• Journal of Microbiology and Biotechnology
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• v.31 no.10
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• pp.1383-1392
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• 2021

Carbapenem-resistant Enterobacteriaceae (CRE) that produce Klebsiella pneumoniae carbapenemase are increasingly reported worldwide and have become more and more resistant to nearly all antibiotics during the past decade. The emergence of K. pneumoniae strains with decreased susceptibility to carbapenems, which are used as a last resort treatment option, is a significant threat to hospitalized patients worldwide as K. pneumoniae infection is responsible for a high mortality rate in the elderly and immunodeficient individuals. This study used Lactobacillus fermentum as a candidate probiotic for treating CRE-related infections and investigated its effectiveness. We treated mice with L. fermentum originating from the vaginal fluid of a healthy Korean woman and evaluated the Lactobacilli's efficacy in preventive, treatment, nonestablishment, and colonization mouse model experiments. Compared to the control, pre-treatment with L. fermentum significantly reduced body weight loss in the mouse models, and all mice survived until the end of the study. The oral administration of L. fermentum after carbapenem-resistant Klebsiella (CRK) infection decreased mortality and illness severity during a 2-week observation period and showed that it affects other strains of CRK bacteria. Also, the number of Klebsiella bacteria was decreased to below 5.5 log₁₀ CFU/ml following oral administration of L. fermentum in the colonization model. These findings demonstrate L. fermentum's antibacterial activity and its potential to treat CRE infection in the future.

• Korean Journal of Clinical Laboratory Science
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• v.51 no.4
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• pp.428-435
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• 2019

The rapid increase and dissemination of carbapene mases, such as Klebsiella pneumoniae carbapenemase (KPC), has become a major problem within the field of healthcare-related infection. There are few antibiotics to treat carbapenem-resistant Enterobacteriaceae (CRE) infections, so the identification of resistant bacterial mechanisms is critical to initiate infection control and conduct epidemiological research. A rapid and effective method for detecting KPC-producing bacteria is needed to avoid therapeutic failures and introduce measures to prevent and control the dissemination of these multi-resistant bacteria. During the study period, 31 isolates (seven isolates of Acinetobacter spp., six isolates of Morganella morganii, five isolates of Pseudomonas aeruginosa, five isolates of Proteus mirabilis, one isolate of Proteus vulgaris, two isolates of Enterobacter cloacae, one isolate of Enterobacter aerogenes, one isolate of Klebsiella pneumoniae, one isolate of Klebsiella oxytoca, one isolate of Serratia marcescens and one isolate of Escherichia coli) were identified by the VITEK. Gram negative rod bacteria were the most frequently isolated from urine (35.5%), blood (19.4%), sputum (16.1%), pus (9.7%), ascitic fluid (9.7%), tracheal aspirates (6.5%) and bile juice (3.2%). Analysis using the PCR method identified the bla_KPC gene in the K. oxytoca1 strain, but the bla_IMP, bla_VIM and bla_OXA-48 genes are not amplified. In conclusion, diagnosis using the PCR method can accurately and quickly diagnose KPC, thus establishing quick preventive measures to prevent the spread of KPC in hospitals.

• Microbiology and Biotechnology Letters
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• v.51 no.4
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• pp.500-506
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• 2023

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is emerging as a worldwide public health threat. Recently, Klebsiella pneumoniae carbapenemase-2 (KPC-2)-producing sequence type (ST) 307 was identified main clone of CRKP, and dissemination of ST307 was reported in South Korea. This study examined the molecular characteristic and antimicrobial resistance pattern of 50 CRKP isolated from a tertiary hospital in Daejeon, from March 2020 to December 2021. Epidemiological relationship was analyzed by Multilocus sequence typing (MLST) and antimicrobial susceptibility test was determined using disk-diffusion method. PCR and DNA sequence analysis were performed to identify carbapenemase genes. CRKP infections were significantly more frequent in males and the patients aged ≥ 60 years. Among the 50 CRKP isolates, 46 isolates (92.0%) were multidrug-resistant (MDR), and 44 isolates (88.0%) were carbapenemase-producing K. pneumoniae (CPKP). The major carbapenemase type was KPC-2 (36 isolates, 72.0%) and New Delhi metalloenzyme-1 (NDM-1) and NDM-5 were identified in 7 isolates (14.0%) and 1 isolate (2.0%), respectively. In particular, 88.9% (32/36) of KPC-2-producing K. pneumoniae belonged to ST307, whereas 87.5% (7/8) of NDM-1,-5-producing K. pneumoniae belonged to non-ST307. These results suggest that proper infection control and effective surveillance network need to prevent not olny the spread of ST307, but also the development of non-ST307.

• Microbiology and Biotechnology Letters
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• v.48 no.3
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• pp.389-398
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• 2020

The prevalence of carbapenem-resistant Enterobacteriaceae (CRE) is increasing globally, resulting in high mortality rates. Although CRE is a relatively recent problem in Korea (the first case was not diagnosed until 2010), it is responsible for serious morbidities at an alarming rate. In this study, we carried out a molecular genetic analysis to determine the incidence of CRE and carbapenemase-producing Enterobacteriaceae (CPE) at a general hospital in Korea between August 2017 and August 2019. Forty strains of CPE were isolated from various clinical specimens and analyzed via antimicrobial susceptibility testing, polymerase chain reaction to detect β-lactamase genes, deoxyribonucleic acid sequencing, multilocus sequence typing, curing testing, and conjugal transfer of plasmids. The results demonstrated that all 40 isolates were multidrug-resistant. The fluoroquinolone susceptibility test showed that 75% of the Enterobacteriaceae isolates were resistant to ciprofloxacin, whereas 72.5% were resistant to trimethoprim-sulfamethoxazole. Further, conjugation accounted for 57.5% of all resistant plasmid transfer events, which is 4.3-fold higher than that observed in 2010 by Frost et al. Finally, the high detection rate of transposon Tn4401 was associated with the rapid diffusion and evolution of CPE. Our results highlight the rapid emergence of extensively drugresistant strains in Korea and emphasize the need for employing urgent control measures and protocols at the national level.

• Genomics & Informatics
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• v.20 no.4
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• pp.47.1-47.13
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• 2022

Klebsiella pneumoniae is a gram-negative bacterium that is known for causing infection in nosocomial settings. As reported by the World Health Organization, carbapenem-resistant Enterobacteriaceae, a category that includes K. pneumoniae, are classified as an urgent threat, and the greatest concern is that these bacterial pathogens may acquire genetic traits that make them resistant towards antibiotics. The last class of antibiotics, carbapenems, are not able to combat these bacterial pathogens, allowing them to clonally expand antibiotic-resistant strains. Most antibiotics target essential pathways of bacterial cells; however, these targets are no longer susceptible to antibiotics. Hence, in our study, we focused on a hypothetical protein in K. pneumoniae that contains a DNA methylation protein domain, suggesting a new potential site as a drug target. DNA methylation regulates the attenuation of bacterial virulence. We integrated computational-aided drug design by using a bioinformatics approach to perform subtractive genomics, virtual screening, and fingerprint similarity search. We identified a new potential drug, koenimbine, which could be a novel antibiotic.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.4
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• pp.265-272
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• 2022

The emergence and dissemination of carbapenemase-producing Enterobacteriaceae (CPE), particularly the Klebsiella pneumoniae carbapenemase-2 (KPC-2) producing Klebsiella pneumoniae, has been rapidly increasing worldwide and is becoming a serious public health threat. Since the epidemiology and characteristics of these KPC-2-producing K. pneumoniae vary according to the region and period under consideration, this study investigated the prevalence of carbapenemases and the epidemiological relationship of 78 carbapenem-resistant K. pneumoniae (CRKP) isolated from a tertiary hospital in Daejeon, from March 2017 to December 2020. The antimicrobial susceptibility tests were identified using the disk-diffusion method. PCR and DNA sequencing were used to determine the carbapenemase genes. In addition, molecular epidemiology was performed by multilocus sequence typing (MLST). Among the 78 CRKP isolates, 35 isolates (44.9%) were carbapenemase-producing K. pneumoniae (CPKP) and the major carbapenemase type was KPC-2 (30 isolates, 85.7%). The New Delhi metallo-enzyme-1 (NDM-1) and NDM-5 were identified in 4 isolates (11.4%) and 1 isolate (2.9%), respectively. Multilocus sequence typing (MLST) analysis showed 10 sequence types (STs) and the most prevalent ST was ST307 (51.4%, 18/35). All the ST307 isolates were KPC-2-producing K. pneumoniae and were multidrug-resistant (MDR). In addition, ST307 has gradually emerged during a four-year period. These findings indicate that continuous monitoring and proper infection control are needed to prevent the spread of KPC-2-producing K. pneumoniae ST307.

• Biomedical Science Letters
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• v.30 no.3
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• pp.101-112
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• 2024

This review provides an overview of carbapenem-resistant Enterobacterales (CRE) studies. CRE, called superbugs, has a high mortality rate and an increased resistance rate in several countries. The bacteria representing CRE are Klebsiella species and Escherichia spp., and they cause urinary tract infections (UTIs) and bloodstream infections (BSIs). CRE acquires resistance due to several mechanisms, typically divided into carbapenemase-producing (CP)-CRE and non-CP-CRE. Furthermore, although there are several antibiotics developed to treat CRE, they have their limitations; thus, antibiotic combination therapies or novel treatments are being developed. Therefore, since research on CRE and the use of appropriate antibiotics is important, some CRE-resistant mechanisms that enhance them are discussed. This review article was written using information obtained from Google Scholar and the National Center for Biotechnology Information website.

• Journal of Medicine and Life Science
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• v.20 no.2
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• pp.67-72
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• 2023

Carbapenem-resistant Enterobacteriaceae (CRE) infections have increased rapidly over the past decade and are recognized as a severe health threat in Korea and worldwide. This study aimed to identify the status and characteristics of CRE infection in Jeju province and provide important basic data for the prevention and management of CRE infection. A descriptive epidemiological analysis was performed on reported cases of CRE infection in Jeju Province between 2018 and 2021 using the integrated management system for disease, an infectious disease reporting system from the Korea Disease Control and Prevention Agency. The annual difference and distribution trends of CRE infection were analyzed using CRE isolates, carbapenemase-producing CREs (CP-CRE) and their genotypes, and the type of medical institution in Jeju Province. CRE infections steadily increased in Jeju from 2018 to 2021, and the proportion of CP-CRE among the CREs also showed a statistically significant increase each year. Among the CRE isolates, Klebsiella pneumoniae (KPC, 62.13%) was the most common, and among the CP-CRE genotypes, KPC (81.62%) showed the highest distribution and increased each year. As the distribution of CP-CRE in have increased over the past 4 years, measures to prevent the spread and outbreak of CRE infections are warranted. The results of this study are expected to be used as basic data for prevention and management of CRE infections in the province.

• Journal of Korean Biological Nursing Science
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• v.25 no.4
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• pp.285-294
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• 2023

Purpose: This study aimed to identify the colonization rate of carbapenem-resistant Enterobacteriaceae (CRE), the characteristics of CRE isolates, and risk factors for CRE colonization in patients transferred to the general wards of a small/medium-sized hospital. Methods: This retrospective study was conducted on patients who underwent CRE culture tests within 24 hours of admission among patients transferred to a small/medium-sized hospital. Forty-seven patients confirmed as positive for CRE were classified as belonging to the patient group. For the control group, 235 patients (five times the number of the patient group) were matched by sex, age, and diagnosis, and then selected at random. Data were analyzed using descriptive analysis and multiple logistic regression analysis. Results: The CRE colonization rate was 5% (47 out of 933 patients), and Klebsiella pneumoniae (68.0%) was the most common isolate of CRE. The positivity rate of carbapenemase-producing Enterobacteriaceae was 61.7%. The risk factors for CRE colonization included renal disease (odds ratio [OR]=4.93; 95% confidence interval [CI], 1.49-16.31), heart disease (OR=3.86; 95% CI, 1.35-11.01), indwelling urinary catheters (OR=4.43; 95% CI, 1.59-12.36), and cephalosporin antibiotic use (OR=8.57; 95% CI, 1.23-59.60). Conclusion: Having a comorbid renal or cardiac disease, an indwelling urinary catheter, or a history of exposure to cephalosporin antibiotics could be classified as risk factors for CRE colonization in patients transferred to small and medium-size hospitals. It is necessary to perform active infection control through proactive CRE culture testing of patients with risk factors.

• Pediatric Infection and Vaccine
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• v.28 no.2
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• pp.82-91
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• 2021

Background: The purpose of this study was to investigate the association between antibiotic use and the antimicrobial resistance of gram-negative bacteria isolated from blood cultures in a pediatric population. Methods: From January 2014 to June 2018, the antibiotic resistance pattern of Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa obtained from bacteremic patients aged ≤18 years hospitalized at Asan Medical Center Children's Hospital was analyzed and the parenteral antibiotic consumption data were retrieved. Results: During the study period, the blood culture was positive for K. pneumoniae (6.4%; 105/1,628), E. coli (5.6%; 91/1,628), P. aeruginosa (3.3%; 54/1,628), and A. baumannii (2.5%; 41/1,628), and the extended-spectrum antibiotic resistance rate of gram-negative bacteria was consistently high. The overall resistance rate of E. coli and K. pneumoniae to extendedspectrum cephalosporin was 49.3% and 54.4%, respectively. Carbapenem-resistant E. coli was first detected in 2014; its overall resistance rate to carbapenem was 5.3%. There was a linear correlation between the usage of 3rd generation cephalosporin and the resistance of A. baumannii (r²=0.96, P=0.004) and carbapenem usage and the resistance of K. pneumoniae (r²=0.79, P=0.045). Conclusions: A positive linear correlation was observed between antibiotic resistance and the corresponding antibiotic usage in 3rd generation cephalosporin resistant A. baumannii and carbapenem resistant K. pneumoniae. The judicious use of antibiotics in healthcare settings is important to minimize selection for extended-spectrum β-lactamase (ESBL) and carbapenem resistance in gram-negative bacteria.