Prevalence Of Carbapenemase-producing Enterobacteriaceae Research Articles

Carbapenemase-Producing Enterobacteriaceae detected in a Large Canadian Tertiary Care Hospital: Five-year retrospective study

Background: The prevalence of carbapenemase-producing Enterobacteriaceae (CPE) is increasing worldwide. In Canada, where rates of healthcare-associated (HA) transmission of CPE remains relatively low, there is a need to share early experience of universal screening programs and risk factors for HA acquisition. Method: In 2018, universal screening was introduced throughout our large Canadian tertiary care hospital across, all critical care and oncology units. Additionally, risk-factor based screening was applied in all other inpatient units, with further targeted screening of roommate exposures or all inpatients on unit following identification of a single HA case. A retrospective cohort study was carried out on CPE cases detected between January 2018 and December 2023. We assessed the proportion of HA CPE cases, defined as CPE identified in patients with prior admission to our facility or after >72 hours after admission. HA cases were examined for relevant risk factors, including known roommate with CPE, the presence of other CPE on the unit, exposure to outbreak units, prior travel history, travel by a family member, and antibiotic exposure within the past 90 days. Result: A total of 150 CPE cases were identified, with 66 (44%) classified as HA. Among these HA cases, 14 (21%) were associated with presence of known case on the unit. The remaining 52 (79%) represented sporadic nosocomial cases without a known exposure or further transmission on the unit. Upon further retrospective review, 6 (9.2%) HA cases had documented travel history or exposure to a family member with recent travel to China, India, Sri Lanka, or the United States within the past year. Nearly all HA cases (62, 95.4%) had antibiotic exposure within 90 days of CPE detection; specifically, 47 (72.3%) received beta-lactams, 42 (64.6%) cephalosporin, 25 (38.5%) glycopeptide, 20 (30.8%) carbapenem, and 8 (12.3%) macrolide. Conclusion: HA CPE acquisition identified during the first 5-years of universal screening were mostly sporadic and not associated with known exposures or other risk factors. Receipt of prior antibiotics was present in nearly all cases.

Phenotypic Characterization of Carbapenemase-Producing Enterobacteriaceae Strains in a Referral Teaching Hospital in Yaoundé, Cameroon

Background: Carbapenemase-producing Enterobacteriaceae (CPE) are an important and increasing threat to global health. They are nowadays more encountered routinely in hospitals and cause high morbidity and mortality due to limited therapeutic alternatives. This study sought to determine the prevalence of CPE in Yaoundé teaching hospital, Cameroon, and the associated risk factors. Materials and Method: To achieve this goal, a descriptive cross-sectional study coupled to an analytical component with consecutive collection of Enterobacteria strains was carried out during a three-month period (from 27th July to 24th October 2018) in the University Teaching Hospital of Yaoundé, Cameroon. The oxidase and biochemical identification tests using a miniaturized Api 20 E system were performed on colonies grown on Eosin Methylene Blue (EMB) medium and subcultured on nutrient agar. Drug susceptibility testing was carried out according to the Antibiogram Committee of the French Society of Microbiology (CA-SFM 2018.V.2.0). The detection of carbapenemase production was performed by the CA-SFM 2018 algorithm for the screening of carbapenemase-producing enterobacteriaceae and its classification by inhibitory synergy tests. Results: Out of the 104 isolates, Escherichia coli (50%) was the most prevalent species, followed by Klebsiella pneumoniae (37.5%) and Citrobacter frendii (12.5%). Drugs susceptibility patterns showed a high resistance to penicillins group (97.4% to amoxicillin), cephalosporins (68.4% to cefotaxim, 58.1% to cefixim, 60.7% to ceftazidim, 57.1% of cefoxitin) and aztreonam (55.7%). However, 11.9% carbapenems related resistance was noticed: 14.4% to imipenem, 13.8% to ertapenem and 7.5% to meropenem. Numerous co-resistance to quinolones (65.8%), fluoroquinolones (49.6%), aminoglycosides (49.6%) and cotrimoxazole (71.8%) were also observed. From 104 isolates, AmpC production represented 23.08% (25/104) and 36.54% (38/104) were ESBL-isolates. The overall prevalence of CPE was 25% (26/104) with K.pneumoniae predominant (61.53%). Besides, Class A and class B carbapenemase were mainly produced with respectively 20% (21/104) and 5% (5/104). Univariate analysis revealed a significant association of carbapenemase production to Klebsiella pneumoniae (p = 0.01), ESBL and AmpC production ((P = 0.01 and P = 0.001 respectively) while that association was only significant to Klebsiella spp (p = 0.04) and AmpC production (p = 0.02) in multivariate analysis. Conclusion: The multi-resistance of Enterobacteriaceae to antibiotics in Cameroon has considerably increased. More attention should be paid to those bacteria to stall antimicrobial resistance spread.

Outbreak of Carbapenemase-Producing Enterobacteriaceae in a Regional Burn Center.

Antimicrobial resistance is an increasing problem in hospitals worldwide; however, the prevalence of carbapenemase-producing Enterobacteriaceae (CPE) in our region is low. Burn patients are vulnerable to infection because of the loss of the protective skin barrier, thus burn centers prioritize infection prevention and control (IP&C). This report describes a CPE outbreak in a regional burn center. In a period of 2.5 months, four nosocomial cases of CPE were identified, three containing the Klebsiella pneumoniae carbapenemase (KPC) gene and one Verona integrin-encoded metallo-β-lactamase (VIM) gene. The first two cases were identified while there was no CPE patient source on the unit. CPE KPC gene was then isolated in sink drains of three rooms. In addition to rigorous IP&C practices already in place, we implemented additional outbreak measures including restricting admissions to patients with complex burns or burns ≥10% TBSA, admitting patients to other in-patient units, and not permitting elective admissions. We began cohorting patients using nursing team separation for CPE-positive and -negative patients and geographical separation on the unit. Despite aggressive IP&C measures already in place, hospital-acquired CPE colonization/infection occurred. Given that CPE contaminated sinks of the same enzyme were identified, we believe hospital sink drains may the source. This highlights the importance of sink design and engineering solutions to prevent the formation of biofilm and reduce splashing. CPE infections are associated with poor outcomes in patients and significant health system costs due to a longer length of stay and additional institutional resources.

Probabilistic microsimulation to examine the cost-effectiveness of hospital admission screening strategies for carbapenemase-producing enterobacteriaceae (CPE) in the United Kingdom

BackgroundAntimicrobial resistance has been recognised as a global threat with carbapenemase- producing-Enterobacteriaceae (CPE) as a prime example. CPE has similarities to COVID-19 where asymptomatic patients may be colonised representing a source for onward transmission. There are limited treatment options for CPE infection leading to poor outcomes and increased costs. Admission screening can prevent cross-transmission by pre-emptively isolating colonised patients.ObjectiveWe assess the relative cost-effectiveness of screening programmes compared with no- screening.MethodsA microsimulation parameterised with NHS Scotland date was used to model scenarios of the prevalence of CPE colonised patients on admission. Screening strategies were (a) two-step screening involving a clinical risk assessment (CRA) checklist followed by microbiological testing of high-risk patients; and (b) universal screening. Strategies were considered with either culture or polymerase chain reaction (PCR) tests. All costs were reported in 2019 UK pounds with a healthcare system perspective.ResultsIn the low prevalence scenario, no screening had the highest probability of cost-effectiveness. Among screening strategies, the two CRA screening options were the most likely to be cost-effective. Screening was more likely to be cost-effective than no screening in the prevalence of 1 CPE colonised in 500 admitted patients or more. There was substantial uncertainty with the probabilities rarely exceeding 40% and similar results between strategies. Screening reduced non-isolated bed-days and CPE colonisation. The cost of screening was low in relation to total costs.ConclusionThe specificity of the CRA checklist was the parameter with the highest impact on the cost-effectiveness. Further primary data collection is needed to build models with less uncertainty in the parameters.

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.

112 Outbreak of Carbapenemase-Producing Enterobacteriaceae in a Regional Burn Centre

Abstract Introduction Antimicrobial resistance is an increasing problem in hospitals worldwide, though the prevalence of carbapenemase-producing Enterobacteriaceae (CPE) in our region is low. Burn patients are among the most vulnerable to infection because of the loss of the protective skin barrier. Because of this, burn centres prioritize infection prevention and control with measures like additional precautions, enhanced environmental cleaning, dedicated facilities, and mandatory use of personal protective equipment (PPE). Methods This report describes a CPE outbreak in a regional burn centre. We hypothesized that contamination of in-room hand hygiene sinks with CPE was a potential source of transmission. In a period of 2.5 months, four nosocomial cases of CPE were identified, three containing the KPC gene and one VIM gene. There was more than one month between the first and second KPC case, with no overlap in patient stay or rooms. Results The first two cases were identified while there was no CPE patient source on the unit. CPE KPC gene was isolated in sink drains of three different rooms. In addition to the rigorous infection control practices already in place due to the unique patient population, additional outbreak control measures were implemented. The burn centre restricted admissions to complex burns or burns >10% total body surface area, in consultation with the attending surgeon. No elective admissions were permitted. To avoid CPE exposure to new patients, initial admissions were rerouted to the emergency department and, if possible, the patient was admitted to another unit. Patient cohorting was implemented through nursing team separation for CPE positive and negative patients and geographical separation of CPE positive cases to one side of the unit. Conclusions Despite aggressive infection control measures already in place at our burn centre, there was hospital acquired CPE colonization/infection. Given there was CPE acquisition when there was no positive patients on the unit and CPE contaminated sinks of the same enzyme were identified, it suggests that hospital sink drains can become a potential source of CPE.

Emergence of Enterobacter cloacae Complex Co-Producing IMP-10 and CTX-M, and Klebsiella pneumoniae Producing VIM-1 in Clinical Isolates in Japan.

Background: Carbapenemase-producing Enterobacteriaceae (CPE) are an emerging threat in healthcare settings worldwide. Objectives: We evaluated the presence of carbapenemase genes in CPE in a tertiary care university hospital in Tokyo, Japan. Methods: Carbapenem-resistant clinical isolates were collected in 2018 at Teikyo University Hospital (Tokyo, Japan). Bacterial species were identified using MALDI-TOF MS. Carbapenemase production was evaluated using a carbapenemase inactivation method. The presence of carbapenemase genes was confirmed by multiplex PCR and DNA sequencing. Results: Four CPE isolates were identified: two Enterobacter cloacae complex strains and Klebsiella oxytoca and Klebsiella pneumoniae strains. Three of the isolates (E. cloacae complex and K. oxytoca) were IMP-1-type producers, including IMP-10 in their produced metallo-β-lactamase, and are epidemic in East Japan. The IMP-10-producing E. cloacae complex strain also produced CTX-M ESBL. The other CPE isolate (K. pneumoniae) is a VIM-1 producer. VIM-1-producing K. pneumoniae is epidemic in Europe, especially in Greece. Accordingly, the VIM-1 producer was isolated from a patient with a medical history in Greece. Conclusions: This study revealed the emergence of E. cloacae complex co-producing IMP-1-type carbapenemase and CTX-M ESBL, and K. pneumoniae producing VIM-1 carbapenemase in clinical isolates in Japan. Metallo-β-lactamase was the most prevalent type of carbapenemase at Teikyo University Hospital, especially IMP-1-type carbapenemase. The detection of VIM-1-producing K. pneumoniae suggests that epidemic CPE from overseas can spread to countries with low CPE prevalence, such as Japan, highlighting the need for active surveillance.

Routinely available antimicrobial susceptibility information can be used to increase the efficiency of screening for carbapenemase-producing Enterobacteriaceae.

Introduction. Increased carbapenem resistance is often caused by carbapenemase production.Aim. The objective of our study was to assess which antibiotic susceptibility patterns, as tested by automated systems, are highly associated with the absence of carbapenemase production in Enterobacteriaceae isolates, and could therefore be used as a screening tool.Methodology. Routine antibiotic susceptibility testing data from 42 medical microbiology laboratories in the Netherlands in the period between January 2011 and June 2017 were obtained from the national antimicrobial resistance surveillance programme. Data on Enterobacteriaceae isolates that had an elevated minimum inhibitory concentration (MIC) for carbapenems (meropenem >0.25 mg l-1 or imipenem >1.0 mg l-1) were selected and subjected to phenotypic or genotypic carbapenemase production testing. Routinely available amoxicillin/clavulanic acid, piperacillin/tazobactam, cefuroxime and ceftriaxone/cefotaxime susceptibilities were studied in relation to carbapenemase production by calculating the negative predictive value.Results. No evidence for carbapenemase-producing Enterobacteriaceae (CPE) was found in 767 of 1007 (76 %) isolates. The negative predictive value was highest for amoxicillin/clavulanic acid (99.6 %) and piperacillin/tazobactam (98.8 %).Conclusion. Enterobacteriaceae isolates with elevated carbapenem MICs that are susceptible to amoxicillin/clavulanic acid or piperacillin/tazobactam are unlikely to be carbapenemase producers. Preselection based on this susceptibility pattern may lead to increased laboratory efficiency and reduction of costs. Whether this is also true for countries with a different distribution of CPE species and types or a higher prevalence of CPE needs to be studied.

Epidemiological Study of an Outbreak of KPC-2-producing Klebsiella pneumoniae in a Tertiary Hospital in Korea

Background: The prevalence of carbapenemase-producing Enterobacteriaceae (CPE), especially the KPC-2-producing Klebisella pneumoniae, is rapidly increasing and becoming a menace to global public health. This study aims to present the molecular epidemiology of the KPC-2-producing K. pneumoniae isolates emerged in a tertiary hospital in South Korea and describe its clinical significance. Methods: This study included carbapenem-resistant K. pneumoniae isolates collected from a tertiary hospital from April to December in 2018. Antimicrobial susceptibility of K. pneumoniae isolates was tested using disk diffusion method. PCR and DNA sequence analyses were performed to identify the resistance genotype. In addition, the molecular epidemiology was investigated using pulsed-field gel electrophoresis (PFGE) and multilocus sequencing typing (MLST). Results: Total 100 KPC-2-producing K. pneumoniae isolates were collected, which were mainly classified into two pulsotypes according to the XbaI restriction digestion pattern by PFGE analysis (pulsotype A, n = 31; pulsotype B, n = 63). The isolates exhibiting pulsotype A belonged to ST395 and the remaining isolates exhibiting pulsotype B were attributed to ST307 by MLST analysis. Conclusion: This study investigated clinical information and molecular bacterial profiles for KPC-2-producing K. pneumoniae isolates. These findings indicate that the proper infection control activities are needed to prevent the spread of multidrug-resistant organisms such as CPE, which could cause high mortality in clinical field.

Prevalence and Characteristics of Carbapenemase-Producing Enterobacteriaceae in Three Tertiary-Care Korean University Hospitals between 2017 and 2018.

The aim of this study was to evaluate the prevalence and characteristics of carbapenemase-producing Enterobacteriaceae (CPE) from 3 tertiary-care Korean university hospitals between 2017 and 2018. Non-duplicated clinical isolates of Enterobacteriaceae showing resistance to any carbapenem agents were collected prospectively from 3 tertiary university hospitals between 2017 and 2018. The presence of carbapenemase genes was detected by multiplex PCR and sequencing for blaKPC, blaVIM, blaNDM, blaIMP, blaOXA, and blaGES was performed. Among the 690 potential carbapenem-resistant Enterobacteriaceae (CRE) isolates, 66.8% (N = 461) were CPE. The species distribution of CPE was as follows: Klebsiella pneumoniae was most common (75.9%), followed by Escherichia coli (15.0%), Citrobacter freundii (4.6%), Enterobacter cloacae (2.6%), Klebsiella. aerogenes (0.7%), and Klebsiella. oxytoca (0.4%). All 11 CPE genes were detected, particularly K. pneumoniae carbapenemase (KPC)-2 (87.6%), New Delhi metallo-β-lactamase (NDM)-1 (7.4%), NDM-5 (1.7%), KPC-3 (1.3%), oxacillinase (OXA)-232 (1.1%), and OXA-181 (1.1%). Six isolates produced 2 or 3 carbapenemases. The majority of the carbapenemase-producing C. freundii tested positive for NDM-1. We confirmed a high proportion of CPE among the CRE isolates with a high prevalence of KCP-2-producing K. pneumoniae and E. coli. Therefore, there is a need for undertaking continuous surveillance to monitor the prevalence of CPE.

Prevalence and associated factors for carriage of Enterobacteriaceae producing ESBLs or carbapenemase and methicillin-resistant Staphylococcus aureus in Hong Kong community

ObjectivesWe conducted a cross-sectional study in Hong Kong community to estimate the carriage prevalence, associated factors and genotypes of extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E), methicillin-resistant Staphylococcus aureus (MRSA) and carbapenemase-producing Enterobacteriaceae (CPE). MethodsSeemingly healthy subjects were asked to provide nasal, handprint and stool samples from March to April 2017. Isolates were characterized by molecular methods. We used multivariable logistic regression models within a generalized estimating equation framework to identify risk factors for ESBL-E carriage. Characteristics of MRSA/CPE carriage were summarized. ResultsThe prevalence of ESBL-E, MRSA and CPE were 52.8% (104/197), 2.5% (5/197) and 0.5% (1/197) respectively. Most ESBL-E isolates were E. coli (85.6%; 113/132). Most ESBL genes belonged to blaCTX−M-G9 (68.9%) and blaTEM (53.0%) types. Self-reported antibiotic consumption (≥2 courses) in the past six months was associated with ESBL-E carriage (adjusted odds ratio: 4.71–5.47). ConclusionsAbundance of ESBL-E in the community are causes of concern, and antibiotic use is associated with its carriage. Presence of MRSA and CPE in community members without clear healthcare exposure hints on a change in their epidemiology. This study establishes a baseline to formulate infection control policies and future studies in combating antimicrobial resistance.

Prevalence and Characteristics of Extended-Spectrum-β-Lactamase-Producing and Carbapenemase-Producing Enterobacteriaceae from Freshwater Fish and Pork in Wet Markets of Hong Kong.

This study identified and characterized extended-spectrum-β-lactamase-producing Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) from farmed freshwater fish and pig offal procured from the wet markets across Hong Kong. During March 2018 to January 2019, 730 food animal samples, namely, 213 snakehead fish, 198 black carp, and 339 pig organs, were examined. ESBL-E and CPE were isolated from the homogenized samples plated on selective media and identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS). All ESBL-E and CPE strains were tested for antimicrobial susceptibilities. ESBL-E and CPE gene groups were detected by multiplex PCR and blaCTX-M-1/-2/-9 group strains were Sanger sequenced for CTX-M types. All CPE isolates were whole-genome sequenced. Isolation of ESBL-E from pig small (52.4%) and large (50%) intestines and tongues (25.1%) was significantly (P < 0.05) more frequent than from snakehead (0.94%) and black carp (0.5%) fish. ESBL-E isolates (n = 171) revealed resistance rates of 16.3%, 29.8%, 35.6%, 53.2%, 55.0%, and 100% to piperacillin-tazobactam, amoxicillin-clavulanate, cefepime, gentamicin, ciprofloxacin, and ampicillin, respectively, whereas CPE (n = 28) were resistant to almost all the antibiotics tested except gentamicin, ciprofloxacin, and fosfomycin. The predominant ESBL gene groups in fishes and pig offals were blaCTX, where blaCTX-M-55 was the major subtype in the blaCTX-M-1 group (64.4% of isolates in the group). blaCTX-M-14/-17 was the major genotype in the blaCTX-M-9 group (32.2%). All CPE strains possessed blaNDM genes. High rates of ESBL-E and CPE were identified in food animals from wet markets of Hong Kong, which may serve as a potential reservoir of antimicrobial-resistant genes and increase the challenges in tackling antimicrobial resistance beyond health care settings.IMPORTANCE Extended-spectrum-β-lactamase-producing Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) are of global health importance, yet there is a paucity of surveillance studies on food animals in Hong Kong. Here, we report a high prevalence of ESBL-E (ranging from 0.5% to 52.4%) and CPE (0% to 9.9%) from various food animal samples procured from wet markets across Hong Kong. All CPE strains were characterized by whole-genome sequencing and possessed NDM-1 and -5 genes and other resistance determinants. Given the increased resistance profile of these strains, this study highlights the emerging threat of ESBL-E and CPE disseminated in farmed animals. Furthermore, our data enriched our understanding of antibiotic resistance reservoirs from a One Health perspective that can widely spread across various niches, beyond health care settings.

Environmental Presence and Genetic Characteristics of Carbapenemase-Producing Enterobacteriaceae from Hospital Sewage and River Water in the Philippines.

This study aimed to evaluate the prevalence and genetic characteristics of carbapenemase-producing Enterobacteriaceae (CPE) in hospital sewage and river water in the Philippines, which has a typical tropical maritime climate. We collected 83 water samples from 7 hospital sewage and 10 river water sites. CPE were identified using CHROMagar mSuperCARBA, and Gram-negative strains were identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) or 16S rRNA gene sequencing. Resistance genes in Enterobacteriaceae strains were identified using PCR and DNA sequencing, and transferability of carbapenemase genes from the CPE was investigated with conjugation experiments. Genotyping was performed using multilocus sequence typing (MLST) for Escherichia coli and Klebsiella pneumoniae Out of 124 Enterobacteriaceae isolates, we identified 51 strains as CPE and divided these into 7 species, 11 E. coli, 14 Klebsiella spp., 15 Enterobacter spp., and 11 others, including 4 additional species. Conjugation experiments via broth mating and using E. coli J53 revealed that 24 isolates can transfer carbapenemase-encoding plasmids. MLST analysis showed that 6 of 11 E. coli isolates belonged to clonal complex 10 (CC10). Of 11 K. pneumoniae strains, 9 unique sequence types (STs) were identified, including ST147. Five types of carbapenemase genes were identified, with the most prevalent being NDM (n = 39), which is epidemic in clinical settings in the Philippines. E. coli CC10 and K. pneumoniae ST147, which are often detected in clinical settings, were the dominant strains. In summary, our results indicate that hospital sewage and river water are contaminated by CPE strains belonging to clinically important clonal groups.IMPORTANCE Carbapenemase-producing Enterobacteriaceae (CPE) cause severe health care-associated infections, and their increasing prevalence is a serious concern. Recently, natural ecosystems have been recognized as important reservoirs of antibiotic resistance genes. We investigated the prevalence and genetic characteristics of CPE isolated from the environment (hospital sewage and river water) in the Philippines and found several CPE, including Escherichia coli and other species, with different carbapenemases. The most prevalent carbapenemase gene type was NDM, which is endemic in clinical settings. This study revealed that isolates belonging to carbapenemase-producing E. coli CC10 and K. pneumoniae sequence type 147 (ST147), which are often detected in clinical settings, were dominant in the natural environment. Our work here provides a report on the presence and characteristics of CPE in the environment in the Philippines and demonstrates that both hospital sewage and river water are contaminated by CPE strains belonging to clinically important clonal groups.

Characterization of VIM-1-Producing E. coli Isolated From a German Fattening Pig Farm by an Improved Isolation Procedure.

A few reports indicate that livestock might represent a new reservoir for carbapenemase-producing Enterobacteriaceae (CPE). In 2015, VIM-1-producing Escherichia coli were detected at slaughter in colon contents of animals from a German fattening pig farm within the national monitoring on ESBL-producing E. coli. In this study, pooled faces samples from pigs, as well as samples from the barn surrounding environment of this fattening farm were taken, to evaluate the dissemination of CPEs. Several modifications of the culture-dependent detection procedure were investigated for their potential to improve the sensitivity of the CPE isolation method. The current reference procedure was adapted by adding a real-time PCR pre-screening and additional enrichment steps. It was possible to isolate 32 VIM-1-producing E. coli from four fecal samples of three different barns using two serial enrichment steps in combination with real-time PCR and selective agar plates. By genetic typing, we confirmed the presence of two E. coli clonal lineages circulating on this particular farm: one was harboring the blaVIM–1 on an IncHI2 plasmid while the second lineage carried the gene on the chromosome. Despite its different locations, the blaVIM–1 gene was harbored on a class 1 integron in both clonal lineages. Whole-genome sequencing revealed that the VIM-1-carrying plasmids exhibited only slight variability in its compositions and sizes. We assume that the prevalence of CPEs in animal production in Germany and other European countries might be underestimated and there is a concern of further spread of VIM-1-producing bacteria in German livestock and food.

Ertapenem non-susceptibility and independent predictors of the carbapenemase production among the Enterobacteriaceae isolates causing intra-abdominal infections in the Asia-Pacific region: results from the Study for Monitoring Antimicrobial Resistance Trends (SMART).

ObjectivesThis study investigated the prevalence rates of carbapenemase positivity, antibiotic susceptibility, and independent predictors of carbapenemase producers among the Enterobacteriaceae isolates recovered from patients with intra-abdominal infections (IAI) in the Asia-Pacific region between 2008 and 2014.Materials and methodsMultiplex PCR was used for the detection of specific β-lactamases, while the broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of antibiotics among the IAI-related Enterobacteriaceae isolates. We studied the abovementioned parameters in 484 ertapenem-non-susceptible (Erta-NS) isolates and explored the independent predictors of carbapenemase-producing Enterobacteriaceae (CPE) isolates.ResultsEighty (16.5%) Erta-NS-IAI Enterobacteriaceae isolates were found to be CPE. Vietnam and the Philippines had the highest CPE prevalence rates. The IAI isolates of Enterobacter species and Klebsiella pneumoniae followed by Escherichia coli were the three major pathogens with 77.4%, 40.9%, and 11.7% Erta-NS prevalence rates, respectively. Furthermore, the highest CPE prevalence (35%) was noted among the Erta-NS-K. pneumoniae isolates. The CPE isolates harboring the blaNDM, blaKPC, or blaOXA-48-like alleles had higher imipenem MIC levels than those harboring the blaIMP alleles. Using multivariate logistic regression analysis, we concluded that Erta-NS-IAI isolates with an imipenem non-susceptible phenotype (OR, 56.4), with cefepime MIC >8 µg/mL (OR, 4.4), cultured from the peritoneal space samples (tissue or abscess; OR, 3.3), and harboring the extended-spectrum β-lactamase encoding allele (OR, 11.5) are independent predictors of CPE.ConclusionImipenem non-susceptibility, cefepime MIC >8 µg/mL, and the peritoneal space as a culture site are independent clinical predictors of CPE among the Erta-NS-IAI Enterobacteriaceae isolates in the Asia-Pacific region.

Activity of ceftazidime-avibactam against carbapenemase-producing Enterobacteriaceae from urine specimens obtained during the infection-carbapenem resistance evaluation surveillance trial (iCREST) in Spain

The increasing rates of carbapenemase-producing Enterobacteriaceae (CPE) represent an important threat to health care systems and treatment of CPE infections is a challenge. The aim of the infection-carbapenem resistance evaluation surveillance trial (iCREST) was to determinate the prevalence of CPE in urine specimens in Spain and to evaluate the in vitro activity of ceftazidime-avibactam. Urine specimens (n = 11 826) were included and activity of ceftazidime-avibactam and comparators were investigated by broth microdilution in CPE. Carbapenemases were characterised by polymerase chain reaction (PCR) and sequencing as well as by whole genome sequencing (WGS). Overall prevalence of CPE was 1.6%. OXA-48 was the most prevalent (86.8%), followed by KPC (6.9%), VIM (4.8%), NDM (1.1%) and IMP (0.6%) carbapenemases. Klebsiella pneumoniae was the most common carbapenemase producer (87.8%). An uncommon carbapenemase type (IMP-8) in Spain was identify by WGS in an Enterobacter cloacae isolate, reinforcing the utility of surveillance programmes as effectives tools to detect unexpected genes that encode antimicrobial resistance. Ceftazidime-avibactam showed 100% susceptibility in KPC and OXA-48 producers and the rates of susceptibility in CPE non-susceptible to ceftazidime or meropenem were 92.1% and 96.9%, respectively. Ceftazidime-avibactam could be considered an adequate treatment option for urinary tract infections caused by KPC and OXA-48 producers.

Molecular and epidemiological characterization of carbapenemase-producing Enterobacteriaceae in Norway, 2007 to 2014.

The prevalence of carbapenemase-producing Enterobacteriaceae (CPE) is increasing worldwide. Here we present associated patient data and molecular, epidemiological and phenotypic characteristics of all CPE isolates in Norway from 2007 to 2014 confirmed at the Norwegian National Advisory Unit on Detection of Antimicrobial Resistance. All confirmed CPE isolates were characterized pheno- and genotypically, including by whole genome sequencing (WGS). Patient data were reviewed retrospectively. In total 59 CPE isolates were identified from 53 patients. Urine was the dominant clinical sample source (37%) and only 15% of the isolates were obtained from faecal screening. The majority of cases (62%) were directly associated with travel or hospitalization abroad, but both intra-hospital transmission and one inter-hospital outbreak were observed. The number of CPE cases/year was low (2–14 cases/year), but an increasing trend was observed. Klebsiella spp. (n = 38) and E. coli (n = 14) were the dominant species and blaKPC (n = 20), blaNDM (n = 19), blaOXA-48-like (n = 12) and blaVIM (n = 7) were the dominant carbapenemase gene families. The CPE isolates were genetically diverse except for K. pneumoniae where clonal group 258 associated with blaKPC dominated. All isolates were multidrug-resistant and a significant proportion (21%) were resistant to colistin. Interestingly, all blaOXA-48-like, and a large proportion of blaNDM-positive Klebsiella spp. (89%) and E. coli (83%) isolates were susceptible in vitro to mecillinam. Thus, mecillinam could have a role in the treatment of uncomplicated urinary tract infections caused by OXA-48- or NDM-producing E. coli or K. pneumoniae. In conclusion, the impact of CPE in Norway is still limited and mainly associated with travel abroad, reflected in the diversity of clones and carbapenemase genes.

Prospective Surveillance and Rapid Whole-Genome Sequencing Detects Two Unsuspected Outbreaks of Carbapenemase-Producing Klebsiella pneumoniae in a UK Teaching Hospital

BackgroundThe increasing incidence of carbapenemase-producing Enterobacteriaceae (CPE) is a global health concern, as treatment options are extremely limited. The prevalence of CPE in UK hospitals is unknown, as national screening guidelines only recommend screening in patients considered to be at high-risk of CPE. Patients in intensive care units (ICU) are at high-risk of healthcare-associated infections caused by multidrug-resistant organisms (MDRO).MethodsWe conducted a six-month prospective surveillance study to determine the prevalence of MDRO in a UK teaching hospital ICU. Between June and December 2016, all adult patients admitted to ICU were screened for MDRO on admission, on discharge, and weekly during their ICU stay. Surveillance samples included stool or rectal swabs, urine, sputum or tracheal aspirates, and wound swabs (if wounds were present). Isolates were characterized phenotypically before undergoing whole-genome sequencing (WGS), epidemiological, and phylogenetic analyses.ResultsDuring the first week of the study we identified stool carriage of a multidrug-resistant Klebsiella pneumoniae strain in two patients neither of whom had recognized risk factors for CPE. Both isolates were resistant to all antibiotics tested, apart from colistin, and were PCR-positive for the blaNDM-1 gene. Enhanced surveillance by the infection control team identified four additional patients in several wards who had stool carriage (n = 3) or bloodstream infection (n = 1) with a blaNDM-1K. pneumoniae isolate. Epidemiological links were identified between these six patients. Five months later, a second outbreak of multidrug-resistant K. pneumoniae was detected, involving stool carriage by four patients on two different wards. Environmental screening identified environmental contamination with multidrug-resistant K. pneumoniae on one ward. DNA sequence analysis confirmed that a novel blaNDM-1K. pneumoniaelineage (ST78) was responsible for both outbreaks in the hospital.ConclusionWe identified two unsuspected blaNDM-1K. pneumoniae outbreaks in patients with no recognized risk factors for CPE. This highlights the importance of prospective surveillance for MDRO in high-risk settings, such as ICUs, and supports the use of rapid WGS to support outbreak investigations in real-time.Disclosures All authors: No reported disclosures.

Geographical variation in therapy for bloodstream infections due to multidrug-resistant Enterobacteriaceae: a post-hoc analysis of the INCREMENT study

We describe regional differences in therapy for bloodstream infection (BSI) caused by extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). Patients (n = 1482) in 12 countries from an observational study of BSI caused by ESBL-E or CPE were included. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for the influence of country of recruitment on empirical use of β-lactam/β-lactamase inhibitors (BLBLIs) or carbapenems, targeted use of BLBLIs for ESBL-E and use of targeted combination therapy for CPE. Compared with Spain, BLBLI use for empirical therapy was least likely in sites from Israel (aOR 0.34, 95% CI 0.14–0.81), Greece (aOR 0.49, 95% CI 0.26–0.94) and Canada (aOR 0.31, 95% CI 0.11–0.88) but more likely in Italy (aOR 1.58, 95% CI 1.11–2.25) and Turkey (aOR 2.09, 95% CI 1.14–3.81). Empirical carbapenem use was more likely in sites from Taiwan (aOR 1.73, 95% CI 1.03–2.92) and USA (aOR 1.89, 95% CI 1.05–3.39) and less likely in Italy (aOR 0.44, 95% CI 0.28–0.69) and Canada (aOR 0.10, 95% CI 0.01–0.74). Targeted BLBLIs for ESBL-E was more likely in Italian sites. Treatment at sites within Israel, Taiwan, Turkey and Brazil was associated with less combination therapy for CPE. Although this study does not provide precise data on the relative prevalence of ESBL-E or CPE, significant variation in therapy exists across countries even after adjustment for patient factors. Better understanding of what influences therapeutic choices for these infections will aid antimicrobial stewardship efforts.

The relative importance of large problems far away versus small problems closer to home: insights into limiting the spread of antimicrobial resistance in England

BackgroundTo combat the spread of antimicrobial resistance (AMR), hospitals are advised to screen high-risk patients for carriage of antibiotic-resistant bacteria on admission. This often includes patients previously admitted to hospitals with a high AMR prevalence. However, the ability of such a strategy to identify introductions (and hence prevent onward transmission) is unclear, as it depends on AMR prevalence in each hospital, the number of patients moving between hospitals, and the number of hospitals considered ‘high risk’.MethodsWe tracked patient movements using data from the National Health Service of England Hospital Episode Statistics and estimated differences in regional AMR prevalences using, as an exemplar, data collected through the national reference laboratory service of Public Health England on carbapenemase-producing Enterobacteriaceae (CPE) from 2008 to 2014. Combining these datasets, we calculated expected CPE introductions into hospitals from across the hospital network to assess the effectiveness of admission screening based on defining high-prevalence hospitals as high risk.ResultsBased on numbers of exchanged patients, the English hospital network can be divided into 14 referral regions. England saw a sharp increase in numbers of CPE isolates referred to the national reference laboratory over 7 years, from 26 isolates in 2008 to 1649 in 2014. Large regional differences in numbers of confirmed CPE isolates overlapped with regional structuring of patient movements between hospitals. However, despite these large differences in prevalence between regions, we estimated that hospitals received only a small proportion (1.8%) of CPE-colonised patients from hospitals outside their own region, which decreased over time.ConclusionsIn contrast to the focus on import screening based on assigning a few hospitals as ‘high risk’, patient transfers between hospitals with small AMR problems in the same region often pose a larger absolute threat than patient transfers from hospitals in other regions with large problems, even if the prevalence in other regions is orders of magnitude higher. Because the difference in numbers of exchanged patients, between and within regions, was mostly larger than the difference in CPE prevalence, it would be more effective for hospitals to focus on their own populations or region to inform control efforts rather than focussing on problems elsewhere.