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Background For more effective and safer usage of antibiotics, the dosing strategy should be individualized based on the patients’ characteristics, including race. The aim of this study was to investigate the population pharmacokinetic (PK) profiles of piperacillin and tazobactam in Korean patients with acute infections. Materials and Methods At least four consecutive 2/0.25 g or 4/0.5 g doses of piperacillin/tazobactam (TZP) were intravenously infused over 1 h every 8 h for patients with creatinine clearance (CLcr) ≤50 ml/min or CLcr >50 mL/min, respectively. Blood samples from 33 patients at a steady-state were taken pre-dose and at 0 min, 30 min, and 4-6 h after the fourth infusion. The population PK analysis was conducted using a non-linear mixed-effects method. A likelihood ratio test was used to select significant covariates, with significance levels of P

Despite advances in therapy, sepsis still has a high mortality rate. To improve the treatment outcome, early diagnosis and treatment is essential, as reflected in many publications about biomarkers for sepsis. Recent models of automatic cell analyzers provide the delta neutrophil index (DN), which corresponds to the fraction of immature granulocytes in circulating blood. This study investigated DN as a prognostic marker in patients with bacteraemia.We retrospectively collected data on adult patients with bacteraemia admitted to an urban hospital between November 2009 and April 2010. The DN was measured at the onset of bacteraemia and at 24 and 72 h later. Factors associated with 28-day mortality were assessed using logistic regression.A total of 102 patients were included in the analysis, and 24 patients died within 28 days. In the univariate analysis, appropriate antibiotic treatment, multidrug-resistant bacterial infection, history of intensive care unit (ICU) stay before the onset of bacteraemia, healthcare-associated infection, DN at 72 h after the onset of bacteraemia (DN-72 h), and platelet count at the onset of bacteraemia were significantly associated with survival. In multivariate analysis, DN-72 h (odds ratio (OR) 1.246, 95% confidence interval (CI) 1.030-1.508; p = 0.023), platelet count at the onset of bacteraemia (OR 0.986, 95% CI 0.977-0.995; p = 0.003), and history of ICU stay before the onset of bacteraemia (OR 4.907, 95% CI 1.045-23.051; p = 0.044) were the independent factors associated with survival.DN at 72 h after bacteraemia may be valuable to assess the prognosis of patients with bacteraemia.

Objective Combined antiretroviral therapy (cART) has significantly improved the survival rate and quality of life for HIV-infected subjects, but it contributes to the development of metabolic complications including coronary artery disease (CAD). Recent studies have reported that high plasma levels of the soluble receptor for advanced glycation end products (sRAGE) were associated with a lower incidence of CAD in non-HIV infected patients. However, there has been no report of an association of sRAGE and subclinical carotid atherosclerosis in HIV-infected patients receiving cART. Methods We examined the association of circulating sRAGE in HIV-infected patients with carotid intima–media thickness (IMT) and other metabolic variables. We prospectively enrolled 76 HIV-infected patients receiving cART for ≥6 months. Results sRAGE had a significantly negative correlation with body mass index (r = −0.324, p = 0.005), waist-to-hip ratio (r = −0.335, p = 0.003), systolic blood pressure (BP) (r = −0.359, p = 0.002), diastolic BP (r = −0.343, p = 0.004), total cholesterol (r = −0.240, p = 0.037), low-density lipoprotein-cholesterol (r = −0.284, p = 0.024), log(homeostasis model assessment of insulin resistance [HOMA-IR]) (r = −0.380, p = 0.002) and carotid IMT including max-IMT and mean-IMT (r = −0.358, p = 0.001 and r = −0.329, p = 0.004, respectively). By the use of multiple stepwise regression analyses, systolic BP (p = 0.001) and log[HOMA-IR] (p = 0.001) remained significant independently. Conclusions These results suggest that sRAGE may have a protective effect against subclinical atherosclerosis by preventing inflammatory responses mediated by the activation of cell surface RAGE in HIV-infected patients receiving cART.

Urinary tract infection (UTI) is the most frequent cause of bacteremia/sepsis in elderly people and increasing antimicrobial resistance in uropathogens has been observed. To describe the characteristics of bacteremic UTI in elderly patients and to identify the independent risk factors of all-cause in-hospital mortality, a retrospective cohort study of bacteremic UTI patients of age over 65 was performed at a single 2000-bed tertiary hospital. Bacteremic UTI was defined as the isolation of the same organism from both urine and blood within 48 h. Eighty-six elderly bacteremic UTI patients were enrolled. Community-acquired infection was the case for most patients (79.1%), and Escherichia coli accounted for 88.6% (70/79) among Gram-negative organisms. Non-E. coli Gram-negative organisms were more frequent in hospital-acquired cases and male patients while chronic urinary catheter insertion was related with Gram-positive urosepsis. The antibiotic susceptibility among Gram-negative organisms was not different depending on the source of bacteremic UTI, while non-E. coli Gram-negative organisms were less frequently susceptible for cefotaxime, cefoperazone/sulbactam, and aztreonam. All-cause in-hospital mortality was 11.6%, and functional dependency (adjusted hazard ratio=HR=10.9, 95% confidence interval=95%CI=2.2-54.6) and low serum albumin (adjusted HR=27.0, 95%CI=2.0-361.2) were independently related with increased all-cause in-hospital mortality.

Seventy-six treatment-naive human immunodeficiency virus (HIV)-1-infected patients were recruited from Korea and China to evaluate transmitted drug resistance (TDR). Although no major TDR was observed within the study population, some resistance-associated mutations in the reverse transcriptase region were observed (V118I 9.2%, V179D 7.9%). The frequencies of resistance-associated mutations in NNRTI (V179D) and PI minor mutations were higher in Korean patients compared with Chinese patients (13.6% vs. 0%, 45.5% vs. 12.5%, p

BACKGROUND The ratio of the steady-state 24-hour area under the concentration-time curve (ssAUC24) to the MIC (AUC24/MIC) for vancomycin has been recommended as the preferred pharmacodynamic index. The aim of this study was to assess whether the calculated AUC24 (cAUC24) using the creatinine clearance (CLcr) differs from the ssAUC24 based on the individual pharmacokinetic data estimated by a commercial software. MATERIALS AND METHODS The cAUC24 was compared with the ssAUC24 with respect to age, body mass index, and trough concentration of vancomycin and the results were expressed as median and interquartile ranges. A correlation between the cAUC24 and ssAUC24 and the trough concentration of vancomycin was evaluated. The probability of reaching an AUC24/MIC of 400 or higher was compared between the cAUC24 and ssAUC24 for different MICs of vancomycin and different daily doses by simulation in a subgroup with a trough concentration of 10 mg/L and higher. RESULTS The cAUC24 was significantly lower than the ssAUC24 (392.38 vs. 418.32 mg·hr/L, P < 0.0001) and correlated weakly with the trough concentration (r = 0.649 vs. r = 0.964). Assuming a MIC of 1.0 mg/L, the probability of reaching the value of 400 or higher was 77.5% for the cAUC24/MIC and 100% for the ssAUC24/MIC in patients with a trough concentration of 10 mg/L and higher. If the MIC increased to 2.0 mg/L, the probability was 57.7% for the cAUC24/MIC and 71.8% for the ssAUC24/MIC at a daily vancomycin dose of 4,000 mg. CONCLUSIONS The cAUC24 using the calculated CLcr is usually underestimated compared with the ssAUC24 based on individual pharmacokinetic data. Therefore, to obtain a more accurate AUC24, therapeutic monitoring of vancomycin rather than a simple calculation based on the CLcr should be performed, and a more accurate biomarker for renal function is needed.

Previous attempts to predict bacteremia have focused on selecting significant variables. However, these approaches have had limitations such as poor reproducibility in prediction accuracy and inconsistency in predictor selection. Here we propose a Bayesian approach to predict bacteremia based on the statistical distributions of clinical variables of previous patients, which has recently become possible through the adoption of electronic medical records.In a derivation cohort, Bayesian prediction models were derived and their discriminative performance was compared with previous models under varying combinations of predictors. Then the Bayesian models were prospectively tested in a validation cohort. According to Bayesian probabilities of bacteremia, patients in both cohorts were grouped into bacteremia risk groups.Using the same prediction variables, the Bayesian predictions were more accurate than conventional rule-based predictions. Moreover, their better discriminative performance remained consistent despite variations in clinical variables. The receiver operating characteristic (ROC) area of the Bayesian model with 20 predictors was 0.70 ± 0.007 in the derivation cohort and 0.70 ± 0.018 in the validation cohort. The prevalence of bacteremia in groups I, II, and VI (grouped according to probability ratio) were 1.9%, 3.4%, and 20.0% in the derivation cohort, and 0.4%, 3.2%, and 18.4% in the validation cohort, respectively. The overall prevalence of bacteremia was 6.9% in both cohorts.In the present study, the Bayesian prediction model showed stable performance in predicting bacteremia and identifying risk groups, as the previous models did. The clinical significance of the Bayesian approach is expected to be demonstrated through a multicenter trial.

We developed a population pharmacokinetic model of vancomycin by integrating the effects of cystatin C and other demographic factors in a large population of Korean patients with normal serum creatinine concentrations to elucidate the precise role of serum cystatin C concentrations in the prediction of vancomycin clearance. A population pharmacokinetic model of vancomycin was developed using NONMEM software from a total of 1,373 vancomycin concentration measurements in 678 patients whose serum creatinine concentrations were lower than 1.2 mg/dL. Covariate selection revealed that cystatin C was the most influential factor and had negative influence ((-0.78)) in the relationship. Total body weight, sex, age, and serum creatinine were also significantly correlated with the clearance. The estimated intersubject variabilities of clearance and volume of distribution were 24.7% and 25.1%, respectively. A 14-fold difference in predicted trough concentrations was observed according to only cystatin C concentrations in a population of simulated individuals with median demographic characteristics. The use of serum cystatin C as marker of vancomycin clearance for more accurate predictions of serum vancomycin concentrations could be useful, particularly among patients with normal serum creatinine concentrations.

Public health authorities recommend that isolation precautions for influenza should be continued for 7 days after illness onset or until 24 h after the resolution of symptoms, whichever event lasts longer. However, little data are available regarding the duration of isolation for patients with 2009 pandemic H1N1 (pH1N1). We recruited patients with confirmed pH1N1 virus infection at a 2,000-bed tertiary care center. Influenza viral loads from oropharyngeal swab specimens were serially determined by reverse transcriptase quantitative polymerase chain reaction every other day, and the risk factors for prolonged viral shedding were investigated. To evaluate the current recommendations for isolation precautions, we measured the intervals between symptom onset and the last viral RNA detection, and that between the last viral RNA detection and the point at which the patient was symptom-free for 24 h. From November 2009 to January 2010, 26 patients were enrolled, and viral RNA was detected in more than half of the eligible patients (10 of 19, 52.6%) for ≥7 days after symptom onset. While evaluating the policy for lifting quarantine, we found that viral RNA was detected in 4 of 15 patients (26.7%) beyond the recommended duration of isolation. In conclusion, viral RNA was detected in a substantial proportion of hospitalized patients even when they fulfilled the recommended conditions for lifting quarantine, and we believe that more prudence is required in this aspect.

Over the last 2 decades, Burkholderia cepacia complex has emerged as a serious human pathogen, especially in critically ill patients. B. cepacia complex has been associated with increased morbidity and mortality in intensive care unit patients. However, in our literature search, we could not find studies on risk factors for mortality in patients with B. cepacia complex bacteraemia. Therefore, we investigated risk factors for mortality in B. cepacia complex bacteraemia.Clinical characteristics and laboratory parameters of 27 patients with 1 or more blood cultures positive for B. cepacia complex from January 2006 to October 2010 in Severance Hospital, Yonsei University College of Medicine, Korea were retrospectively analyzed. The main outcome measure was overall 28-day mortality. Appropriate initial empirical antimicrobial use was defined as administration of agent(s) to which the organism was susceptible within 24 h of obtaining blood for culture.The overall 28-day mortality rate was 41% (11/27). In univariate analysis, underlying diabetes mellitus (p = 0.033), inappropriate initial empirical antimicrobial therapy (p = 0.033), and an elevated Sequential Organ Failure Assessment (SOFA) score (p = 0.002) were significantly associated with mortality. In multivariate analysis, inappropriate initial empirical antimicrobial therapy and an elevated SOFA score were independent risk factors for increased mortality (p = 0.032 and p = 0.028, respectively).An elevated SOFA score and inappropriate initial empirical antimicrobial therapy were significantly associated with adverse outcome in patients with B. cepacia complex bacteraemia.

Summary Objectives The QuantiFERON-TB Gold In-Tube (QFT-G IT) test is based on the cellular immune response, and this assay can result in indeterminate results for the diagnosis of tuberculosis. The occurrence of indeterminate results may decrease the clinical usefulness of this test. Therefore, we investigated possible predictive factors that can influence the occurrence of indeterminate results from the QFT-G IT test. Methods We conducted a case-control study with 162 case patients who had indeterminate results from a QFT-G IT test at a tertiary hospital in South Korea, from September 2006 to September 2009. Results Of the 1276 patients, 162 (12.7%) cases that underwent QFT-G IT testing were reported as indeterminate results. Severe lymphopenia (odds ratio [OR] = 8.839; p p = 0.007), autoimmune disease (OR = 2.527; p = 0.017) and chronic lung disease (OR = 3.169; p = 0.007) were independent predictive factors for indeterminate results from a QFT-G IT test. Conclusion The patients with lower lymphocyte counts or immunosuppressive conditions showed a higher probability of indeterminate results from the QFT-G IT test. Careful attention to the pre-analytical conditions may be able to minimize this proportion.

Background Sepsis is a syndrome that results in high morbidity and mortality. We investigated the delta neutrophil index (DN) as a predictive marker of early mortality in patients with gram-negative bacteremia. Materials and Methods We conducted a retrospective study at a tertiary referral hospital in South Korea from November 2010 to March 2011. The DN was measured at onset of bacteremia and 24 hours and 72 hours later. The DN was calculated using an automatic hematology analyzer. Factors associated with 10-day mortality were assessed using logistic regression. Results A total of 172 patients with gram-negative bacteremia were included in the analysis; of these, 17 patients died within 10 days of bacteremia onset. In multivariate analysis, Sequental organ failure assessment scores (odds ratio [OR]: 2.24, 95% confidence interval [CI]: 1.31 to 3.84; P = 0.003), DN-day 1 ≥ 7.6% (OR: 305.18, 95% CI: 1.73 to 53983.52; P = 0.030) and DN-day 3 ≥ DN-day 1 (OR: 77.77, 95% CI: 1.90 to 3188.05; P = 0.022) were independent factors associated with early mortality in gram-negative bacteremia. Of four multivariate models developed and tested using various factors, the model using both DN-day 1 ≥ 7.6% and DN-day 3 ≥ DN-day 1 was most predictive early mortality. Conclusions DN may be a useful marker of early mortality in patients with gram-negative bacteremia. We found both DN-day 1 and DN trend to be significantly associated with early mortality.

Correspondence to Young Goo Song, M.D., Ph.D. Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul 135-720, Korea Tel: +82-2-2019-3319, Fax: +82-2-3463-3882, E-mail: imfell@yuhs.ac Copyrightc 2014 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 마제신 환자에서 발생한 Enterococcus hirae 신우신염 1예

Mycobacterium massiliense (M. massiliense) was identified recently as a species that separated from M. abscessus. Unlike M. abscessus, M. massiliense responds well to clarithromycin-based antibiotic treatment. Many cases of M. massiliense infections related to iatrogenic procedures have been reported. We report a case of skin and soft tissue infection by M. massiliense, which was not caused by medical appliances, that was treated successfully using clarithromycin monotherapy for -6 months after initial treatment with empirical antibiotics for 4 weeks. (Korean J Med 2014;87:510-513)

Systemic capillary leak syndrome is a rare disease characterized by life-threatening attacks of reversible plasma extravasation and vascular collapse accompanied by hypotension, hemoconcentration, and hypoalbuminemia. A 36-year-old woman was admitted to this hospital with a fever, along with symptoms consistent with an upper respiratory tract infection and hypotension. Initial laboratory tests revealed several abnormal findings, including an elevated leukocyte count and hematocrit, hypoalbuminemia, and acute renal failure. Here, we report a case of successful treatment of systemic capillary leak syndrome, which can be difficult to distinguish from septic shock. (Korean J Med 2014;87:761-764)

Hemangioma of the liver is usually asymptomatic and incidentally discovered. However, giant hemangioma of the liver may be symptomatic, which is an indication for treatment. A 31-year-old female was admitted with a fever and 1-month history of a nonproductive cough. Her blood test results revealed thrombocytopenia, anemia, and mild coagulopathy. A giant hemangioma of the liver was the cause of her symptoms and signs, and was too large for surgical treatment. Therefore, we performed two sessions of transcatheter hepatic arterial embolization (TAE). The patient has been doing well without fever for 1 year following the second TAE procedure. Surgical resection and enucleation are the traditional treatments of choice for symptomatic giant hemangioma of the liver. However, the signs and symptoms of giant hemangioma of the liver improved by TAE in the present case. We herein report a case of complicated giant hemangioma of the liver that was partially treated by TAE and conservative management. (Korean J Med 2014;87:505-509)

Metabolic syndrome is an important long term complication in chronic asymptomatic HIV-infected subjects under highly active antiretroviral therapy (HAART), because it can contribute to morbidity and mortality via cardiovascular disease (CVD). Therefore, a predictive marker for early detection of metabolic syndrome may be necessary to prevent CVD in HIV-infected subjects. Retinol-binding protein- 4 (RBP-4) has been shown to be associated with metabolic syndrome in various non-HIV-infected populations. We performed a cross-sectional study to evaluate whether serum RBP-4 levels are correlated with metabolic syndrome in HIV-infected subjects receiving HAART. In total, 98 HIV-infected Koreans who had been receiving HAART for at least 6 months were prospectively enrolled. Metabolic syndrome was diagnosed according to the Adult Treatment Panel III criteria, and serum RBP-4 concentrations were measured using human RBP-4 sandwich enzyme- linked immunosorbent assay. Serum RBP-4 levels were significantly higher in HIV-infected subjects receiving HAART with metabolic syndrome (n=33, 33.9±7.7 μg/mL) than in those without it (n=65, 29.9±7.2 μg/mL) (p=0.012). In multivariate linear regression analysis, the number of components of metabolic syndrome presented and waist circumference were independently, significantly correlated with RBP-4 (p=0.018 and 0.030, respectively). In conclusion, we revealed a strong correlation between RBP-4 and the number of components of metabolic syndrome in HIV-infected subjects receiving HAART.

From April 2008 to November 2008, many cases of hepatitis A were reported in Seoul and Gyeonggi Province in Korea. Furthermore, the rate of severe or fulminant hepatitis have significantly increased during the latest epidemic (13.4% vs. 5.2%, p=0.044). Therefore, widespread use of vaccine is warranted to reduce the burden of hepatitis A in Korea.

Libman-Sacks endocarditis (LSE) is a valvular heart disease that is associated with autoimmune diseases such as systemic lupus erythematosus and antiphospholipid syndrome (APS). Cases of LSE and APS associated with infection have been reported during the last several years. Herein, we present a patient who was suspected to have developed LSE and catastrophic APS during the treatment of her definite infective endocarditis, which was caused by Staphylococcus aureus, and the patient’s condition was complicated with cerebral abscess, sensorineural hearing loss, endophthalmitis, renal infarction, splenic abscess, and septic arthritis.

Ochrobactrum anthropi는 그람 음성 호기성 간균으로 자 연환경(토양, 물) 및 병원 내 수액, 투석액 등에서 발견되며 대장 내 정상균총인 균주로, 1980년 첫 인체감염 증례보고 이후 면역기능저하 환자에서 유치카테터 관련 감염 등, 관련 보고가 점차 증가하고 있다. O. anthropi의 인체 감염에 대 한 병태 생리기전에 대한 연구들이 이루어지고 있다(1-4). 저자들이 PUBMED 검색을 통해 조사한 바에 따르면 50 건의 O. anthropi 감염증 보고가 있었고 이중 균혈증은 29건 이었다. 국내에서 보고된 O. anthropi 감염증은 총 3예가 있 었고 균혈증, 안내염, 자발성 복막염 각 1예가 보고되었다 (5-7). 지금까지 보고된 O. anthropi 균주는 carbapenem을 제외한 베타락탐계 항생제에 내성을 나타내는 경우가 대부