Population Pharmacokinetics and Monte Carlo Simulation of Cefepime in Critically Ill Patients with Hospital-Acquired/Ventilator-Associated Pneumonia

Seo Hyeonji,Kim Yong Kyun,Park Sunghoon,Kim Hwan-il,Lee Dong-Hwan 대한감염학회 2023 Infection and Chemotherapy Vol.55 No.1

Background: This study aimed to investigate the population pharmacokinetics (PK) profile and determine the optimal dosage regimen of cefepime in critically ill adult patients with hospital-acquired pneumonia (HAP) or ventilatorassociated pneumonia (VAP). Materials and Methods: Population-PK models for cefepime were developed using a nonlinear mixed-effect modeling approach. The percentage of time within 24 h in which the free concentration exceeded the minimum inhibitory concentration (MIC) at a steady state (50%fT>MIC, 100%fT>MIC, and 100%fT>4×MIC) for various combinations of dosage regimens and renal function was explored using Monte Carlo simulation. Results: Twenty-one patients were prospectively enrolled in this study. Cefepime PK was best described using a twocompartment model in which creatinine clearance (CLCR) through Cockcroft-Gault (CG) was a significant covariate for the total clearance of cefepime. The simulation results to determine the optimal cefepime dosing regimen for 50%fT>MIC as treatment target with Cmin <20 mg/L as safety target showed that a dosage regimen of 2 g through intravenous (IV) infusion every 12 h administered over 4 h was optimal at an MIC of 4 mg/L, rather than the currently recommended dosage regimen of 2 g administered through IV infusion every 8 h, in patients with normal renal function (CLCR = 90 - 130 mL/min). For a treatment target of 100%fT>MIC with Cmin <35 mg/L as a safety target, a dosage regimen of 0.75 g administered through continuous infusion over 24 h would be sufficient at an MIC equal to or less than 8 mg/L in patients with renal dysfunction (CLCR = 10 - 30 mL/min). Conclusion: Our results suggest that clinicians should consider renal function and potential neurotoxicity when deciding the dosing regimen of cefepime in critically ill patients with HAP or VAP. Therapeutic drug monitoring (TDM) to adjust cefepime trough levels may be useful to improve clinical outcomes and reduce cefepime neurotoxicity.

Fluvoxamine Treatment of Patients with Symptomatic COVID-19 in a Community Treatment Center: A Preliminary Result of Randomized Controlled Trial

Seo Hyeonji,Kim Haein,Bae Seongman,Park Seonghee,Chung Hyemin,Sung Heungsup,Jung Jiwon,Kim Min-Jae,Kim Sung-Han,Lee Sang-Oh,Choi Sang-Ho,Kim Yang Soo,Son Ki Young,Chong Yong Pil 대한감염학회 2022 Infection and Chemotherapy Vol.54 No.1

Background This study aimed to evaluate whether fluvoxamine reduces clinical deterioration in adult patients with mild to moderate coronavirus disease 2019 (COVID-19), and to identify risk factors for clinical deterioration in patients admitted to a community treatment center (CTC). Materials and Methods A randomized, placebo-controlled trial was conducted in a CTC, in Seoul, Korea from January 15, 2021, to February 19, 2021. Symptomatic adult patients with positive results of severe acute respiratory syndrome coronavirus 2 real time-polymerase chain reaction within 3 days of randomization were assigned at random to receive 100 mg of fluvoxamine or placebo twice daily for 10 days. The primary outcome was clinical deterioration defined by any of the following criteria: oxygen requirement to keep oxygen saturation over 94.0%, aggravation of pneumonia with dyspnea, or World Health Organization clinical progression scale 4 or greater. Results Of 52 randomized participants [median (interquartile range) age, 53.5 (43.3 - 60.0) years; 31 (60.0%) men], 44 (85.0%) completed the trial. Clinical deterioration occurred in 2 of 26 patients in each group (P >0.99). There were no serious adverse events in either group. Clinical deterioration occurred in 15 (6.0%) of 271 patients admitted to the CTC, and all of them were transferred to a hospital. In multivariate analysis, age between 55 and 64, fever and pneumonia at admission were independent risk factors for clinical deterioration. Conclusion In this study of adult patients with symptomatic COVID-19 who were admitted to the CTC, there was no significant differences in clinical deterioration between patients treated with fluvoxamine and placebo (ClinicalTrials.gov Identifier: NCT04711863). Background This study aimed to evaluate whether fluvoxamine reduces clinical deterioration in adult patients with mild to moderate coronavirus disease 2019 (COVID-19), and to identify risk factors for clinical deterioration in patients admitted to a community treatment center (CTC). Materials and Methods A randomized, placebo-controlled trial was conducted in a CTC, in Seoul, Korea from January 15, 2021, to February 19, 2021. Symptomatic adult patients with positive results of severe acute respiratory syndrome coronavirus 2 real time-polymerase chain reaction within 3 days of randomization were assigned at random to receive 100 mg of fluvoxamine or placebo twice daily for 10 days. The primary outcome was clinical deterioration defined by any of the following criteria: oxygen requirement to keep oxygen saturation over 94.0%, aggravation of pneumonia with dyspnea, or World Health Organization clinical progression scale 4 or greater. Results Of 52 randomized participants [median (interquartile range) age, 53.5 (43.3 - 60.0) years; 31 (60.0%) men], 44 (85.0%) completed the trial. Clinical deterioration occurred in 2 of 26 patients in each group (P >0.99). There were no serious adverse events in either group. Clinical deterioration occurred in 15 (6.0%) of 271 patients admitted to the CTC, and all of them were transferred to a hospital. In multivariate analysis, age between 55 and 64, fever and pneumonia at admission were independent risk factors for clinical deterioration. Conclusion In this study of adult patients with symptomatic COVID-19 who were admitted to the CTC, there was no significant differences in clinical deterioration between patients treated with fluvoxamine and placebo (ClinicalTrials.gov Identifier: NCT04711863).

Reply: Correspondence on Fluvoxamine Treatment of Patients with Symptomatic COVID-19

Seo Hyeonji,Chong Yong Pil 대한감염학회 2022 Infection and Chemotherapy Vol.54 No.2

Risk Factors for Mortality in Patients with Klebsiella pneumoniae Carbapenemase-producing K. pneumoniae and Escherichia coli bacteremia

Seo Hyeonji,Bae Seongman,Kim Min-Jae,Chong Yong Pil,Kim Sung-Han,Lee Sang-Oh,Choi Sang-Ho,Kim Yang Soo,Jung Jiwon 대한감염학회 2021 Infection and Chemotherapy Vol.53 No.3

Background: Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales bacteremia is associated with significant mortality; however, no optimal antibiotic strategy is available. We aimed to evaluate the clinical outcomes according to the antibiotic regimens and identify risk factors for mortality in patients with KPC-producing K. pneumoniae and Escherichia coli bacteremia. Materials and Methods: This retrospective cohort study included all adult patients with monomicrobial bacteremia (KPC-producing K. pneumoniae or E. coli) between January 2011 and March 2021 at a 2,700-bed tertiary center. Results: Ninety-two patients were identified; 7 with E. coli bacteremia, and 85 with K. pneumoniae bacteremia. Thirty-day mortality was 38.0% (35/92). Non-survivors were more likely to have had nosocomial infection (88.6% vs. 63.2%, P = 0.01), high APACHE II scores (mean [interquartile range], 22.0 [14.0 - 28.0] vs. 14.0 [11.0 - 20.5], P <0.001), and septic shock (51.4% vs. 26.3%, P <0.001) and less likely to have been admitted to the surgical ward (5.7% vs. 22.8%, P = 0.04), undergone removal of eradicable foci (61.5% vs. 90.6%, P = 0.03), and received appropriate combination treatment (57.1% vs. 78.9%, P = 0.03) than survivors. No significant difference in mortality was observed according to combination regimens including colistin, aminoglycoside, and tigecycline. In multivariable analysis, high APACHE II scores (adjusted odds ratio [aOR], 1.14; 95% confidence interval [CI], 1.06 - 1.23, P <0.001), and appropriate definitive treatment (aOR, 0.25; CI, 0.08 - 0.74, P = 0.01) were independent risk factors for mortality. Conclusion: High APACHE II scores and not receiving appropriate definitive treatment were associated with 30-day mortality. Mortality did not significantly differ according to combination regimens with conventional drugs such as aminoglycoside and colistin.

Radiologically Suspected Organizing Pneumonia in a Patient Recovering from COVID-19: A Case Report

Seo Hyeonji,Jung Jiwon,Kim Min-Jae,Jang Se Jin,Kim Sung-Han 대한감염학회 2022 Infection and Chemotherapy Vol.54 No.1

We report a case of coronavirus disease 2019 (COVID-19)-associated radiologically suspected organizing pneumonia with repeated negative Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) results from nasopharyngeal swab and sputum samples, but positive result from bronchoalveolar lavage fluid. Performing SARS-CoV-2 RT-PCR in upper respiratory tract samples only could fail to detect COVID-19-associated pneumonia, and SARS-CoV-2 could be an etiology of radiologically suspected organizing pneumonia.

A study on the determination of a Health based Guidance Value of Formaldehyde

Hyeonji Oh,Heeju Choi,Yongmu Kim,Seo Yun Kim,Jae-Hong Park,Haejung Yoon,Yun-Sook Kang 한국식품영양과학회 2021 한국식품영양과학회 학술대회발표집 Vol.2021 No.10

Formaldehyde can be exposed through various routes, including the environment such as air and water, food and cosmetics. Therefore, a risk assessment is necessary to identifiy and manage human health effect. This study aims to identify the relationship between formaldehyde exposure and adverse effects as a hazard characterization step in the risk assessment process and to establish and propose a Health based Guidance Value. In order to carry out ther research, we used some online databases to find scientific papers, reports and opinions published by other institutions. Data for dose-response assessment were selected and classified, as properties of toxicity, and then the most appropriate study for establishing Health based Guidance Value was finally decided. Til et al (1989), 2-years carcinogenicity study with rats, was the optimal toxicity data. As the toxicity endpoint, the Health based Guidance Value TDI 0.15 mg/kg bw/day was proposed by applying an uncertainty factor of 100(interspecies difference 10, intraspeices difference 10) to NOAEL 15 mg/kg bw/day for chronic atrophic gastritis, focal ulceration and glandular hyperplasia in the landular forestomach.

PIV 측정 및 수치해석을 이용한 구강암 수술에 따른 기도 형상 내 유동 특성

홍현지(Hyeonji Hong),안세현(Se Hyeon An),서희림(Heerim Seo),송재민(Jae Min Song),염은섭(Eunseop Yeom) 한국가시화정보학회 2021 한국가시화정보학회지 Vol.19 No.3

Oral cancer surgery typically consists of resection of lesion, neck dissection and reconstruction, and it has an impact on the position of hyoid bone. Therefore, morphological change of airway can occur since the geometric parameter of airway is correlated with the hyoid bone. Airflow is affected by geometry of the airway. In this study, flow characteristics were compared between pre- and post-surgery models by both particle image velocimetry (PIV) and numerical simulation. 3D model of upper airway was reconstructed based on CT data. Velocity is accelerated by the reduced channel area, and vortex and recirculation region are observed in pre- and post-surgery models. For the post-surgery model, high pressure distribution is developed by significantly decreased hydraulic diameter, and the longitudinal flow stream is also interrupted.

오픈소스 기반 문서형 악성코드 차단 프로그램의 개발

서민정 ( Minjeong Seo ),고희수 ( Huisu Ko ),양현지 ( Hyeonji Yang ),강민주 ( Minju Kang ),김관영 ( Gwanyeong Kim ) 한국정보처리학회 2020 한국정보처리학회 학술대회논문집 Vol.27 No.2

인터넷의 활발한 이용으로 인해 악성코드의 유포 경로가 다양해지고 있다. 그 중, 문서형 악성 코드 감염 사례가 증가하고 있다. 문서형 악성코드는 이메일, 온라인에서 다운로드 받는 PDF, DOCX 파일의 취약점을 통해 유포되고 있다. 이로 인해 우리는 쉽게 바이러스에 감염될 수 있다. 그러므로 문서형 악성코드의 예방은 매우 중요하다. 우리는 악성코드로 의심되는 문서 파일을 안전한 PDF 파일로 변환해 주는 오픈 소스 프로그램인 Dangerzone1을 활용하여 개인과 기업에서 프로그램을 쉽고 편리하게 사용할 수 있도록 웹, 데스크톱 형태로 확장 개발한다.

The First Case of Multisystem Inflammatory Syndrome in Adult after COVID-19 in Korea

Chung Hyemin,Seo Hyeonji,Park Sunghee,Kim Haein,Jung Jiwon,Chong Yong Pil,Kim Sung-Han,Lee Sang-Oh,Choi Sang-Ho,Kim Yang Soo,Kim Min Jae 대한의학회 2021 Journal of Korean medical science Vol.36 No.25

Multisystem inflammatory disease in children is a Kawasaki disease like illness occurring after severe acute respiratory syndrome coronavirus 2 infection in children. As the pandemic progresses, similar syndromes were also reported in adult with a decreased incidence. Multisystem inflammatory syndrome in adults (MIS-A) can be characterized with shock, heart failure, and gastrointestinal symptoms with elevated inflammatory markers after coronavirus disease 2019 (COVID-19) infection. Herein, we describe the first case of MIS-A in South Korea. A 38-year-old man presented to our hospital with a 5-day history of abdominal pain and fever. He had been treated with antibiotics for 5 days at the previous hospital, but symptoms had worsened and he had developed orthopnea on the day of presentation. He suffered COVID-19 six weeks ago. Laboratory data revealed elevated white blood cell counts with neutrophil dominance, C-reactive protein, and B-type natriuretic peptide. Chest X-ray showed normal lung parenchyme and echocardiography showed severe biventricular failure with normal chamber size. We diagnosed him as MIS-A and treated with intravenous immunoglobulin and steroid.

Performance of a Community-based Noncommunicable Disease Control Program in Korea: Patients 65 Years of Age or Older

Lim Sun Mi,Seo Sung-Hyo,Park Ki Soo,Hwangbo Young,Suh Yeonok,Ji Sungin,Kang Jeongmook,Hwang Hyeonji,Cruz Jose Rene Bagani,박윤형 대한의학회 2020 Journal of Korean medical science Vol.35 No.31

Background: In Korea, the Korean Community-based Noncommunicable Disease Prevention and Control Program (KCNPC) was implemented in 2012 for the management of patients with chronic diseases. Nineteen primary care clinics, public health centers, and education and consulting centers (ECCs) participated in the implementation of this program. This study assessed the effectiveness of this chronic disease control model by comparing mortality rate and the incidence of complications between patients participating in the KCNPC program and a control group. Methods: Using data from the National Health Insurance Service and data from hypertension and diabetes patients registered with 19 ECCs between January 1, 2010 and December 31, 2012, hypertension and diabetes patients who had been treated at a clinic were selected. The final analysis included 252,900 patients, with the intervention group and control group having 126,450 patients each. Survival for the two groups was analyzed using the Kaplan- Meier method. Complications were analyzed using the Cox proportional hazards model. Results: The 5-year survival rate in the intervention group (0.88) was higher than that in the control group (0.86). Cox proportional hazards analysis showed that the intervention group had lower risk for mortality (0.84; 95% confidence interval [CI], 0.82–0.86) compared to the control group. Hospitalization due to complications and the proportional risk of hospitalization were also lower in the intervention group. Conclusion: The KCNPC model for prevention and control of chronic disease in Korea was found to be effective for hypertension and diabetes patients. Therefore, the KCNPC will be necessary to strengthen the capabilities of local communities, primary medical institutions, and individuals for prevention and control of chronic disease. Expanding the efficient prevention and control policies of the KCNPC to a nationwide scale may be effective as has been demonstrated through limited implementation in some regions.