1.Prevalence and molecular characteristics of β-lactam resistance in non-typeable Haemophilus influenzae isolates in Korea
Eun-Young KIM ; Yeon Chan CHOI ; Hyeon Jin CHOI ; Si Hyun KIM ; Jihyun CHO ; Seok Hoon JEONG ; Dokyun KIM ; Hyun Soo KIM ; Soo Hyun KIM ; Young Ah KIM ; Young Ree KIM ; Nam Hee RYOO ; Jong Hee SHIN ; Kyeong Seob SHIN ; Young UH ; Jeong Hwan SHIN
Annals of Clinical Microbiology 2025;28(4):23-
Background:
Haemophilus influenzae is the causative pathogen for various infectious diseases, such as respiratory infections, otitis media, sinusitis, and meningitis. This study aimed to investigate the prevalence and molecular characteristics of β-lactam resistance in non-typeable H. influenzae isolates in South Korea.
Methods:
In total, 115 non-duplicated H. influenzae isolates were included in this study.Bacterial identification and serotyping were performed using matrix assisted laser desorption ionization-time of flight mass spectrometry and polymerase chain reaction (PCR) of bexA, respectively. Antimicrobial susceptibility was tested using the broth microdilution method.The production of β-lactamase was determined using nitrocefin disks. The presence of blaTEM and blaROB was confirmed using PCR. ftsI was analyzed to identify amino acid mutations in penicillin-binding protein (PBP) 3.
Results:
Resistance rates to ampicillin, amoxicillin–clavulanate, and cefuroxime were 67.8%, 13.9%, and 32.2%, respectively. None of the isolates were resistant to cefotaxime or ceftriaxone. Among 78 ampicillin-resistant isolates, 71 were β-lactamase-producing ampicillinresistant (BLPAR), and 7 were β-lactamase-non-producing ampicillin-resistant. All BLPAR isolates carried blaTEM, and none carried blaROB. Among 16 amoxicillin–clavulanate-resistant isolates, 15 β-lactamase producers harbored blaTEM. Four to 7 PBP3 mutations per isolate were detected in all 16 non-β-lactamase-producing ampicillin-resistant or cephalosporinresistant isolates.
Conclusion
Beta-lactam resistance in non-typeable H. influenzae isolates is highly prevalent in South Korea, primarily because of blaTEM and various PBP3 mutations. Therefore, continuous monitoring of antimicrobial resistance rates and mechanisms in non-typeable H.influenzae is necessary.
2.Four genotypes of carbapenem-resistant Acinetobacter baumannii strains lacking OXA-23 production in Korea
Young Ah KIM ; Seok Hoon JEONG ; Jong Hee SHIN ; Kyeong Seob SHIN ; Jeong Hwan SHIN ; Young Ree KIM ; Hyun Soo KIM ; Young UH ; Nam Hee RYOO
Annals of Clinical Microbiology 2024;27(2):143-147
During nationwide Fantimicrobial surveillance (Korea Global Antimicrobial Resistance Surveillance System [Kor-GLASS]), the recent emergence of non-oxacillinase (OXA)-23 production by carbapenem-resistant Acinetobacter baumannii (CRAB) isolates was noted. In this study, we evaluated resistance mechanisms other than OXA-23 production to elucidate the shift in considerable CRAB clones. The presence of OXA carbapenemase genes, such as blaOXA-23 , blaOXA-24 , blaOXA-58 , and blaOXA-51-ISAba1, was determined by PCR. Other carbapenemase genes, such as blaIMP , blaVIM , blaNDM , blaKPC , blaGES , and blaOXA-48 , were determined using sequencing. Strains lacking carbapenemase genes were subjected to whole genome sequencing, and resistance genes were analyzed using ResFinder. Four CRAB strains were collected through a Kor-GLASS study in 2022, in which OXA-23 production was not identified. The carbapenemase genotypes of the four CRAB strains lacking blaOXA-23 were blaOXA-51 -ISAba1, blaOXA-66/ACD25 , blaOXA-182, and blaNDM-1 . To the best of our knowledge, this is the first study to identify CRAB producing New Delhi metallo-β-lactamase (NDM)-1 in Korea. In conclusion, domestic CRAB resistance mechanisms may undergo subtle changes. Continuous observations are required to monitor the emergence of new clones.
3.Clinical and Radiologic Predictors of Response to Atezolizumab-Bevacizumab in Advanced Hepatocellular Carcinoma
Se Jin CHOI ; Sung Won CHUNG ; Jonggi CHOI ; Kang Mo KIM ; Hyung-Don KIM ; Changhoon YOO ; Baek-Yeol RYOO ; Seung Soo LEE ; Won-Mook CHOI ; Sang Hyun CHOI
Cancer Research and Treatment 2024;56(4):1219-1230
Purpose:
This study aimed to identify clinical and radiologic characteristics that could predict response to atezolizumab-bevacizumab combination therapy in patients with advanced hepatocellular carcinoma (HCC).
Materials and Methods:
This single-center retrospective study included 108 advanced HCC patients with intrahepatic lesions who were treated with atezolizumab-bevacizumab. Two radiologists independently analyzed imaging characteristics of the index tumor on pretreatment computed tomography. Predictive factors associated with progressive disease (PD) at the best response based on Response Evaluation Criteria in Solid Tumors, ver. 1.1 were evaluated using logistic regression analysis. Progression-free survival (PFS) was estimated by the Kaplan-Meier method and compared with the log-rank test.
Results:
Of 108 patients with a median PFS of 15 weeks, 40 (37.0%) had PD during treatment. Factors associated with PD included the presence of extrahepatic metastases (adjusted odds ratio [aOR], 4.13; 95% confidence interval [CI], 1.19 to 14.35; p=0.03), the infiltrative appearance of the tumor (aOR, 3.07; 95% CI, 1.05 to 8.93; p=0.04), and the absence of arterial-phase hyperenhancement (APHE) (aOR, 6.34; 95% CI, 2.18 to 18.47; p < 0.001). Patients with two or more of these factors had a PD of 66.7% and a median PFS of 8 weeks, indicating a significantly worse outcome compared to the patients with one or no of these factors.
Conclusion
In patients with advanced HCC treated with atezolizumab-bevacizumab treatment, the absence of APHE, infiltrative appearance of the intrahepatic tumor, and presence of extrahepatic metastases were associated with poor response and survival. Evaluation of early response may be necessary in patients with these factors.
4.Changing Epidemiology of Pathogenic Bacteria Over the Past 20 Years in Korea
Mi Hyun BAE ; Min-Sun KIM ; Taek Soo KIM ; Sunjoo KIM ; Dongeun YONG ; Gyoung Yim HA ; Nam Hee RYOO ; Young UH ; Jong Hee SHIN ; Hye Soo LEE ; Yong-Hak SOHN ; Sue SHIN ; Mi-Na KIM
Journal of Korean Medical Science 2023;38(10):e73-
Background:
The epidemiology of pathogenic bacteria varies according to the socioeconomic status and antimicrobial resistance status. However, longitudinal epidemiological studies to evaluate the changes in species distribution and antimicrobial susceptibility of pathogenic bacteria nationwide are lacking. We retrospectively investigated the nationwide trends in species distribution and antimicrobial susceptibility of pathogenic bacteria over the last 20 years in Korea.
Methods:
From 1997 to 2016, annual cumulative antimicrobial susceptibility and species distribution data were collected from 12 university hospitals in five provinces and four metropolitan cities in South Korea.
Results:
The prevalence of Staphylococcus aureus was the highest (13.1%) until 2012 but decreased to 10.3% in 2016, consistent with the decrease in oxacillin resistance from 76.1% in 2008 to 62.5% in 2016. While the cefotaxime resistance of Escherichia coli increased from 9.0% in 1997 to 34.2% in 2016, E. coli became the most common species since 2013, accounting for 14.5% of all isolates in 2016. Pseudomonas aeruginosa and Acinetobacter baumannii rose to third and fifth places in 2008 and 2010, respectively, while imipenem resistance increased from 13.9% to 30.8% and 0.7% to 73.5% during the study period, respectively.Streptococcus agalactiae became the most common pathogenic streptococcal species in 2016, as the prevalence of Streptococcus pneumoniae decreased since 2010. During the same period, pneumococcal penicillin susceptibility decreased to 79.0%, and levofloxacin susceptibility of S. agalactiae decreased to 77.1% in 2016.
Conclusion
The epidemiology of pathogenic bacteria has changed significantly over the past 20 years according to trends in antimicrobial resistance in Korea. Efforts to confine antimicrobial resistance would change the epidemiology of pathogenic bacteria and, consequently, the diagnosis and treatment of infectious diseases.
5.Serotype Distribution and Antimicrobial Resistance of Streptococcus pneumoniae Causing Invasive Pneumococcal Disease in Korea Between 2017 and 2019 After Introduction of the 13-Valent Pneumococcal Conjugate Vaccine
Gyu Ri KIM ; Eun-Young KIM ; Si Hyun KIM ; Hae Kyung LEE ; Jaehyeon LEE ; Jong Hee SHIN ; Young Ree KIM ; Sae Am SONG ; Joseph JEONG ; Young UH ; Yu Kyung KIM ; Dongeun YONG ; Hyun Soo KIM ; Sunjoo KIM ; Young Ah KIM ; Kyeong Seob SHIN ; Seok Hoon JEONG ; Namhee RYOO ; Jeong Hwan SHIN
Annals of Laboratory Medicine 2023;43(1):45-54
Background:
Streptococcus pneumoniae is a serious pathogen causing various infections in humans. We evaluated the serotype distribution and antimicrobial resistance of S. pneumoniae causing invasive pneumococcal disease (IPD) after introduction of pneumococcal conjugate vaccine (PCV)13 in Korea and investigated the epidemiological characteristics of multidrug-resistant (MDR) isolates.
Methods:
S. pneumoniae isolates causing IPD were collected from 16 hospitals in Korea between 2017 and 2019. Serotyping was performed using modified sequential multiplex PCR and the Quellung reaction. Antimicrobial susceptibility tests were performed using the broth microdilution method. Multilocus sequence typing was performed on MDR isolates for epidemiological investigations.
Results:
Among the 411 S. pneumoniae isolates analyzed, the most prevalent serotype was 3 (12.2%), followed by 10A (9.5%), 34 (7.3%), 19A (6.8%), 23A (6.3%), 22F (6.1%), 35B (5.8%), 11A (5.1%), and others (40.9%). The coverage rates of PCV7, PCV10, PCV13, and pneumococcal polysaccharide vaccine (PPSV)23 were 7.8%, 7.8%, 28.7%, and 59.4%, respectively. Resistance rates to penicillin, ceftriaxone, erythromycin, and levofloxacin were 13.1%, 9.2%, 80.3%, and 4.1%, respectively. MDR isolates accounted for 23.4% of all isolates. Serotypes 23A, 11A, 19A, and 15B accounted for the highest proportions of total isolates at 18.8%, 16.7%, 14.6%, and 8.3%, respectively. Sequence type (ST)166 (43.8%) and ST320 (12.5%) were common among MDR isolates.
Conclusions
Non-PCV13 serotypes are increasing among invasive S. pneumoniae strains causing IPD. Differences in antimicrobial resistance were found according to the specific serotype. Continuous monitoring of serotypes and antimicrobial resistance is necessary for the appropriate management of S. pneumoniae infections.
6.Erratum: Emergence of NDM-1–producing Pseudomonas aeruginosa Sequence Type 773 Clone: Shift of Carbapenemase Molecular Epidemiology and Spread of 16S rRNA Methylase Genes in Korea
Yu Jeong CHOI ; Young Ah KIM ; Junglim KIM ; Seok Hoon JEONG ; Jong Hee SHIN ; Kyeong Seob SHIN ; Jeong Hwan SHIN ; Young Ree KIM ; Hyun Soo KIM ; Young UH ; Nam Hee RYOO
Annals of Laboratory Medicine 2023;43(4):398-398
7.Guidelines for the Laboratory Diagnosis of Monkeypox in Korea
Ki Ho HONG ; Gab Jung KIM ; Kyoung Ho ROH ; Hyukmin LEE ; Ok Kyu PARK ; Taek Soo KIM ; Jae-Seok KIM ; Jaehyeon LEE ; Moon-Woo SEONG ; So Yeon KIM ; Jae-Sun PARK ; Younhee PARK ; Hee Jae HUH ; Namhee RYOO ; Hyun Soo KIM ; Heungsup SUNG ; Cheon Kwon YOO ;
Annals of Laboratory Medicine 2023;43(2):137-144
While the coronavirus disease 2019 pandemic is ongoing, monkeypox has been rapidly spreading in non-endemic countries since May 2022. Accurate and rapid laboratory tests are essential for identifying and controlling monkeypox. Korean Society for Laboratory Medicine and the Korea Disease Prevention and Control Agency have proposed guidelines for diagnosing monkeypox in clinical laboratories in Korea. These guidelines cover the type of tests, selection of specimens, collection of specimens, diagnostic methods, interpretation of test results, and biosafety. Molecular tests are recommended as confirmatory tests. Skin lesion specimens are recommended for testing in the symptomatic stage, and the collection of both blood and oropharyngeal swabs is recommended in the presymptomatic or prodromal stage.
8.Emergence of NDM-1–producing Pseudomonas aeruginosa Sequence Type 773 Clone: Shift of Carbapenemase Molecular Epidemiology and Spread of 16S rRNA Methylase Genes in Korea
Yu Jeong CHOI ; Young Ah KIM ; Junglim KIM ; Seok Hoon JEONG ; Jong Hee SHIN ; Kyeong Seob SHIN ; Jeong Hwan SHIN ; Young Ree KIM ; Hyun Soo KIM ; Young UH ; Nam Hee RYOO
Annals of Laboratory Medicine 2023;43(2):196-199
Imipenemase (IMP)-6–producing Pseudomonas aeruginosa sequence type (ST) 235 is a dominant clone of carbapenemase-producing P. aeruginosa (CPPAE) in Korea. As part of the Antimicrobial Resistance Surveillance System in Korea, we found an increase in the carbapenem resistance rate of P. aeruginosa isolates from blood cultures and a shift in the molecular epidemiology of CPPAE. A total of 212 non-duplicated P. aeruginosa blood isolates were obtained from nine general hospitals and two nursing homes. Twenty-four isolates were identified as CPPAE. We observed the emergence of the NDM-1 P. aeruginosa ST 773 clone (N=10), mostly from Gyeongsang Province. The IMP-6 ST 235 clone (N=11) was detected in all provinces. CPPAE isolates showed very high resistance rates to amikacin, and all NDM-1 P. aeruginosa strains carried rmtB. This is the first nationwide surveillance of the recently emerged NDM-1–producing P. aeruginosa ST773 clone in Korea. Continuous surveillance is necessary to prevent the infection and transmission of carbapenem- and amikacin-resistant P. aeruginosa in Korea.
9.Survival Benefit of Adjuvant Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma Who Underwent Surgery Following Neoadjuvant FOLFIRINOX
So Heun LEE ; Dae Wook HWANG ; Changhoon YOO ; Kyu-pyo KIM ; Sora KANG ; Jae Ho JEONG ; Dongwook OH ; Tae Jun SONG ; Sang Soo LEE ; Do Hyun PARK ; Dong Wan SEO ; Jin-hong PARK ; Ki Byung SONG ; Jae Hoon LEE ; Woohyung LEE ; Yejong PARK ; Bong Jun KWAK ; Heung-Moon CHANG ; Baek-Yeol RYOO ; Song Cheol KIM
Cancer Research and Treatment 2023;55(3):956-968
Purpose:
The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population.
Materials and Methods:
This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status.
Results:
Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months [95% confidence interval (CI), 11.0 to 19.1] vs. 8.2 months [95% CI, 6.5 to 12.0]; p < 0.001; and OS: median, 38.0 months [95% CI, 32.2 to not assessable] vs. 25.7 months [95% CI, 18.3 to not assessable]; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio [HR], 0.51 [95% CI, 0.36 to 0.71; p < 0.001]; OS: HR, 0.45 [95% CI, 0.29 to 0.71; p < 0.001]).
Conclusion
Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.
10.Analysis of Plasma Circulating Tumor DNA in Borderline Resectable Pancreatic Cancer Treated with Neoadjuvant Modified FOLFIRINOX: Clinical Relevance of DNA Damage Repair Gene Alteration Detection
Dong-Hoon LIM ; Hyunseok YOON ; Kyu-pyo KIM ; Baek-Yeol RYOO ; Sang Soo LEE ; Do Hyun PARK ; Tae Jun SONG ; Dae Wook HWANG ; Jae Hoon LEE ; Ki Byung SONG ; Song Cheol KIM ; Seung-Mo HONG ; Jaewon HYUNG ; Changhoon YOO
Cancer Research and Treatment 2023;55(4):1313-1320
Purpose:
There are no reliable biomarkers to guide treatment for patients with borderline resectable pancreatic cancer (BRPC) in the neoadjuvant setting. We used plasma circulating tumor DNA (ctDNA) sequencing to search biomarkers for patients with BRPC receiving neoadjuvant mFOLFIRINOX in our phase 2 clinical trial (NCT02749136).
Materials and Methods:
Among the 44 patients enrolled in the trial, patients with plasma ctDNA sequencing at baseline or post-operation were included in this analysis. Plasma cell-free DNA isolation and sequencing were performed using the Guardant 360 assay. Detection of genomic alterations, including DNA damage repair (DDR) genes, were examined for correlations with survival.
Results:
Among the 44 patients, 28 patients had ctDNA sequencing data qualified for the analysis and were included in this study. Among the 25 patients with baseline plasma ctDNA data, 10 patients (40%) had alterations of DDR genes detected at baseline, inclu-ding ATM, BRCA1, BRCA2 and MLH1, and showed significantly better progression-free survival than those without such DDR gene alterations detected (median, 26.6 vs. 13.5 months; log-rank p=0.004). Patients with somatic KRAS mutations detected at baseline (n=6) had significantly worse overall survival (median, 8.5 months vs. not applicable; log-rank p=0.003) than those without. Among 13 patients with post-operative plasma ctDNA data, eight patients (61.5%) had detectable somatic alterations.
Conclusion
Detection of DDR gene mutations from plasma ctDNA at baseline was associated with better survival outcomes of pati-ents with borderline resectable pancreatic ductal adenocarcinoma treated with neoadjuvant mFOLFIRINOX and may be a prognostic biomarker.

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