Spread Of Carbapenem-resistant Enterobacteriaceae Research Articles

Epidemiological and genomic analysis revealed the significant role of flies in dissemination of carbapenem-resistant Enterobacteriaceae (CRE) in China

While the role of flies as potential vectors for bacterial transmission is well recognized, the epidemiological features and genomic characteristics of associated antimicrobial-resistant strains remain underexplored. This study conducted a nationwide surveillance including 3689 flies and 838 isolates from sixteen human communities (HCs) and eight animal farms (AFs) across 21 provinces in China. Our findings revealed high carriage rates of carbapenem-resistant Enterobacteriaceae (CRE) in flies, with 27.0 % in AFs and 15.3 % in HCs. Among the 705 CRE strains identified, Providencia spp. (n = 356) and Escherichia coli (n = 231) were predominant, with 90.6 % attributed to the dissemination of the blaNDM gene. Phylogenetic tree analysis highlighted frequent clonal transmission events, with over 18 and 13 clonal evolutionary clades in Providencia spp. and E. coli, respectively. Notably, spearman analysis linked the increase of CRE prevalence in AFs flies to environmental factors like precipitation (p < 0.028) and temperature (p < 0.037), while in HCs, it positively corelated with the total meat production (p < 0.027) in each province except for Hainan. Despite significant differences in ciprofloxacin resistance (p ≤ 0.001) among E. coli strains from HCs and AFs, core genome cluster analysis and Uniform Manifold Approximation and Projection (UMAP) approach indicated these strains exhibiting close relatedness to clinical strains. This comprehensive study underscores the critical role of flies in the escalation of CRE spread within the ecosystem in China. Flies found in both HCs and AFs contribute to the dissemination of CRE, highlighting the need for urgent interventions to address this pressing issue.

Molecular epidemiology and risk factors for carbapenem-resistant Enterobacteriaceae infections during 2020-2021 in Northwest China

Severe infection caused by Carbapenem-resistant Enterobacteriaceae (CRE) is a challenge for clinical anti-infective therapy, and clinical intervention to improve control of CRE is of great significance. The study aims to determine the molecular epidemiology and risk factors of CRE infections to provide evidence for effective control of nosocomial infection in patients with CRE. A total of 192 non-repetitive CRE strains were collected from January 2020 to December 2021 in Northwest China. To explore the risk factors of CRE infection by univariate and Logistic regression analysis, 1:1 case-control study was used to select Carbapenem sensitive Enterobacteriaceae (CSE) infection patients at the same period as the control group. Among the 192 CRE strains, the most common isolates included Klebsiella pneumoniae (Kpn) and Enterobacter cloacae (Ecl). The CRE strain showed the lowest rate of resistance to amikacin at 58.3. 185 CRE strains carried carbapenemase resistance genes of concern in this study. KPC-2 (n=94) was the most common carbapenemase, followed by NDM-1 (n=69), NDM-5 (n=22) and IMP-4 (n=5). OXA-48 and VIM were not detected. And KPC-2 was the most common in all strains. Logistic regression analysis implicated days of invasive ventilator-assisted ventilation (OR=1.452; 95 % CI 1.250～1.686), antibiotic combination therapy (OR=2.149; 95 % CI 1.128～4.094), hypoalbuminemia (OR=6.137; 95 % CI 3.161～11.913), history of immunosuppressant use (OR=25.815; 95 % CI 6.821～97.706) and days of hospitalization (OR=1.020; 95 % CI 1.006～1.035) as independent risk factors associated with CRE infection. Age (OR=0.963; 95% CI 0.943～0.984) and history of hormone use (OR=0.119; 95 % CI 0.028～0.504) were protective factors for CRE infection (P < 0.05). The resistance of commonly used antibiotics in clinical is severe, and CRE strains mainly carry KPC-2 and NDM-1. Multiple risk factors for CRE infection and their control can effectively prevent the spread of CRE.

Detection of carbapenem resistant enterobacteriaceae from various clinical samples: A record based study in a tertiary care hospital in Mandya

: Carbapenem Resistant Enterobacteriaceae (CRE) has gradually evolved as one of the serious global health concern due to its high mortality and limited treatment options. Overuse of the antibiotic and improper sanitation has led to its rapid spread. To determine the proportion of Carbapenem resistant Enterobacteriaceae from various clinical samples received in the Department of Microbiology, MIMS Mandya for Culture and sensitivity by using Meropenem and Imipenem disk.This is a retrospective study conducted over a period of 6 months from March 2021 to august 2021. The samples tested were all the clinical specimens like sputum, pus, urine, body fluids coming to our Microbiology laboratory. The specimens were processed by the standard laboratory methods. Bacteria was isolated and identified by standard biochemical reactions and antimicrobial susceptibility testing was done on Mueller Hinton Agar by Kirby Bauer disk diffusion method and interpreted according to CLSI guidelines.A total of 1624 samples were included in the study, among which 211 isolates were identified as members of Enterobacteriaceae family. 50 out of 211 isolates were confirmed as Carbapenem resistant giving a prevalence rate of 23.69%. Urine (42%) was the major contributor of CRE, followed by pus (34%). Among CRE, (54%) was the major organism isolated followed by (20%).Our study showed high CRE prevalence rate of 23.69%, indicating the rapid emergence of CRE. Hence, a strict adherence to antibiotic policy and basic infection control measures to be applied in view of reducing the spread of CRE in the community.

Hospital-Acquired Infections Caused by Carbapenem-Resistant Enterobacteriaceae: An Observational Study.

Worldwide, hospital-acquired infections (HAIs) are continuously rising within healthcare settings, leading to high mortality and morbidity rates. Many hospitals have reported the spread of carbapenemases globally, specifically within the E. coli and K. pneumoniae species. This study was aimed at analyzing the state of hospital-acquired, carbapenem-resistant E. coli and K. pneumoniae in the United Kingdom between 2009 and 2021. Moreover, the study analyzed the most efficacious approaches to patient management for controlling the carbapenem-resistant Enterobacteriaceae (CRE) spread. Initially, 1094 articles were identified as relevant for screening, and among them, 49 papers were eligible for full-text screening, with a total of 14 articles meeting the inclusion criteria. The information was recorded from published articles through PubMed, the Web of Science, Scopus, Science Direct, and the Cochrane library and was used to search for hospital-acquired carbapenem-resistant E. coli and K pneumoniae in the UK between 2009 and 2021, in order to evaluate the spread of CRE in hospitals. The total number of carbapenem-resistant E. coli was 1083 and this was 2053 for carbapenem-resistant K. pneumoniae in more than 63 UK hospitals. KPC was the dominant carbapenemase produced by K. pneumoniae. The results showed that the treatment options considered depended on the type of carbapenemase produced; K. pneumoniae showed more resistance to a treatment options, i.e., Colistin, than the other carbapenemase. The current state of the UK is at minimal risk for a CRE outbreak; however, appropriate treatment and infection control measures are highly required to prevent this CRE spread at the regional and global levels. The present study findings have an important message for physicians, healthcare workers, and policymakers about hospital-acquired carbapenem-resistant E. coli and K. pneumoniae spread and approaches to patient management.

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

ANTIBIOTIC SUSCEPTIBILITY PATTERN OF CARBAPENEM RESISTANT ENTEROBACTERIACEAE AMONG UROPATHOGENS ISOLATED IN A REFERRAL LABORATORY OF KARACHI

Objective: To determine the antibiotic susceptibility pattern of Carbapenem resistant Enterobacteriaceae among uropathogens isolated in a referral laboratory in Karachi. Methodology: It is a retrospective cross-sectional study, carried out at the Department of Microbiology of Dow Diagnostic Research and Reference Laboratory. All urine samples collected during the study period of 6 months from October 2020 to March 2021 were tested for culture and sensitivity patterns by the disc diffusion method. Data of urine culture and sensitivity test reports were taken from the medical record. and analyzed by using SPSS version 16. Results: Out of the total 10925 uropathogens isolated, 67% belonged to Enterobacteriaceae family. The most frequent isolate among them was Escherichia coli 84% followed by Klebsiella species at 10%. The overall frequency of Carbapenem resistance was 6%. The frequency of Carbapenem resistance was higher in Klebsiella species 27% than Escherichia coli 8%. Multi-drug resistance was observed in both Escherichia coli and Klebsiella species especially against Ampicillin, followed by Cefixime, Cefuroxime, Ceftriaxone, Cotrimoxazole and Ciprofloxacin. Conclusion: The study showed a significant rate of Carbapenem resistance among Enterobacteriaceae which emphasizes the need for formulating an antimicrobial policy with its strict implementation and regular surveillance to control the spread of Carbapenem resistant Enterobacteriaceae at the hospital and community level.

425. Spread of Carbapenem-resistant Enterobacteriaceae in Intensive Care Unit and effective preventative strategies: Agent-based model study

Abstract Background Carbaepenem-resistant Enterbacteriaceae (CRE) could propagate through person-to-person contacts such as contaminated hands of staff, contamination of the environment, or the use of contaminated medical equipment by spreading carbapenemase encoded in plasmid and cause healthcare associated infections (HAIs). Critically ill patients in a compact space of Intensive care unit (ICU) are at significantly high risk of CRE infection, which should be protected by effective infection control strategies. Agent-based model (ABM) has been employed to examine the spread of infectious organisms and estimate the impact of intervention as it reflects behaviors of heterogeneous individuals. We aimed to create an ABM reflecting the medical ICU and identify preventative strategies to reduce CRE infection in the ICU. Methods The blueprint of the medical ICU in a tertiary hospital in Republic of Korea was obtained. Researchers had a meeting with the head staffs to get information about healthcare workers (HCWs), patients, and the spatial unit. In this unit, HCWs visiting a patient in ICU are required to wash their hands and wear personal protective equipment. We did a survey to collect data of the routes and the handwashing rates of HCWs. An ABM was made using Python’s Mesa library which simulates the situation in the ICU and the status of CRE. Figure 1.(A) Blueprint of ICU in Severance Hospital, (B) Simulated ICU in agent-based modelFigure 2.Dynamics between agents and environment Results Medical ICU consists of two units, and each unit holds fifteen beds. Five nurses work in each unit and six doctors and three technicians take rounds daily, contacting patients in the ICU. The dynamics among agents and environment were constructed.. Parameters were set up from the real world data or the clinical studies. At any given moment, there are about 2.5 patients infected with CRE, and transmission probability and isolation factors were calibrated according to this target. Interventions were enhanced environment cleansing, handwashing of HCWs, and prompt isolation of infected patients through tests and actions. We found those interventions effectively reduced HAIs, and combining effects lead to better results. Figure 3.Parameters and variables in agend-based modelFigure 4.Healthcare associated infections in study periods according to (A) interval of clensing environment, (B) handwashing of HCWs, (C) isolation of infected patients, (D) combined of environmental cleansing and patient isolation Conclusion Increasing handwashing rates, environment cleansing, and prompt isolation of infected patients have drastic effects of reducing HAIs caused by CRE in this model, and bundle approach should be considered to prevent the spread of CRE. Disclosures All Authors: No reported disclosures.

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.

Reducing Carbapenem-Resistant Enterobacteriaceae Using the Targeted Solution Tool: A Quality Improvement Project.

Carbapenem-resistant Enterobacteriaceae (CRE) is a worldwide urgent health problem. Hand hygiene (HH) is an effective intervention to reduce the spread of CRE. In 2017, an increase in the rate of health care-associated (HA) CRE colonization was observed in a large multiorgan transplant center in Italy. This study aimed to reduce the HA-CRE colonization rates by improving HH compliance. A pre-/post-intervention project was conducted from November 2017 through December 2020. The DMAIC (Define, Measure, Analyze, Improve, and Control) framework was used to implement the HH Targeted Solution Tool (TST). Hand hygiene compliance increased from 49% to 76.9% after the Improve phase ( P = .0001), and to 81.9% after the second Control phase ( P = .0001). The rate of HA-CRE decreased from 24.9% to 5.6% ( P = .0001). Using the DMAIC framework to implement the TST can result in significant improvements in HH compliance and HA-CRE colonization rates.

Intestinal Colonization with Carbapenem-Resistant Enterobacteriaceae in Acute Leukemia Patients: Risk Factors and Molecular Characteristics.

BackgroundCarbapenem-resistant Enterobacteriaceae (CRE) colonization is associated with bacterial translocation, which can result in subsequent endogenous CRE infection. In the present study, we aim to investigate the colonization-related risk factors and molecular epidemiological characteristics of CRE in patients with acute leukemia.MethodsFrom January 2021 to December 2021, acute leukemia patients were screened for CRE by fecal/perianal swabs. We identified the species, carbapenemase-encoding genes, and virulence genes of the colonizing strains and performed antimicrobial susceptibility tests and ERIC-PCR typing. Risk factors for CRE colonization were identified by univariate and multivariate analysis.ResultsWe collected a total of 21 colonizing strains from 320 patients. All strains were resistant to meropenem. Klebsiella pneumoniae was the most abundant species, and ERIC-PCR typing showed low diversity. Univariate analysis showed that age, cephalosporins, penicillins, tigecyclines, and hematopoietic stem cell transplantation status were risk factors for CRE colonization; simultaneously discovered CRE strains played a dominant role in invasive infection of colonized patients. Logistic multivariate regression analysis showed that age, cephalosporins, and tigecyclines were independent risk factors for CRE intestinal colonization.ConclusionCRE colonization can increase the incidence of CRE infection in patients with acute leukemia. Early detection of CRE colonization through CRE screening is an important measure to control the spread of CRE.

Expression of plasmid-mediated resistance genes ESBLs and PMQR among uropathogens, isolated from non-dialysis CKD patients with pyelonephritis

Urinary tract infections (UTIs) are thought to be the most common group of bacterial infections, worldwide. It is estimated that the proportion of UTIs remains at a high level reaching 150 million episodes per year worldwide and accounting for $6 billion in health care expenditures. In USA more than 100,000 hospital admissions per year are the UTIs patients, among them the patients with pyelonephritis are the most frequent. For the US outpatients, approximately 15 % of antibiotics used are prescribed for UTIs. However, recent studies in Europe and the United States have demonstrated a steady increase in the rate of uropathogen resistance to commonly prescribed antibiotics, and this obviously will lead to a reduction in therapeutic possibilities of UTI. CDC has estimated that more thаn 2 million infections and 23,000 deaths are due to antibiotic resistance each year. By 2050, it is estimated, that antibiotic resistance will cause 10 million deaths every year. Infection is an importаnt cause of mоrbidity and mоrtality amоng patients with kidney failurе and is the sеcond lеading causе of death following CVD. At the EU/EEA level, more than half (54 %) of the E.coli isolates reported to EARS-Net for 2020 were resistant to at least one of the antimicrobial groups under regular surveillance, i.e. aminopenicillins, fluoroquinolones, third-generation cephalosporins, aminoglycosides and carbapenems. A majority (87.4 %) of the third-generation cephalosporin-resistant E.coli isolates from 2020 were extended-spectrum beta-lactamase (ESBL) positive. Use of broad-spectrum antimicrobials is a known risk factor for colonization and spread of resistant Enterobacteriaceae, including E.coli. The high levels of ESBLs and increasing resistance to key antimicrobial groups might also lead to an increased consumption of carbapenems, which in turn can increase the selection pressure and facilitated the spread of carbapenem-resistant Enterobacteriaceae. The article presents data on the antibacterial susceptibility of isolated uropathogens, and their association with the presence or absence of plasmid-mediated resistance genes ESBLs and PMQR.

Quantitative Risk Assessment for the Introduction of Carbapenem-Resistant Enterobacteriaceae (CPE) into Dutch Livestock Farms.

Early detection of emerging carbapenem-resistant Enterobacteriaceae (CPE) in food-producing animals is essential to control the spread of CPE. We assessed the risk of CPE introduction from imported livestock, livestock feed, companion animals, hospital patients, and returning travelers into livestock farms in The Netherlands, including (1) broiler, (2) broiler breeder, (3) fattening pig, (4) breeding pig, (5) farrow-to-finish pig, and (6) veal calf farms. The expected annual number of introductions was calculated from the number of farms exposed to each CPE source and the probability that at least one animal in an exposed farm is colonized. The total number of farms with CPE colonization was estimated to be the highest for fattening pig farms, whereas the probability of introduction for an individual farm was the highest for broiler farms. Livestock feed and imported livestock are the most likely sources of CPE introduction into Dutch livestock farms. Sensitivity analysis indicated that the number of fattening pig farms determined the number of high introductions in fattening pigs from feed, and that uncertainty on CPE prevalence impacted the absolute risk estimate for all farm types. The results of this study can be used to inform risk-based surveillance for CPE in livestock farms.

Regional dissemination of carbapenem-resistant Enterobacteriaceae accompanying with enhanced resistance in Northern Osaka, Japan

With the rapid spread of multidrug-resistant bacteria, carbapenem-resistant Enterobacteriaceae (CRE) has been reported worldwide as a major concern because of limited treatment options. Carbapenem resistance is mainly due to carbapenem-ase, a carbapenem-degrading enzyme, which is mainly encoded on a plasmid to spread across bacterial species. However, there have been only small-scale attempts to determine the similarities or accommodations of the plasmids disseminating regionwide. We analysed the 230 CRE isolates carrying blaIMP from 43 medical facilities in the northern Osaka area focusing on the plasmids, the main carriers of the drug resistance genes. Combination of whole genome sequencing and Southern blotting revealed the predominant dissemination of blaIMP-6 by the pKPI-6 plasmid among genetically distinct isolates, as well as the emergences of derivatives that acquired various advantages. We iden-tified heteroresistance likely causing stealth transmissions, which was generated by the transcriptional regu-lation of blaIMP-6, stabilization of blaIMP-6 through chromosomal integration, enhanced carbapenem resistance through plasmid multimerization, or broadened antimicrobial resistance due to a single point mutation in blaIMP-6. In this article, I dis-cussed the mechanisms of regional spread of CRE and enhancement of carbapenem resistance providing the insights to prevent their disseminations.

Characterization of Carbapenem-Resistant Enterobacteriaceae Cultured From Retail Meat Products, Patients, and Porcine Excrement in China.

The emergence and dissemination of carbapenem-resistant Enterobacteriaceae (CRE) is a growing concern to animal and public health. However, little is known about the spread of CRE in food and livestock and its potential transmission to humans. To identify CRE strains from different origins and sources, 53 isolates were cultured from 760 samples including retail meat products, patients, and porcine excrement. Antimicrobial susceptibility testing was carried out, followed by phylogenetic typing, whole-genome sequencing, broth mating assays, and plasmids analyses. Forty-three Escherichia coli, nine Klebsiella pneumoniae, and one Enterobacter cloacae isolates were identified, each exhibiting multidrug-resistant phenotypes. Genetically, the main sequence types (STs) of E. coli were ST156 (n = 7), ST354 (n = 7), and ST48 (n = 7), and the dominant ST of K. pneumoniae is ST11 (n = 5). blaNDM–5 (n = 40) of E. coli and blaKPC–2 (n = 5) were the key genes that conferred carbapenem resistance phenotypes in these CRE strains. Additionally, the mcr-1 gene was identified in 17 blaNDM-producing isolates. The blaNDM–5 gene from eight strains could be transferred to the recipients via conjugation assays. Two mcr-1 genes in the E. coli isolates could be co-transferred along with the blaNDM–5 genes. IncF and IncX3 plasmids have been found to be predominantly associated with blaNDM gene in these strains. Strains isolated in our study from different sources and regions tend to be concordant and overlap. CRE strains from retail meat products are a reservoir for transition of CRE strains between animals and humans. These data also provide evidence of the dissemination of CRE strains and carbapenem-resistant genes between animal and human sources.

Neonates with Maternal Colonization of Carbapenemase-Producing, Carbapenem-Resistant Enterobacteriaceae: A Mini-Review and a Suggested Guide for Preventing Neonatal Infection.

Carbapenemase-producing, carbapenem-resistant Enterobacteriaceae (CP-CRE) are highly drug-resistant Gram-negative bacteria. They include New Delhi metallo-ß-lactamase (NDM)-producing carbapenemase (50.4% of all species in Ontario). Antibiotic challenges for resistant bacteria in neonates pose challenges of unknown dosing and side effects. We report two antenatally diagnosed CP-CRE colonization scenarios with the NDM 1 gene. The case involves extreme preterm twins who had worsening respiratory distress at birth requiring ventilator support, with the first twin also having cardiovascular instability. They were screened for CP-CRE, and a polymyxin antibiotic commenced. In the delivery room, neonatal intensive care unit (NICU) and the follow-up clinic, in collaboration with the interdisciplinary group, contact precautions and isolation procedures were instituted. None of the infants exhibited infection with CP-CRE. Consolidating knowledge with regard to CP-CRE and modifying human behavior associated with its spread can mitigate potential negative consequences. This relates to now and later, when travel and prolific human to human contact resumes, from endemic countries, after the current COVID-19 pandemic. Standardized efforts to curb the acquisition of this infection would be judicious given the challenges of treatment and continued emerging antibiotic resistance. Simple infection control measures involving contact precautions, staff education and parental cohorting can be useful and cost-effective in preventing transmission. Attention to NICU specific measures, including screening of at-risk mothers (invitro fertilization conception) and their probands, careful handling of breastmilk, judicious antibiotic choice and duration of treatment, is warranted. What does this study add? CP-CRE is a nosocomial infection with increasing incidence globally, and a serious threat to public health, making it likely that these cases will present with greater frequency to the NICU team. Only a few similar cases have been reported in the neonatal literature. Current published guidelines provide a framework for general hospital management. Still, they are not specific to the NICU experience and the need to manage the parents’ exposure and the infants. This article provides a holistic framework for managing confirmed or suspected cases of CP-CRE from the antenatal care through the NICU and into the follow-up clinic targeted at preventing or containing the spread of CP-CRE.

Dissemination of Carbapenemases (OXA-48, NDM and VIM) Producing Enterobacteriaceae Isolated from the Mohamed VI University Hospital in Marrakech, Morocco

The emergence and spread of carbapenem-resistant Enterobacteriaceae (CRE) represent a major clinical problem and raise serious health concerns. The present study aimed to investigate and ascertain the occurrence of CRE among hospitalized patients of Mohamed VI University Hospital, Marrakech, Morocco. Biological samples were collected over a one-year period (2018). The bacterial isolates were identified by MALDI-TOF-MS. Antibiotic susceptibility testing was performed using disc diffusion and Etest. The modified Hodge test and combined disc diffusion test were used for phenotypic detection. CRE hydrolyzing enzyme encoding genes: blaOXA-48, blaKPC, blaIMP, blaVIM, and blaNDM were characterized by PCR and DNA sequencing. In total, 131 non-duplicate CRE clinical strains resistant to Ertapenem were isolated out of 1603 initial Enterobacteriaceae. Klebsiella pneumoniae was the most common species (59%), followed by Enterobacter cloacae (24%), E. coli (10%), Citrobacter freundii (3%), Klebsiella oxycota (2%), Serratia marcescens (1%), and Citrobacter braakii (1%). Of these, 56.49%, 21.37%, 15.27%, 3.38%, and 3.05% were collected from blood, urine, pus, catheters and respiratory samples, respectively. Approximately 85.5% (112/131) of the isolates were carbapenemase producers (40 blaOXA-48, 27 blaNDM, 38 blaOXA-48 + blaNDM and 7 blaVIM). All metallo-β-lactamases isolates were NDM-1 and VIM-1 producers. This is the first documentation of blaOXA-48 genes from C. freundii and C. braakii in Morocco.

Carbapenem-Resistant Enterobacteriaceae-Implications for Treating Acute Leukemias, a Subgroup of Hematological Malignancies.

Acute leukemias (AL) are a group of aggressive malignant diseases associated with a high degree of morbidity and mortality. Patients with AL are highly susceptible to infectious diseases due to the disease itself, factors attributed to treatment, and specific individual risk factors. Enterobacteriaceae presence (e.g., Klebsiella pneumonia and Escherichia coli) is a frequent cause of bloodstream infections in AL patients. Carbapenem-resistant Enterobacteriaceae (CRE) is an emerging health problem worldwide; however, the incidence of CRE varies greatly between different regions. Carbapenem resistance in Enterobacteriaceae is caused by different mechanisms, and CRE may display various resistance profiles. Bacterial co-expression of genes conferring resistance to both broad-spectrum β-lactam antibiotics (including carbapenems) and other classes of antibiotics may give rise to multidrug-resistant organisms (MDROs). The spread of CRE represents a major treatment challenge for clinicians due to lack of randomized clinical trials (RCTs), a limited number of antibiotics available, and the side-effects associated with them. Most research concerning CRE infections in AL patients are limited to case reports and retrospective reviews. Current research recommends treatment with older antibiotics, such as polymyxins, fosfomycin, older aminoglycosides, and in some cases carbapenems. To prevent the spread of resistant microbes, it is of pivotal interest to implement antibiotic stewardship to reduce broad-spectrum antibiotic treatment, but without giving too narrow a treatment to neutropenic infected patients.

Risk factors of carbapenem-resistant Enterobacteriaceae infection and colonisation: a Malaysian tertiary care hospital based case-control study.

Carbapenem-resistant Enterobacteriaceae (CRE) infection has become a major challenge to clinicians. The aim of this study is to identify the risk factors of acquiring CRE to guide more targeted screening for hospital admissions. This is a retrospective case-control study (ratio 1:1) where a patient with CRE infection or colonisation was matched with a control. The control was an individual who tested negative for CRE but was a close contact of a patient testing positive and was admitted at the same time and place. Univariate and multivariate statistical analyses were done. The study included 154 patients. The majority of the CRE was Klebsiella species (83%). From univariate analysis, the significant risk factors were having a history of indwelling devices (OR: 2.791; 95% CI: 1.384-5.629), concomitant other MDRO (OR: 2.556; 95% CI: 1.144-5.707) and hospitalisation for more than three weeks (OR: 2.331; 95% CI: 1.163-4.673). Multivariate analysis showed that being unable to ambulate on admission (adjusted OR: 2.345; 95% CI: 1.170-4.699) and antibiotic exposure (adjusted OR: 3.515; 95% CI: 1.377-8.972) were independent predictors. The in-hospital mortality rate of CRE infection was high (64.5%). CRE acquisition resulted in prolonged hospitalisation (median=35 days; P<0.001). CRE infection results in high morbidity and mortality. On top of the common risk factors, patients with mobility restriction, prior antibiotic exposures and hospitalisation for more than three weeks should be prioritised in the screening strategy to control the spread of CRE.

Multi-faceted strategies improve collection compliance and sample acceptance rate for carbapenem-resistant Enterobacteriaceae (CRE) active surveillance testing

Active surveillance testing (AST) is one element of a comprehensive Carbapenem-resistant Enterobacteriaceae (CRE) prevention strategy. However, the utility of AST may be impacted by compliance with sample collection and the quality of specimens. Here, we describe strategies used to optimize a CRE AST program at a large academic medical center. Tests ordered, collected, rejected, and processed were tracked weekly for each participating unit. Sample collection compliance and acceptance rates were calculated and tracked weekly. Strategies were implemented to improve collection compliance and sample acceptance rates, including computerized provider order entry, printed educational materials, and audit and feedback. Weekly dedicated Infection Preventionist (IP) time was estimated. Over 35 months, mean collection compliance increased from 82.7% to 91.2%, and then decreased to 86.2%. Over 27 months, sample acceptance rate increased from 57.7% to 83.6%, and then remained stable at 83.4%. Over 39 months, dedicated weekly IP time decreased 92%. Use of evidence-based quality improvement strategies optimized our CRE AST program. Optimizing the AST process aids in early CRE detection, leading to timely isolation and preventing the spread of CRE to other patients. Other hospitals may benefit from these lessons and enhance local AST programs.

Companion Animals Emerged as an Important Reservoir of Carbapenem-Resistant Enterobacteriaceae: A Report from India.

The emergence and spread of carbapenem-resistant Enterobacteriaceae (CRE) are perceived as a serious public-health threat world-wide. Despite sporadic reports, no systemic study has been carried out on CRE in companion animalsin Indian subcontinent. In total, 237 canine specimens collected from five veterinary polyclinics in and around Kolkata were analyzed for isolation, antimicrobial resistance profiling and molecular characterization of carbapenem-resistant (CR) E. coli. Of the 29 CR isolates, 19 were identified as metallo-β-lactamase producers (MP-CRE) and 10 as metallo-β-lactamase non-producers (MNP-CRE). Eleven of them were extended spectrum β-lactamase and/or AmpC type β-lactamase producers and harboured fluoroquinolone-, tetracycline-, sulfonamide- and aminoglycoside-resistant genes. Beside uropathogenic virulence determinants, they carried the adhesion factors mediating biofilm production which was remarkably higher in 6 MP-CRE and one MNP-CRE isolates. Although the CRE were of diverse origin including the healthyand the diseased dogs, these were more frequently isolated from canine pyometra. The MP-CRE harboured plasmids of IncF and IncA/C types. Phylo-type B1 was observed in38% of the CR isolates, followed by A0 in31% and rest were attributed to A1 and D1. The Enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR) revealed that these isolates were genetically diverse and constituted of a heterogenous population. Detection of CRE in pet dogs despite the fact that carbapenems are not used in animals in India emphasizes the need for active surveillance to identify the transmission and dynamics of such pathogens in companion animals.