The Impact of an Antimicrobial Stewardship Program on Days of Therapy in the Pediatric Center: An Interrupted Time-Series Analysis of a 19-Year Study

Kim Kyung-Ran,Park Hyo Jung,Baek Sun-Young,Choi Soo-Han,Lee Byung-Kee,Kim SooJin,Kim Jong Min,Kang Ji-Man,Kim Sun-Ja,Choi Sae Rom,Kim Dongsub,Choi Joon-sik,Yoon Yoonsun,Park Hwanhee,Kim Doo Ri,Shin Ar 대한의학회 2024 Journal of Korean medical science Vol.39 No.21

Background: We aimed to analyze the effects of an antimicrobial stewardship program (ASP) on the proportion of antimicrobial-resistant pathogens in bacteremia, antimicrobial use, and mortality in pediatric patients. Methods: A retrospective single-center study was performed on pediatric inpatients under 19 years old who received systemic antimicrobial treatment from 2001 to 2019. A pediatric infectious disease attending physician started ASP in January 2008. The study period was divided into the pre-intervention (2001–2008) and the post-intervention (2009–2019) periods. The amount of antimicrobial use was defined as days of therapy per 1,000 patientdays, and the differences were compared using delta slope (= changes in slopes) between the two study periods by an interrupted time-series analysis. The proportion of resistant pathogens and the 30-day overall mortality rate were analyzed by the χ2 . Results: The proportion of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia increased from 17% (39 of 235) in the pre-intervention period to 35% (189 of 533) in the post-intervention period (P < 0.001). The total amount of antimicrobial use significantly decreased after the introduction of ASP (delta slope value = −16.5; 95% confidence interval [CI], −30.6 to −2.3; P = 0.049). The 30-day overall mortality rate in patients with bacteremia did not increase, being 10% (55 of 564) in the pre-intervention and 10% (94 of 941) in the post-intervention period (P = 0.881). Conclusion: The introduction of ASP for pediatric patients reduced the delta slope of the total antimicrobial use without increasing the mortality rate despite an increased incidence of ESBL-producing gram-negative bacteremia.

지난 2년간의 학회지 "신경정신의학" 심사 평가보고

김찬형,김세주,김도관,김성곤,박원명,송동호,박용천,이영문,오강섭,정영철,이상열,김주한,이동영,이헌정,함병주,김율리,김문두,김정진,이강욱,천근아,김재진,홍진표,홍승철 大韓神經精神醫學會 2007 신경정신의학 Vol.46 No.6

Malignancy in Patients With Inborn Errors of Immunity Beyond Infectious Complication: Single Center Experience for 30 Years

( Doo Ri Kim ),( Kyung-ran Kim ),( Hwanhee Park ),( Joon-sik Choi ),( Yoonsun Yoon ),( Sohee Son ),( Hee Young Ju ),( Jihyun Kim ),( Keon Hee Yoo ),( Kangmo Ahn ),( Hee-jin Kim ),( Eun-suk Kang ),( Ju 대한소아감염학회 2023 Pediatric Infection and Vaccine Vol.30 No.3

목적: 선천면역장애 환자들은 감염에 취약할 뿐만 아니라, 면역이 정상인 사람들에 비해 암 발생률도 높은 것으로 알려져 있다. 본 연구는 단일 기관에서 추적 중인 선천면역장애 환자들에서의 암 발생을 조사하여 보고자 하였다. 방법: 1994년 11월부터 2023년 9월까지 삼성서울병원에서 선천면역장애 진단 하에 추적하는 환자를 대상으로 후향적으로 의무기록을 리뷰하였다. 선천면역장애 환자 중에서 암으로 진단된 환자를 확인하였다. 결과: 총 194명의 선천면역장애 환자 중, 7명(3.6%)의 환자에서 암이 진단되었다. 5명의 환자가 림프종으로 진단받았으며 그 중 4명의 환자는 Epstein-Barr 바이러스 연관 림프종이었다. 나머지 암은 위암과 다발 골수종이었다. 암 진단 당시 나이는 중앙값 18세 (범위, 1세-75세)였다. 암이 발생한 환자들의 면역결핍 질환은 X-linked lymphoproliferative disorder-1 (XLP-1) 3명, activated phosphoinositide 3-kinase delta disease (APDS) 2명, cytotoxic T-lymphocyte antigen 4 (CTLA-4) haplo-insufficiency 2명이었다. 개별 질환별로 분석하였을 때, XLP-1 환자의 75.0%, APDS 환자의 40.0%, CTLA-4 환자의 50.0%에서 암이 발생하였다. XLP-1 환자는 APDS 및 CTLA-4 haplo-insufficiency 환자에 비해 더 이른 나이에 암이 발생하였다 (중앙연령 5세, P<0.001). 한 명은 조혈모세포 이식 치료 중 사망하였다. 결론: 국내 단일 기관에서 진료받는 선천면역장애 환자들의 3.6%에서 암이 발생하였다. 선천면역장애 환자들을 진료하는 의료진들은 이들 환자에서 감염이나 염증 등의 문제외에도 암 발생의 가능성, 특히 Epstein-Barr 바이러스 감염과 연관된 암의 비중이 높은 것에 대한 인식을 갖는 것이 중요하다 Purpose: Cancer incidence is known to be higher in patients with inborn errors of immunity (IEI) compared to the general population in addition to traditionally well-known infection susceptibility. We aimed to investigate cancer occurrence in patients with IEI in a single center. Methods: Medical records of IEI patients treated at Samsung Medical Center, Seoul, Korea were retrospectively reviewed from November 1994 to September 2023. Patients with IEI and cancer were identified. Results: Among 194 patients with IEI, seven patients (3.6%) were diagnosed with cancer. Five cases were lymphomas, 4 of which were Epstein-Barr virus (EBV)-associated lymphomas. The remaining cases included gastric cancer and multiple myeloma. The median age at cancer diagnosis was 18 years (range, 1-75 years). Among patients with cancer, underlying IEIs included X-linked lymphoproliferative disease-1 (XLP-1, n=3), activated phosphoinositide 3-kinase delta syndrome (APDS, n=2), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) haplo-insufficiency (n=2). Seventy-five percent (3/4) of XLP-1 patients, 40.0% (2/5) of APDS patients, and 50.0% (2/4) of CTLA-4 haplo-insufficiency patients developed cancer. Patients with XLP-1 developed cancer at earlier age (median age 5 years) compared to those with APDS and CTLA-4 (P<0.001). One patient with APDS died during hematopoietic cell transplantation. Conclusions: Cancer occurred in 3.6% of IEI patients at a single center in Korea. In addition to infectious complications and inflammation, physicians caring for IEI patients should be aware of the potential risk of cancer, especially in association with EBV infection

Severe Human Rhinovirus Lower Respiratory Tract Infections in Young Children

( Doo Ri Kim ),( Kyung-ran Kim ),( Hwanhee Park ),( Esther Park ),( Joongbum Cho ),( Jihyun Kim ),( Hee Jae Huh ),( Kangmo Ahn ),( Nam Yong Lee ),( Yae-jean Kim ) 대한소아감염학회 2023 Pediatric Infection and Vaccine Vol.30 No.3

목적: 리노바이러스의 감염은 하기도 감염을 일으키기도 한다. 본 연구에서는 리노바이러스에 의한 중증 하기도 감염을 보이는 소아환자의 특성을 알아보고자 하였다. 방법: 2016년부터 2020년까지 삼성서울병원 소아청소년과에 리노바이러스 하기도감염으로 입원한 환자의 의무기록을 후향적으로 분석하였다. 입원 시 연령이 생후90일 이상, 5세 미만인 소아 환자를 대상으로 하였다. 다른 호흡기 병원체와의 동시 감염이 확인된 환자는 제외하였다. 리노바이러스에 의한 중증 하기도감염은 고유량 산소요법 치료가 필요한 경우, 기계 호흡이 필요한 경우 또는 중환자실 입원하는 경우로 정의하였다. 결과: 해당 기간 동안 총 115건의 리노바이러스 하기도 감염 입원이 확인되었다. 연령 중앙값은 17개월 (범위, 3-56개월) 이었으며, 입원 일수 중앙값은 4일 (범위, 2-31일) 이었다. 115 건 중 18건의 입원 (15.7%)은 중증 리노바이러스 하기도 감염 그룹으로 분류되었다. 중증 경과 그룹 환자의 연령 중앙값은 그렇지 않은 그룹에 비해 연령 중앙값이 낮았다 (9.5개월 vs. 19.0 개월, P=0.001). 18명의 중증 리노바이러스 하기도 감염 그룹 환자 중 11명 (61.1%)는 기저질환을 가지고 있었으며, 만성 폐질환이 가장 많은 비율을 차지하였다 (63.6%). 여섯 명의 환자는 (33.3%) 기계 호흡을 필요로 하였다. 일곱 명의 기저질환이 없는 환자도 중증 리노바이러스 하기도 감염 그룹에 포함되어 있었다. 이들 일곱 명의 환자 중 네 명은 추후에 천식으로 진단되었다. 115건의 입원을 기저질환이 없는 환자군 (n=60)과 기저질환이 있는 환자군 (n=55)으로 나누어 분석하였을 때, 리노바이러스에 의한 중증 하기도 감염을 보이는 비율은 각각 11.7% 와 20.0%였다 (P=0.219). 결론: 리노바이러스 감염은 중증 하기도감염의 원인이 될 수 있으며, 기저질환자 뿐 아니라 건강한 소아에서도 중증 하기도감염을 일으킬 수 있다 Purpose: Human rhinovirus (HRV) infections can result in lower respiratory tract infections (LRTIs). We aimed to investigate the characteristics of severe HRV LRTI in young children. Methods: Medical records were reviewed retrospectively in patients who were hospitalized for HRV LRTIs from 2016 to 2020 at the Samsung Medical Center in Seoul, Korea. Patients aged 90 days or older and younger than 5 years were included. Patients with co-infections with other respiratory pathogens were excluded. Severe HRV LRTI was defined as the following: the need for high-flow oxygenation, mechanical ventilation, or intensive care unit admission. Results: A total of 115 cases were identified. The median age was 17 months (range, 3-56 months) and the median hospital days were 4 days (range, 2-31 days). Of the 115 cases, 18 patients (15.7%) developed severe HRV LRTI. The median age was younger in the severe group compared to the non-severe group (9.5 months vs. 19.0 months, P=0.001). Of 18 patients with severe HRV LRTI, 11 (61.1%) had underlying diseases - chronic lung diseases accounted for the largest proportion (63.6%). Six patients (33.3%) required mechanical ventilation. Of note, 7 previously healthy children were diagnosed with severe HRV LRTI. Of those 7 children, 4 of them were diagnosed with asthma later. When the 115 cases were divided into previously healthy (n=60) and underlying disease (n=55) groups, severe courses of HRV LRTI were observed in 11.7% and 20.0% of children, respectively (P=0.219). Conclusions: HRV can cause severe LRTI even in previously healthy children as well as in children with comorbidities

The Multifaceted Clinical Characteristics of Congenital Cytomegalovirus Infection: From Pregnancy to Long-Term Outcomes

Kim Yejin,Kim Yoo-min,Kim Doo Ri,Kim Han Gyeol,Sung Ji-Hee,Choi Suk-Joo,Oh Soo-young,Kim Yae-Jean,Chang Yun Sil,Kim Dongsub,Kim Jung-Sun,Moon Il Joon,Roh Cheong-Rae 대한의학회 2023 Journal of Korean medical science Vol.38 No.32

Background: The aim of this study was to capture multifaceted clinical characteristics of congenital cytomegalovirus (CMV) infection from diagnosis to treatment using a multidisciplinary approach including obstetrics, pediatrics, pathology, and otorhinolaryngology-head and neck surgery. Methods: This is a retrospective study including 30 consecutive cases of congenital CMV infection that were diagnosed at a single tertiary hospital located in Seoul, Korea from January 2009 to December 2020. Congenital CMV infection was defined as a positive result by polymerase chain reaction from urine, saliva or cerebrospinal fluid or positive CMV IgM from neonatal blood sampled within 3 weeks after birth. All cases were analyzed with respect to whole clinical characteristics from diagnosis to treatment of congenital CMV by a multidisciplinary approach including prenatal sonographic findings, maternal immune status regarding CMV infection, detailed placental pathology, neonatal clinical manifestation, auditory brainstem response test, and antiviral treatment (ganciclovir or valganciclovir). Long-term outcomes including developmental delay and hearing loss were also investigated. Results: The total number of births during the study period in our institution was 19,385, with the prevalence of congenital infection estimated to be 0.15%. Among 30 cases of congenital CMV, the median gestational age at delivery was 32.2 weeks [range, 22.6–40.0] and 66.7% of these infants were delivered preterm at less than 37 weeks. Suspected fetal growth restriction was the most common prenatal ultrasound finding (50%) followed by ventriculomegaly (17.9%) and abnormal placenta (17.9%), defined as thick placenta with calcification. No abnormal findings on ultrasound examination were observed in one-third of births. Maternal CMV serology tests were conducted in only 8 cases, and one case each of positive and equivocal IgM were found. The most common placental pathologic findings were chronic villitis (66.7%) and calcification (63.0%), whereas viral inclusions were identified in only 22.2%. The most common neonatal manifestations were jaundice (58.6%) followed by elevation of aspartate aminotransferase (55.2%) and thrombocytopenia (51.7%). After excluding cases for which long-term outcomes were unavailable due to death (n = 4) or subsequent follow up loss (n = 3), developmental delay was confirmed in 43.5% of infants (10/23), and hearing loss was confirmed in 42.9% (9/21) during the follow-up period. In our cohort, 56.7% (17/30) of neonates were treated for congenital CMV with ganciclovir or valganciclovir. Conclusion: Our data show that prenatal findings including maternal serologic tests and ultrasound have limited ability to detect congenital CMV in Korea. Given that CMV is associated with high rates of developmental delay and hearing loss in infants, there is an urgent need to develop specific strategies for the definite diagnosis of congenital CMV infection during the perinatal period by a multidisciplinary approach to decrease the risks of neurologic impairment and hearing loss through early antiviral treatment.

Myositis as an Initial Presentation of Ulcerative Colitis before Gastrointestinal Symptoms

Kim, Doo Ri,Kim, DongSub,Choi, SangJoon,Suh, Yeon-Lim,Yoo, So-Young,Kim, Mi Jin,Choe, Yon Ho,Kim, Yae-Jean The Korean Society of Pediatric Gastroenterology 2020 Pediatric gastroenterology, hepatology & nutrition Vol.23 No.3

The musculoskeletal system can be involved as an extra-intestinal manifestation of inflammatory bowel disease. Among these, myositis in ulcerative colitis (UC) is very rare. A 14-year-old girl was admitted due to severe shoulder tenderness. She had complained of left jaw pain and swelling for the past 10 days. Inflammatory markers were elevated with no evidence of infectious etiology. Myositis was suspected by shoulder magnetic resonance imaging. Three days after admission, she developed hematochezia. Muscle biopsy and colonoscopy was performed due to worsening left mandibular area pain and persistent hematochezia. Colonoscopy showed consistent findings with UC. She was finally diagnosed with UC with myositis as an extra-intestinal manifestation. She showed a dramatic response to UC treatment. Gastrointestinal symptoms were well-controlled. After 14 months, UC symptoms and muscle pain were aggravated, which were relieved after steroid and cyclosporin treatment. We report a unique case of UC initially presented with myositis, preceding gastrointestinal symptoms.

Dynein light chain LC8 inhibits osteoclast differentiation and prevents bone loss in mice.

Kim, Hyeryeon,Hyeon, Seungha,Kim, Hojin,Yang, Yoohee,Huh, Ji Young,Park, Doo Ri,Lee, Hyojung,Seo, Dong-Hyun,Kim, Han-Sung,Lee, Soo Young,Jeong, Woojin Williams Wilkins 2013 JOURNAL OF IMMUNOLOGY Vol.190 No.3

<P>NF-κB is one of the key transcription factors activated by receptor activator of NF-κB ligand (RANKL) during osteoclast differentiation. The 8-kDa dynein L chain (LC8) was previously identified as a novel NF-κB regulator. However, its physiological role as an NF-κB inhibitor remains elusive. In this study, we showed the inhibitory role of LC8 in RANKL-induced osteoclastogenesis and signaling pathways and its protective role in osteolytic animal models. LC8 suppressed RANKL-induced osteoclast differentiation, actin ring formation, and osteoclastic bone resorption. LC8 inhibited RANKL-induced phosphorylation and subsequent degradation of IκBα, the expression of c-Fos, and the consequent activation of NFATc1, which is a pivotal determinant of osteoclastogenesis. LC8 also inhibited RANKL-induced activation of JNK and ERK. LC8-transgenic mice exhibited a mild osteopetrotic phenotype. Moreover, LC8 inhibited inflammation-induced bone erosion and protected against ovariectomy-induced bone loss in mice. Thus, our results suggest that LC8 inhibits osteoclast differentiation by regulating NF-κB and MAPK pathways and provide the molecular basis of a new strategy for treating osteoporosis and other bone diseases.</P>

소아 신장이식 환자에서 발생한 파르보바이러스 B19에 의한 심한 빈혈에 대한 증례 보고 및 문헌 고찰

Kim Kyung-Ran,Park Hwanhee,Kim Doo Ri,Cho Heeyeon,Lee Sanghoon,Lee Suk-Koo,Kim Yae-Jean 대한소아감염학회 2021 Pediatric Infection and Vaccine Vol.28 No.3

Anemia commonly occurs in kidney transplantation (KT) recipients. Many factors such as viral infection, bleeding, erythropoietin deficiency, and immunosuppressants are the causes of chronic anemia in KT recipients. We report 2 cases who developed severe anemia caused by parvovirus B19 infection and were successfully treated with intravenous immunoglobulin in pediatric KT recipients. 신장이식 환자에서 만성 빈혈은 치료 과정 중 발생하는 합병증으로 바이러스 감염, 적혈구형성호르몬결핍, 출혈, 면역억제제의 부작용 등과 관련이 있다. 신장이식 환자에서 파르보바이러스 B19에 의한 빈혈은 초감염 혹은 기존 감염의 재활성화로 발생할 수 있으며, 아직 이에 대한 치료법은 정립이 되어 있지 않다. 특히, 소아청소년 신장이식 환자에 대한 보고나 자료는 더욱 드물다. 저자들은 소아청소년 신장이식 환자에서 발생한 심각한 빈혈을 파르보바이러스 B19 PCR 검사법으로 진단하고, 정맥내글로불린으로 재발 없이 성공적으로 치료한 두 증례와 문헌 고찰을 보고하는 바이다.

Comparison of Three, Motion-Resistant MR Sequences on Hepatobiliary Phase for Gadoxetic Acid (Gd-EOB-DTPA)-Enhanced MR Imaging of the Liver

Kim, Doo Ri,Kim, Bong Soo,Lee, Jeong Sub,Choi, Guk Myung,Kim, Seung Hyoung,Goh, Myeng Ju,Song, Byung-Cheol,Lee, Mu Sook,Lee, Kyung Ryeol,Ko, Su Yeon Korean Society of Magnetic Resonance in Medicine 2017 Investigative Magnetic Resonance Imaging Vol.21 No.2

Purpose: To compare three, motion-resistant, T1-weighted MR sequences on the hepatobiliary phase for gadoxetic acid-enhanced MR imaging of the liver. Materials and Methods: In this retrospective study, 79 patients underwent gadoxetic acid-enhanced, 3T liver MR imaging. Fifty-nine were examined using a standard protocol, and 20 were examined using a motion-resistant protocol. During the hepatocyte-specific phase, three MR sequences were acquired: 1) gradient recalled echo (GRE) with controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA); 2) radial GRE with the interleaved angle-bisection scheme (ILAB); and 3) radial GRE with golden-angle scheme (GA). Two readers independently assessed images with motion artifacts, streaking artifacts, liver-edge sharpness, hepatic vessel clarity, lesion conspicuity, and overall image quality, using a 5-point scale. The images were assessed by measurement of liver signal-to-noise ratio (SNR), and tumor-to-liver contrast-to-noise ratio (CNR). The results were compared, using repeated post-hoc, paired t-tests with Bonferroni correction and the Wilcoxon signed rank test with Bonferroni correction. Results: In the qualitative analysis of cooperative patients, the results for CAIPIRINHA had significantly higher ratings for streak artifacts, liver-edge sharpness, hepatic vessel clarity, and overall image quality as compared to, radial GRE, (P < 0.016). In the imaging of uncooperative patients, higher scores were recorded for ILAB and GA with respect to all of the qualitative assessments, except for streak artifact, compared with CAIPIRINHA (P < 0.016). However, no significant differences were found between ILAB and GA. For quantitative analysis in uncooperative patients, the mean liver SNR and lesion-to-liver CNR with radial GRE were significantly higher than those of CAIPIRINHA (P < 0.016). Conclusion: In uncooperative patients, the use of the radial GRE sequence can improve the image quality compared to GRE imaging with CAIPIRINHA, despite the data acquisition methods used. The GRE imaging with CAIPIRINHA is applicable for patients without breath-holding difficulties.

Myositis as an Initial Presentation of Ulcerative Colitis before Gastrointestinal Symptoms

Doo Ri Kim,DongSub Kim,SangJoon Choi,Yeon-Lim Suh,유소영,Mi Jin Kim,최연호,김예진 대한소아소화기영양학회 2020 Pediatric gastroenterology, hepatology & nutrition Vol.23 No.3

The musculoskeletal system can be involved as an extra-intestinal manifestation of inflammatory bowel disease. Among these, myositis in ulcerative colitis (UC) is very rare. A 14-year-old girl was admitted due to severe shoulder tenderness. She had complained of left jaw pain and swelling for the past 10 days. Inflammatory markers were elevated with no evidence of infectious etiology. Myositis was suspected by shoulder magnetic resonance imaging. Three days after admission, she developed hematochezia. Muscle biopsy and colonoscopy was performed due to worsening left mandibular area pain and persistent hematochezia. Colonoscopy showed consistent findings with UC. She was finally diagnosed with UC with myositis as an extra-intestinal manifestation. She showed a dramatic response to UC treatment. Gastrointestinal symptoms were well-controlled. After 14 months, UC symptoms and muscle pain were aggravated, which were relieved after steroid and cyclosporin treatment. We report a unique case of UC initially presented with myositis, preceding gastrointestinal symptoms.