BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) are associated with poor clinical outcomes and can spread rapidly in healthcare settings. Environmental reservoirs are increasingly recognized as playing an important part in some nosocomial outbreaks.
OBJECTIVE: To describe the investigation and control of a CPE outbreak, lasting several years, across two separate hospital sites within one organization.
METHODS: Investigation of multiple ward-level CPE cross-transmissions with a number of sporadic cases. Environmental sampling of ward environments, catering facilities and electric floor scrubbers was undertaken.
RESULTS: Eleven patients over a 19-month period were identified as carrying healthcare-associated New Delhi metallo-beta-lactamase (NDM)-producing Enterobacter cloacae, and a further patient carried NDM Escherichia coli. E. cloacae isolates were indistinguishable on pulsed-field gel electrophoresis typing, supporting acquisition with a single point source. Environmental sampling found contamination of the electric floor scrubbers used for cleaning the hospital catering facilities and in the associated toilets. Standard outbreak response measures achieved control of ward outbreaks. Sporadic cases and hospital-wide cross-transmission were controlled after interventions on the central food-handling unit and by decommissioning affected floor scrubbers. Electric floor scrubbers were found to have the potential to disperse Gram-negative bacteria into the surrounding environment under experimental conditions.
CONCLUSIONS: This outbreak report demonstrates that catering facilities and kitchens can be involved in widespread healthcare outbreaks of enteric organisms. This is also the first report of the potential role of electric floor scrubbers in causing significant environmental contamination with CPE which may indicate a role in nosocomial transmission.

Carbapenemase-producing Enterobacterales (CPE) cases increases every year in Denmark and the proportion of CPE-positive cases with a travel history decreases. Several epidemiological links show transmission in Danish healthcare setting indicating infection prevention and control challenges and raising questions about the Danish CPE screening protocol. The aim of this review was to identify additional risk factors to those described in the Danish CPE-screening protocol in order to detect the Danish CPE-positive patients and thereby reduce the risk of transmission and outbreaks. A systematic literature search was conducted in PubMed, Embase and Cochrane Library during March 2022. A total of 1487 articles were screened, and 19 studies were included. Retrieved studies dealt with patients with laboratory-confirmed CPE (colonization and/or infection) and associated risk factors. Antimicrobial therapy, especially broad-spectrum antimicrobial agents, prior or current hospitalization of approximately one week in ICU and 20-28 days in other wards and travel history with or without hospitalization abroad were significant risk factors associated with CPE acquisition. Comorbidities and invasive procedures were identified as risk factors, but without identifying specific comorbidities or invasive procedures associated with risk for CPE-acquisition. This study suggests the need to develop an additional algorithm for CPE-screening in Denmark. In addition to risk-based screening on admission, screening of inpatients should be considered. The screening protocol might include screening of inpatients with comorbidities who are hospitalized >1 week in ICU or >3 weeks in other wards and who have previously received or currently are receiving antibiotic treatment. Further research is needed to develop a new CPE-screening algorithm.

Antimicrobial resistance (AMR) presents a growing threat to global healthcare. This descriptive epidemiological study investigates the prevalence and characteristics of Enterobacterales with AMR factors in a tertiary teaching hospital in Italy over the course of the year 2021. In 2021, the prevalence of colonisation by Enterobacterales with AMR factors in patients was 1.08%. During the observation period, a total of 8834 rectal swabs were performed, with 1453 testing positive. A total of 5639 rectal swabs were performed according to a hospital procedure for the active screening of MDRO colonisation at the time of admission. Of these, 679 were positive for microorganisms under surveillance, and 74 patients were colonised with Enterobacterales, predominantly Klebsiella pneumoniae and Escherichia coli. Antibiotic resistance factors were observed in 61 of these 74 patients (82.43%) of these patients, with NDM and KPC being the most frequent resistance factors. A statistically significant trend in positive swabs was observed across different ward categories (surgery, ICUs, and medical wards). Regarding specific trends, the rate of positive admission screening in medical and surgical wards was higher than in ICU wards. The results highlight the ease with which Enterobacterales develops resistance across different ward categories. The findings underscore the need for adjusted screening protocols and tailored infection prevention strategies in various care settings.

UNASSIGNED: To investigate the clinical, microbiological characteristics and outcomes of patients with bloodstream infections (BSI) due to carbapenemase-producing Enterobacterales (CPE).
UNASSIGNED: A multicentre retrospective observational study of patients with BSIs due to CPE admitted to six UK hospitals was conducted between 2011 and 2021. Multivariate analysis was used to identify factors predicting 30-day case fatality rate (CFR).
UNASSIGNED: There were 84 episodes of CPE-BSIs, 37 (44%) due to OXA-48, 35 (42%) to metallo-betalactamases (MBL) and 12 (14%) to KPC. 63% of patients were male with a median age of 64 years. Common organisms included Klebsiella spp. (61%), Escherichia coli (20%) and Enterobacter spp. (13%). Urinary devices were more often involved in OXA-48 BSIs (12/37; 32%) compared to infections caused by MBL and KPC (4/35; 11% and 1/12; 8%; P = 0.046). In contrast, central venous catheters were more frequently present in KPC-BSIs (10/12; 92%) compared with OXA-48 and MBL (11/37; 30% and 20/35; 57%; P = 0.002). Effective definitive antimicrobials were received by 72/84 (86%) patients, comprising monotherapy (32/72; 44%) or combination therapy (40/72; 56%). 30-day case fatality rate (CFR) was 38%. Sepsis or septic shock was associated with death [OR 3.81 (CI 1.19-12.14), P = 0.024].
UNASSIGNED: Strategies targeting high-risk patients and adherence to infection prevention bundles for urinary devices and central venous catheters can reduce OXA-48 and KPC-BSIs. Early recognition and management of severe sepsis, prompt initiation of appropriate antimicrobial therapy and development of novel antimicrobials are crucial to mitigate the high CFR associated with CPE-BSIs.

A higher diversity of species, clones and genes have been increasingly implicated in carbapenemases spread, though the mobile genetic elements responsible for their acquisition and dispersion at local and global levels are less explored, particularly in species other than Klebsiella pneumoniae or Escherichia coli. We aim to explain the emergence of NDM-1 and KPC-3 carbapenemases in a Kluyvera cryocrescens isolate, and to shed light on the heterogeneity of genetic platforms and acquisition routes of blaNDM-1 in diverse Enterobacterales species in Portugal.
A KPC-3 and NDM-1-producing K. cryocrescens colonizing a hospitalized patient in 2019 was characterized by whole-genome sequencing and antibiotic resistance profiling following standard methods. Conjugative transfer of carbapenemases genes was assessed by filter mating. Plasmids were reconstructed with in silico and in vitro approaches. blaNDM-1 genetic context was compared with that of diverse NDM-1-producing Enterobacterales species, previously described in Portugal.
K. cryocrescens K629 showed a multidrug resistance profile. Resistance gene blaKPC-3 was harboured by a Tn4401d transposon within a worldwide-spread IncN-ST15 plasmid (pKLU-KPC3), whereas blaNDM-1 was located in a Tn3000 within a non-typeable mosaic plasmid (pKLU-NDM1). The heterogeneous blaNDM-1 genetic platforms and variable plasmid backbones identified in various Enterobacterales species suggested multiple introductions of blaNDM-1 in Portugal, mediated by variable insertion sequences.
We report the convergence of KPC-3 and NDM-1 in K. cryocrescens and the variable dissemination modes of these carbapenemases in different Enterobacterales species, underlining the need to track down genetic platforms responsible for carbapenemases diffusion.

The spread of carbapenemase-producing Enterobacterales (CPE) is of major public health concern. The transmission dynamics of CPE in hospitals, particularly at the national level, are not well understood. Here, we describe a retrospective nationwide genomic surveillance study of CPE in Ireland between 2012 and 2017. We sequenced 746 national surveillance CPE samples obtained between 2012 and 2017. After clustering the sequences, we used thresholds based on pairwise SNPs, and reported within-host diversity along with epidemiological data to infer recent putative transmissions. All clusters in circulating clones, derived from high-resolution phylogenies, of a species (Klebsiella pneumoniae, Escherichia coli, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter hormaechei and Citrobacter freundii) were individually examined for evidence of transmission. Antimicrobial resistance trends over time were also assessed. We identified 352 putative transmission events in six species including widespread and frequent transmissions in three species. We detected putative outbreaks in 4/6 species with three hospitals experiencing prolonged outbreaks. The bla OXA-48 gene was the main cause of carbapenem resistance in Ireland in almost all species. An expansion in the number of sequence types carrying bla OXA-48 was an additional cause of the increasing prevalence of carbapenemase-producing K. pneumoniae and E. coli.

This study aimed to assess the proportion of carbapenemase-producing Enterobacterales (CPE) infections among all infectious episodes in CPE carriers, compare the time-to-onset of CPE infections with that of other infections, assess the mortality of patients with CPE infections, and identify risk factors for CPE infections in CPE carriers. A retrospective cohort study was performed over a 10-year period in our University Hospital, and 274 CPE carriers were identified. All infectious episodes within the first 6 months following the diagnosis of CPE rectal carriage were considered. Risk factor analysis for CPE infections in CPE carriers was performed by univariate and multivariate analyses. This study revealed an incidence of 24.1% (66/274) of CPE infection within 6 months of CPE carriage diagnosis. The 28-day all-cause mortality due to CPE infections was 25.7%. CPE infections represented 52.6% (70/133) of all infectious episodes in CPE carriers in the first 6 months following CPE carriage detection, and these significantly occurred earlier than non-CPE infections, with a median time of 15 versus 51 days, respectively (P < 0.01). Based on the multivariate analysis, prior neurological disease was the only risk factor associated with CPE infections in CPE carriers. CPE infections have an early onset, accounting for a large proportion of infections in CPE carriers, and are associated with high mortality. IMPORTANCE Carbapenemase-producing Enterobacterales (CPE) infections are emerging infections and may represent a therapeutic challenge, while effective antibiotic therapy is likely to be delayed. We aimed to assess the proportion of CPE infections in CPE carriers and to identify risk factors of CPE infections among this population that could guide empirical antibiotic therapy. We showed that CPE infections are frequent in CPE carriers, have an early onset after CPE carriage diagnosis, and represent a significant proportion of all infectious episodes in CPE carriers. No significant risk factors for CPE infections could be identified. Overall, this study suggests that empirical antibiotic treatment covering CPE might be initiated in CPE carriers at least in the first month after its diagnosis and in severe infections due to the high frequency and early occurrence of CPE infections in these patients.

Infections due to Klebsiella pneumoniae have been increasing in intensive care units (ICUs) in the last decade. Such infections pose a serious problem, especially when antimicrobial resistance is present. We created a task force of experts, including specialists in intensive care medicine, anaesthesia, microbiology and infectious diseases, selected on the basis of their varied experience in the field of nosocomial infections, who conducted a comprehensive review of the recently published literature on the management of carbapenemase-producing Enterobacterales (CPE) infections in the intensive care setting from 2012 to 2022 to summarize the best available treatment. The group established priorities regarding management, based on both the risk of developing infections caused by K. pneumoniae and the risk of poor outcome. Moreover, we reviewed and updated the most important clinical entities and the new antibiotic treatments recently developed. After analysis of the priorities outlined, this group of experts established a series of recommendations and designed a management algorithm.

BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) can colonize the gut and are of major clinical concern. Identification of CPE colonization is problematic; there is no gold-standard detection method, and the effects of antibiotic exposure and microbiota dysbiosis on detection are unknown.
OBJECTIVE: Based on a national survey we selected four CPE screening assays in common use. We used a clinically reflective in vitro model of human gut microbiota to investigate the performance of each test to detect three different CPE strains under different, clinically relevant antibiotic exposures.
METHODS: Twelve gut models were seeded with a pooled faecal slurry and exposed to CPE either before, after, concomitant with, or in the absence of piperacillin-tazobactam (358 mg/L, 3 × daily, seven days). Total Enterobacterales and CPE populations were enumerated daily. Regular screening for CPE was performed using Cepheid Xpert® Carba-R molecular test, and with Brilliance™ CRE, Colorex™ mSuperCARBA and CHROMID® CARBA SMART agars.
RESULTS: Detection of CPE when the microbiota are intact is problematic. Antibiotic exposure disrupts microbiota populations and allows CPE proliferation, increasing detection. The performances of assays varied, particularly with respect to different CPE strains. The Cepheid assay performed better than the three agar methods for detecting a low level of CPE within an intact microbiota, although performance of all screening methods was comparable when CPE populations increased in a disrupted microbiota.
CONCLUSIONS: CPE strains differed in their dynamics of colonization in an in vitro gut model and in their subsequent response to antibiotic exposure. This affected detection by molecular and screening methods, which has implications for the sensitivity of CPE screening in healthcare settings.

The FecalSwab® displays high performances for stool culture, but it was not assessed for carbapenemase-producing Enterobacterales (CPE) screening. We assess the performances of the Xpert Carba-R v2® with the FecalSwab®. Using a collection of 12 CPE strains, the limit of detection was assessed at 158 CFU/swab [interquartile range 93-589]. In 2019, 1540 swabs were included by 4 hospital laboratories, of which 39 (2.5%) yield an invalid result. Among the 1501 valid, 87 (5.8%) were positives by culture and PCR and 25 (1.7%) were discrepant: 7 PCR-negative culture-positive, and 18 PCR-positive culture-negative. Two PCR-positive culture-negative results involved non-Enterobacterales strains: a KPC-producing Acinetobacter baumannii and a KPC-producing Aeromonas spp. The overall percent agreement was 98.3% and the Kappa value was 0.88. FecalSwab® is an accurate sampling device for CPE screening. It allows performing all eXDR screening using a single swab, simplifying the sample collection, and improving the patient comfort. Regarding discrepant, we suggest combining a CPE screening by both culture and Xpert Carba-R v2® methods.