Protective effect of Lycium barbanun glycopeptide on human keratinocytes against radiation-induced oxidative stress damage and its mechanism / 中国生物制品学杂志

@#Objective To investigate the protective effect of Lycium barbanun glycopeptide(LbGP)on human keratinocyte HaCaT cells against radiation-induced cytotoxicity and its mechanism. Methods HaCaT cells were exposed to radiation with linear accelerator(rate 6 Gy/min)at doses of 4,8,12,16,20,24 and 28 Gy respectively,and the cell activity was detected by CCK-8 assay. HaCaT cells were treated with LbGP(0,0. 05,0. 1,0. 5,0. 8,1. 0,1. 5 and 3 mg/mL)for 4 h,exposed to radiation of 12 Gy,and detected for the cell viability by CCK-8 assay. HaCaT cells were divided into control group(without LbGP and radiation),radiation group(radiation of 12 Gy)and LbGP + radiation group(0. 8 mg/mL LbGP for 24 h,radiation of 12 Gy). After irradiation for 1 h,the reactive oxygen species(ROS)production was measured by flow cytometry,the superoxide dismutase(SOD)activity was determined by WST-8 assay and the expression of nuclear factor-E2 related factor 2(Nrf2),p-Nrf2,NADPH quinone oxidoreductase 1(NQO1)and heme oxygenase-1(HO-1)were detected by Western blot;The mRNA transcription levels of Nrf2,HO-1 and NQO1 were detected by qRT-PCR at 1,3 and 5 h after irradiation. Results Radiation of12 Gy induced about 50% cell death,and 0. 8 mg/mL LbGP showed the best protective effect on the activity of irradiated cells. After irradiation for 1 h,compared with the control group,the content of ROS in HaCaT cells increased significantly in radiation group(F = 2. 55,P < 0. 001),the activity of SOD decreased significantly(F = 1. 23,P < 0. 01),the contents of NQO1 and Nrf2 protein had no significant difference(F = 1. 78 and 1. 00,respectively,P > 0. 05),the content of HO-1protein increased significantly(F = 1. 37,P < 0. 05),and the content of p-Nrf2 protein decreased significantly(F = 2. 75,P < 0. 01);Compared with the radiation group,the content of ROS in HaCaT cells of LbGP + radiation group decreased significantly(F = 3. 61,P < 0. 001),the activity of SOD increased significantly(F = 1. 23,P < 0. 05),and the contents of Nrf2,p-Nrf2,HO-1 and NQO1 protein increased significantly(F = 4. 00,2. 25,6. 25 and 1. 27,respectively,P < 0. 05). In addition,the mRNA levels of Nrf2,HO-1 and NQO1 genes in LbGP + radiation group were significantly higher than those in radiation group at 1,3 and 5 h after irradiation(F = 0. 20～36. 00,P < 0. 05). Conclusion LbGP can mitigate oxidative stress damage of HaCaT cells induced by radiation and protect cell activity,which may play a role by activating Nrf2 and increasing the levels of its downstream antioxidant enzymes SOD,HO-1 and NQO1.

Global characterization of modifications to the charge isomers of IgG antibody / 药物分析学报

Posttranslational modifications of antibody products affect their stability,charge distribution,and drug activity and are thus a critical quality attribute.The comprehensive mapping of antibody modifications and different charge isomers(CIs)is of utmost importance,but is challenging.We intended to quanti-tatively characterize the posttranslational modification status of CIs of antibody drugs and explore the impact of posttranslational modifications on charge heterogeneity.The CIs of antibodies were fraction-ated by strong cation exchange chromatography and verified by capillary isoelectric focusing-whole column imaging detection,followed by stepwise structural characterization at three levels.First,the differences between CIs were explored at the intact protein level using a top-down mass spectrometry approach;this showed differences in glycoforms and deamidation status.Second,at the peptide level,common modifications of oxidation,deamidation,and glycosylation were identified.Peptide mapping showed nonuniform deamidation and glycoform distribution among CIs.In total,10 N-glycoforms were detected by peptide mapping.Finally,an in-depth analysis of glycan variants of CIs was performed through the detection of enriched glycopeptides.Qualitative and quantitative analyses demonstrated the dynamics of 24 N-glycoforms.The results revealed that sialic acid modification is a critical factor ac-counting for charge heterogeneity,which is otherwise missed in peptide mapping and intact molecular weight analyses.This study demonstrated the importance of the comprehensive analyses of antibody CIs and provides a reference method for the quality control of biopharmaceutical analysis.

Research progress of new antimicrobial agents for drug-resistant pathogenic bacteria / 中华临床感染病杂志

This article reviews the status quo of new antimicrobial agents that have been approved or undergoing phase Ⅱ/Ⅲ clinical trials in last five years at home and abroad, including new β-lactamase inhibitors and their compound preparations, oxazolidinones, tetracyclines, aminoglycosides, glycopeptides, quinolones, new antifungal agents, cyclic lipopeptides and new anti-mycobacterial agents. The antibacterial activities, main mechanisms of drug resistance, and progress of clinical studies of 27 new drugs were introduced to provide a reference for their clinical application.

Protective effect of Ganoderma lucidum spore glycopeptide on liver injury in mice / 中国药科大学学报

@#Models of acute and chronic liver injury in mice were established using carbon tetrachloride (CCl4) and ethanol to explore the protective effects of Ganoderma lucidum spore glycopeptide on liver injury.Different dosage of Ganoderma lucidum spore glycopeptide (65,130,260 mg/kg) were given by gavage.The liver index and the levels of serum aspartate transaminase (AST) and alanine transaminase (ALT) were determined.The contents of liver interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and inducible nitric oxide synthase (iNOS) were tested by enzyme-linked immunosorbent assay (ELISA).The pathological injury of liver tissue was observed by HE staining.The results showed that Ganoderma lucidum spore glycopeptide could significantly reduce the liver index and the contents of serum AST and ALT in mice of acute and chronic liver injury.In mice of chronic liver injury induced by CCl4, Ganoderma lucidum spore glycopeptide could significantly decrease the contents of liver IL-6, TNF-α and iNOS, and alleviate the pathological damage of liver tissue.Results suggested that Ganoderma lucidum spore glycopeptide might reduce acute and chronic liver injury with anti-inflammatory effects in mice.

N-Glycans and intact glycopeptide-based characterization of N-glycosylation of monoclonal antibody drugs / 药学学报

In recent years, the biopharmaceutical industry has grown rapidly, and the market size of monoclonal antibody drugs has increased significantly. Accurate structural characterization and quality control are the supporting technologies for the development of monoclonal antibody drugs. As a significant post-translational modification of antibody drugs, glycosylation has an important influence on its efficacy, stability, and immunogenicity. The existing literature usually uses liquid chromatography-mass spectrometry to perform major glycosylation modifications of monoclonal antibody drugs. Characterization, there are few studies on low-abundance glycosylation, but the characterization and control of low-abundance glycosylation cannot be ignored. In this study, we have established a qualitative and quantitative analysis technology for N-glycans based on RapiFluor-MS reagent-labeled monoclonal antibody drugs. This method has a short sample processing time and high sensitivity. It can not only characterize the main glycoforms of three monoclonal antibody drugs (adalimumab, bevacizumab, and trastuzumab) but also can quantify low-abundance N-glycans. The results of the study showed that the main glycoforms specified in the Pharmacopoeia could be detected in different batches of monoclonal antibody drugs, but the content of N-glycans in different batches of samples is not identical. After that, we analyzed the N-glycans connection sites and glycoforms at the intact glycopeptide level, further enriching the N-glycans structure information of the monoclonal antibody. The qualitative and quantitative analysis technology of N-glycans based on RapiFluor-MS reagent-labeled monoclonal antibody drugs can realize the in-depth characterization and control of glycosylation modification of monoclonal antibody drugs.

Comparing different domains of analysis for the characterisation of N-glycans on monoclonal antibodies / 药物分析学报

With the size of the biopharmaceutical market exponentially increasing, there is an aligned growth in the importance of data-rich analyses, not only to assess drug product safety but also to assist drug development driven by the deeper understanding of structure/function relationships. In monoclonal antibodies, many functions are regulated by N-glycans present in the constant region of the heavy chains and their mechanisms of action are not completely known. The importance of their function focuses analytical research efforts on the development of robust, accurate and fast methods to support drug development and quality control. Released N-glycan analysis is considered as the gold standard for glycosylation characterisation;however, it is not the only method for quantitative analysis of glycoform heterogeneity. In this study, ten different analytical workflows for N-glycan analysis were compared using four monoclonal antibodies. While observing good comparability between the quantitative results generated, it was possible to appreciate the advantages and disadvantages of each technique and to summarise all the observations to guide the choice of the most appropriate analytical workflow ac-cording to application and the desired depth of data generated.

Rapid Characterization of Impurity Profiles in Vancomycin Raw Material by Column-Switching LC/MSn / 中国药学杂志

OBJECTIVE: To characterize the impurity structures in vancomycin raw material. METHODS: Impurities were eluted gradiently on a Chromasil 100-5 C18(4.6 mm×250 mm, 5 μm) column, with triethylamine buffer solution (pH 3.2)-acetonitrile-tetrahydrofuran (92∶7∶1, V/V/V) as mobile phase A, and triethylamine buffer solution (pH 3.2)-acetonitrile-tetrahydrofuran (70∶29∶1, V/V/V) as mobile phase B. Stress tests were performed on the raw material to specify those impurities. By application of on-line LC/MSn method, the impurities were analyzed in positive mode and their structures were characterized based on the degradation mechanism and mass fragmentation regularity of sugar-lipopeptides. RESULTS: Totally 14 impurities were characterized in the raw material, seven of which were reported for the first time. The relationships between the chemical structures and chromatographic behaviors of vancomycin, demethylvancomycin and methylated vancomycin with their two β-isomers were summarized. CONCLUSION: The structures of related impurities in vancomycin raw material can be rapidly identified by on-line LC/MSn method together with stress degradation experiments.

Structures of ginseng glycopeptides and anti-apoptotic effect on PC12 cells treated with Aβ25-35 / 吉林大学学报(医学版)

Objective: To study the structures of ginseng glycopeptides, and to explore the protective effect on the apoptosis of PCI 2 cells treated with amyloid beta25-35 (Aβ25-35), and to lay a theoretical foundation for the development of ginseng anti-Alzheimer' s disease (AD) drugs. Methods: The structures of ginseng glycopeptides were analyzed by reversed-phase high performance liquid chromatography coupled with Q Exactive Orbitrap mass spectrometry. The PCI2 cells were divided into 6 groups, and treated with the medium including different concentrations 0, 6. 25, 12. 50, 25. 00, 50. 00, and 100. 00 mol • L_ 1 ) of Aβ25-35 , and the survival rates of PC12 cells were measured by cell counting kit-8 (CCK-8) method. The PC12 cells were divided into blank control group, model group, and ginseng glycopeptides administration group. The medium including 50. 00 jumol • L_ 1 Aβ25-35, was added in model group, and different concentrations 0. 03, 0.10, 0. 30, and of 1. 00 g • L_ 1 ) ginseng glycopeptides+ 50 jumol • L_ 1 Aβ25-35 were added in administration groups. The survival rates of PC12 cells were measured by CCK-8 method. The apoptotic rates of PCI 2 cells after treated with glycopeptides and Aβ25-35, were detected by Annexin V-FITC/PI method. The PCI 2 cells were divided into blank control group, model group (50.00 jumol • L_ 1 Aβ25-35) and different concentrations (0 . 1 0 and 0.30 g • L_ 1 ) of ginseng glycopeptides administration groups; the percentages of PCI 2 cells in different cell cycles were tested by flow cytometry. Results: More than 20 glycopeptide structures were obtained, such as the peptide chain was NLSHYHSGSS, the glycosyl group was Nl-HexNAc, and the peptide chain was SGSSSSSSSEDDGMGR, the glycosyl group was S6-HexNAc. When the concentration of Aβ25-35 was 50 jumol • L_ 1 , the survival rate of PC12 was (55. 45 + 2. 3 4) % and the survival rate was significantly lower than that in blank control group (P < 0 . 0 1) . Compared with blank control group, the survival rate of the PC12 cells in model group was significantly decreased (P < 0 01); compared with model group, the survival rates of the PCI2 cells in administration groups were significantly increased (P< 0. 05). Compared with blank control group, the apoptotic rate of the PC12 cells in model group were increased (P < 0. 01); compared with model group, the apoptotic rates of the PC12 cells in administration groups were decreased (P < 0 . 05). Compared with blank control group, the percentage of PC12 cells in S phase in model group was increased (P

Clinical Review of Staphylococcal Scalded Skin Syndrome in a Single Institution for 18 Years, 2001–2018 / 계명의대학술지

Staphylococcal scalded skin syndrome (SSSS) is a disease caused by exfoliative toxin. The purpose of this study is to analyze clinical features, laboratory findings and treatment outcome of patients who diagnosed with SSSS in a single institution for 18 years. From January 2001 to December 2018, 137 patients were diagnosed with SSSS at Daegu Fatima hospital. We retrospectively reviewed the 131 patients' medical records except 6 patients who were unable to identify the exact medical records. The median age of the patients was 32 months (5 days to 97 months) and 78% of the patients were under 4 years. The mean annual number of cases was 7.3 ± 3.7, the number of patients was increased since 2013, and occurred mainly from August to January. Skin cultures were performed in 62 patients and methicillin-resistant Staphylococcus aureus was cultured in 37 patients. The result of the treatment was good without the dead patient. SSSS is a disease occurred frequently in young children, at August to January. The number of patients was increased since 2013. MRSA was cultured a lot, but uniform use of glycopeptide is not necessary.

Novel Tetrapeptide Hydrophilic Interaction Chromatography Materials for High-efficiency Glycopeptide Enrichment / 分析化学

In this study, a novel tetrapeptide hydrophilic interaction chromatography (HILIC) material was synthesized, and corresponding enrichment method for glycopeptides was developed.The tetrapeptide modified silica gel materials (denoted as Poly-DAPD) were synthesized by atom-transfer radical-polymerization (ATRP) and characterized by N2 adsorption desorption and thermometer, thermal gravimetric analyzer (TGA) and X-ray photoelectron spectrometer (XPS).The characterization results indicated that tetrapeptide had been successfully synthesized on silica gel.Poly-DAPD materials showed high enrichment selectivity toward fetuin glycopeptides under solid-phase extraction (SPE) mode.Comparing with commercialized ZIC-HILIC in glycopeptides enrichment of fetuin digest which mixed with 5 mole ratio of albumin bovine (BSA), the as-prepared materials showed higher selectivity in both aspects of the identified number of glycopeptides and anti-interference property.The SPE results demonstrated that the tetrapeptide-based HILIC materials could be a potential tool in large-scale glycosylation analysis.

Study Advances in the Analytical Methods for Teicoplanin / 中国药师

Teicoplanin is a kind of glycopeptide antibiotic extracted from actinomycetes after fermentation, which is mainly used for the treatment of multidrug-resistant gram-positive cocci infection. The domestic and overseas research literatures on the advances in the analytical methods for teicoplanin were consulted, reviewed and analyzed. The determination methods of teicoplanin mainly includ-ed in vivo and in vitro pharmaceutical analysis. The analytical methods involved high-performance liquid chromatography analysis, bio-assay determination, liquid chromatography-mass spectrometry analysis and micellar electrokinetic capillary chromatography, and a-mong them, HPLC technology was most commonly utilized in the determination of teicoplanin in biological samples and teicoplanin preparations. Much progress has been made in the analytical methods for teicoplanin, and further exploration of determination methods in vivo and in vitro will be beneficial to the quality control of the drug and guiding clinical rational administration.

Prevalence and Clinical Impact of Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Isolated From Hospitalized Patients

BACKGROUND: We estimated the prevalence and clinical impact of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA). The concordance between macromethod and glycopeptide resistance detection (GRD) E tests was determined. In addition, predictors of clinical outcomes in hospitalized patients with S. aureus bacteremia (SAB) or pneumonia (SAP) were evaluated. METHODS: We obtained 229 consecutive S. aureus isolates from all hospitalized patients at two university hospitals located in Busan and Yangsan, Korea. Standard, macromethod, and GRD E tests were performed. Additionally, we reviewed the medical records of all patients. Among the 229 patients, predictors of clinical outcomes were analyzed for 107 patients with SAB and 39 with SAP. RESULTS: Among the 229 isolates, 34.5% of S. aureus isolates and 50.7% of methicillin-resistant S. aureus isolates exhibited the hVISA phenotype based on the macromethod E test. hVISA was nearly associated with treatment failure in patients with SAB (P=0.054) and was significantly associated with treatment failure in patients with SAP (P=0.014). However, hVISA was not associated with 30-day mortality in patients with SAB or SAP. The concordance between the macromethod and GRD E tests was 84.2%. CONCLUSIONS: hVISA is quite common in the southeastern part of Korea. hVISA is associated with treatment failure in patients with SAP.

Quantification of free sugars in glycopeptide drugs by high performance anion exchange chromatograghy-pulsed amperometric detection / 中国药学杂志

OBJECTIVE: To establish a new determination method for free monosaccharides or disaccharides in glycopeptide drugs to eliminate their influence on polysaccharide content assay by colorimetric method adopted by the current national specifications. METHODS: Solid phase extraction column was used for matrix elimination. A high performance anion exchange chromatograghy (HPAEC) in conjunction with pulsed amperometric detector (PAD) was performed on a CarboPac®PA20, using 200 mmol · L-1 sodium hydroxide solution and 1 mol · L-1 sodium acetate solution as mobile phase. RESULTS: Twenty batches of raw materials and preparations of Bozhi glycopeptides, mannatide and polystictus glycopeptide were tested. Free monosaccharides of high content were detected in eight batches of samples, including glucose, sucrose, mannose, and fructose. CONCLUSION: The HPAEC-PAD method is specific, sensitive, rapid and applicable widely, compared with other methods of saccharide detection, thus has good prospect of application and development. The assay methods in the current national specifications of glycopeptides drugs need to be improved.

Glycopeptide Antibiotics: Structure and Mechanisms of Action

Glycopeptides of the clinically important antibiotic drugs are glycosylated cyclic or polycyclic nonribosomal peptides. Glycopeptides such as vancomycin and teicoplanin are often used for the treatment of gram-positive bacteria in patients. The increased incidence of drug resistance and inadequacy of these therapeutics against gram-positive bacterial infections would be the formation and clinical development of more variable second generation of glycopeptide antibiotics: semisynthetic lipoglycopeptide analogs such as telavancin, dalbavancin, and oritavancin with improved activity and better pharmacokinetic properties. In this review, we describe the development of and bacterial resistance to vancomycin, teicoplanin, and semisynthetic glycopeptides (teicoplanin, dalbavancin, and oritavancin). The clinical influence of resistance to glycopeptides, particularly vancomycin, are also discussed.

Susceptibility of Glycopeptide-Resistant Enterococci to Linezolid, Quinupristin/dalfopristin, Tigecycline and Daptomycin in a Tertiary Greek Hospital / 감염과화학요법

We investigated the antibiotic susceptibility of glycopeptide-resistant enterococci (GRE). Seventy consecutive GRE were tested. Sixty-two isolates were identified as Enterococcus faecium (88.6%), and 8 (11.4%) as Enterococcus faecalis. All strains were susceptible to linezolid and daptomycin, while 17.1% (12/70) and 11.4% (8/70) were resistant to quinupristin/dalfopristin (QD) and tigecycline, respectively. All E. faecalis isolates were resistant to QD, while 4 of 62 (6.5%) E. faecium isolates were resistant to QD. All E. faecalis isolates were susceptible to tigecycline, while 14.5% (9/62) E. faecium isolates were resistant. Continued surveillance of GRE antibiotic susceptibilities is important for combating these multi-resistant nosocomial pathogens.

Clinical investigation of compound glycyrrhizin combined with bozhi glycopeptide in treatment of erythema nodosum / 中国医师进修杂志

Objective To investigate the clinical effect and safety of compound glycyrrhizin combined with bozhi glycopeptide in treatment of erythema nodosum.Methods Sixty-four patients with erythema nodosum were divided into treatment group (36 cases) and control group (28 cases) by random digits table method.The patients in treatment group were given compound glycyrrhizin 120 mg,intravenous drip,once a day;and bozhi glycopeptide 4 ml,intravenous drip,once a day.The patients in control group were given compound glycyrrhizin 120 mg,intravenous drip,once a day.The clinical efficacy and recurrence were compared between 2 groups.Results The total effective rate in treatment group was significantly higher than that in control group [86.1％ (31/36) vs.57.1％ (16/28)],there was statistical difference (P ＜ 0.05).Follow-up for 3 months,the rate of recurrence in treatment group was significantly lower than that in control group [16.1％(5/31) vs.8/16],there was statistical difference (P＜ 0.05).Conclusion Compound glycyrrhizin combined with bozhi glycopeptide can effectively control the erythema nodosum,and has no significant adverse reactions,reduces the rate of recurrence,and it is worthy of promotion and application.

Compound Tianmamihuan Glycopeptide Tablets for Postconcussion Syndrome:Observation of Clinical Efficacy / 中国药房

OBJECTIVE:To evaluate the efficacy of Compound tianmamihuan glycopeptide tablets for postconcussion syndrome.METHODS:100 patients with postconcussion syndrome were randomly divided into two groups:50 in the trial group were assigned to receive Tianmamihuan glycopeptide tablets(2 tablets/time tid) for 30 days,and the another 50 in the control group to receive Citicoline sodium injection 0.5～0.75 g(diluted with 0.9% Sodium chloride injection)250 mL iv qd for 30 days.RESULTS:The cure rate in the trial group was 92.0% versus 70.0% in the control group,showing significant difference between the two groups(P

Clinical Features and Risk Factors of the Septic Shock in Patients with Neutropenic Fever / 감염과화학요법

BACKGROUND: The purpose of this study was to evaluate the etiologic organisms, risk factors, and other infectious features of febrile neutropenic patients developing septic shock. METHODS: We reviewed medical record of 457 patients developing neutropenic fever after chemotherapy or hematopoietic stem cell transplantation (HSCT) at Catholic HSCT Center from Jan 1998 to Dec 1999. Out of them, age/sex matched patients without septic shock were enrolled into the control group, and retrospective case-control study was conducted. RESULTS: Overall incidence of septic shock was 8.5%. Most common underlying disease of the two groups was acute leukemia. Microbiologically defined infection (MDI), especially Gram-negative bacterial infection, was significantly more common in the septic shock group than in the control group. Escherichia coli was the most common organism in the two groups (51.3% vs 27.7%, P<0.001). However, empirical use of glycopeptide was more frequent in the shock group (P<0.05). Differing from other report, fatal infection due to viridans streptococci was not observed in spite of quinolone prophylaxis. Mean leukocyte count at the onset of fever was 207/mm3 and 355/mm3 (P=0.027) and mean duration of total febrile day was 12.3 days and 7.8 days, respectively (P=0.001). On multivariate analysis, MDI and leukocyte count at the onset of fever were the significant risk factors for the septic shock. Overall mortality showed higher tendency in the shock group than in the control group (23.1% vs. 12.0%, P=0.057). Especially, in patients with Gram-positive bacterial infection, infection related mortality was significantly higher in the shock group than in the control group (50% vs. 8.9%, P=0.013). CONCLUSION: Although Gram-positive bacterial infection has been increasing, Gram-negative bacteria, including E. coli, were the most common causative organisms for sepctic shock in febrile neutropenic patients. However, considering high mortality in the septic shock caused by Gram-positive bacteria, glycopeptide must immediately be administered to the febrile neutropenic patients developing septic shock.

Clinical Features and Risk Factors of the Septic Shock in Patients with Neutropenic Fever / 감염과화학요법

BACKGROUND: The purpose of this study was to evaluate the etiologic organisms, risk factors, and other infectious features of febrile neutropenic patients developing septic shock. METHODS: We reviewed medical record of 457 patients developing neutropenic fever after chemotherapy or hematopoietic stem cell transplantation (HSCT) at Catholic HSCT Center from Jan 1998 to Dec 1999. Out of them, age/sex matched patients without septic shock were enrolled into the control group, and retrospective case-control study was conducted. RESULTS: Overall incidence of septic shock was 8.5%. Most common underlying disease of the two groups was acute leukemia. Microbiologically defined infection (MDI), especially Gram-negative bacterial infection, was significantly more common in the septic shock group than in the control group. Escherichia coli was the most common organism in the two groups (51.3% vs 27.7%, P<0.001). However, empirical use of glycopeptide was more frequent in the shock group (P<0.05). Differing from other report, fatal infection due to viridans streptococci was not observed in spite of quinolone prophylaxis. Mean leukocyte count at the onset of fever was 207/mm3 and 355/mm3 (P=0.027) and mean duration of total febrile day was 12.3 days and 7.8 days, respectively (P=0.001). On multivariate analysis, MDI and leukocyte count at the onset of fever were the significant risk factors for the septic shock. Overall mortality showed higher tendency in the shock group than in the control group (23.1% vs. 12.0%, P=0.057). Especially, in patients with Gram-positive bacterial infection, infection related mortality was significantly higher in the shock group than in the control group (50% vs. 8.9%, P=0.013). CONCLUSION: Although Gram-positive bacterial infection has been increasing, Gram-negative bacteria, including E. coli, were the most common causative organisms for sepctic shock in febrile neutropenic patients. However, considering high mortality in the septic shock caused by Gram-positive bacteria, glycopeptide must immediately be administered to the febrile neutropenic patients developing septic shock.

A Case of Septicemia by Transient Glycopeptide: Dependent Enterococcus faecium / 감염

The isolation of clinical strains of enterococci requiring vancomycin for growth has been reported, but transient strain has not been reported. Transient glycopeptide-dependent Enterococcus f aecium was isolated from the blood of a 59-year-old female with advanced rectal carcinoma during long term broad-spectrum antimicrobial therapy. This strain showed transient glycopeptide dependency, but glycopeptide-resistant revertants were found on subculture to blood agar without vancomycin. It was found to be the vanA genotype by the polymerase chain reaction analysis.