• Journal of Microbiology and Biotechnology
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• 제31권10호
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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.

• 대한임상검사과학회지
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• 제51권4호
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• pp.428-435
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• 2019

Klebsiella pneumoniae carbapenemase (KPC)와 같은 carbapenem 분해효소의 급속한 증가와 보급은 의료 관련 감염 분야 내에서 주요한 문제가 되었다. Carbapenem-resistant Enterobacteriaceae (CRE) 감염을 치료하기 위한 항생제는 거의 없으므로 내성의 박테리아 메커니즘의 확인은 감염 통제와 역학 연구에 매우 중요하다. 그러므로 KPC 균주를 검출하는 신속하고 효과적인 방법은 치료상의 실패를 피하고, 이러한 다제 내성세균의 유통을 방지 및 통제하는 대책으로 도입할 필요가 있다. 분석에 이용한 31균주에서 Acinetobacter spp. 7균주, Morganella morganii 6균주, Pseudomonas aeruginosa 5균주, Proteus mirabilis 5균주, Proteus vulgaris 1균주, Enterobacter cloacae 2균주, Enterobacter aerogenes 1균주, Klebsiella pneumoniae 1균주, Klebsiella oxytoca 1균주, Serratia marcescens 1균주, Escherichia coli 1균주를 확인하였다. 그람음성 간균이 분리된 검체의 빈도는 urine (35.5%), blood (19.4%), sputum (16.1%), pus (9.7%), ascitic fluid (9.7%), tracheal aspirates (6.5%), bile juice (3.2%) 순으로 나타났다. PCR 방법을 이용한 유전자분석 결과 bla_IMP, bla_VIM, bla_OXA-48 에서는 증폭이 확인된 균주가 없었으나, Klebsiella oxytoca 1 균주에서 bla_KPC 유전자를 확인하였다. 결론적으로, PCR 방법을 이용한 진단법은 KPC를 정확하고 신속하게 진단할 수 있으며, 그로 인해 병원 내 KPC의 전파방지를 위한 신속한 예방대책 수립이 가능하다 할 수 있다.

• 한국미생물·생명공학회지
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• 제51권4호
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• pp.500-506
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• 2023

Carbapenem 내성 Klebsiella pneumoniae (Carbapenem-resistant K. pneumonia, CRKP)는 전 세계적인 공중 보건 문제로 대두되고 있다. 최근 Klebsiella pneumoniae carbapenemase-2 (KPC-2) 생성 sequence type (ST)307은 CRKP의 주요 클론으로 확인되었으며, 국내에서 ST307의 확산이 보고되었다. 본 연구에서는 2020년 3월부터 2021년 12월까지 대전지역의 3차 병원에서 분리된 CRKP 50균주를 대상으로, 분자 특성과 항균제 내성 양상을 조사하였다. 역학적 관계는 multilocus sequence typing (MLST)를 통해 분석하였고, 항균제 감수성 검사는 디스크 확산법을 통해 확인하였다. PCR과 DNA 염기서열분석은 carbapenemase 유전자 확인을 위해 수행하였다. CRKP감염은 남성과 60세 이상의 환자에서 훨씬 더 빈번하게 확인되었다. CRKP 50균주 중 46균주(92.0%)는 다제내성(MDR)을 보였고, 44균주(88.0%)는 carbapenemase-producing K. pneumoniae (CPKP)로 확인되었다. 주요 carbapenemase 유형은 KPC-2 (36균주, 72.0%)였으며, New Delhi metallo-enzyme-1 (NDM-1)과 NDM-5는 각각 7균주(14.0%)와 1균주(2.0%)에서 확인되었다. 특히, KPC-2 생성 K. pneumoniae의 88.9% (32/36)가 ST307에 속한 반면, NDM-1,-5 생성 K. pneumoniae의 87.5% (7/8)가 non-ST307에 속한 것을 확인하였다. 이러한 결과는 ST307의 확산 뿐만 아니라 non-ST307의 발달을 예방하기 위한 적절한 감염관리와 효과적인 감시체계가 필요하다고 사료된다.

• 한국미생물·생명공학회지
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• 제48권3호
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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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• 제20권4호
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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.

• 대한임상검사과학회지
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• 제54권4호
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• pp.265-272
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• 2022

Carbapenemase 생성 장내 세균(carbapenemase-producing Enterobacteriaceae, CPE) 중 특히 KPC-2 생성 Klebsiella pneumoniae의 출현과 확산은 전 세계적으로 급격히 증가하고 있으며, 심각한 공중 보건 위협이 되고 있다. 이러한 KPC-2 생성 K. pneumoniae의 역학과 특징은 지역 및 기간에 따라 다르기 때문에, 본 연구에서는 2017년 3월부터 2020년 12월까지 대전지역의 3차 병원에서 분리된 carbapenem 내성 K. pneumoniae (carbapenem-resistant K. pneumoniae, CRKP) 78 균주를 대상으로 carbapenemase 유전자를 분석하고, 이에 대한 역학 관계를 조사하였다. 항균제 감수성 양상은 디스크 확산법으로 확인하였고, carbapenemase 유전자의 분석을 위해 PCR과 DNA 염기서열분석을 수행하였다. 또한, 역학관계는 MLST (multilocus sequence typing)를 통해 조사하였다. 78 균주의 CRKP 중 35 균주(44.9%)가 carbapenemase 생성 K. pneumoniae였으며, 주요 carbapenemase 유형은 KPC-2 (30주, 85.7%)로 확인되었다. NDM-1과 NDM-5는 각각 4 균주(11.4%)와 1 균주(2.9%)에서 확인되었다. MLST 분석에서 10개의 sequence type (ST)이 확인되었고, 가장 흔한 ST는 ST307 (51.4%, 18/35)이었다. ST307 균주는 모두 KPC-2 생성 K. pneumonia였고, 다제내성으로 확인되었다. 또한, ST307은 4년 동안 지속적으로 출현하였다. 이러한 결과는 KPC-2 생성 K. pneumoniae ST307의 확산을 방지하기 위해 지속적인 모니터링과 적절한 감염 관리가 필요할 것으로 사료된다.

• Journal of Medicine and Life Science
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• 제20권2호
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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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• 제25권4호
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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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• 제28권2호
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• pp.82-91
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• 2021

목적: 본 연구에서는 소아환자의 혈액에서 분리된 주요 그람음성 균주의 항생제 내성 양상을 파악하고 항생제 사용량과의 관계를 알아보고자 하였다. 방법: 2014년 1월부터 2018년 6월까지 서울아산병원 어린이병원에 입원한 18세 이하의 소아청소년에서 발생한 그람음성 균주 균혈증 중 Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, 총 4가지 균주를 대상으로 항생제 내성 양상을 분석하였다. 또 원내에서 소아에게 주로 사용하는 정주용 항생제의 사용량과 항생제 내성률의 변화와의 관련성을 분석하였다. 결과: 본 연구 기간 동안 전체 혈액배양에서, K. pneumoniae (6.4%; 105/1,628), E. coli (5.6%; 91/1,628), P. aeruginosa (3.3%; 54/1,628) 및 A. baumannii (2.5%; 41/1,628)의 순으로 분리되었다. 2014-2018년에 분리된 E. coli와 K. pneumoniae의 광범위 cephalosporin 계열에 대한 내성률은 각각 49.3%와 54.4%였다. 2014년도에는 carbapenem에 내성을 보이는 E. coli 균종이 처음 출현하였고, 5년간의 내성률은 5.3%였다. 연구기간 동안 항생제 사용량과 항생제 내성률 사이의 상관관계를 분석하여, 3세대 cephalosporin 사용량과 A. baumannii의 내성률(r²=0.96, P=0.004) 그리고 carbapenem의 사용량과 K. pneumoniae의 내성률(r²=0.79, P=0.045) 간에 양의 상관관계를 확인하였다. 결론: 국내 소아에서 발생한 그람음성균 균혈증 분석 시 3세대 및 4세대 cephalosporin에 대한 높은 내성률이 확인되며, carbapenem에 대한 내성도 확인되고 있다. 일부 항생제 사용량과 해당 약제에 대한 내성률에 선형 상관관계가 있었으며, 이는 항생제 사용량이 내성률에 영향을 미칠 수 있음을 시사한다. 이에 지속적인 원내 항생제 사용량 및 내성률에 대한 감시가 필요하며, 적절한 항생제의 선택 및 관리는 내성균주 출현 예방 및 치료 성적 향상에 필수적이다.

• 한국임상약학회지
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• 제30권2호
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• pp.120-126
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• 2020

Objective: The rising number of carbapenemase-resistant Enterobacteriaceae (CRE) cases has become a concern worldwidely. This study investigated patient characteristics with CRE and analyzed the risk factors associated with its acquisition. Methods: A retrospective review of the electronic medical records of the Kangbuk Samsung Medical Center from May 2016 to April 2019 was performed. The inclusion criterion was hospitalized patients aged ≥18 years with confirmed CRE acquisition. Patients were divided by CRE acquired and non-required patients. CRE acquired patients were those with CRE confirmed by their active surveillance cultures, while non-acquired patients were those with carbapenemase-sensitive Enterobacteriaceae (CSE). If CRE was isolated more than once during hospitalization, only the first isolation was used for data analysis. Patient characteristics, antibiotic used, and the duration of use were compared between two groups using univariate analysis, and the risk factors associated with CRE were analyzed using multiple logistic regression analysis. Results: Among the 73 CRE acquired patients, 44 (60.3%) were positive for carbapenemase-producing Enterobacteriaceae (CPE). Infection from Klebsiella pneumonia (42 cases, 57.5%), Escherichia coli (17 cases, 23.3%), and Enterobacter cloacae (5 cases, 6.8%). The risk of CRE acquisition was significantly increased by 4.99 times [confidence interval (CI), 1.40-17.78; p=0.013] with mechanical ventilation, 3.86 times (CI, 1.59-9.36; p=0.003) with penicillin administration, and 21.19 times (CI, 6.53-68.70; p<0.001) with carbapenem administration. Conclusions: Proper antibiotic use including the selection, frequency, and duration, and patients on mechanical ventilators need close monitoring.