Sang Taek Heo

CD26/DPP4 Levels in Peripheral Blood and T Cells in Patients With Type 2 Diabetes Mellitus

CONTEXT Dipeptidyl peptidase 4 (CD26/DPP4) is expressed on blood T cells and also circulates in a soluble form (sCD26/DPP4). OBJECTIVE We aimed to evaluate blood T cell and circulating CD26/DPP4 and its association with metabolic parameters in patients with type 2 diabetes mellitus (T2DM). DESIGNS We measured CD26/DPP4 expression (percentage of CD26(+) cells using flow cytometry) on CD4(+) and CD8(+) T cells, serum CD26/DPP4 level and activity, and various metabolic parameters in T2DM patients not on DPP4 inhibitor therapy (n = 148). Nondiabetic subjects (n = 50) were included as a control group. RESULTS Compared with the healthy controls, CD26/DPP4 expression on CD4(+) T cells and CD8(+) T cells was higher in T2DM patients. Serum CD26/DPP4 levels and enzymatic activities were also higher in patients with T2DM than in the control group only when metformin and/or thiazolidinedione-treated T2DM patients were excluded; metformin and/or thiazolidinedione-treated T2DM patients had lower values compared with other T2DM patients. Various parameters in T2DM patients were related to CD26/DPP4 expression on the T cells (hemoglobin A1c), serum sCD26/DPP4 (hemoglobin A1c and insulin resistance assessed by updated homeostasis model assessment), and serum CD26/DPP4 activity (insulin resistance assessed by updated homeostasis model assessment, γ-glutamyl transferase, and alanine aminotransferase) by multivariate analyses. After active glucose control for 12 weeks in drug-naive T2DM patients (n = 50), CD26/DPP4 expression on blood T cells was significantly decreased. CONCLUSIONS Our results suggest that the CD26/DPP4 level on blood T cells was associated with glucose control status in patients with T2DM.

Predominance of an ST11 extended-spectrum β-lactamase-producing Klebsiella pneumoniae clone causing bacteraemia and urinary tract infections in Korea.

To investigate the antimicrobial resistance, extended-spectrum beta-lactamases (ESBLs) and clones of Klebsiella pneumoniae isolates causing bacteraemia or urinary tract infection (UTI) in Korea, a total of 406 K. pneumoniae isolates from patients with bacteraemia (221 isolates) and UTI (185 isolates) were collected from 10 tertiary-care Korean hospitals from July 2006 to October 2007. In vitro antimicrobial susceptibility testing was performed for all isolates and ESBL production was tested. Multilocus sequence typing (MLST) analyses were performed to characterize genotypes of ESBL-producing K. pneumoniae isolates. PFGE was performed for sequence type 11 (ST11) isolates. Forty-seven UTI isolates (25.4 %) produced ESBLs, while 30 bacteraemia isolates (13.6 %) produced ESBLs (P=0.002). Among 77 ESBL-producing isolates, thirty-two (41.6 %) produced SHV-type ESBLs. bla(CTX-M) genes such as bla(CTX-M-14) and bla(CTX-M-15) were detected in 36.4 %. MLST and PFGE analyses showed that ST11 was dominant in ESBL-producing K. pneumoniae isolates causing UTI (57.4 %) and in those causing bacteraemia (70.0 %) and has been prevalent in Korean hospitals. ST11 isolates harbour a combination of different ESBL genes. The ST11 clone of ESBL-producing K. pneumoniae isolates prevails in Korea, but most isolates might acquire ESBL genes independently or several different clones might be distributed in Korea.

Dissemination of ST131 and ST393 community-onset, ciprofloxacin-resistant Escherichia coli clones causing urinary tract infections in Korea

OBJECTIVE Ciprofloxacin-resistant Escherichia coli is growing concern in clinical settings. In this study, we investigated the distribution of virulence determinants and phylogenetic groups among community-onset, ciprofloxacin-resistant E. coli isolates causing urinary tract infections (UTIs) in Korea. In addition, the evidence of clonal spread in the community was also examined. METHODS From November 2006 to August 2007, 543 community-onset E. coli isolates causing UTIs were collected as part of a multicenter surveillance study. In vitro susceptibility testing was performed using broth microdilution method. Distribution of virulence determinants and phylogenetic groupings were examined. In addition, multilocus sequence typing (MLST) analysis was performed. RESULTS In vitro antimicrobial susceptibility testing revealed that 154 isolates (28.4%) were ciprofloxacin-resistant. Of these, 129 ciprofloxacin-resistant E. coli isolates were further characterized. As a result of phylogenetic subgrouping, we found that phylogenetic subgroup D was the most predominant (46 isolates, 35.7%), followed by B2 (44 isolates, 34.1%), A (21 isolates, 16.3%), and B1 (18 isolates, 14.0%). MLST analysis showed 48 sequence types (STs). The most prevalent ST was ST131 (32 isolates, 24.8%), followed by ST393 (23 isolates, 17.8%). While all ST131 isolates belonged to phylogenetic subgroup B2, which is known to be a highly virulent, all ST393 isolates belonged to subgroup D. ST131 and ST393 showed different profiles of virulence factors; papA, papG allele III, and traT genes were significantly more prevalent in ST131 than in ST393 (p values, <0.001). CONCLUSIONS Based on genotyping, it is suggested that epidemic and virulent ciprofloxacin-resistant E. coli clones such as ST131 and ST393 have disseminated in Korea. However, the diversity of CTX-M genes in ST131 isolates may indicate that ESBL genes have been acquired independently or several ESBL-producing, ciprofloxacin-resistant E. coli clones may have disseminated in the Korean community.

Characterization of Staphylococcus aureus nasal carriage from children attending an outpatient clinic in Seoul, Korea.

Nasal swabs were collected to isolate S. aureus in 296 children, who visited the pediatrics department with a variety of symptoms. Staphylococcus aureus was isolated from 95 children (32.1%). Of the isolates, 18 were methicillin-resistant S. aureus (MRSA) (18.9%). Antimicrobial susceptibility testing was performed for all S. aureus cultured and the molecular characteristics were investigated. Forty-nine spa types were identified among the S. aureus isolates, and were classified into 13 spa groups (A-L). The most prevalent clone (34 isolates, 35.8%) belonged to the spa group B (spa repeat motif, WG/FKAOMQ), which corresponded to sequence type 30 (ST30) and its variants. Sixteen different spa types, within the spa group B, suggested that this group has evolved over a long period of time. In addition, all S. aureus isolates belonging to the spa group B were methicillin-susceptible, indicating that this group might represent successful adaptation of this clone in the community setting with low antibiotic pressure. The most frequently found clone in the MRSA group was spa group C (spa repeat motif, DMGGM) and SCCmec type IVA, which represented half of the MRSA isolates and corresponded to ST72. ST5-MRSA-II, the most prevalent MRSA clone in Korean hospitals, was found in only two isolates. These findings suggest that strains of S. aureus nasal carriage in Korean children visiting an outpatient pediatric department were different from the strains identified in hospital infections.

Two distinct clones of carbapenem-resistant Acinetobacter baumannii isolates from Korean hospitals

We investigated the characteristics of 48 carbapenem-resistant Acinetobacter baumannii isolates collected from 5 tertiary care hospitals in Korea by multilocus sequencing typing, pulsed-field gel electrophoresis, and polymerase chain reaction amplification of the antimicrobial resistance determinants. We identified 2 distinct main clones of carbapenem-resistant A. baumannii isolates, which showed different antimicrobial resistance profiles and are also differentiated by the kinds of oxacillinase (OXA) carbapenemases and Acinetobacter-derived cephalosporinase (ADC) beta-lactamases. One main clone, ST22:A, had 27 carbapenem-resistant isolates (56.3%), showed high polymyxin B and colistin resistances (33.3% and 37.0%, respectively), and contained both bla(OXA-51-like) and bla(OXA-23-like) genes and the bla(ADC-29) or bla(ADC-30) gene. In contrast, the other main clone, ST28:B, included 15 isolates (31.3%), showed complete susceptibilities to polymyxin B and colistin, and contained only the bla(OXA-51-like) gene and bla(ADC-31) or bla(ADC-32) genes. The distribution of these main carbapenem-resistant A. baumannii clones did not relate to locality, indicating that they are widespread in Korean hospitals. In addition, we found new types of PER beta-lactamases, PER-6.

Plasma exchange and ribavirin for rapidly progressive severe fever with thrombocytopenia syndrome

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by a novel bunyavirus. Although the increasing numbers of cases and deaths is of great concern, an effective treatment strategy for SFTS has not been established. We present the cases of two patients with rapidly progressing SFTS who were successfully treated with plasma exchange and ribavirin.

Genetic correlation of community-associated methicillin-resistant Staphylococcus aureus strains from carriers and from patients with clinical infection in one region of Korea.

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is an increasingly common worldwide and colonizing S. aureus strains may serve as the causative pathogen for overt clinical infections. This study was performed to determine whether the pathogenic CA-MRSA isolate in clinical infections was genetically related to the MRSA isolates in community carriers. We prospectively collected a total of 42 CA-MRSA isolates (23 clinical infection isolates and 19 colonization isolates) in a local region of Korea. Antimicrobial susceptibility tests, staphylococcal toxin assays, SCCmec typing, multilocus sequence typing (MLST), and spa (staphylococcal protein A) typing were performed with all isolates. Thirty-four (81%) of 42 CA-MRSA isolates belonged to sequence type (ST) 72 in the MLST analysis. The distribution of STs did not differ significantly between colonization and clinical infection isolates (89.5% [17/19] vs. 73.9% [17/23], P=0.26). Among the ST72-MRSA isolates, spa type t664 (18, 52.9%) and t324 (8, 23.5%) were common in both groups. This study demonstrates that the community-associated MRSA strains from patients with clinical infections are closely related to the strains found in carriers from one local community.

Phylogenetic Analysis of Severe Fever with Thrombocytopenia Syndrome Virus in South Korea and Migratory Bird Routes Between China, South Korea, and Japan

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne viral disease. The SFTS virus (SFTSV) has been detected in the Haemaphysalis longicornis, which acts as a transmission host between animals and humans. SFTSV was first confirmed in China in 2009 and has also been circulating in Japan and South Korea. However, it is not known if a genetic connection exists between the viruses in these regions and, if so, how SFTSV is transmitted across China, South Korea, and Japan. We therefore hypothesize that the SFTSV in South Korea share common phylogenetic origins with samples from China and Japan. Further, we postulate that migratory birds, well-known carriers of the tick H. longicornis, are a potential source of SFTSV transmission across countries. Our phylogenetic analysis results show that the SFTSV isolates in South Korea were similar to isolates from Japan and China. We connect this with previous work showing that SFTSV-infected H. longicornis were found in China, South Korea, and Japan. In addition, H. longicornis were found on migratory birds. The migratory bird routes and the distribution of H. longicornis are concurrent with the occurrence of SFTSV. Therefore, we suggest that migratory birds play an important role in dispersing H. longicornis-borne SFTSV.

Synergy of Arbekacin-based Combinations Against Vancomycin Hetero-intermediate Staphylococcus aureus

This study was undertaken to evaluate the in vitro activities of arbekacin-based combination regimens against vancomycin hetero-intermediate Staphylococcus aureus (hetero-VISA). Combinations of arbekacin with vancomycin, rifampin, ampicillin-sulbactam, teicoplanin, or quinipristin-dalfopristin against seven hetero-VISA strains and two methicillin-resistant S. aureus strains were evaluated by the time-kill assay. The combinations of arbekacin with vancomycin, teicoplanin, or ampicillin-sulbactam showed the synergistic interaction against hetero-VISA strains. Data suggest that these arbekacin-based combination regimens may be useful candidates for treatment options of hetero-VISA infections.

The Effects of Climate Change and Globalization on Mosquito Vectors: Evidence from Jeju Island, South Korea on the Potential for Asian Tiger Mosquito (Aedes albopictus) Influxes and Survival from Vietnam Rather Than Japan

Background Climate change affects the survival and transmission of arthropod vectors as well as the development rates of vector-borne pathogens. Increased international travel is also an important factor in the spread of vector-borne diseases (VBDs) such as dengue, West Nile, yellow fever, chikungunya, and malaria. Dengue is the most important vector-borne viral disease. An estimated 2.5 billion people are at risk of infection in the world and there are approximately 50 million dengue infections and an estimated 500,000 individuals are hospitalized with dengue haemorrhagic fever annually. The Asian tiger mosquito (Aedes albopictus) is one of the vectors of dengue virus, and populations already exist on Jeju Island, South Korea. Currently, colder winter temperatures kill off Asian tiger mosquito populations and there is no evidence of the mosquitos being vectors for the dengue virus in this location. However, dengue virus-bearing mosquito vectors can inflow to Jeju Island from endemic area such as Vietnam by increased international travel, and this mosquito vectors survival during colder winter months will likely occur due to the effects of climate change. Methods and Results In this section, we show the geographical distribution of medically important mosquito vectors such as Ae. albopictus, a vector of both dengue and chikungunya viruses; Culex pipiens, a vector of West Nile virus; and Anopheles sinensis, a vector of Plasmodium vivax, within Jeju Island, South Korea. We found a significant association between the mean temperature, amount of precipitation, and density of mosquitoes. The phylogenetic analyses show that an Ae. albopictus, collected in southern area of Jeju Island, was identical to specimens found in Ho Chi Minh, Vietnam, and not Nagasaki, Japan. Conclusion Our results suggest that mosquito vectors or virus-bearing vectors can transmit from epidemic regions of Southeast Asia to Jeju Island and can survive during colder winter months. Therefore, Jeju Island is no longer safe from vector borne diseases (VBDs) due to the effects of globalization and climate change, and we should immediately monitor regional climate change to identify newly emerging VBDs.