Carbapenemase-producing Enterobacteriaceae Colonization Research Articles

#237 Carbapenemase producing Enterobacteriaceae rectal colonization in dialysis patients: a large monocentric retrospective analysis

Abstract Background and Aims Carbapenemase-producing Enterobacteriaceae (CPE) represent a growing global public health concern due to their increasing prevalence and resistance to carbapenems. Dialysis patients are particularly vulnerable to infections that represent the second cause of death in dialysis’ cohorts. Considering the immunosuppression, dialysis patients constitute a highly immunocompromised population and represent a unique setting similar to intensive care, hematology, or transplant recipients. Several studies have already been conducted in these populations, demonstrating the high infectious risk, increased mortality and morbidity burdened by CPE. Our study aims to analyze a large dialysis population and assess if there is an increased risk of mortality, sepsis, and/or hospitalizations within this cohort. Considering the frequency of evaluations for these patients, we have also decided to evaluate the treatments to which these patients are subjected, their antibiotic exposure, the number of hospitalizations and specific infections, while seeking predisposing or protective factors within this specific patient group. Method Our work is a retrospective, single-center cohort study that analyzes patients on HD and PD who were followed by the Nephrology and Dialysis Department of the Ravenna Hospital from 01/01/2015 to 31/12/2021 (674 patients). We analyzed demographic data (Date of birth, gender, blood type), comorbidities (Diabetes, hypertension), dialysis data (type of dialysis technique, dialytic age), blood tests (hemoglobin, white blood cells, platelets, albumin, ALT, lipase, C-reactive protein), serology and markers (HBV, HCV, HIV, EBV, CMV, Quantiferon, Helicobacter pylori colonization, SARS-COV2), therapies (antihypertensives, proton pump inhibitors, calcium-based phosphorus binders, non-calcium-based phosphorus binders, potassium binders, iron therapy, erythropoietin-stimulating agents), antibiotics (cephalosporins, penicillins, fluoroquinolones, macrolides, aminoglycosides, carbapenems, tetracyclines, vancomycin, linezolid, cefepime/avibactam), hospitalizations, colonization or lack thereof by CPE bacteria, infections (urinary tract infections and pneumonias) or sepsis and responsible microorganisms, survival. We exclude patients who had stomas or those who received chemotherapy or immunotherapy for a period longer than 3 months. Results Overall we considered for our analysis 528 patients and 51 presented CPE positive rectal swab during the period of observation. In our population CPE colonized patients present a higher risk to develop pneumonias (HR 2.048, p = 0.003). 178 patients presented 497 episodes of sepsis, 451 episodes in the non CPE colonized and 46 episodes in the CPE colonized (HR 2.057, p-value 0.001). Considering CPE-induced sepsis, a substantial difference was observed between the two groups. The colonized patient group had 7 (15.2%) cases of CPE sepsis, while the non-colonized group did not have any (0%). The result shows statistical significance, although the limited number of infections does not allow for definitive conclusions on this matter. Concerning the re-hospitalization rate we evidenced a significative difference between the two groups, displaying an involvement of CPE colonization (HR1.367, p-value = 0.038). Conclusion Our study highlighted that a colonization by CPE lead to a greater number of episodes of all bacterial sepsis, of CPE sepsis, of pneumonias and of re-hospitalizations. Colonization by CPE conferm an increased risk of CPE sepsis, and therefore, future research should focus on determining whether it is worthwhile to treat hyperpyrexia in colonized CPE dialysis patients as if it were CPE-related sepsis. This is a significant question that can guide our clinical practice.

286. The Effect of Fecal Microbiota Transplantation on Decolonization of Multidrug-resistant Organisms in the gut

Abstract Background Gut colonization of multidrug-resistant organisms (MDROs), such as carbapenemase-producing Enterobacteriaceae (CPE) and vancomycin-resistant Enterococci (VRE), precedes clinical infections. It increases the risk of patient-to-patient transmission of MDROs as well as clinical infections such as bacteremia. Therefore, decolonization of MDROs in the gut by restoring colonization resistance through fecal microbiota transplantation (FMT) could be an effective infection control strategy for MDROs. Methods From March 2019 to November 2022, FMT for CPE and VRE decolonization in the gut was conducted at Hallym University Chuncheon Sacred Heart Hospital. Frozen or capsulized stool (MicroBiotix FMT Delivery Microbiota Preparation) from unrelated pre-screened healthy donor was used for each FMT. The rates of and the time to successful decolonization, defined as 3 consecutive negative results from rectal swab culture repeated with 3-day intervals after the initial FMT, were investigated in CPE and VRE rectal colonizers, respectively. Results FMT was performed in 60 CPE rectal carriers (KPC=55, KPC & NDM=2, KPC & IMP=1, NDM=1, NDM & OXA=1) and in 15 VRE rectal carriers (E. faecium=14, E. faecalis=1). Among patients with follow-up data after initial FMT, decolonization success rates for CPE and VRE rectal carriers were 44.8% (26/58) and 66.7% (10/15) at 1 month, 77.1% (37/48) and 92.9% (13/14) at 3 months, 95.5% (42/44) and 100% (14/14) at 6 months, respectively. Median and mean times to decolonization after initial FMT were 30 and 43 days in CPE rectal colonizers and 14 and 29 days in VRE rectal colonizers, respectively. FMT results for decolonization of MDROs in the gut of Chuncheon Sacred Heart Hospital (ClinicalTrials.gov number, NCT04583098) Conclusion FMT as a microbiome restoration therapy is an effective method to control CPE and VRE colonization (ClinicalTrials.gov number, NCT04583098). Disclosures All Authors: No reported disclosures

817. Appropriate Sites for the Active Surveillance of Carbapenemase-producing Enterobacteriaceae

Abstract Background Active surveillance tests for carbapenemase-producing Enterobacteriaceae (CPE) are recommended in patients showing risk factors for colonization by these bacteria. There are limited data however on whether surveillance tests for anatomic sites other than the stool would be useful to detect CPE colonization, and we investigated this in our present study. Methods Retrospective analysis was performed on cases at our tertiary care hospital during a 5-year period. The study patients with CPE colonization had been admitted to our surgical intensive care unit (SICU) or sub-ICU for liver transplantation in this period and undergone surveillance tests for both the stool and other sites. Patients were grouped as stool CPE negative (but which included CPE positive cases from initial sputum and other site tests) or positive. Results Among the total study cohort of 158 patients, 138 (87.3%) were included in the stool CPE positive group and the remaining 20 (12.7%) in the stool CPE negative group. While the sensitivity of CPE surveillance testing of the stool was 87.3% (95% CI 81.1-92.1), the sensitivity when combining stool and sputum samples was 93.7% (88.7-96.9). The transmission rates were similar for patients showing CPE positivity in the stool, sputum and other sites, at 4.8% (27/557), 4.7% (3/64), and 6.7% (1/15), respectively (p = 0.95). Conclusion The sensitivity of CPE detection in a stool sample is suboptimal for ruling out CPE colonization and the transmission rates are similar between stool-positive or -negative cases. Combining surveillance of the stool with other sites may be needed for detecting CPE. Disclosures All Authors: No reported disclosures

Validation of the Giannella Risk Score for the Prediction of Infection by Carbapenemase-producing Enterobacteriaceae in the Pediatric Population.

Despite efforts made to prevent the spread of multi-drug-resistant bacteria, carbapenemase-producing Enterobacteriaceae (CPE) has become one of the most dangerous threat worldwide. However, data on the epidemiology of CPE and on the correlation between CPE colonization and infection are scanty. The objectives of this study were first to describe the epidemiologic characteristics of colonizations and invasive CPE infections in the pediatric population, and second, to apply the Giannella Risk Score (GRS) to the pediatric population for the assessment of the risk of invasive CPE infection in patients with already known colonization. Pediatric patients with evidence of colonization by CPE were retrospectively enrolled. For each colonized patient, the subsequent development of an infection by CPE was then assessed for a 90-day period after the first CPE isolation; GRSs were compared between patients who had developed any type of CPE infection and those without infection. A total of 215 patients (113 males and 102 females) with at least 1 isolation of CPE during hospitalization were analyzed. Median age was 5.6 years [interquartile range (IQR), 1.89-12.2 years]. Overall, 28 CPE infections (13%) were documented: 23 blood stream infections and 5 complicated urinary tract infections. The 30-day mortality of invasive CPE infections was 34.8%. The GRS values in patients with any CPE infection were statistically higher than in noninfected patients: median GRS 9 (IQR, 4-12.5) versus 4 (IQR, 2-4), respectively; P < 0.0001. The analysis of the receiver operating characteristic curves identified a GRS cut-off value ≥8 as the best predictor of CPE infection. The likelihood ratio of the results was <2 and the informedness of the test had a value <0.50. Our study confirms that the spread of CPE is an impelling problem also in the pediatric population, with a high mortality rate of invasive infections. However, the application of the GRS appears to be poorly informative in the pediatric setting; it might sometimes help to identify patients at very low-risk of CPE infection, in whom it is reasonable to spare targeted antimicrobial treatments.

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.

Carbapenem-resistant bacteria in an intensive care unit during the coronavirus disease 2019 (COVID-19) pandemic: A multicenter before-and-after cross-sectional study.

To assess the incidence of colonization and infection with carbapenemase-producing Enterobacteriaceae (CPE) and carbapenem-resistant Acinetobacter baumannii (CR-Ab) in the ICUs of our city hospitals before and during the coronavirus disease 2019 (COVID-19) pandemic. We conducted a multicenter, before-and-after, cross-sectional study to compare the rates of colonization and infection with CPE and/or CR-Ab in 2 study periods, period 1 (January-April 2019) and period 2 (January-April 2020). Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) of weekly colonization and infection rates for each period were compared for the 2 study periods using Poisson regression. Weekly trends in the incidence of colonization or infection for each study period were summarized using local weighted (Loess) regression. We detected no significant change in either IRR and weekly trend in CPE colonization and infection during the 2 study periods. A shift from KPC to other CPE mechanisms (OXA-48 and VIM) was observed during period 2. Compared to period 1, during period 2 the IRR of colonization and infection with CR-Ab increased 7.5- and 5.5-fold, respectively. Genome sequencing showed that all CR-Ab strains belonged to the CC92/IC2 clonal lineage. Clinical strains clustered closely into a single monophyletic group in 1 of the 3 centers, whereas they segregated in 2 different clusters in the other 2 centers, which strongly indicates horizontal transmission. Our findings indicate the need to conduct infection control activities targeted against the spread of antimicrobial resistance between and within hospitals during the COVID-19 pandemic, and if necessary, remodulating them according to the new organizational structures imposed by the pandemic.

Frequency of Bacteremia due to Carbapenemase-producing Enterobacteriaceae in Pediatric Hematology-Oncology Can Be Reduced by Measures of Hospital Infection Control

Objectives: The spread of carbapenemase-producing Enterobacteriaceae (CPE) is an emerging problem in children undergoing cancer-directed chemotherapy. A previous Italian survey reported a threefold increase in CPE colonization rate and a fourfold increase of CPE bloodstream infections in a 2 year-observation time interval. Methods: To assess the efficacy of the measures put in place to control this emergency, a second survey was performed in the years 2016-2017 and the results were compared. Results: The overall rate of colonization was comparable between the two study periods: 0.50% (2016-2017) vs. 0.48% (2012-2013). MDR/CPE bacteremia was now reported in 13 children from six centers. The rate of MDR/CPE bacteremia was 0.12 for 1,000 days of hospitalization (95% CI, 0.07-0.21) and compared favorably with that observed in the previous survey (0.42 for 1,000 days of hospitalization; 95% CI, 0.31-0.57; p<0.0001). The strains responsible for bacteremia were Klebsiella pneumonia in 9/13 children, Escherichia coli in 2/13, Citrobacter spp. and Stenotrophomonas maltophilia in one case each. The antibiotic susceptibility was available for 10 MDR/CPE strains. Conclusion: The number of patients colonized by CPE remained stable over the years, while the number of bloodstream infections decreased, as well as the resulting mortality. We conclude that children undergoing chemotherapy are at risk for CPE colonization/infection but the awareness of their colonization status may allow reducing CPE morbidity and mortality. J Microbiol Infect Dis 2021; 11(1):27-31.

The use of multi-pronged screening strategy to understand the epidemiology of carbapenemase-producing Enterobacteriaceae in Hong Kong: transition from epidemic to endemic setting.

A multi-pronged carbapenemase-producing Enterobacteriaceae (CPE) screening strategy was implemented in Hong Kong West healthcare network. Of 199,192 fecal specimens from 77,194 patients screening from 1 July 2011 to 30 June 2019, the incidence of CPE per 1000 patient admission significantly increased from 0.01 (2012) to 1.9 (2018) (p<0.01). With appropriate infection control measures, the incidence of nosocomial CPE per 1000 CPE colonization day decreased from 22.34 (2014) to 10.65 (2018) (p=0.0094). Exposure to wet market for purchasing raw pork (p=0.007), beef (p=0.017), chicken (p=0.026), and vegetable (p=0.034) for >3 times per week significantly associated with community acquisition of CPE. Strategic CPE control measures should be implemented in both the hospital and the community.

Carbapenemase-producing Enterobacteriaceae in transplant patients.

Carbapenemase-producing Enterobacteriaceae (CPE) are a serious public health concern and represent a major threat to immunocompromised hosts, including solid organ (SOT) and stem cell transplant (HSCT) recipients. Transplant patients are at particular risk of developing CPE colonization and/or infection due to their frequent exposure to prolonged courses of broad-spectrum antibiotics, altered immunocompetence and exposure to invasive procedures and immunosuppressive drugs. Gut colonization with CPE, in particular carbapenem-resistant Klebsiella pneumoniae, may occur before or after SOT in 2%-27% of patients and among 2%-9% of HSCT and has been associated with increased risk of developing CPE infections. In endemic areas, CPE infections occur in up to 18% of SOT, and HSCT patients can account for 5%-18% of all patients with CPE bacteraemia. Mortality rates up to 70% have been associated with CPE infections in both patient populations. The rapid initiation of an active therapy against CPE is advocated in these infections. Therapeutic options, however, are limited by the paucity of novel compounds that are currently available and by potential antibiotic-associated toxicities. Therefore, a multidisciplinary approach involving infection control and antimicrobial stewardship programmes still represents the mainstay for the management of CPE infections among transplant patients. The evidence for the use of prevention strategies such as CPE-targeted perioperative prophylaxis or gut decolonization is still scarce. Large, multicentre trials are required to better define prevention strategies and to guide the management of CPE infections in the transplant setting.

Stool Samples of Acute Diarrhea Inpatients as a Reservoir of ST11 Hypervirulent KPC-2-Producing Klebsiella pneumoniae.

The emergence and spread of carbapenem-resistant hypervirulent Klebsiella pneumoniae sequence type 11 (ST11-CR-HvKP) in China are a great concern in the public health community. However, the underlying mechanism that enables its wide dissemination in China remains unclear. Here, we investigated the prevalence of carriage of carbapenemase-producing Enterobacteriaceae (CPE) among inpatients with diarrhea in a teaching hospital over 1 year to identify ST11-CR-HvKP reservoirs and to understand the genetic background and plasmid profiles of these pathogens. As assessed by stool analysis, the CPE colonization rate (12.4%) among the inpatients with diarrhea was high (12.4%). Antibiotic exposure, surgical history, and CPE positivity were correlated. Genomic investigation of 65 carbapenem-resistant K. pneumoniae isolates indicated a shared bacterial population in various wards. According to maximum likelihood phylogenetic tree analysis, these isolates were partitioned into three major clades. Analysis of the wzi locus revealed three different K types (KL105, KL47, and K64) among the ST11 isolates, indicating the genetic diversity of these isolates. Genetic and sequence mapping revealed the complexity of virulence and resistance plasmid sets harbored by the isolates. These observations indicate that the dissemination of resistant bacteria is more complex than initially anticipated and possibly involves multiple K. pneumoniae ST11 lineages and a variety of virulence plasmids. Collectively, we show for the first time that stool may be a source of ST11-CR-HvKP isolates. Furthermore, the findings reveal the silent dissemination of ST11-CR-HvKP bacteria in Zhejiang Province, China. Future investigations are warranted to determine the association between rectal colonization by ST11-CR-HvKP and clinical infections.IMPORTANCE China has been experiencing a rapid increase in the number of nosocomial infections caused by carbapenem-resistant Klebsiella pneumoniae ST11 (ST11-CRKP) for decades. The emergence of hypervirulent ST11-CRKP (ST11-CR-HvKP) strains is expected to become a serious public health issue in China, considering that carbapenem resistance and virulence have converged in an epidemic clone. K. pneumoniae strains that colonize the human intestinal tract may become a reservoir of virulence and carbapenemase-encoding genes. Here, we first characterized the genotypes and antimicrobial phenotypes of ST11-CR-HvKP strains isolated from diarrheal stool samples of inpatients in Zhejiang Province, China. Active surveillance approaches based on the findings of the present study should be implemented, particularly in intensive care units, to combat the spread of ST11-CR-HvKP and to improve treatment.

Outbreak of carbapenemase-producing Enterobacteriaceae associated with a contaminated water dispenser and sink drains in the cardiology units of a Korean hospital

Concerns are growing over the importance of the hospital water environment for the transmission of carbapenemase-producing Enterobacteriaceae (CPE). To report a large outbreak in the cardiology units involving intensive care units (ICUs) and wards at a tertiary-care hospital. This was a contact tracing, case-control study to find the risk factors for acquisition of CPE and environmental sampling was performed during a CPE outbreak between July and December 2018. A total of 87 patients with CPE infection or colonization were identified in the cardiology units of the Asan Medical Centre. Diverse organisms were identified containing blakpc, blaNDM-1, blaVIM or blaIMP, blaOXA-48, and co-producing organisms. A case-control study indicated that using the sinks in the ward patient room bathroom for teeth brushing was associated with CPE acquisition (83% vs 30%; P=0.03). The environment was cultured and Klebsiella pneumoniae carbapenemase (KPC)-producing Escherichia coli was isolated from a water dispenser and New Delhi metallo-beta-lactamase (NDM) 1-producing Citrobacter freundii and Enterobacter cloacae from sinks in patient rooms. Pulsed-field gel electrophoresis (PFGE) analysis of KPC-producing E.coli from patients and the water dispenser in ICU and NDM-1-producing E.cloacae from the patient and sink drain showed the same pulsotypes. The water dispenser and sink drain were suspected as possible reservoirs of CPE in this outbreak. Close contacts with contaminated water such as tooth brushing were identified as risk factors for CPE acquisition. Education for the adequate use of the water environment system as well as the control of the hospital water environment should be implemented to prevent the CPE outbreaks.

530. Sequential Screening of High-Risk Patients for Carbapenemase-Producing Enterobacteriaceae Colonization

BackgroundEarly identification of patients colonized with carbapenemase-producing Enterobacteriaceae (CPE) facilitates the implementation of appropriate infection control measures and reduces nosocomial transmission. Sequential screening for CPE colonization of close contacts of known cases to confirm initial negative results is recommended. Fraser Health (FH) expanded sequential screening to patients with recent exposure to other risk factors following the identification of CPE in patients who initially screened negative.MethodsFH screens patients for CPE who report healthcare outside of Canada or travel to endemic countries within the previous 12 months. Patients remain on contact precautions and are re-screened 7 and 21 days after the last known exposure date. We reviewed CPE cases with foreign healthcare or travel to endemic countries who screened negative on admission but subsequently screened positive within 30 days. Patients without confirmation of colonization through a rectal screen or possible exposure to a current nosocomial source were excluded. Whole-genome sequencing results were examined to confirm foreign healthcare or travel as the likely source of acquisition. Medical records were reviewed to obtain patient history and clinical details.ResultsBetween November 2015 and January 2019, 21 patients had a positive CPE screen within 30 days of a negative screen, with no known CPE exposures during that time. The median time between the last date of known exposure and positive CPE screen was 20 days (range: 7–77 days). Twelve (57%) cases were hospitalized outside of Canada, 8 (38%) reported other foreign healthcare encounters, and 1 (5%) had no reported healthcare outside of Canada but had traveled to an endemic country. Sixteen (71%) cases received antibiotics prior to the positive CPE screen.ConclusionPatients with unrecognized CPE colonization are a source for nosocomial transmission. Patients screening negative for CPE with recent exposure to risk factors other than contact with a known case may screen positive at a later date. This may be due to higher colonization levels or antibiotic selection pressures. Consideration should be given to sequential CPE screening of high-risk patients based on the last day of exposure.Disclosures All authors: No reported disclosures.

2455. Outbreak of carbapenemase-producing Enterobacteriaceae in cardiology units associated with contaminated water dispenser and sink drain in Korea

BackgroundThere is a growing concern about the importance of hospital water environment for the transmission of carbapenemase-producing Enterobacteriaceae (CPE). Herein, we report a large outbreak in cardiology units involving intensive care units (ICU) and wards at a tertiary care hospital.MethodsDuring a CPE outbreak between July and December 2018, contact tracing and environmental sampling were performed. For outbreak control, we performed education to healthcare workers, hand hygiene enforcement, active surveillance test, preemptive isolation, chlorhexidine bathing for CPE positive patients, and deep terminal cleaning including UV and hydrogen peroxide non-touch disinfection. Patients with CPE were isolated at a single room with dedicated staffs, contact precaution was implemented, and when case patients were located in multi-patient room, we performed surveillance culture for exposed patients in the room.ResultsA total of 87 patients with CPE infection or colonization were identified at two cardiology ICUs and three cardiology wards. CPE from the first two index patients were identified from sputum culture suspecting pneumonia, and the remaining 85 patients were identified to harbor CPE through surveillance culture (exposed patients n = 22, active surveillance test n = 63). Diverse organisms were identified; organisms with blakpc (n = 13), blaNDM-1 (n = 55), blaVIM or blaIMP (n = 12), blaOXA-48 (n = 3), and co-producing organisms (n = 4). We performed environmental culture; KPC-producing Escherichia coli was isolated from water dispenser in ICU and NDM-1 producing Citrobacter freundii and Enterobacter cloacae were isolated from sinks in the patient room. Outbreak ended after the removal of water dispenser and the replacement of sink drain with pouring bleach to the sink drain.ConclusionWater dispenser and sink drain were suspected for the possible reservoirs of CPE in this outbreak. Replacement of plumbing system and use of bleach for pouring to sink as well as the removal of water dispenser was needed to control outbreak. Investigation of water system is warranted for finding the source of CPE. Disclosures All authors: No reported disclosures.

Infection prevention and control practices related to carbapenemase-producing Enterobacteriaceae (CPE) in acute-care hospitals in Ontario, Canada.

To determine infection prevention and control (IPAC) practices for carbapenemase-producing Enterobacteriaceae (CPE), an emerging threat, at acute-care hospitals in Ontario, Canada. A descriptive cross-sectional survey. We surveyed IPAC directors and managers at all acute-care hospitals in Ontario, Canada, to gather information on IPAC practices related to CPE, including admission screening, other patient screening, environmental testing, use of precautions to prevent transmission, and outbreak management. Of 116 acute-care hospitals, 105 (91%) responded. Admission screening included patients previously colonized or infected with CPE (n = 64, 61%), patients recently hospitalized outside of Canada (Indian subcontinent, n = 62, 59%; other countries, n = 56, 53%), and patients recently hospitalized in Canada (n = 22, 21%). Fifty-one hospitals (49%) screened patients for colonization during an outbreak. Almost all hospitals (n = 101, 96%) used precautions to prevent transmission from patients with CPE colonization or infection; most hospitals (n = 54, 53%) continued precautions indefinitely. Few hospitals (n = 19, 18%) performed environmental cultures. Eight hospitals (8%) reported at least 1 outbreak, and 6 hospitals (6%) reported transmission from sink or shower drains to patients. Variability in practices may result from lack of evidence and challenges in updating guidelines as evidence emerges. A coordinated approach to slow the emergence of CPE should be considered in our population.

The impact of carbapenemase-producing Enterobacteriaceae colonization on infection risk after liver transplantation: a prospective observational cohort study

ObjectiveTo investigate the impact of colonization with carbapenemase-producing Enterobacteriaceae (CPE) on the CPE infection risk after liver transplantation (LT). MethodsProspective cohort study of all adult patients undergoing LT at our centre over an 8-year period (2010–2017). Individuals were screened for CPE colonization by rectal swabs at inclusion onto the waiting list, immediately before LT and weekly after LT until hospital discharge. Asymptomatic carriers did not receive decolonization, anti-CPE prophylaxis or pre-emptive antibiotic therapy. Participants were followed up for 1 year after LT. ResultsWe analysed 553 individuals who underwent a first LT, 38 were colonized with CPE at LT and 104 acquired colonization after LT. CPE colonization rates at LT and acquired after LT increased significantly over the study period: incidence rate ratios (IRR) 1.21 (95% CI 1.05–1.39) and 1.17 (95% CI 1.07–1.27), respectively. Overall, 57 patients developed CPE infection within a median of 31 (interquartile range 11–115) days after LT, with an incidence of 3.05 cases per 10 000 LT-recipient-days and a non-significant increase over the study period (IRR 1.11, 95% CI 0.98–1.26). In multivariable analysis, CPE colonization at LT (hazard ratio (HR) 18.50, 95% CI 6.76–50.54) and CPE colonization acquired after LT (HR 16.89, 95% CI 6.95–41.00) were the strongest risk factors for CPE infection, along with combined transplant (HR 2.60, 95% CI 1.20–5.59), higher Model for End-Stage Liver Disease at the time of LT (HR 1.03, 95% CI 1.00–1.07), prolonged mechanical ventilation (HR 2.63, 95% CI 1.48–4.67), re-intervention (HR 2.16, 95% CI 1.21–3.84) and rejection (HR 2.81, 95% CI 1.52–5.21). ConclusionsCPE colonization at LT or acquired after LT were the strongest predictors of CPE infection. Prevention strategies focused on LT candidates and recipients colonized with CPE should be investigated.

Dissemination of multiple carbapenem resistance genes in an in vitro gut model simulating the human colon.

Carbapenemase-producing Enterobacteriaceae (CPE) pose a major global health risk. Mobile genetic elements account for much of the increasing CPE burden. To investigate CPE colonization and the impact of antibiotic exposure on subsequent resistance gene dissemination within the gut microbiota using a model to simulate the human colon. Gut models seeded with CPE-negative human faeces [screened with BioMérieux chromID® CARBA-SMART (Carba-Smart), Cepheid Xpert® Carba-R assay (XCR)] were inoculated with distinct carbapenemase-producing Klebsiella pneumoniae strains (KPC, NDM) and challenged with imipenem or piperacillin/tazobactam then meropenem. Resistant populations were enumerated daily on selective agars (Carba-Smart); CPE genes were confirmed by PCR (XCR, Check-Direct CPE Screen for BD MAX™). CPE gene dissemination was tracked using PacBio long-read sequencing. CPE populations increased during inoculation, plateauing at ∼105 log10 cfu/mL in both models and persisting throughout the experiments (>65 days), with no evidence of CPE 'washout'. After antibiotic administration, there was evidence of interspecies plasmid transfer of blaKPC-2 (111742 bp IncFII/IncR plasmid, 99% identity to pKpQIL-D2) and blaNDM-1 (∼170 kb IncFIB/IncFII plasmid), and CPE populations rose from <0.01% to >45% of the total lactose-fermenting populations in the KPC model. Isolation of a blaNDM-1K. pneumoniae with one chromosomal single-nucleotide variant compared with the inoculated strain indicated clonal expansion within the model. Antibiotic administration exposed a previously undetected K. pneumoniae encoding blaOXA-232 (KPC model). CPE exposure can lead to colonization, clonal expansion and resistance gene transfer within intact human colonic microbiota. Furthermore, under antibiotic selective pressure, new resistant populations emerge, emphasizing the need to control exposure to antimicrobials.

Carbapenemase-producing Enterobacteriaceae digestive carriage at hospital readmission and the role of antibiotic exposure

Colonization by carbapenemase-producing Enterobacteriaceae (CPE) may persist for several months after hospital discharge, especially in patients with altered microbiota. To identify how many previously OXA-48 CPE-positive patients identified during an outbreak period were readmitted; to evaluate their CPE-positive or -negative digestive tract colonization at hospital readmission and during readmission stay; and to assess the role of antibiotic exposure on their CPE colonization status during readmission. All CPE cohort patients from June 2013 to May 2016 (N= 189) were registered in a survey database and were systematically identified at readmission by a daily informatics and alert program using specific hospital population number. Each cohort patient was systematically screened for CPE colonization on the day of readmission and then weekly if the length of stay was more than six days. In all, 114 (60.3%) patients previously CPE-colonized were readmitted to our hospital. Excluding the 12 patients who were not screened because their period of readmission was <24 h, 88 patients were negative (86.3%) and 14 were positive (13.7%) for CPE colonization at first hospital readmission. The 14 CPE-positive patients did not change their infectious status and remained CPE-positive during the study period. Of the 88 negative patients, 65 remained negative during the study period, and 23 subsequently became CPE-positive after the negative readmission screening. CPE-positive colonization was significantly associated with antibiotic exposure during readmission periods (P < 0.001). Negative screens at hospital readmission did not necessarily predict resolution of CPE carriage. Antibiotic exposure appears to influence the risk of remaining CPE positive.

Survey of screening methods, rates and policies for the detection of carbapenemase-producing Enterobacteriaceae in English hospitals

Multi-drug-resistant Gram-negative bacteria are of major clinical concern. The increasing prevalence of carbapenemase-producing Enterobacteriaceae (CPE), resistant to all beta-lactams including carbapenems and able to colonize the large intestine, represents a key threat. Rapid, accurate detection of intestinal CPE colonization is critical to minimize transmission, and hence reduce costly, difficult-to-treat CPE infections. There is currently no 'gold standard' CPE detection method. A survey of diagnostic laboratories in England found considerable heterogeneity in diagnostic CPE testing methods and procedures.

Colonization and infection due to carbapenemase-producing Enterobacteriaceae in liver and lung transplant recipients and donor-derived transmission: a prospective cohort study conducted in Italy

ObjectivesA prospective cohort study was conducted in Italy in order to describe the microbiologic aspects of colonization/infection by carbapenemase-producing Enterobacteriaceae (CPE) in donors and recipients of lung and liver transplants and the possible CPE transmission from donors to recipients. MethodsBetween 15 January 2014 and 14 January 2015, all recipients of solid organ transplants (SOT) at ten lung and eight liver transplantation centres and the corresponding donors were enrolled. Screening cultures to detect CPE were performed in donors, and screening and clinical cultures in recipients with a 28-day microbiologic follow-up after receipt of SOT. Detection of carbapenemase genes by PCR, genotyping by multilocus sequence typing, and pulsed-field gel electrophoresis and whole-genome sequencing were performed. ResultsOf 588 screened donors, 3.4% were colonized with CPE. Of the liver first transplant recipients (n = 521), 2.5% were colonized before receipt of SOT and 5% acquired CPE during follow-up. CPE colonization was higher in lung first transplant recipients (n = 111, 2.7% before SOT and 14.4% after SOT). CPE infections occurred in 1.9% and 5.3% of liver or lung recipients, respectively. CPE isolates were mostly Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae belonging to CG258. Three events of donor–recipient CPE transmission, confirmed by whole-genome sequencing and/or pulsed-field gel electrophoresis, occurred in lung recipients: two involving K. pneumoniae sequence type 512 and one Verona integron-encoded metallo-β-lactamase (VIM)-producing Enterobacter aerogenes. ConclusionsThis study showed a low risk of donor–recipient CPE transmission, indicating that donor CPE colonization does not necessarily represent a contraindication for donation unless colonization regards the organ to be transplanted. Donor and recipient screening remains essential to prevent CPE transmission and cross-infection in transplantation centres.

An evaluation of a toolkit for the early detection, management, and control of carbapenemase-producing Enterobacteriaceae: a survey of acute hospital trusts in England

Following hospital outbreaks of carbapenemase-producing Enterobacteriaceae (CPE), Public Health England published a toolkit in December 2013 to promote the early detection, management, and control of CPE colonization and infection in acute hospital settings. To examine awareness, uptake, implementation and usefulness of the CPE toolkit and identify potential barriers and facilitators to its adoption in order to inform future guidance. A cross-sectional survey of National Health Service (NHS) acute trusts was conducted in May 2016. Descriptive analysis and multivariable regression models were conducted, and narrative responses were analysed thematically and informed using behaviour change theory. Most (92%) acute trusts had a written CPE plan. Fewer (75%) reported consistent compliance with screening and isolation of CPE risk patients. Lower prioritization and weaker senior management support for CPE prevention were associated with poorer compliance. Awareness of the CPE toolkit was high and all trusts with patients infected or colonized with CPE had used the toolkit either as provided (32%), or to inform (65%) their own local CPE plan. Despite this, many respondents (80%) did not believe that the CPE toolkit guidance offered an effective means to prevent CPE or was practical to follow. CPE prevention and control requires robust IPC measures. Successful implementation can be hindered by a complex set of factors related to their practical execution, insufficient resources and a lack of confidence in the effectiveness of the guidance. Future CPE guidance would benefit from substantive user involvement, processes for ongoing feedback, and regular guidance updates.