Interpretation of Epithelial Lining Fluid Concentrations of Antibiotics against Methicillin Resistant Staphylococcus aureus

Sungmin Kiem,Jerome J. Schentag 대한감염학회 2014 Infection and Chemotherapy Vol.46 No.4

Although antibiotics whose epithelial lining fluid (ELF) concentrations are reported high tend to be preferred in treatment ofpneumonia, measurement of ELF concentrations of antibiotics could be misled by contamination from lysis of ELF cells andtechnical errors of bronchoalveolar lavage (BAL). In this review, ELF concentrations of anti-methicillin resistant Staphylococcusaureus (MRSA) antibiotics were interpreted considering above confounding factors. An equation used to explain antibiotic diffusioninto CSF (cerebrospinal fluid) was adopted: ELF/free serum concentration ratio = 0.96 + 0.091 × ln (partition coefficient/ molecular weight1/2). Seven anti-MRSA antibiotics with reported ELF concentrations were fitted to this equation to see if theirELF concentrations were explainable by the penetration capacity only. Then, outliers were modeled under the assumption ofvarying contamination from lysed ELF cells (test range 0-10% of ELF volume). ELF concentrations of oritavancin, telavancin,tigecycline, and vancomycin were well described by the diffusion equation, with or without additional impact from cell lysis. For modestly high ELF/free serum concentration ratio of linezolid, technical errors of BAL should be excluded. Although teicoplaninand iclaprim showed high ELF/free serum ratios also, their protein binding levels need to be cleared for proper interpretation. At the moment, it appears very premature to use ELF concentrations of anti-MRSA antibiotics as a relevant guide fortreatment of lung infections by MRSA.

Self-Assessment Questionnaire for Efficient and Safe Evaluation of Patients with Mild COVID-19

Jeong Hyeongseok,Lee Jooyeon,김정옥,천신혜,손경목,김연숙,Kiem Sungmin 대한감염학회 2020 Infection and Chemotherapy Vol.52 No.2

As the outbreak of coronavirus disease 2019 continues and the number of confirmed cases requiring isolation increases, there is a need for a safe and efficient system to assess patients' condition. We developed and evaluated a self-assessment questionnaire consisting of 23 symptoms with linear-scale scores from 0 to 10. Patients were asked to indicate their worst score for each symptom daily, and medical personnel assessed clinical improvement or deterioration based on the changes in scores. Focused communication on severity of specific symptoms was the primary advantage for the clinicians, and a thorough check for their symptoms was helpful for patients.

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

이지영,오원섭,고관수,Sang Taek Heo,Chi Sook Moon,Hyun Kyun Ki,Sungmin Kiem,백경란,송재훈 대한의학회 2006 Journal of Korean medical science Vol.21 No.2

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 ampicillinsulbactam 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.

Guidelines on Implementing Antimicrobial Stewardship Programs in Korea

Yoon Young Kyung,Kwon Ki Tae,Jeong Su Jin,Moon Chisook,Kim Bongyoung,Kiem Sungmin,Kim Hyung-sook,Heo Eunjeong,Kim Shin-Woo 대한감염학회 2021 Infection and Chemotherapy Vol.53 No.3

These guidelines were developed as a part of the 2021 Academic R&D Service Project of the Korea Disease Control and Prevention Agency in response to requests from healthcare professionals in clinical practice for guidance on developing antimicrobial stewardship programs (ASPs). These guidelines were developed by means of a systematic literature review and a summary of recent literature, in which evidence-based intervention methods were used to address key questions about the appropriate use of antimicrobial agents and ASP expansion. These guidelines also provide evidence of the effectiveness of ASPs and describe intervention methods applicable in Korea.

Population Pharmacokinetic Analysis of Doripenem after Intravenous Infusion in Korean Patients with Acute Infections

Lee, Dong-Hwan,Kim, Yong Kyun,Jin, Kyubok,Kang, Myoung Joo,Joo, Young-Don,Kim, Yang Wook,Moon, Young Soo,Shin, Jae-Gook,Kiem, Sungmin American Society for Microbiology 2017 Antimicrobial Agents and Chemotherapy Vol.61 No.5

<P>We investigated the population pharmacokinetics (PK) of doripenem in Korean patients with acute infections and determined an appropriate dosing regimen using a Monte Carlo simulation for predicting pharmacodynamics (PD). Patients (n = 37) with a creatinine clearance (CLCR) of 20 to 50 ml/min or >50 ml/min who received a 250-mg or 500-mg dose of doripenem over the course of 1 h every 8 h, respectively, were included in this study. Blood samples were taken predosing and 0 h, 0.5 h, and 4 to 6 h after the fourth infusion. A nonlinear mixed-effect modeling tool was used for the PK analysis and pharmacodynamic simulation; doripenem PK were well described by a one-compartment model. The population mean values of the body weight (WT)-normalized clearance (CL/WT) and the body weight-normalized volume of distribution (V/WT) were 0.109 liter/h/kg of body weight (relative standard error, 9.197%) and 0.280 liter/kg (relative standard error, 9.56%), respectively. Doripenem CL was significantly influenced by CLCR. The proposed equation to estimate doripenem CL in Korean patients was CL/WT = 0.109 X WT X (CLCR/57) (0.688), where CL/WT is in liters per hour per kilogram. CL in Korean patients was expected to be lower than that in Caucasian patients, regardless of renal function. The Monte Carlo simulation showed that 90% attainment of target PK/PD magnitudes could be achieved with the usual dosing regimens when the MIC was <= 1 mg/liter. However, prolonged infusions (4 h) should be considered, especially when patients have augmented renal function and for patients infected with pathogens with a high MIC. Our results provide an individualized doripenem dosing regimen for patients with various renal functions and for patients infected with bacteria with decreased susceptibility.</P>

Development of Antibiotic Classification for Measuring Antibiotic Usage in Korean Hospitals Using a Modified Delphi Method

Kim Bongyoung,Yoon Young Kyung,Kim Dong-Sook,Jeong Su Jin,안성복,Park Sun Hee,Kwon Ki Tae,Kim Hong Bin,Park Yoon Soo,Kim Shin-Woo,Kiem Sungmin,최준용,The Korean Society of Infectious Diseases,The Korean Soc 대한의학회 2020 Journal of Korean medical science Vol.35 No.30

In 2019, a project designed to develop a system for measuring and comparing antibiotic usage in hospitals was launched in Korea. As part of this project, we developed a means to classify antibiotic usage in Korean hospitals using a modified Delphi method. In results, the following categories of antibiotic classification were accepted for use in Korean hospitals: 1) broad-spectrum antibacterial agents predominantly used for hospital-onset infections in adults, 2) broad-spectrum antibacterial agents predominantly used for community-acquired infections in adults, 3) antibacterial agents predominantly used for resistant gram-positive infections in adults, 4) narrow-spectrum beta-lactam agents in adults, 5) antibacterial agents predominantly used for extensive antibiotic resistant gram-negative bacteria in adults, and 6) total antibacterial agents.

Population Pharmacokinetic Analysis of Meropenem After Intravenous Infusion in Korean Patients With Acute Infections

Kim, Yong Kyun,Lee, Dong-Hwan,Jeon, Jaehyun,Jang, Hang-Jea,Kim, Hyeon-Kuk,Jin, Kyubok,Lim, Sung-Nam,Lee, Sung Sook,Park, Bong Soo,Kim, Yang Wook,Shin, Jae-Gook,Kiem, Sungmin Elsevier 2018 Clinical therapeutics Vol.40 No.8

<P><B>Abstract</B></P> <P><B>Purpose</B></P> <P>The aim of this study was to investigate the population pharmacokinetic (PK) profile of meropenem in Korean patients with acute infections.</P> <P><B>Methods</B></P> <P>The study included 37 patients with a creatinine clearance ≤50 or >50 mL/min who received a 500- or 1000-mg dose of meropenem, respectively, infused intravenously over 1 hour every 8 hours. Blood samples were collected before and at 1, 1.5, and 5 hours after the start of the fourth infusion. The population PK analysis was conducted by using nonlinear mixed effect modeling software (NONMEM). Monte-Carlo simulations were performed to identify optimal dosing regimens.</P> <P><B>Findings</B></P> <P>Thirty-seven subjects completed the study. Meropenem PK variables were well described by using a one-compartment model. The typical values (relative SE) for weight-normalized clearance (CL) and V<SUB>d</SUB> were 0.266 L/h/kg (12.29%) and 0.489 L/kg (11.01%), respectively. Meropenem CL was significantly influenced by the serum creatinine level, which explained 11% of the interindividual CK variability. The proposed equation to estimate meropenem CL in Korean patients was as follows: CL (L/h) = 0.266 × weight × [serum creatinine/0.74]<SUP>–1.017</SUP> <SUB>.</SUB> The simulation results indicate that the current meropenem dosing regimen may be suboptimal in patients infected with normal or augmented renal function.</P> <P><B>Implications</B></P> <P>Prolonged infusions of meropenem over at least 2 hours should be considered, especially in patients with augmented renal function and those infected with pathogens for which the minimum inhibitory meropenem concentration is >1 μg/mL. Our results suggest an individualized meropenem dosing regimen for patients with abnormal renal function and those infected with pathogens with decreased in vitro susceptibility.</P>