infection control and antibiotic stewardship play important roles in decreasing the spread of resistance.

P568 An open-label, multicenter, phase ib, pharmacokinetic (pk) and safety study of a fimh blocker, Sibofimloc (TAK-018/EB8018), in patients with Crohn’s disease (CD)

Abstract Background Sibofimloc (EB8018/TAK-018) is a gut-restricted orally administered, first-in-class, FimH blocker that targets FimH, a TLR4 receptor, expressed on E. coli and other Enterobacteriaceae in patients with CD. In a previous study, sibofimloc up to 1500 mg twice daily was well tolerated when administered to healthy subjects over a 14-day period. PK results indicated that sibofimloc was detectable in plasma at a very low level. The current study investigated the PK, safety, and pharmacodynamic effects of sibofimloc following 13 days of 1500 mg twice daily oral administration in patients with CD. Objectives of this study were to determine the PK (primary) and safety profiles, effects on inflammatory biomarkers, gut microbiome and on stool frequency and pain score. Methods We conducted a multicenter open-label study to enrol 8 adult patients with active CD (faecal calprotectin (FCP) ≥150 µg/g and/or ulcers at colonoscopy). Pregnant women were excluded. This study was divided into two parts. 1)Two patients received a single dose of 3000 mg sibofimloc followed, after a wash-out period, by a 13 day-period with1500 mg twice daily. 2)After review of data from these two patients, the 6 remaining patients received 1500 mg sibofimloc twice daily for a 13 day period. Results Cmax values for the 2 initial patients (after single dose 3000 mg sibofimloc) were 51.3 and 348 ng/ml respectively and allowed part 2 of the study. The main safety and PK data of an interim analysis after the first 4 patients had been treated with sibofimloc 1500 mg twice daily are presented in the table. In a previous study in 7 healthy subjects, after 14 days sibofimloc 1500 mg twice daily, median Cmax[min-max] at Day14 was 49[19.2–86.6]ng/ml. Conclusion These preliminary data confirmed that sibofimloc was well tolerated. In the small subset of patients analyzed, there was a slightly higher plasma exposure and interpatient variability compared with what has been seen earlier in healthy subjects. The safety and PK data allowed the continuation of the clinical development program with the initiation of a phase 2 trial for postoperative maintenance in patients with CD.

Emergence of ST11-K47 and ST11-K64 hypervirulent carbapenem-resistant Klebsiella pneumoniae in bacterial liver abscesses from China: a molecular, biological, and epidemiological study

ABSTRACT Background: Multidrug-resistant bacteria, especially those with high virulence, are an emerging problem in clinical settings. Methods: We conducted a multicentre epidemiological and comparative genomic analysis on the evolution, virulence and antimicrobial resistance of carbapenem-resistant Enterobacteriaceae in patients with bacterial liver abscesses from 2012 to 2016. Results: A total of 477 bacterial isolates were collected. Enterobacteriaceae were the main pathogen (89.3%) with K. pneumoniae (52.4%) predominating followed by Escherichia coli (26.8%). All CRKps (3.2%) were of sequence type (ST) 11 and serotypes K47 or K64, and simultaneously possessed acquired bla KPC-2/bla KPC-5 and bla CTX-M-65 together with the multidrug transporter EmrE. Seven Hv-CRKps (five ST11-K47, two ST11-K64) were confirmed by bacteriological test, neutrophil killing assay and Galleria mellonella infection model. Genomic analysis indicated that the emergence of one ST11-K64 Hv-CRKp strain was related to the acquisition of rmpA/rmpA2 genes and siderophore gene clusters, while ST11-K47 Hv-CRKp lacked these traditional virulence genes. Further complete genome analysis of one ST11-K47 Hv-CRKp strain, R16, showed that it acquired a rare plasmid (pR16-Hv-CRKp1) carrying bla KPC-2, bla SHV-12, bla TEM-1, bla CTX-M-65, rmtB and a predicted virulence gene R16_5486 simultaneously. Conclusion: The emergence of the ST11-K47/K64 Hv-CRKps, which are simultaneously multidrug-resistant and hypervirulent, requires urgent control measures to be implemented.

Positivity of Carbapenemase-producing Enterobacteriaceae in Patients Following Exposure within Long-term Care Facilities in Seoul, Korea.

BackgroundCarbapenemase-producing Enterobacteriaceae (CPE) are emerging as a worldwide threat. Long-term care facilities (LTCFs) are considered a reservoir for CPE and play a central role in transmission to acute care hospitals. We investigated the CPE positivity in patients exposed to CPE in LTCFs. Furthermore, we analyzed the CPE positivity rates in the environment exposed to CPE.MethodsWe collected rectal swab specimens from patients residing in LTCFs who were exposed to CPE. Environmental sampling was performed by infection control practitioners from sites classified as patient private space, common space in the patient room, common space other than patient rooms, and nursing station. Each sample was cultured on a Chrom Klebsiella pneumoniae carbapenemase (KPC) agar for CPE screening. The positive isolates were subjected to a polymerase chain reaction to identify the presence of blaKPC, blaVIM, blaIMP, blaOXA-48, and blaNDM and determine CPE genotype.ResultsFrom 65 index cases, a total of 24 hospitals and 481 patients were enrolled; 414 patients who had resided in the same patient room as a patient with confirmed CPE and 67 patients who were newly admitted to that patient room. A total of 117 (24.3%) patients were positive for CPE among which 93 (22.5%, 93/414) were already admitted patients and 24 (35.8%, 24/67) were newly admitted patients. A total of 163 CPEs were detected and K. pneumoniae (n = 104, 63.8%) was the most common bacteria followed by Escherichia coli (n = 43, 26.4%) and Citrobacter koseri (n = 11, 6.7%). Environmental sampling was performed in 24 hospitals and 604 sites. A total of 12 sites (2.0%) were positive for CPE and sink in the nursing station (n = 6, 4.2%) was the most contaminated space.ConclusionCPE colonization rates in patients exposed to CPE in LTCFs were higher than those found in acute care hospitals. Proper infection control measures for detecting and reducing CPE colonization in patients residing in LTCFs are required. Newly admitted patients could also be carriers; therefore, infection control for newly admitted patients also needs to be thorough.

Riboflavin Supplementation in Patients with Crohn’s Disease [the RISE-UP study

Background and AimsCrohn’s disease [CD] is characterised by chronic intestinal inflammation and dysbiosis in the gut. Riboflavin [vitamin B2] has anti-inflammatory, antioxidant and microbiome-modulatory properties. Here, we analysed the effect of riboflavin on oxidative stress, markers of inflammation, clinical symptoms, and faecal microbiome in patients with CD.MethodsIn this prospective clinical intervention study, patients received 100 mg riboflavin [DSM, Nutritional Products Ltd] daily for 3 weeks. Clinical disease activity [Harvey-Bradshaw Index: HBI], serum biomarkers of inflammation and redox status [plasma free thiols], and faecal microbiome taxonomical composition and functionality [fluorescent in situ hybridisation: FISH; and metagenomic shotgun sequencing: MGS], were analysed before and after riboflavin intervention.ResultsIn total, 70 patients with CD with varying disease activity were included. Riboflavin supplementation significantly decreased serum levels of inflammatory markers. In patients with low faecal calprotectin [FC] levels, IL-2 decreased, and in patients with high FC levels, C-reactive protein [CRP] was reduced and free thiols significantly increased after supplementation. Moreover, HBI was significantly decreased by riboflavin supplementation. Riboflavin supplementation led to decreased Enterobacteriaceae in patients with low FC levels as determined by FISH; however, MGS analysis showed no effects on diversity, taxonomy, or metabolic pathways of the faecal microbiome.ConclusionsThree weeks of riboflavin supplementation resulted in a reduction in systemic oxidative stress, mixed anti-inflammatory effects, and a reduction in clinical symptoms [HBI]. FISH analysis showed decreased Enterobacteriaceae in patients with CD with low FC levels, though this was not observed in MGS analysis. Our data demonstrate that riboflavin supplementation has a number of anti-inflammatory and anti-oxidant effects in CD.

535. Multicenter Study of the Prevalence of Rectal Colonization by Carbapenem-Resistant Enterobacteriaceae in Patients Admitted to the Intensive Care Units of 7 Major Hospitals in Kuwait

BackgroundThe emergence of carbapenem-resistant Enterobacteriaceae (CRE) has become an important epidemiological change in infectious diseases in the last 10 years. The gut is an important reservoir for these isolates thereby creating an opportunity for dissemination in a hospital setting especially the intensive care units (ICUs). The objective of this study was to investigate the colonization rates of patients, by CRE, admitted to the ICUs of 7 teaching hospitals.MethodsRectal swabs were collected during July 2017 to November 2018 from all patients on the day of ICU admission and 1 week after in each hospital. The samples were screened by direct plating on MacConkey agar containing 10-μg meropenem. Bacterial species identification was performed using the VITEK-2 system. The minimum inhibitory concentrations (MICs) of 14 antibiotics were determined by using Etest. Genes encoding carbapenem resistance was detected by PCR and sequencing. Their clonal relationship was determined by pulsed-field gel electrophoresis (PFGE).ResultsA total of 2580 Enterobacteriaceae were isolated from all patients. Seventy-four (2.9%) were confirmed as CRE most of which were from patients in Adan (AH: 36.5%) and Mubarak (MH: 46%) hospitals. Sixty (81.1%) harbored one or more of the tested carbapenemases genes. Forty-six (62.2%) carried blaOXA-181, 9 (12.2%) blaOXA-48, one blaKPC-2, while 14 (18.9%) carried 2 genes. Combinations of blaKPC-2 and blaOXA-181 genes were found in 5 (6.8%), blaVIM-1 and blaOXA-181 in 4 (5.4%), blaNDM-5 and blaOXA-181 in 3 (4.1%) and blaNDM-1 and blaOXA-181 in 2 (3.3%). The XbaI PFGE profile-based Dendrogram, at 85% similarity criterion, resolved 7 pulsotypes among isolates carrying blaOXA-181 in AH and MH designated A, B, C, D, E, F, and G. Further analysis revealed that 7 subpulsotypes A1, A2, A5, A6, C1, C2, and E1 were from unit D in the medical ICU of MH and A3, A4, B1, B3, D1, D2, D3, D4, F1, F2, F3, G1, and G2 were from surgical/medical ICUs in AH. 100% similarity was demonstrated among 8 isolates from AH and 2 from MH.ConclusionThe prevalence of rectal colonization by CRE in the ICU patients was lower than expected. Detection of blaOXA-181 variety and blaNDM-5 is new to the milieu of genes so far described in isolates from Kuwait.Disclosures All authors: No reported disclosures.