Slide Session : OS-IFD-07 ; Infectious Disease : In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus

( Myung Jin Lee ),( Kye Hyung Kim ),( Jong Youn Yi ),( Su Jin Choi ),( Chung Jong Kim ),( Nak Hyun Kim ),( Kyoung Ho Song ),( Pyoeng Gyun Choi ),( Ji Hwan Bang ),( Wan Beom Park ),( Eu Suk Kim ),( San 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus Myung Jin LEE1, Kye-Hyung KIM1, Jongyoun YI2, SuJin CHOI1, Chung-Jong KIM1, Nak- Hyun KIM1, Kyoung-Ho SONG1, Pyoeng Gyun CHOI1, Ji-Hwan BANG1, Wan Beom PARK1, Eu Suk KIM1, Sang-Won PARK1, Hong Bin KIM1, Nam Joong KIM1, Myoung- Don OH1 Seoul National University College of Medicine, Korea1, Pusan National University School of Medicine, Korea2 Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV). No effective antiviral therapy is proven yet, but clinical use of ribavirin (RBV) has been tried. We investigated the antiviral effect of RBV against SFTSV in vitro. Methods: To test for cytotoxicity of RBV, Vero cells were treated with different concentrations of RBV (3.90 to 500 μg/mL, two-fold dilution) and analyzed by cell viability MTS assay 48h post-infection. To determine antiviral activity of RBV against SFTSV, Vero cells were infected with SFTSV strain Gangwon/Korea/2012 at 100 TCID50 (50% tissue culture infective dose) per well in a 96-well plate, and RBV was added at the concentrations showing no or minimal cytotoxicity. Viral RNAs were extracted from the culture supernatants and quantifi ed using one-step real-time reverse transcription- PCR to amplify the partial large segment of SFTSV. Statistical analysis was done by one-way ANOVA with Tukey`s post hoc test. Results: Cytotoxicity due to RBV was not observed at RBV concentration =31.3 μg/ mL. Viral RNAs at 24h post-RBV treatment were reduced with increasing RBV concentrations (1-32 μg/mL), compared with those of mock-treated cells (P <0.01, Figure). Half maximal inhibitory concentration (IC50) of RBV was 3.69 μg/mL at 24h post-RBV treatment. Conclusions: Our study shows that RBV has antiviral effect against SFTSV in a dose-dependent manner. Further studies are required to evaluate the effi cacy of RBV in SFTS.

국내 Epstein-Barr 바이러스 일차감염의 임상적 특성

김백남,곽이경,문치숙,김의석,박상원,이창섭 대한감염학회 2007 감염과 화학요법 Vol.39 No.6

In this study, the clinical features of 264 patients of primary Epstein-Barr virus (EBV) infection between the years of 2002-2006 were evaluated retrospectively. The median age of the patients was 6 years old (0-69), and the hospitalization rate was 78.0%. Fever (83.3%) and sore throat (50.4%) were the most common symptoms. Cervical lymphadenopathy (71.2%), tonsillitis (51.1%), splenomegaly (26.1 %), hepatomegaly (25.8%), rash (10.2%) and jaundice (1.5%) were observed. Cervical lymphadenopathy was less frequent in older age groups. The annual number of primary EBV infections according to the age group during the study period did not change significantly in this study.

쯔쯔가무시병에서 가피의 위치와 복장과의 관계

김백남,곽이경,문치숙,김의석,박상원,이창섭 대한감염학회 2006 감염과 화학요법 Vol.38 No.6

목적 : 쯔쯔가무시병의 예방을 위하여 위험지역에서 긴소매 윗옷을 입고 바지 끝을 양말 속에 넣는 것이 권장되고 있다. 이러한 예방조치의 효용성을 알아보기 위하여 우리는 쯔쯔가무시병에서 가피의 위치와 신발과 복장과의 관계를 살펴보았다. 재료 및 방법 : 2005년 10-12월 사이 6개 병원에서 전형적인 임상양상, 가피의 존재, 혈청검사 결과로 쯔쯔가무시병이 의심되거나 확진된 159명의 성인을 대상으로 가피의 위치, 추정 감염일, 야외활동, 당시 착용한 신발과 복장 등 을 조사하였다. 결과 : 혈청검사는 5명에서 시행되지 않았고 99명이 양성이었으며, 가피는 142명에서 발견되었다. 몸의 두 군데에서 발견된 6명을 제외한 136명 중 82명(60.3%)에서 가피는 하반신(아랫배, 엉덩이, 서혜부, 생식기, 넓적다리, 종아리)에 있었다. 감염일이 추정가능하고 가피가 1개만 있는 44명을 대상으로 하였을 때, 가피가 하반신에서 발견된 17명에서 슬리퍼를 신거나 맨발인 경우는 5명이었으나 상반신에 있는 27명 중에는 아무도 없었다(P=0.006). 바지아랫단을 양말 속에 집어 넣은 4명 중 1명은 하반신에서 3명은 상반신에서 가피가 발견되었다. 42명이 긴 소매 윗옷을 입었는데, 이중 16명은 하반신에서 26명은 상반신에서 가피가 발견되었다(P=1.00). 결론 : 쯔쯔가무시병 환자에서 신발을 신지 않거나 발이 잘 보호되지 않았을 때 가피는 하반신에 더 잘 생겼다. 바지 아랫단의 처리방법이나 긴 소매 윗옷의 착용은 가피의 위치와 통계적으로 유의한 연관관계는 발견되지는 않았다. 그러나 표본수가 적고 유충의 침범경로에 영향을 줄수 있는 다른 요인이 있기 때문에 가피의 위치와 연관관계가 없다고 이 연구에서 단정할 수는 없다. 따라서 쯔쯔가무시병의 예방을 위한 실용적인 권고를 위해서는 더 많은 연구가 필요하다. Background:Wearing a long-sleeved shirt and tucking the pants legs into the socks is recommended to prevent scrub typhus. This study investigated associations between the location of eschar and the type of clothes and shoes to evaluate the efficacy of these protective measures. Materials and Methods:One-hundred and fifty nine patients in whom scrub typhus was confirmed or suspected based on the typical clinical manifestations, presence of eschar, or positive results of serologic tests at 6 Korean hospitals from October to December 2005 were included in this study. We collected the information on the location of eschar, presumed exposure date to chiggers, and the clothes and shoes which they had worn. Results:Serologic tests were positive in 99 patients. Eschars were observed in 142 patients and 6 of them exhibited more than 2 eschars. Eighty-two (60.3%) of 136 patients with a single eschar had an eschar on the lower half of the body. Of the 44 patients whose exposure date could be estimated, and who had only a single eschar, 5 of the 17 patients with eschars in the lower half of their bodies, and none of the 27 patients with eschars in the upper half of their bodies went barefoot or wore open footware (P=0.006). Only 4 patients tucked the pants into their socks, and an eschar was found in the lower half in one patient, and in the upper half of the body in the other 3 patients. Of 42 patients who wore long-sleeved shirts, eschars were found in their lower bodies in 16, and on their upper bodies in 26 (P=1.00). Conclusion:When the feet were not protected properly with shoes, eschars were found more frequently on the lower half of the body than on the upper half. Wearing a long-sleeved shirt or tucking the pants legs into the socks was not found to be significantly correlated to the location of eschars. Further studies involving larger samples are necessary for the development of practical guidelines of protective measures to prevent scrub typhus.

발작과 쇼크를 동반한 토착형 삼일열 말라리아 1예

윤상구,김민환,정은숙,한금현,곽이경,조종래,엄태현,김의석 대한감염학회 2007 감염과 화학요법 Vol.39 No.4

삼일열 말라리아는 일반적으로 경미한 임상경과를 거치며, 열대열 말라리아와 달리 뇌형말라리아, 폐부종, 신부전등의 치명적인 합병증을 일으키지 않는 것으로 알려져 있다. 저자들은 특이한 과거력이 없던 건강하던 성인이 국내에서 삼일열 말라리아에 걸린 후 발작과 쇼크가 발생하여, 항말라리아 약제와 대증치료로 치료된 증례를 경험하였다. Vivax malaria reemerged in the Republic of Korea in 1993. Vivax malaria is generally a benign disease with few severe complications. Even in the worldwide literature, there is only a small number of case reports on severe complications in vivax malaria. We report a unique case of P. vivax infection complicated by seizure and shock. A 58 year-old male showed generalized tonic-clonic seizure and shock after P. vivax infection. The species of malarial parasite was identified using peripheral blood film examination and polymerase chain reaction (PCR). He successfully recovered after treatment with hydroxychloroquine.

급결제 및 혼화제 종류가 숏크리트 내구성에 미치는 영향에 관한 연구

백신원,권소진,이영수,김의성,신용석 한국안전학회 2003 한국안전학회지 Vol.18 No.3

Concrete and shotcrete should withstand the conditions for which they have been designed, without deterioration, over a period of years. But concrete and shotcrete are being deteriorated according to aging by internal and external causes. Recently, many studies on the durability of concrete have been conducted. But the durability of shotcrete is rarely studied. So, in this study, chloride ion penetration test, freeze and thaw test, neutralization test were conducted to examine the durability characteristics of shotcrete with several accelerator and chemical admixture types. These results indicate that shotcrete with alkali free accelerator and with superplasticizer are durable. Therefore, the present study provides a firm base to make high performance shotcrete.

Clinical Course and Outcomes of Patients with Severe Acute Respiratory Syndrome Coronavirus 2 Infection: a Preliminary Report of the First 28 Patients from the Korean Cohort Study on COVID-19

Eu Suk Kim,Bum Sik Chin,강창경,Nam Joong Kim,Yu Min Kang,Jae-Phil Choi,Dong Hyun Oh,Jeong-Han Kim,Boram Koh,Seong Eun Kim,Na Ra Yun,Jae Hoon Lee,Jin Yong Kim,Yeonjae Kim,Ji Hwan Bang,송경호,Hong Bin Kim,Ki- 대한의학회 2020 Journal of Korean medical science Vol.35 No.13

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pneumonia emerged in Wuhan, China in December 2019. In this retrospective multicenter study, we investigated the clinical course and outcomes of novel coronavirus disease 2019 (COVID-19) from early cases in Republic of Korea. Methods: All of the cases confirmed by real time polymerase chain reaction were enrolled from the 1st to the 28th patient nationwide. Clinical data were collected and analyzed for changes in clinical severity including laboratory, radiological, and virologic dynamics during the progression of illness. Results: The median age was 40 years (range, 20–73 years) and 15 (53.6%) patients were male. The most common symptoms were cough (28.6%) and sore throat (28.6%), followed by fever (25.0%). Diarrhea was not common (10.7%). Two patients had no symptoms. Initial chest X-ray (CXR) showed infiltration in 46.4% of the patients, but computed tomography scan confirmed pneumonia in 88.9% (16/18) of the patients. Six patients (21.4%) required supplemental oxygen therapy, but no one needed mechanical ventilation. Lymphopenia was more common in severe cases. Higher level of C-reactive protein and worsening of chest radiographic score was observed during the 5–7 day period after symptom onset. Viral shedding was high from day 1 of illness, especially from the upper respiratory tract (URT). Conclusion: The prodromal symptoms of COVID-19 were mild and most patients did not have limitations of daily activity. Viral shedding from URT was high from the prodromal phase. Radiological pneumonia was common from the early days of illness, but it was frequently not evident in simple CXR. These findings could be plausible explanations for the easy and rapid spread of SARS-CoV-2 in the community.

Incidence of Clostridioides difficile Infections in Republic of Korea: A Prospective Study With Active Surveillance vs. National Data From Health Insurance Review & Assessment Service

Kim Jieun,Myung Rangmi,Kim Bongyoung,Kim Jinyeong,Kim Tark,Lee Mi Suk,Kim Uh Jin,Park Dae Won,Kim Yeon-Sook,Lee Chang-Seop,Kim Eu Suk,Lee Sun Hee,Chang Hyun-Ha,Lee Seung Soon,Park Se Yoon,Choi Hee Jun 대한의학회 2024 Journal of Korean medical science Vol.39 No.12

Background: Since the emergence of hypervirulent strains of Clostridioides difficile, the incidence of C. difficile infections (CDI) has increased significantly. Methods: To assess the incidence of CDI in Korea, we conducted a prospective multicentre observational study from October 2020 to October 2021. Additionally, we calculated the incidence of CDI from mass data obtained from the Health Insurance Review and Assessment Service (HIRA) from 2008 to 2020. Results: In the prospective study with active surveillance, 30,212 patients had diarrhoea and 907 patients were diagnosed with CDI over 1,288,571 patient-days and 193,264 admissions in 18 participating hospitals during 3 months of study period; the CDI per 10,000 patientdays was 7.04 and the CDI per 1,000 admission was 4.69. The incidence of CDI was higher in general hospitals than in tertiary hospitals: 6.38 per 10,000 patient-days (range: 3.25–12.05) and 4.18 per 1,000 admissions (range: 1.92–8.59) in 11 tertiary hospitals, vs. 9.45 per 10,000 patient-days (range: 5.68–13.90) and 6.73 per 1,000 admissions (range: 3.18–15.85) in seven general hospitals. With regard to HIRA data, the incidence of CDI in all hospitals has been increasing over the 13-year-period: from 0.3 to 1.8 per 10,000 patient-days, 0.3 to 1.6 per 1,000 admissions, and 6.9 to 56.9 per 100,000 population, respectively. Conclusion: The incidence of CDI in Korea has been gradually increasing, and its recent value is as high as that in the United State and Europe. CDI is underestimated, particularly in general hospitals in Korea.

Ozone Inhalation with 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone and/or Dibutyl Phthalate Induced Cell Cycle Alterations via Wild-type p53 Instability in B6C3F1 Mice

Min Young Kim,Kyung Suk Song,Gun Ho Park,Hyun Woo Kim,Jin Hong Park,Jun Sung Kim,Hwa Jin,Kook Jong Eu,Hyun Sun Cho,Gami Kang,Chanhee Chae,Yoon Shin Kim,Young Chul Kim,Hae Yeong Kim,George Beck,Nancy C 한국독성학회 2004 Toxicological Research Vol.20 No.1

Changes in cell cycle control in the lungs and liver of the B6C3F1 mice (20 males per each group) exposed to ozone (0.5 ppm), 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 1.0 mg/kg), and dibutyl phthalate (DBP, 5,000 ppm) after 52 weeks were examined through Western, Northern blot, and immunohistochemistry based on alterations in protein expression levels of G1/S checkpoints (cyclin D1, cyclin E, and PCNA), G2/M checkpoints (cyclin B1, cyclin G, and cyclin A), negative regulators (p53, p21, GADD45, and p27), and positive regulator (mdm2). Expression levels of cyclins D1, E, G, PCNA, mutant p53, and mdm2 proteins were higher in the lungs<br/> and livers treated with combination of toxicants than in those treated with ozone only. Expression levels of the wild-type and mutant p53, p21, GADD45, p27, and mdm2 proteins and mRNAs were<br/> higher in toxicant-treated groups than those of the control. Immunohistochemical analysis revealed staining intensities of the PCNA, cyclin D1, c-myc and mdm2 protein- treated lungs and livers were stronger than those of the control group. Our results showed that combined treatment of ozone with NNK/DBP altered the cell cycle control through instability of the wild-type p53 gene. Such pivotal p53-mediated cell cycle alterations may be responsible for the toxicity observed under our experimental condition. These results may be applied to risk assessment of mixture-induced toxicity.

국내 다기관에서 조사한 지역사회획득 메티실린내성 황색포도알균의 빈도와 임상적 특성

송진수,최평균,송경호,조재현,김성한,방지환,이창섭,박경화,박경운,신수,최희정,김의석,김동민,이미숙,박완범,김남중,오명돈,김의종,김홍빈,최강원 대한감염학회 2006 감염과 화학요법 Vol.38 No.6

목적 : 최근 전세계적으로 지역사회획득 메티실린내성 황색포도알균(community-associated methicillin-resistant Staphylococcus aureus, CA-MRSA)의 보고가 증가하고 있다. 하지만, 우리나라에서는 CA-MRSA 감염증에 대한 증례보고만 있을 뿐 아직까지 체계적인 연구결과가 없는 실정이다. 저자들은 국내에서 CA-MRSA의 빈도, 감염증의 임상적 양상, 분리된 균주의 항균제내성 양상을 조사하였다. 재료 및 방법 : 2005년 1월부터 2005년 6월까지 7개 병원에서 MRSA가 분리된 환자의 명단을 파악한 후 의무기록지와 건강보험심사평가원의 자료를 검토하였다. 외래나 응급실에서 혹은 입원 후 72시간 이내에 균주가 분리되고 MRSA 획득과 관련된 위험인자가 없는 경우 CA-MRSA로 정의하였으며, 분리된 균주의 임상적 의미에 따라 원인병원체(pathogen), 집락화(colonizer), 미결정(undetermined)으로 분류하였다. Penicillin과 oxacillin을 제외하고 3개 이상의 다른 계열 항균제에 내성이면 다제내성으로 정의하였다. 결과 : 연구기간동안 총 3,251주의 황색포도알균이 분리되었으며, 이 중 MRSA는 1,900주(58.4%)였다. MRSA 가운데 CA-MRSA는 114주(6.0%) 였으며, 이들이 분리된 부위는 귀(62주), 비뇨기계(14주), 피부 및 연부조직(11주), 호흡기계(10주), 혈액(3주) 등이었다. CA-MRSA 균주 가운데 집락균은 22주, 원인병원체는 22주였으며, 나머지 균주에 대해서는 그 임상적 의미를 결정할 수 없었다. 항균제 감수성 검사를 시행한 73균주 중 47주(64.4%)는 다제내성이었다. CA-MRSA 감염증 22예 중 피부 및 연부조직 감염(9예)과 중이염/외이도염(9예)이 가장 흔하였다. 침습적 감염증(invasive infection)은 4명(원발성 균혈증 3예, 감염성 관절염 1예)에서 확인되었지만, CA-MRSA 감염증으로 사망한 환자는 없었다. 결론 : 병원내 감염증에서는 MRSA가 심각한 문제이지만, 아직까지 지역사회 감염증에서 CA-MRSA는 흔하지 않았다. Background : Methicillin-resistant Staphylococcus aureus (MRSA) infection has emerged in patients who do not have the established risk factors. In Korea, little is known about the epidemiology and clinical features of community-associated MRSA (CA-MRSA). Material and Methods : Clinical microbiology laboratory databases of 7 hospitals were reviewed to identify the patients from whom MRSA was isolated during the period of January to July 2005. Only one isolate per patient was enrolled. In order to identify the risk factors of MRSA acquisition, the medical records and the Health Insurance Review Agency databases were reviewed. CA-MRSA was defined as MRSA isolated from patient without established risk factors. We analyzed patient demographics, underlying medical conditions, characteristics of infection, and antimicrobial susceptibility profiles. Results : Of total 3,251 S. aureus isolates, 1900 (58.4%) were MRSAs. Of the MRSA isolates, 114 (6.0%) were CA-MRSA. Of 114 CA-MRSA isolates, 22 (19.3%) were colonizers, 22 (19.3%) were pathogens, and the clinical significance of remaining 70 (61.4%) could not be determined. Median age of the 22 patients with CA-MRSA disease was 47 years. Nine patients had skin and soft tissue infections, 9 ear infections, 3 bacteremia, 1 septic arthritis. Seven patients had underlying medical disease. None died of the CA-MRSA infections. Of the 73 isolates of CA-MRSA, 47 (64.4%) were resistant to more than 3 classes of antibiotics besides β-lactams. Conclusion : Although MRSA is highly prevalent among hospital-associated S. aureus infection, CA-MRSA infections are not common.

Effects of Phage Endolysin SAL200 Combined with Antibiotics on <i>Staphylococcus aureus</i> Infection

Kim, Nak-Hyun,Park, Wan Beom,Cho, Jeong Eun,Choi, Yoon Jeong,Choi, Su Jin,Jun, Soo Youn,Kang, Chang Kyung,Song, Kyoung-Ho,Choe, Pyoeng Gyun,Bang, Ji-Hwan,Kim, Eu Suk,Park, Sang Won,Kim, Nam-Joong,Oh, American Society for Microbiology 2018 Antimicrobial Agents and Chemotherapy Vol.62 No.10

<P>Phages and their derivatives are increasingly being reconsidered for use in the treatment of bacterial infections due to the rising rates of antibiotic resistance. We assessed the antistaphylococcal effect of the endolysin SAL200 in combination with standard-of-care (SOC) antibiotics. The activity of SAL200 when it was combined with SOC antibiotics was assessed in vitro by checkerboard and time-kill assays and in vivo with murine bacteremia and Galleria mellonella infection models. SAL200 reduced the SOC antibiotic MICs and showed a >= 3-log(10)-CFU/ml reduction of Staphylococcus aureus counts within 30 min in time-kill assays. Combinations of SAL200 and SOC antibiotics achieved a sustained decrease of >2 log(10) CFU/ml. SAL200 significantly lowered the blood bacterial density within 1 h by >1 log(10) CFU/ml in bacteremic mice (P < 0.05 versus untreated mice), and SAL200 and SOC antibiotic combinations achieved the lowest levels of bacteremia. The bacterial density in splenic tissue at 72 h postinfection was the lowest in mice treated with SAL200 and SOC antibiotic combinations. SAL200 combined with SOC antibiotics also improved Galleria mellonella larva survival at 96 h postinfection. The combination of the phage endolysin SAL200 with SOC antistaphylococcal antibiotics showed synergistic effects in vitro and in vivo. The combination of SAL200 with SOC antibiotics could help in the treatment of difficult-to-treat S. aureus infections.</P>