국내 시판 항생제의 허가 용량 및 용법의 적정성에 대한 고찰 : 국내 약제사용설명서(package insert)와 미국 Physicians' Desk Reference의 비교 Comparison of Domestic Package Inserts with Physicians' Desk Reference

이재갑,이연주,황병연,정혜원,정성주,김성범,정희진,김우주,김민자,박승철 대한감염학회 2003 감염과 화학요법 Vol.35 No.5

목적 : 국내 시판중인 항생제의 1일 투여량과 투여간격의 적정성을 확인하고 적응증 및 중증도에 따른 항생제 용량 제시 여부를 확인하기 위하여 항생제 시판시 KFDA의 허가사항을 담은 약제사용설명서을 미국 FDA 공인 약제에 대한 사용지침으로 쓰이고 있는 PDR(Physicians' Desk Peference)과 비교하였다. 방법 : PDR에 등재되어 있는 항생제 중에서 시럽 및 도포용 항생제를 제외한 총 61종에서, 국내에 시판되어 있는 51종 항생제의 약제사용설명서를 대상으로 1일 투여량, 투약횟수, 적응증 및 중증도에 따른 설명 정도를 비교하였다. 결과 : 1) 1일 투여량 비교 : 비교 가능한 전체 항생제에서, 약제사용설명서가 PDR보다 적은 용량을 제시한 경우는 경구용 8종, 주사용 11종으로 총 19종(37%)였으며, 많은 용량을 제시한 경우는 경구용만 2(4%)종이었고, 동일하거나 비슷한 용량을 제시한 경우는 경구용 15종, 주사용 15종으로 총 30(59%)종이었다. 약제사용설명서에서 적은 용량이 제시된 항생제 중 경구용인 cefdnir, cefixime, cefpodoxime, ofloxacin, levofloxacin, norfloxacin(6종), 주사용인 cefazolin, cefotetan, ceftizoxime, meropenem (4종) 등 반수이상의 약제가 일본제약회사로부터 국내에 수입된 약들이었으며 일본의 약제 사용설명서와 동일한 용량을 제시한 것을 알 수 있다. 2) 투여간격 비교 : 비교가능한 항생제 51종 중에서 국내약제사용설명서가 PDR과 동일한 투약횟수, 투여간격을 제시한 항생제는 30종(59%)이었다. 국내 약제사용설명서가 PDR보다 적은 투약횟수, 긴 투여간격을 제시한 항생제는 9종(17%)이었다. 오히려 많은 투약횟수, 짧은 투여간격을 제시한 항생제가 12종(24%)이나 되었다. 경구용만 비교하였을 경우 국내 약제사용설명서가 PDR보다 적은 투약횟수를 제시한 항생제는 없었으며, 동일하세 제시한 경우는 15종, 빈번한 투약횟수를 제시한 경우는 10종이었다. 주사용 항생제에서 국내 약제사용설명서가 PDR보다 긴 투여간격을 제시한 항생제는 9종, 동일한 경우는 15종, 짧은 투여간격을 제시한 경우는 2종이었다. 3) 적응증 및 중증도에 따른 비교 : 약제사용설명서에서 적응증 또는 중증도에 따른 용량에 대한 설명이 부족한 경우는 경구용 13종, 주사용 7종으로 총 20종(39%)이었으며, PDR에서는 경구용 1종, 주사용 2종으로 총 3종(6%)이었다. 결론 : 항생제에 첨부되는 약제사용설명서 및 약제사용설명서를 바탕으로 편집되는 의약품집이 항생제를 처방하는 의사들이 용법과 용량을 결정함에 있어 참고 역할을 하고 있으나, 국내의 시판 허가사항을 담은 약제사용설명서가 많은 수에서 적응증 또는 중증도에 따른 1일 투여량과 투여간격에 대한 정확한 정보를 제공하고 있지 못하고 있다. Background : The appropriate usage of antibiotics needs informations such as its effectiveness for a given infection, administration route, the amount of effective dose, and the dose intervals. In this study, in order to find any significant discrepancy regarding to the details of explanation of the necessary information for appropriate antibiotic usages, we compares informations about 51 antibiotics, one from package inserts in Korea and the other from physician's desk reference (PDR) certified by FDA in the United States of America. Materials and Methods : Package inserts about antibiotics, only oral or parenteral agent, wereperused to collect three categories of data: the recommended dosage, dose interval, and adjustment of dose to indications or the severity of infection. These data available in Korea were compared with 61 antibiotics (32 oral and 29 parenteral agents) cited in PDR. Results : Package inserts for 51 antibiotics were gathered, because the remaining 10 antibiotics in PDR are not domestically commercialized. Among data on antibiotics comparable with those in PDR, 59% (30 cases: 15 oral and 15 parenteral agents) suggested the dose similar to that of PDR, 37% (19 cases: 8 oral and 11 parenteral agents) recommend less dose, and 4% in only 2 oral agents showed more dose. About half of the drugs recommending lower dosage were imported from Japanese pharmaceutical company, and the recommended doses of these antimicrobial agents were similar to those in Japan. About 59% (30 cases: 15 oral and 15 parenteral agents) directed dose interval or duration similar to those of PDR and 17% (9 parenteral agents) suggested less administration or longer duration. Surprisingly, in contrast to only 6% (3 cases) of PDR, 24% (12 cases : 10 oral and 2 parenteral agents) recommended more administration or shorter duration. About 39% (24 cases: 13 oral and 7 parenteral agents) revealed no information for dose adjustment commons to indications or the severity of infection. Conclusion : This study revealed that many guidelines in Korea recommend lower doses and/or unreasonable dose intervals. In future studies, improved antibiotic usage guidelines should be established based on pharmacokinetic and pharmacodynamic researches, on the aspect of optimal dosage, dose interval, and dose adjustment commensurate to the indications and the severity of the infection.

다제내성 그람양성균에 대한 Linezolid(Zyvox^(�))의 시험관내 항균력 비교

박대원,정희진,엄중식,황병연,김성범,이재갑,이연주,정혜원,정성주,박재형,이진수,손장욱,김우주,김민자,박승철 대한감염학회 2003 감염과 화학요법 Vol.35 No.5

배경 : MRSA, VRE, VRSA같은 다제 내성 그람 양성균의 등장에 따라 glycopeptide를 대체할 새로운 항생제의 개발이 필요하게 되었고 결과적으로 새로운 항생제인 linezolid라는 항생제가 개발되었다. Linezolid는 이전의 항생제와는 다른 새로운 계열의 oxazolidinone으로 경구 이용률이 우수하다. 원내 및 원외감염의 중요한 원인균이 되고 있는 MRSA, VRE에 대한 적절한 경구용 항균제가 없는 국내에서 폐렴 및 피부 연조직 감염에서 경구용으로 사용해 볼 수 있는 약제이다. 본 연구에서는 고대 구로 병원에서 분리된 MRSA, VRE 등을 대상으로 다른 여러 항균제와 비교한 linezolid의 시험관내 항균력을 조사하고자 하였다. 재료 및 방법 : 연구대상은 1998년 1월부터 2000년 12월까지 본원에서 입원 및 외래를 통하여 피부 연조직 감염증 및 호흡기 감염증, 요로감염증으로 진단된 환자들의 가검물로부터 분리된 MRSA 60균주, VRE 43균주, PRSP 25균주를 액체배지 또는 한천배지 희석법을 통하여 linezolid 및 기타 항균제에 대한 최소발육억제농도를 구하였다. 결과 : 실험에 사용한 S. aureus는 모두 MRSA였고 이들은 linezolid에 대해 MIC_(90) 2㎍/㎖(MIC 범위 1-2㎍/㎖), Enterococcus spp는 모두 VRE로 linezolid의 MIC_(90)은 2㎍/㎖로 MIC 범위는 1-4㎍/㎖였다. 한 개의 균주에서 MIC 4㎍/㎖로 중등도 감수성을 보였으나 MIC breakpoint가 (8㎍/㎖인 내성균주는 없고 모두 감수성을 보였다. S. pneumoniae의 경우 penicillin 내성이었고, linezolid MIC_(90) 1㎍/㎖ (MIC 범위 0.5-1㎍/㎖)로 전부 감수성을 보였다. 결론 : Linezolid는 MRSA를 위시한 VRE, PRSP 등의 다제 내성 그람 양성균에 대하여 우수한 시험관내 항균력을 보임을 알 수 있었다. Background : The emergence of multi-drug resistant Gram-positive cocci, such as MRSA, VRE, and VRSA, necessitated to develop new antibiotics, which could replace the glycopeptide. As a result, a new antibiotics named linezolid was developed. Linezolid is different line of oxazolidinones with a good oral bioavailability, compared to other antibiotics. Since appropriate oral antibiotics are not presently available for MRSA, which is a major cause of nosocomial and community acquired infections, the introduction of linezolid will have favorable effect on treatment of infections such as pneumonia or skin infections. In this study, we investigated the antibiotic effect of linezolid on MRSA and VRE isolated from patients who were treated in Korea University Guro Hospital. Material and Methods : By using broth microdilution and agar dilution method we measured minimum inhibitory concentration (MIC) with sixty S. aureus, forty three Enterococcus spp., and twenty five S. pneumoniae isolates from patients who were diagnosed as skin, soft tissue, respiratory, and urinary infections in Korea University Guro Hospital from January, 1998 to December, 2002. Results : All of S. aureus used in this study were MRSA, and MIG_(90) of linezolid was below 2 ㎍/㎖ (MIC ranged between 1-2 ㎍/㎖). All of Enterococcus spp. were VRE, and had MIG_(90) of 2 ㎍/㎖ (MIC ranged between 1 to 4 ㎍/㎖). One of the VRE showed intermediate susceptibility with MIC of 4 ㎍/㎖. However, none was resistant with MIC breakpoint above 8 ㎍/㎖. All of S. pneumoniae were resistant to penicillin, but they were susceptible to linezolid with MICao of 1 ㎍/㎖(MIC range 0.5-1㎍/㎖). Conclusion : In conclusions, linezolid has an excellent in vitro antibiotic effect on multi-drug resistant Gram-positive cocci, such as MRSA, PRSP, and VRE.

Corrigendum: Clinical Characteristics and Neurologic Outcomes of X-Linked Myotubular Myopathy

Hyewon Woo,이승복,한지연,Woo Joong Kim,Man Jin Kim,Moon-Woo Seong,김수연,Anna Cho,Byung Chan Lim,Ki Joong Kim,채종희 대한소아신경학회 2022 대한소아신경학회지 Vol.30 No.4

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Clinical Characteristics and Neurologic Outcomes of X-Linked Myotubular Myopathy

Hyewon Woo,Seungbok Lee,Ji Yeon Han,Woo Joong Kim,Man Jin Kim,Moon-Woo Seong,Soo Yeon Kim,Anna Cho,Byung Chan Lim,Ki Joong Kim,Jong-Hee Chae 대한소아신경학회 2022 대한소아신경학회지 Vol.30 No.3

Purpose: X-linked myotubular myopathy (XLMTM) is a rare condition of centronuclear myopathy caused by myotubularin 1 (MTM1) mutations. Patients with XLMTM show different neurodevelopmental outcomes after the neonatal period depending on age and acquired hypoxic damage. We aim to evaluate the clinical characteristics and neurodevelopmental outcomes of patients with XLMTM who were followed up at a single center. It is essential to understand the volume and conditions to prepare for being a candidate for new therapeutic strategies. Methods: Patients diagnosed with centronuclear myopathy by muscle pathology and MTM1 mutation analysis were included. We retrospectively investigated motor milestones, communication skills, and bulbar and respiratory function in the patients. The patients were categorized into two groups: with and without hypoxic insults (HI). Results: All 13 patients were severely affected by neonatal hypotonia and required respiratory support and a feeding tube during the neonatal period. The follow-up duration was 4.4 years (range, 0.3 to 8.9). In the non-HI group, developmental milestones were delayed but were slowly achieved. Some patients underwent training in oral feeding with thickened foods and weaning from ventilation. Patients with HI showed poor motor function catch-up and communication skills. Three deaths were associated with acute respiratory failure. Conclusion: Patients with XLMTM without HI can survive long-term with the slow achievement of motor milestones and bulbar and respiratory function. However, hypoxic brain damage following acute respiratory failure negatively influences their developmental potential or even lead to death. Therefore, parental education for proper respiratory management is necessary, especially for young children.

New Daily Persistent Headache after COVID-19 Vaccination in an Adolescent Patient

Hyewon Woo,Jon Soo Kim,Won Seop Kim,Joon Kee Lee 대한소아신경학회 2023 대한소아신경학회지 Vol.31 No.3

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Two cases of Antley-Bixler syndrome caused by mutations in different genes, FGFR2 and POR

Woo, Hyewon,Ko, Jung Min,Shin, Choong Ho,Yang, Sei Won Korean Society of Medical Genetics and Genomics 2016 대한의학유전학회지 Vol.13 No.1

Antley-Bixler syndrome (ABS) is a rare form of syndromic craniosynostosis with additional systemic synostosis, including radiohumeral or radioulnar synostosis. Another characteristic feature of ABS is mid-facial hypoplasia that leads to airway narrowing after birth. ABS is associated with mutations in the FGFR2 and POR genes. Patients with POR mutations present with either skeletal manifestations or congenital adrenal hyperplasia with ambiguous genitalia. We report here two cases of ABS caused by mutations in FGFR2 and POR. Although the patients had craniosynostosis and radiohumeral synostosis in common and cranioplasty was performed in both cases, the male with POR mutations showed an elevated level of $17{\alpha}$-hydroxyprogesterone during newborn screening and was diagnosed with congenital adrenal hyperplasia by adrenocorticotropic hormone stimulation. This patient has been treated with hydrocortisone and fludrocortisone. He had no ambiguous genitalia but had bilateral cryptorchidism. On the other hand, the female with the FGFR2 mutation showed severe clinical manifestations: upper airway narrowing leading to tracheostomy, kyphosis of the cervical spine, and coccyx deformity. ABS shows locus heterogeneity, and mutations in two different genes can cause similar craniofacial and skeletal phenotypes. Because the long-term outcomes and inheritance patterns of the disease differ markedly, depending on the causative mutation, early molecular genetic testing is helpful.

Clinical Significance of Various Pathogens in Acute Exacerbations of COPD: Multi-center Study in Korea

( Hyun Woo Ji ),( Ji Ye Jung ),( Soojoung Yu ),( Hyun Woo Lee ),( Yun Su Sim ),( Hyewon Seo ),( Jeong-Woong Park ),( Kyung Hoon Min ),( Jae Ha Lee ),( Byung-Keun Kim ),( Myung Goo Lee ),( Yeon Mok Oh 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.0

Background One of the major causes of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is respiratory infection. In this study, we investigated types of bacteria and virus identified in AECOPD patients in Korea, and compared clinical difference according to different types of pathogen Methods We reviewed 1186 cases of AECOPD patients recruited at 28 hospitals in Korea from January 2015 to December 2019. Pathogen was identified by microbiological tests. We analyzed bacterial and viral identification rate, along with basic characteristics and clinical presentation of patients associated with the different types of pathogens, and risk factors for potentially drug-resistant (PDR) pathogen. Results The number of patients infected with bacteria, virus, and both bacteria and virus were 262 (22.1%), 265 (22.5%), and 129 (10.9%), respectively. The most common bacteria identified were Pseudomonas aeruginosa (9.8%), Mycoplasma pneumoniae (6.2%), and Streptococcus pneumoniae (5.0%). The most common virus identified Influenza A (10.4%), Rhinovirus (8.7%), and RSV (3.5%) Compared to patients without identified pathogens, patient with identified pathogens had a higher rate of systemic steroid use within six months (22.7% vs 16.9%; P=0.015), presented more cough and sputum (76.4% vs 68.9%; P=0.004, 78.9% vs 68.7%; P=0.015), and required longer period of systemic steroid during AECOPD (11.2days vs 4.4days; P=0.012). Past history of pulmonary tuberculosis (OR 1.66; P=0.046) and bronchiectasis (OR 1.99; P=0.032), and the history of triple inhaler use within six months (OR 2.04; P=0.005) have been confirmed as risk factors for the identification of PDR pathogen. In addition, hospital stay was longer (15.9days vs 12.4days; P=0.018) and ICU admission rate was high (15.9% vs 9.5%; P=0.030) when PDR pathogen was identified Conclusions The various types of pathogens caused AECOPD. In addition, risk factors for the identification of PDR pathogen were past history of pulmonary tuberculosis and bronchiectasis, and history of triple inhaler use.

Risk of Suicide Attempt after Thyroidectomy: A Nationwide Population Study in South Korea

Hyewon Kim,Yuwon Kim,Myung-Hee Shin,Kwan Woo Choi,Man Ki Chung,Hong Jin Jeon 대한신경정신의학회 2021 PSYCHIATRY INVESTIGATION Vol.18 No.1

Objective To investigate the association between thyroidectomy and suicide attempt. Methods A nationwide population-based electronic medical records database of South Korea between January 1, 2009 and June 30, 2016 was used to investigate incidence rate ratios (IRRs) of suicide attempts and probable suicide attempts before and after thyroidectomy using a self-controlled case series design. Results In 2,986 patients who attempted suicide or probable suicide, the IRRs of suicidal behaviors during risk periods one year before and after thyroidectomy were investigated. Generally, after thyroidectomy, there was no increase in IRR compared to the non-risk period. When data were analyzed according to thyroidectomy type, after partial thyroidectomy, IRR increased up to 1.43 (95% CI: 1.03-1.98, p=0.032) in the days 91-181 period. In the subgroup with major depressive disorder (MDD), the IRR increased up to 1.74 (95% CI: 1.21-2.51, p=0.003) before thyroidectomy, and increased up to 1.67 (95% CI: 1.16-2.41, p=0.006) after thyroidectomy. Conclusion Although the general risk of suicide attempt was not increased after thyroidectomy, patients with MDD showed increased risk of suicide attempt before and after thyroidectomy. These results suggest that suicidality should be evaluated when depressive symptoms are present in patients who have undergone thyroidectomy.

Metabolic Engineering of Corynebacterium glutamicum for Co-production of L-Lysine and Heterologous Squalene Using CRISPR-Cas Systems

Hyewon CHANG,Jaehyun PARK,Han Min WOO 한국생물공학회 2023 한국생물공학회 학술대회 Vol.2023 No.4

Synergistic Hybrid Pathway for Enhanced Sustainable Biochemical Production and CO₂ Conversion

Hyewon CHANG,Hyunjeong LEE,Yubeen HEO,Hanmin WOO 한국생물공학회 2023 한국생물공학회 학술대회 Vol.2023 No.10