Carbapenem-resistant Enterobacteriaceae Carriage Research Articles

2076. Intestinal colonization with multidrug-resistant organisms, horizontal transmission and risk for bloodstream infection

Abstract Background The association between rectal colonization and subsequent bloodstream infections (BSI) by multidrug-resistant organisms (MDROs) remains to be clarified. We aimed to investigate the relative risk of BSI in rectal carriers of MDROs and in the case of carbapenem-resistant Enterobacteriaceae (CRE), whether BSI was due to the patient’s own colonizing strain. Methods We retrospectively included all adult inpatients hospitalized from Jan 2019 to Dec 2022, in ICUs or medical wards of 3 Greek hospitals (Athens: “Attikon” Hospital, Piraeus: Tzaneio Hospital, Thessaloniki: AHEPA Hospital), who were screened for intestinal MDRO carriage at admission and weekly. Screening was performed by selective media and immunochromatography for the carbapenemase in CRE. Patients were followed up for BSI by the same colonizing organism; relative risk (95% CI) was estimated after adjustment for ICU hospitalization and age. MDROs included CRE, carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA) and vancomycin-resistant enterococci (VRE). The CRE-colonizers and BSI-pathogens were analyzed for carbapenemase type to identify potential similarities. Results Of 4,427 patients screened, 1,321 (29.8%) were colonized by CRE, 1,255 (28.3%) with CRAB, 252 (5.7%) with CRPA and 859 (27.9% of 3,082 patients tested) with VRE. Of those, 207 (15.7%), 247 (19.7%), 23 (9.1%) and 30 (3.5%) subsequently developed CRE-BSI, CRAB-BSI, CRPA-BSI and VRE-BSI, respectively. Intestinal CRE colonization was associated with 4-fold higher risk of subsequent CRE-BSI, after adjusted for ICU stay and age [RR (95%CI): 4.1 (3.2, 5.2)]. The respective relative risk (95%CI) for BSI in patients with colonization by CRAB, CRPA and VRE were 2.3 (1.9, 2.8), 8.2 (5.1, 13.4) and 2.1 (1.3, 3.4). To evaluate possible horizontal transmission, 286 paired CRE strains from 143 patients were analyzed; in 111 (77.6%), both colonizers and BSI pathogens belonged to the same bacterial species and carried the same carbapenemase type.Table 1:Rectal colonization with MDROs and the risk for BSI from the same pathogenTable 2:Carbapenemase types in rectal carriers of CRE who developed subsequent BSI with the same pathogen Conclusion Intestinal colonization by MDROs was associated with increased risk of BSI by the colonizing bacteria. Clinicians should evaluate this information for empiric treatment, while genome-wide data are needed to substantiate horizontal transmission. Disclosures All Authors: No reported disclosures

Asymptomatic gastrointestinal carriage of multidrug-resistant carbapenemase-producing Enterobacteriaceae among children under five years in a Kenyan hospital

ObjectivesAsymptomatic gastrointestinal carriage of carbapenem-resistant Enterobacteriaceae (CRE) is a threat to global health in developing countries with inadequate safe drinking water, poor hygiene, and weak antimicrobial stewardship; however, epidemiological data to guide CRE infection prevention and control is limited in these settings. We assessed asymptomatic CRE and carbapenem-producing Enterobacteriaceae (CPE) fecal carriage rates and associated risk factors among hospitalized children aged under 5 years. MethodsWe adopted a cross-sectional study at Mama Lucy Kibaki Hospital in Nairobi-City County, Kenya, between June and September 2022. We collected demographic and clinical characteristics using a structured questionnaire and clinical reports and analyzed stool/rectal swab samples by standard and automated bacteriological methods. ResultsAsymptomatic CRE and CPE fecal carriage rate was 2.25% (6/267), with six isolates recovered, predominated by Escherichia coli (33.33%) and Enterobacter cloacae subsp dissolvens (33.33%). Third-generation cephalosporin and ciprofloxacin resistance were highest in Citrobacter farmer and E. cloacae subsp cloacae. All CRE and CPE were multidrug-resistant, and except E. cloacae subsp cloacae, were 100% colistin-resistant. ConclusionsAsymptomatic gastrointestinal carriage of multidrug-resistant-CRE among hospitalized children under 5 years, presents a substantial public health threat. This calls for continuous surveillance including molecular characterization of isolates, to inform infection prevention and antimicrobial stewardship adherence in line with local and global plans on AMR.

Importance of carbapenem-resistant Enterobacteriaceae screening to prevent transmission within an acute-care hospital

Background: Carbapenem-resistant Enterobacteriaceae (CRE) present a serious public health risk because they are transmissible within the acute-care hospital setting, and they are associated with significant morbidity and mortality. Timely identification of CRE among hospitalized patients is essential to ensure that appropriate infection prevention measures are enforced to prevent transmission events. In 2022, 9 index CRE cases (5 Klebsiella pneumoniae carbapenemase (KPC)–producing and 4 New Delhi Metallo-β-lactamase (NDM)–producing cases) were identified within the University of Colorado Hospital (UCH) inpatient population. In response to index case identification, tracing was performed to identify patients with an epidemiologic link for targeted CRE screening to detect asymptomatic CRE carriage. Methods: In total, 645 patients were screened allowing for timely identification of CRE colonization within 6 patients (3-KPC; 1-OXA-48; 1-NDM; 1-KPC/OXA-48). Secondary case identification elicited additional evaluation of service team and mobile-device crossover between positive patients, as well as primary and ancillary treatment locations. Results: Investigations revealed 3 possible transmission events in 0.47% of the total screened population. Identification of secondary CRE cases prompted additional testing of exposed patients performed at 7-day intervals to capture a 21-day colonization period. In total, 95 additional patients were screened for CRE during secondary and tertiary CRE screening events. Discussion: Nursing staff collaboration and engagement were critical to achieving a high rate of compliance with CRE screening activities, not only collecting screening specimens but also providing explanation and reassurance to patients. Due to this partnership and diligence, UCH was able to achieve 77% compliance with initial CRE screening events. Secondary and tertiary CRE screening revealed testing compliance of 83% and 69%, respectively. To further reduce the risk of CRE transmission within hospitalized patients, UCH has implemented an enhanced cleaning process for high-risk patient rooms, which includes patients infected or asymptomatically colonized with CRE. This enhanced process is prompted based on CRE or infection status as documented in the electronic medical record (EMR), and it initiates a mandatory 2-phase cleaning process. Future plans include environmental testing audits to validate room decontamination and leveraging the EMR to capture pertinent healthcare and travel histories. Active engagement with public health partners will be pursued to enable molecular testing of high-risk touch points. Conclusions: Patient screening, enhanced decontamination, and monitoring activities are key elements to effectively prevent the spread of CRE within vulnerable patient populations and must be continuously evaluated for improvement opportunities.Disclosures: None

SG-APSIC1209: Risk factors associated with mortality among carbapenem-resistant Enterobacteriaceae inpatient in a tertiary-care teaching hospital in Malaysia

Objectives: Carbapenem-resistant Enterobacteriaceae (CRE) is a multidrug-resistant gram-negative bacteria (MDR-GNB) that is rapidly emerging as a life-threatening nosocomial disease in many countries. We sought to identify the risk factors associated with mortality for carriage of CRE in patients at a tertiary-care teaching hospital. Methods: A retrospective observational study was conducted between January 2020 to December 2021 in a tertiary-care teaching healthcare facility, University Malaya Medical Centre in Malaysia. The study included all inpatients aged ≥18 years who had a CRE infection or were colonized during the study period. The genotype was identified by polymerase chain reaction (PCR). Statistical analysis of data including a multivariate logistic regression analysis was conducted using SPSS version 23.0 software. Results: In total, 176 cases of CRE (130 infection and 46 colonized) were identified, and the mortality rate was 31.8%. The main sources of CRE were rectal swab (61.9%), blood (11.9%), and respiratory sources (11.9%). Klebsiella pneumoniae (55.7%) was the predominant species, followed by Escherichia coli (21.6%). Among the isolates, 17.7% were non–CPE-CRE and 82.3% were CPE-CRE: NDM (69.3%) and OXA (10.8%). In multivariate analysis, the factors associated with mortality were older age (OR, 1.040; 95% CI, 1.012–1.069), longer length of stay (OR, 0.974; 95% CI, 0.955–0.994), use of central venous catheter (OR, 0.287; 95% CI, 0.094–0.878), and arterial lines (OR, 0.292; 95% CI, 0.095–0.891). Conclusion: Patients with CRE had a high mortality rate. Older age, longer duration of stay, indwelling CVC and arterial line were independent risk factors for death. Infection prevention and control measures to reduce CRE, such as active surveillance, contact precautions, compliance to intravenous catheter care bundles, healthcare worker education, and hand hygiene adherence, should be implemented.

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.

Intestinal Carriage of Carbapenemase-Producing Enterobacteriaceae Members in Immunocompromised Children During COVID-19 Pandemic

Background: Hospital-acquired infection with carbapenem-resistant Enterobacteriaceae (CRE) is a global concern. The administration of antibiotics among the infected and non-infected immunocompromised children with SARS-CoV-2 is associated with an increased risk of intestinal CRE colonization and bacteremia during hospitalization. Objectives: The present study aimed to detect the correlation between the intestinal colonization of carbapenemase encoding Enterobacteriaceae with SARS-CoV-2 infection and antibiotic prescription among immunocompromised children admitted to the oncology and Bone Marrow Transplantation (BMT) wards. Methods: Stool samples were collected from the immunocompromised children, and the members of Enterobacteriaceae were isolated using standard microbiological laboratory methods. Carbapenem resistance isolates were initially characterized by the disc diffusion method according to CLSI 2021 and further confirmed by the PCR assay. SARS-CoV-2 infection was also recorded according to documented real-time PCR results. Results: In this study, 102 Enterobacteriaceae isolates were collected from the stool samples. The isolates were from Escherichia spp. (59/102, 57.8%), Klebsiella spp. (34/102, 33.3%), Enterobacter spp. (5/102, 4.9%), Citrobacter spp. (2/102, 1.9%), and Serratia spp. (2/102, 1.9%). The carbapenem resistance phenotype was detected among 42.37%, 73.52%, 40%, 50%, and 100% of Escherichia spp., Klebsiella spp., Enterobacter spp., Citrobacter spp., and Serratia spp., respectively. Moreover, blaOXA-48 (49.1%) and blaNDM-1 (29.4%), as well as blaVIM (19.6%) and blaKPC (17.6%) were common in the CRE isolates. SARS-CoV-2 infection was detected in 50% of the participants; however, it was confirmed in 65.45% (36/55) of the intestinal CRE carriers. The administration of antibiotics, mainly broad-spectrum antibiotics, had a significant correlation with the CRE colonization in both the infected and non-infected children with SARS-CoV-2 infection. Conclusions: Regardless of the COVID-19 status, prolonged hospitalization and antibiotic prescription are major risk factors associated with the CRE intestinal colonization in immunocompromised children.

High frequency of carbapenem-resistant Enterobacteriaceae fecal carriage among ICU hospitalized patients from Southern Iran.

The worldwide emergence of carbapenem-resistant Enterobacteriaceae (CRE) has become a major therapeutic concern to medical institutions. To date, no study has determined the frequency and risk factors of inpatients with CRE fecal carriage in Southern Iran. We studied the features of carbapenemase-producing Enterobacteriaceae (CPE) collected from the central ICU of a university hospital. Totally, 173 samples, including 124 stool samples from 46 ICU inpatients on admission and different follow-ups, 9 ICU staff, and 40 environmental samples were included. CRE was identified using microbiological methods. Antimicrobial susceptibility was investigated by using the disk diffusion method and E-test. Carbapenemase producers were detected using the mCIM method. Seven carbapenemase genes were characterized. The genetic relationship among 20 CPE was elucidated by PFGE. The overall fecal carriage rate was 28.2%, while CRE acquisition was 6.1%. CRE were classified as Klebsiella pneumoniae (71.4%), Escherichia coli (23.8%), and Enterobacter aerogenes (4.8%). From 21 CRE, 20 (95.2%) produced carbapenemases, of which 10, 15, 10, 25, 5, and 65% were blaKPC, blaSME, blaIMP, blaVIM, blaNDM and blaOXA-48-positive, respectively. Out of 20 CPE, 14 different PFGE patterns were observed, categorized into six clusters, suggestive of non-clonal spread. No difference between the examined risk factors with CRE carriage was shown. The data indicate a high CRE fecal carriage rate among inpatients. Our findings implicate the widespread of OXA-48 carbapenemase together with heterogeneity among CRE with great concern for dissemination and therapeutic threat. Early diagnosis and monitoring of CRE among inpatients are urgent.

Clinical Risk Factors and Microbiological and Intestinal Characteristics of Carbapenemase-Producing Enterobacteriaceae Colonization and Subsequent Infection.

Gastrointestinal colonization with carbapenem-resistant Enterobacteriaceae (CRE) is always a prerequisite for the development of translocated infections. Here, we sought to screen for fecal carriage of CRE and identify the risk factors for CRE colonization as well as subsequent translocated pneumonia in critically ill patients admitted to the intensive care unit (ICU) of a university hospital in China. We further focused on the intestinal flora composition and fecal metabolic profiles in CRE rectal colonization and translocated infection patients. Animal models of gastrointestinal colonization with a carbapenemase-producing Klebsiella pneumoniae (carbapenem-resistant K. pneumoniae [CRKP]) clinical isolate expressing green fluorescent protein (GFP) were established, and systemic infection was subsequently traced using an in vivo imaging system (IVIS). The intestinal barrier, inflammatory factors, and infiltrating immune cells were further investigated. In this study, we screened 54 patients hospitalized in the ICU with CRE rectal colonization, and 50% of the colonized patients developed CRE-associated pneumonia, in line with the significantly high mortality rate. Upon multivariate analysis, risk factors associated with subsequent pneumonia caused by CRE in patients with fecal colonization included enteral feeding and carbapenem exposure. Furthermore, CRKP colonization and translocated infection influenced the diversity and community composition of the intestinal microbiome. Downregulated propionate and butyrate probably play important and multiangle roles in regulating immune cell infiltration, inflammatory factor expression, and mucus and intestinal epithelial barrier integrity. Although the risk factors and intestinal biomarkers for subsequent infections among CRE-colonized patients were explored, further work is needed to elucidate the complicated mechanisms. IMPORTANCE Carbapenem-resistant Enterobacteriaceae have emerged as a major threat to modern medicine, and the spread of carbapenem-resistant Enterobacteriaceae is a clinical and public health problem. Gastrointestinal colonization by potential pathogens is always a prerequisite for the development of translocated infections, and there is a growing need to assess clinical risk factors and microbiological and intestinal characteristics to prevent the development of clinical infection by carbapenem-resistant Enterobacteriaceae.

Bloodstream Infections in Patients with Rectal Colonization by Carbapenem-Resistant Enterobacteriaceae: A Prospective Cohort Study.

PurposeCarbapenem-resistant Enterobacteriaceae (CRE) infection has become a concerning threat, especially in hospital settings; however, its phenotypic characterization, association with rectal colonization and subsequent bloodstream infections (BSI) remain to be clarified. This study aimed to investigate the incidence and risk factors of CRE infection in rectal CRE carriers and to understand the clonality of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains and their association with subsequent BSI in these patients.Patients and MethodsThis was a prospectively designed cohort study. Hospitalized patients treated at our institution from April 2019 to October 2020 with intestinal CRE carriage were screened at admission and weekly thereafter until death or discharge from the hospital. Stool and blood samples were obtained for strain growth and mass spectrometry. The colonization and clinical infection isolates were analyzed by antimicrobial susceptibility testing to identify CRE. The clonality of the CRE strains and their corresponding clinical infection strains was studied by whole-genome sequencing to explore the mechanism of drug resistance and evaluate possible transmission. CRE-associated risk factors were analyzed in combination with epidemiological data.ResultsOf the 1203 patients, 85 were colonized by CRE and 21 developed CRE infection, of whom 13 developed CRE bloodstream infection (BSI). Ninety-one CRE strains were isolated from the rectal specimens of the 85 patients. Tracheotomy and chemotherapy in the past three months were independent risk factors for CRE infection in intestinal CRE carriers. ST11-KL64 (92.3%, 24/26) was the most dominant capsule and multilocus sequence typing (MLST) type among clonal CRKP isolates. Single-nucleotide polymorphism clustering showed homology of representative colonization and infection CRKP strain pairs (n=13) in the same patient. One group of leading clones was endemic in surgical intensive care units (ICUs). Twenty-four CRKP strains carried β-lactamase K. pneumonia carbapenemase 2, and 73.1% (19 strains) of CRKP carried mucoid phenotype regulator genes A2 and iucABCD.ConclusionIn summary, intestinal CRE colonization was detectable at an elevated rate among hospitalized patients and prevalent in ICU patients, with potential rapid horizontal transmission, providing evidence that CRE BSI infection in hospitalized patients might be due to their colonized strains and indicates the correlation between intestinal colonization and BSI.

P1575: DEVELOPMENT OF A RISK PREDICTION MODEL OF SUBSEQUENT BLOOLDSTREAM INFECTION AFTER CARBAPENEM-RESISTANT ENTEROBACTERIACEASE ISOLATED FROM PERIANAL SWABS IN PATIENTS WITH HEMATOLOGICAL DISEASES

Background: Hematological patients are at higher risk of developing carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infection (BSI) and associated with high mortality. Prediction model for a subsequent CRE BSI in hematological patients with CRE isolated from previous perianal swab samples can provide timely and useful target treatment strategies. Aims: To developing a quantified risk prediction model based on the risk factors of subsequent BSI in CRE carriers will help clinicians better identify specific individuals who would truly benefit from early, empiric CRE-targeted treatment. Methods: The data were extracted from patients with CRE isolated from perianal swab samples at the Hematopoietic Stem Cell Transplantation Center of Blood Diseases Hospital, Chinese Academy of Medical Sciences between July 2017 to October 2020 January. Patients who developed subsequent CRE BSI were compared with those who did not develop BSI. Univariate logistic analysis, multivariate logistic analysis and stepwise regression analysis were carried on a variety of clinical factors. Results: A total of 215 cases were included and 29 (13.4%) patients of them with CRE isolated from perianal swab samples developed CRE BSI subsequently. Multivariate analysis showed that C-reactive protein(CRP)﹥30mg/l(OR 10.613，95%CI 2.965~37.985，P=0.000）, perianal infection(OR 6.450, 95%CI 2.223~18.714, P=0.001), concomitant gastrointestinal symptoms (OR 4.175，95%CI 1.476~11.813，P=0.007），age﹥44 years (OR 3.415，95%CI 1.222~9.541，P=0.007）and neutrophil count﹤0.025×109/L (OR 4.583，95%CI 0.939~22.369，P=0.060）were risk factors for CRE BSI in patients with CRE isolated from perianal swab samples (P<0.01). They were included in the Logistic regression model to predict BSI. According to receiver operating characteristic (ROC) curve analysis, the cut-off value of the model was 0.921 (0.851-0.968，P<0.001). Image:Summary/Conclusion: Hematological patients with CRE isolated from perianal swab samples have a relatively low incidence of subsequent BSI but a relatively high risk of death. The risk prediction model based on CRP, perianal infection, concomitant gastrointestinal symptoms, age and valley absolute neutrophil may be used for predicting subsequent CRE BSI in patients with isolated from perianal swab samples and provide timely and effective treatment reference for this kind of patients.

Detection of Carbapenem-resistant Enterobacteriaceae by Real-Time PCR and Assessment of Hospitalization Related Risk Factors Associated with their Fecal Carriage: A Case-control Study

Opportunistic behavior of commensal bacteria during severe infection, especially of the intestine is always considered as a predisposing threat for the severely ill patient admitted to hospitals. A descriptive-analytical case-control study was carried out to detect the prevalence and risk factor analysis of fecal carriage of Carbapenem-resistant Enterobacteriaceae. Patients having fecal carriage of Carbapenem-resistant Enterobacteriaceae were considered as cases and patients who were without Carbapenem-resistant Enterobacteriaceae were taken as the control in a proportion of 1:4. Carbapenem-resistant Enterobacteriaceae (CRE) was confirmed by both conventional as well as molecular methods. Methods such as Combined Disk Test, mCIMtest, and RAPIDEC CarbaNP Test were used for phenotypic identification of CRE, Whereas Real-Time (RT)-PCR was used for the detection of bla-gene encoded for CRE (blaNDM1, blaVIM, blaKPC, blaIMP, and blaOXA48). All patients belonging to medicine wards were included in the study. we screened 436 patients during the study and found 160 patients suitable for our study, out of which 32 (20%) were cases and 128 (80%) were controls. We found a total number of 25 genes out of 16 isolates, where NDM 1 was identified in maximum numbers followed by KPC &amp;VIM. Standard statistical analyses such as chi-squire and odd ratios were conducted to determine the risk factor of different variables. Stepwise multiple logistic regressions were carried out, where we found, that transfer from other wards to medicine ward, use of nebulizer and intravenous catheter, and use of multiple antibiotics were still statistically significant. Implementation of Multi-modal colonization prevention and control is the need for the present situation throughout the world.

Detection of intestinal colonization by carbapenem-resistant Enterobacteriaceae (CRE) among patients admitted to a tertiary care hospital in Egypt

BackgroundThe irrational use of carbapenems in the last years lead to the emergence of carbapenem-resistant Enterobacteriaceae (CRE). This study aimed at determining the prevalence of CRE intestinal carriage among admitted patients in a tertiary care hospital in Egypt, to characterize carbapenemase-producing genes and to identify possible risk factors of CRE colonization. One hundred rectal swabs were collected from patients within 48 h of hospital admission. Culture was done on chromogenic media and then identification and antibiotic susceptibility testing were done using Vitek 2 compact system. Carbapenemase production was confirmed by Rapidec Carba NP test and by multiplex PCR for blaOXA-48-like, blaNDM-like, blaVIM-like, blaIMP-like and blaKPC-like.ResultsA total number of 36 CRE isolates were recovered from 28 patients. Thus, the prevalence of CRE colonization was 28%. Escherichia coli (83%), followed by Klebsiella pneumoniae (17%) were the main species. History of recent hospitalization and prior antibiotic intake were statistically significant risk factors predisposing to CRE colonization. Rapidec Carba NP gave positive results in 29/36 CRE isolates, whereas seven isolates gave negative results; six of them harbored blaOXA-48-like. Overall, the blaOXA-48-like was detected in 24/36 (66.7%), followed by blaNDM-like in 11/36 (30.6%) and lastly blaVIM-like in 1/36 (2.8%).ConclusionsOur findings confirm that CRE colonization is disseminating in our healthcare facility, a fact that should be considered as possible pathogens causing infections in high risk patients. Strict infection control measures should be applied to all CRE carriers at hospital admission and a proper antimicrobial stewardship program should be followed in clinical settings.

Effectiveness of selective digestive decolonization therapy using oral gentamicin for eradication of carbapenem-resistant Enterobacteriaceae carriage.

To evaluate the efficacy of selective digestive decolonization (SDD) therapy using oral gentamicin against carbapenem-resistant Enterobacteriaceae (CRE) colonization and to compare the incidence of novel gentamicin resistance between SDD and non-SDD patient groups. Retrospective cohort study. Acute-care referral center hospital in South Korea. Adults aged ≥20 years identified as rectal CRE carriers hospitalized between October 2019 and June 2020 were enrolled. Patients with a <30-day follow-up were excluded. Among CRE carriers, those who received 80 mg oral gentamicin sulfate (Shin Poong Pharmaceutical, Seoul, South Korea) 4 times daily comprised the SDD group and those who did not receive SDD therapy comprised the non-SDD group. CRE decolonization was compared between groups within 15 days, and new gentamicin resistance was assessed. In total, 73 rectal CRE carriers were identified; 11 patients were lost to follow-up within 30 days and were excluded. Oral gentamicin was administered to 20 of 62 patients. We detected no differences in the basic demographic features between groups. The rate of decolonization within 15 days was higher in the SDD group than in the non-SDD group (70.0% vs 23.8%; P = .001). The time to decolonization was significantly shorter in the SDD group. We detected no difference in acquisition of new gentamicin resistance between the groups. No serious adverse events due to oral gentamicin SDD therapy were reported. SDD therapy using oral gentamicin for CRE-colonized patients may be effective for the decolonization of gut CRE and for the prevention of transmission and subsequent CRE infection.

Rapid increase in occurrence of carbapenem-resistant Enterobacteriaceae in healthy rural residents in Shandong Province, China, from 2015 to 2017

The global increase in carbapenem-resistant Enterobacteriaceae (CRE) is a growing health concern. Infections caused by CRE are associated with increased mortality and length of hospital stay, emphasising the health and economic burden posed by these pathogens. Although CRE can inhabit the human gut asymptomatically, colonisation with CRE is associated with an increased risk of CRE infection and mortality. In this study, we investigated the occurrence and characteristics of CRE in faecal samples from healthy persons in 12 villages in Shandong Province, China. Screening for CRE in faecal samples was performed by selective cultivation. Minimum inhibitory concentrations (MICs) of meropenem were determined by the agar dilution method. Multilocus sequence typing (MLST) and carbapenemase gene carriage of the isolates were determined by whole-genome sequencing. Genetic relatedness of Escherichia coli isolates was determined by core genome MLST. CRE carriage increased from 2.4% in 2015 to 13.4% in 2017. Most CRE isolates (93.0%) were E. coli and all carried NDM-type carbapenemases. Sequence types (STs) among the E. coli isolates were diverse. The single most common ST was the highly epidemic strain ST167, which was only observed in 2017. We report a rapid increase in occurrence of CRE (from 2.4% to 13.4%) among faecal samples collected from healthy rural residents of Shandong Province from 2015 to 2017. Colonisation with CRE is known to increase the risk of CRE infection, and the worrying deterioration of the epidemiological situation in the region reported here indicates a need for further monitoring and possible interventions.

Epidemiology and Transmission of Carbapenemase-Producing Enterobacteriaceae in a Health Care Network of an Acute-Care Hospital and Its Affiliated Intermediate- and Long-Term-Care Facilities in Singapore.

ABSTRACTMovement of patients in a health care network poses challenges for the control of carbapenemase-producing Enterobacteriaceae (CPE). We aimed to identify intra- and interfacility transmission events and facility type-specific risk factors of CPE in an acute-care hospital (ACH) and its intermediate-term and long-term-care facilities (ILTCFs). Serial cross-sectional studies were conducted in June and July of 2014 to 2016 to screen for CPE. Whole-genome sequencing was done to identify strain relatedness and CPE genes (blaIMI, blaIMP-1, blaKPC-2, blaNDM-1, and blaOXA-48). Multivariable logistic regression models, stratified by facility type, were used to determine independent risk factors. Of 5,357 patients, half (55%) were from the ACH. CPE prevalence was 1.3% in the ACH and 0.7% in ILTCFs (P = 0.029). After adjusting for sociodemographics, screening year, and facility type, the odds of CPE colonization increased significantly with a hospital stay of ≥3 weeks (adjusted odds ratio [aOR], 2.67; 95% confidence interval [CI], 1.17 to 6.05), penicillin use (aOR, 3.00; 95% CI, 1.05 to 8.56), proton pump inhibitor use (aOR, 3.20; 95% CI, 1.05 to 9.80), dementia (aOR, 3.42; 95% CI, 1.38 to 8.49), connective tissue disease (aOR, 5.10; 95% CI, 1.19 to 21.81), and prior carbapenem-resistant Enterobacteriaceae (CRE) carriage (aOR, 109.02; 95% CI, 28.47 to 417.44) in the ACH. For ILTCFs, presence of wounds (aOR, 5.30; 95% CI, 1.01 to 27.72), respiratory procedures (aOR, 4.97; 95% CI, 1.09 to 22.71), vancomycin-resistant enterococcus carriage (aOR, 16.42; 95% CI, 1.52 to 177.48), and CRE carriage (aOR, 758.30; 95% CI, 33.86 to 16,982.52) showed significant association. Genomic analysis revealed only possible intra-ACH transmission and no evidence for ACH-to-ILTCF transmission. Although CPE colonization was predominantly in the ACH, risk factors varied between facilities. Targeted screening and precautionary measures are warranted.

Monitoring antibiotic resistance profiles of faecal isolates of Enterobacteriaceae and the prevalence of carbapenem-resistant isolates among food handlers in Kuwait

Carbapenem-resistant Enterobacteriaceae (CRE) have become one of the most challenging problems in infectious diseases worldwide. Unrecognised personnel such as food handlers (FHs) colonised with CRE serve as a reservoir for transmission. This study assessed the prevalence and susceptibility patterns of CRE isolates from FHs working in commercial eateries in the community (CFHs) and healthcare settings (HCFHs) in Kuwait over the period 2016-2018. Representative colonies from faecal samples were identified by API 20E and a VITEK®2 ID System. Susceptibility testing against 21 antibiotics was performed by Etest and agar dilution. A total of 681 isolates of the family Enterobacteriaceae were isolated from 405 FHs, of which 425 (62.4%) were Escherichia coli and 126 (18.5%) were Klebsiella pneumoniae. The prevalence of CRE among FHs was 7.7% (31/405), comprising 32% CFHs (10/31) and 68% HCFHs (21/31). Ampicillin, tetracycline and cefalotin showed very poor activities against most isolates with resistance rates of 63.3%, 41.7% and 40.8%, respectively. The prevalence of multidrug-resistant (MDR) isolates was 30.5%, including 130 E. coli (30.6%) and 22 K. pneumoniae (17.5%). An alarming level of colistin resistance (11.3%) was noted. A significant proportion of FH isolates (13.2%) exhibited extended-spectrum β-lactamases (ESBL) phenotypes, including 80 E. coli (18.8%) and 5 K. pneumoniae (4.0%). This study revealed that asymptomatic intestinal carriage of CRE, including MDR and ESBL isolates, was relatively common in our community. It is conceivable that FHs may pose a significant risk to consumers for the acquisition and spread of resistant strains.

Alteration of Gut Microbiota in Carbapenem-Resistant Enterobacteriaceae Carriers during Fecal Microbiota Transplantation According to Decolonization Periods.

Fecal microbiota transplantation (FMT) has been suggested as an alternative therapeutic option to decolonize carbapenem-resistant Enterobacteriaceae (CRE). However, the analysis of gut microbiota alteration in CRE carriers during FMT is still limited. Here, gut microbiota changes in CRE carriers were evaluated during FMT according to decolonization periods. The decolonization of 10 CRE carriers was evaluated after FMT, using serial consecutive rectal swab cultures. Alterations of gut microbiota before and after FMT (56 serial samples) were analyzed using high-throughput sequencing. The decolonization rates of CRE carriers were 40%, 50%, and 90% within 1, 3 and 5 months after initial FMT, respectively. Gut microbiota significantly changed after FMT (p = 0.003). Microbiota alteration was different between the early decolonization carriers (EDC) and late decolonization carriers (LDC). Microbiota convergence in carriers to donors was detected in EDC within 4 weeks, and keystone genera within the Bacteroidetes were found in the gut microbiota of EDC before FMT. The relative abundance of Klebsiella was lower in EDC than in LDC, before and after FMT. Our results indicate that FMT is a potential option for CRE decolonization. The gut microbiota of CRE carriers could be used to predict decolonization timing after FMT, and determine repeated FMT necessity.

Economic Evaluations of New Antibiotics: The High Potential Value of Reducing Healthcare Transmission Through Decolonization.

Antibiotics designed to decolonize carriers of drug-resistant organisms could offer substantial population health benefits, particularly if they can help avert outbreaks by interrupting person-to-person transmission chains. However, cost effectiveness of an antibiotic is typically evaluated only according to its benefits to recipients, which can be difficult to demonstrate for carriers of an organism that may not pose an immediate health threat to the carrier. We developed a mathematical transmission model to quantify the effects of 2 hypothetical antibiotics targeting carbapenem-resistant Enterobacteriaceae (CRE) among long-term acute care hospital inpatients: one assumed to decrease the death rate of patients with CRE bloodstream infections (BSIs) and the other assumed to decolonize CRE carriers after clinical detection. We quantified the effect of each antibiotic on the number of BSIs and deaths among patients receiving the drug (direct effect) and among all patients (direct and indirect effect) compared to usual care. We applied these results to a cost-effectiveness analysis with effectiveness outcome of life-years gained and assumed costs for antibiotic doses and for CRE BSI. The decolonizing antibiotic, once indirect effects were included, produced increased relative effectiveness and decreased relative costs compared to both usual care and the BSI treatment antibiotic. In fact, in most scenarios, the decolonizing drug was the dominant treatment strategy (ie, less costly and more effective). Antibiotics that decolonize carriers of drug-resistant organisms can be highly cost-effective when considering indirect benefits within populations vulnerable to outbreaks. Public health could benefit from finding ways to incentivize development of decolonizing antibiotics in the US, where drugs with unclear direct benefits to recipients would pose difficulties in achieving FDA approval and financial benefit to the developer.

The Impact of Modifying Empirical Antibiotic Therapy Based on Intestinal Colonization Status on Clinical Outcomes of Febrile Neutropenic Patients.

BackgroundThis paper aimed to inspect factors affecting febrile neutropenia patients with hematologic malignancies. The intestinal colonization rate of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) and carbapenem-resistant Enterobacteriaceae (CRE) was assessed. The rate of subsequent ESBL-E and CRE bacteremia correlated with corresponding bacterial colonization was evaluated. Further, the risk factors for ESBL-E and CRE intestinal colonization were examined. Finally, the impact of rectal swab screening combined with adapted empirical antibiotic therapy on the mortality rate of patients with febrile neutropenia was assessed.Materials and MethodsFebrile neutropenia patients underwent rectal swabs and collection of blood culture specimens upon admission. Empirical treatment was subsequently modified according to rectal swab results if necessary. Bacteremia patients were treated according to blood culture results. Explorative forward-stepwise logistic regression analyses were used to identify risk factors for ESBL-E and CRE fecal carriage and mortality.ResultsIn total, 201 rectal swabs and 402 blood samples were collected from 163 patients during 201 febrile neutropenia episodes. Of these episodes, 38 (18.90%) were colonized with ESBL-E and 30 (14.92%) with CRE. Bloodstream infections developed in 29/201 (14.42%) episodes. Only bacteremia episodes caused by Gram-negative bacilli were included in our analysis. The development of Gram-negative-rod bacteremia was observed in eight out of 38 (21.05%) ESBL-E colonized episodes and four out of 30 (13.33%) CRE-colonized episodes. A BSI developed in three out of 38 (7.89%) ESBL-E colonized episodes, and two out of 30 (6.66%) CRE-colonized episodes developed BSI with the respective organism. Multivariate analysis identified previous quinolone use as the only independent risk factor for fecal colonization of multi-drug-resistant (MDR) Enterobacteriaceae (ESBL-E and CRE) (odds ratio, 17.09; 95% confidence interval, 5.29 - 55.18; P <0.0001). No significant association was observed between ESBL-E and CRE carriage and increased risk of developing subsequent bacteremia. No significant differences were detected between groups receiving modified and non-modified treatments in duration of hospitalization or antibiotic therapy (univariate analysis) and 28-day mortality rate (logistic regression).ConclusionQuinolone exposure was a major risk factor for ESBL-E and CRE fecal carriage. Performing rectal swab screening for MDR Enterobacteriaceae and modifying empirical antibiotic therapy accordingly did not improve clinical outcomes of febrile neutropenia patients.

Prevalence of carbapenem-resistant Enterobacteriaceae and emergence of high rectal colonization rates of blaOXA-181-positive isolates in patients admitted to two major hospital intensive care units in Kuwait.

BackgroundFecal colonization by carbapenem-resistant Enterobacteriaceae (CRE) can be the main reservoir for transmission of these resistant organisms especially in the Intensive Care Units (ICUs).AimThis study was conducted to evaluate the rate of rectal carriage and molecular characterization of CRE in patients hospitalized in the ICUs of 2 major hospitals (Adan and Mubarak Al Kabeer Hospitals) in Kuwait.Materials and methodsRectal swabs were collected from all patients at admission, 48 h after admission and once weekly from April 2017- March 2018. Initial CRE screening was carried out on MacConkey agar on which meropenem disc 10μg was placed. Identification of isolates was by API 20E. Susceptibility testing was performed using the E-test method. Polymerase chain reaction (PCR) was used to detect the carbapenemase-encoding genes. Clonal relationship was investigated by pulsed-field electrophoresis (PFGE). Genes of blaOXA-181 and blaNDM-5–carrying plasmids were detected in some strains.ResultsA total of 590 patients were recruited into the study. Of these, 58 were positive for CRE, giving a prevalence of 9.8%; 25/320 (7.8%) in Adan and 33/270 (12.2%) in Mubarak Al Kabeer Hospitals. All isolates were resistant to multiple antibiotics. Resistance rates to colistin and tigecycline were 17% and 83%, respectively. Single genes of blaOXA-181 were detected in isolates from 38 (65.5%) out of 58 patients and in 5 patients colonized by blaOXA-48-positive CRE. A combination of 2 genes was detected in 12 isolates; 5 blaKPC-2 and blaOXA-181, 4 blaVIM-1 and blaOXA-181, and 3 blaNDM-5 and blaOXA-181. PFGE showed an overall level of similarity of 38%. Southern hybridization studies localized the blaOXA-181 and blaNDM-5 genes to a large plasmid of 200kb in 3 K. pneumoniae isolates and a small plasmid of 80kb in 2 E. coli isolates, respectively.ConclusionThe prevalence of CRE colonization in the 2 hospital ICUs was relatively high and the emergence of blaOXA-181-mediated CRE is a cause for concern as there is the possibility of rapid horizontal spread among hospital patients in Kuwait. Active surveillance of CRE in the ICUs is highly recommended to stem its spread.