{'fraction_non_alphanumeric': 0.039473684210526314, 'fraction_numerical': 0.01738141650422352, 'mean_word_length': 5.467436974789916, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Clinical Laboratory Aspect of Carbapenem-Resistant Enterobacteriaceae

The correct distinction of carbapenem-resistant Enterobacteriaceae (CRE) and ccarbapenemase producing Enterobacteriaceae (CPE) and the rapid detection of CPE are important for instituting the correct treatment and management of clinical infections. Screening protocols are mainly based on cultures of rectal swab specimens on selective media followed by phenotypic tests to confirm a carbapenem-hydrolyzing activity, the rapid carbapenem inactivation method, lateral flow immunoassay, the matrix-assisted laser desorption ionization – time-of-flight test and molecular methods. The CPE is accurate for detection, and is essential for the clinical treatment and prevention of infections. A variety of phenotypic methods and gene-based methods are available for the rapid detection of carbapenemases, and these are expected to be routinely used in clinical microbiology laboratories. Therefore, to control the spread of carbapenemase, many laboratories around the world will need to use reliable, fast, high efficiency, simple and low cost methods. Optimal effects in patient applications would require rapid testing of CRE to provide reproducible support for antimicrobial management interventions or the treatment by various types of clinicians. For the optimal test method, it is necessary to combine complementary test methods to discriminate between various resistant bacterial species and to discover the genetic diversity of various types of carbapenemase for arriving at the best infection control strategy. Copyright © 2020 The Korean for Clinical Laboratory Science. All rights reserved.


INTRODUCTION
Carbapenems are a commonly used primary therapeutic option for serious infections caused by Gram-negative bacilli such as Enterobacteriaceae and are often considered agents. Although current studies on the molecular epidemiology of some carbapenem-a novel non--lactam (diazabicyclooctane) -lactamase inhibitor. Avibactam protects ceftazidime from hydrolysis by Ambler class A and some class D carbapenemases [2].
Overall, isolates associated with OXA-48, VIM-1 and IMP-27 carbapenemases often exhibited minimum inhibitory concentrations (MICs) below the clinical breakpoints, but were detected using the European Committee on antimicrobial susceptibility testing (EUCAST) screening cut-off values or epidemiological cut-off values (ECOFFs). CRE occur globally in livestock, pets, wildlife, and seafood. Studies on the prevalence of CRE have rarely been performed and are challenging because of the variety of bacterial species and the different genetic elements involved [3]. The -lactam antibiotics such as penicillins, cephalosporins, and carbapenems represent of the available treatment options for antibiotic-resistant Gram-negative bacteria. These antibiotics can be hydrolyzed by the production of extended-spectrum beta-lactamases (ESBL) and carbapenemases.
In prevalence of CRE, some recent studies indicated a higher prevalence in Asia (China: 15% in milk samples, India: 1∼3% in piglets, Lebanon: 2.5% in fowl) and Algeria (6% in milk samples, 26% in chickens).
Seafood was contaminated with CRE in ＜1% in Canada.
Among wildlife, two studies found a high prevalence of CRE among silver gulls and yellow-legged gulls in France (19.4%) [4]. The occurrence of CRE in livestock, seafood, wildlife, pets, and directly exposed humans poses a risk for public health. Prospective prevalence studies using molecular and cultural microbiological methods are needed to better define the scope and transmission of CRE [3].  [6].
In the past few years, cases of multiple carbapenemases in the same Enterobacteriaceae isolate have been reported. For example, bla NDM-1 and blaI MP-4 coexisted in KPN [8]. Enterobacter cloacae complex (ECC) were recovered from Enterobacter cloacae or Citrobacter freundii carried both bla NDM-1 and bla KPC-2 in China [9].
Most CRE were K pneumoniae (63.2%), followed by Escherichia coli (14.5%) and Enterobacter spp. (12.8%) at academic medical centers in the United States between 2015 and 2019 [11]. More than half of patients were residents of the intensive care unit (ICU) at infection onset, the median SOFA (sequential organ failure assessment) score was 5. The most common infection sources were respiratory tract (37.4%), followed by urinary tract (19.7%), intra-abdominal (18.7%), skin and soft tissue (8.9%), and osteoarticular (6.9%) [11]. Primary bacteremia or respiratory tract infection and SOFA score were independently associated with higher clinical failure. GES-6 was first identified in a Klebsiella pneumoniae isolate from Greece [12].

Detection of carbapenemases by chromogenic media for CRE screening
Chromogenic plate methods was acceptable specificity, but sensitivities ranging broads. these methods were finally reporting is extended to 48 hr. 100% and 98.8%, respectively [18]. To detect OXA-48like producers, reported that the sensitivity and specificity of CHROMagar for detection of carbapenemase-producing isolates was 88.5% and 86.1% [19].
The sensitivity and specificity of commercialized chromogenic media (Table 1).

Phenotypic detection assays
The carbapenem inactivation method (CIM) is another effective phenotypic test, which method determines the carbapenemase activity of the tested bacteria by measuring the diameter of the inhibition zone of E. coli ATCC 25922 after the carbapenem disk is inactivated by the test bacterium. A study indicated that both the sensitivity and specificity of mCIM were 100% [28]. Because of its simplicity, clear criteria, costeffectiveness, and availability in any laboratory, the mCIM has become a useful tool in microbiology laboratories. A bioluminescence-based carbapenem susceptibility detection assay was reported in 2018 that allows carbapenemase-producing CRE and non-  There are compares with the commercialized carbapenem-resistant Klebsiella pneumoniae detection methods (Table 3).

Recent reported methods
A novel real-time multiplex PCR assay, BD MAX Check-Points CPO, was evaluated to detect carbapenemase-producing organisms in clinical settings on the