Dr. Kyoung Shik Sunwoo: father of homeless, Schweitzer of Yeungdeungpo

No abstract available.

Cytomegalovirus Ventriculoencephalitis after Unrelated Double Cord Blood Stem Cell Transplantation with an Alemtuzumab-containing Preparative Regimen for Philadelphia-positive Acute Lymphoblastic Leukemia

Despite the prophylaxis and preemptive strategies using potent antiviral agents, cytomegalovirus (CMV) remains a major infectious cause of morbidity and mortality in allogeneic stem cell transplantation (SCT) recipients. Delayed immune reconstitution after SCT, such as cord blood and T-cell depleted SCT with the use of alemtuzumab, has been associated with an increased frequency of CMV disease as well as CMV reactivation. CMV disease involving central nervous system is an unusual presentation in the setting of SCT. We report a case of CMV ventriculoencephalitis after unrelated double cord blood SCT with an alemtuzumab-containing preparative regimen for Philadelphia-positive acute lymphoblastic leukemia.

Efficacy and Safety Profile of Voriconazole as Salvage Therapy for Invasive Aspergillosis with Hematologic Diseases in Korea

BACKGROUND: Invasive aspergillosis (IA) is associated with significant morbidity and mortality in patients with hematologic malignancies. We investigated the efficacy and safety of voriconazole (VCZ) when used as salvage therapy for IA in Korean adults with hematologic malignancies who had not responded to prior antifungal therapy. MATERIALS AND METHODS: We retrospectively reviewed data, collected from January 2007 to October 2008, from patients with proven or probable cases of IA. All were probable IA cases, except for one proven case. All cases were refractory or intolerant to antifungal therapy prior to administration of VCZ. Efficacy and safety were assessed in patients treated with VCZ for more than 3 days and for more than one dose, respectively. A favorable response [complete (CR) or partial (PR)] was defined by significant improvement of all clinical symptoms, signs, and radiologic abnormalities. RESULTS: Fifty patients who met the inclusion criteria were enrolled. There were 27 male and 23 female patients with mean age of 44.4 years (range, 15-65 years). Underlying diseases were acute leukemia (35 cases), chronic myelogenous leukemia (4 cases), myelodysplastic syndrome (3 cases), lymphoma (3 cases) and other hematologic diseases (5 cases). Twenty-two patients had received chemotherapy and 13 patients had undergone hematopoietic stem cell transplantation. The lung was the main infection site (94%) followed by the sinus (6%). Amphotericin B deoxycholate alone was the most frequent previous antifungal therapy. The mean duration of antifungal therapy prior to VCZ therapy was 13.9+/-8.8 days (2-44 days). The median duration of VCZ therapy was 19 days (interquartile range, 49 days). Sixteen patients (32.0%) showed favorable responses (CR:PR=8:8) at the end of VCZ therapy. The numbers of patients with stable disease, progression and death were, 6 (12%), 6 (12%) and 22 (44%) respectively. Most of those with unfavorable responses had relapsed underlying malignancies or refractory graft versus host diseases. Twelve patients developed drug-related adverse events but only one patient stopped VCZ treatment prematurely. CONCLUSIONS: VCZ demonstrated an acceptable level of toxicity in patients with hematologic malignancies but further studies are required to prove its efficacy as salvage therapy.

Once-Daily Gentamicin Administration for Community-Associated Methicillin Resistant Staphylococcus aureus in an in vitro Pharmacodynamic Model: Preliminary Reports for the Advantages for Optimizing Pharmacodynamic Index

PURPOSE: Community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) infections are increasing. Although gentamicin (GEN) is usually susceptible against CA-MRSA, GEN is rarely considered for treatment as monotherapy. We employed an in vitro pharmacodynamic model (IVPDM) to compare efficacies of GEN against CA-MRSA with two dosing regimens [thrice-daily (TD), once-daily (OD)]. MATERIALS AND METHODS: Using two strains of CA-MRSA, we adopted IVPDM comprised of two-compartments with a surface-to-volume ratio of 5.34 cm-1. GEN regimens were simulated with human pharmacokinetic data of TD and OD. Experiments were performed over 48 hours in triplicate for each strain and dosing regimen. RESULTS: MICs of GEN for YSSA1 and YSSA15 were 1 and 2 mg/L, respectively. In OD, indices of peak/MIC were > 8.6 at least, in contrast to or = 3-log10 reduction in CFU/mL was demonstrated prior to 4 hours in TD and OD, and continued until 8 hours for both strains. However, reductions in the colony counts at 24 and 48 hours were significantly larger for OD compared to TD in both strains (p < 0.001). During TD, resistance developed in YSSA1 and small colony variants (SCVs) were documented in YSSA15. No resistance or SCVs were observed during OD in both strains. CONCLUSION: TD and OD showed the same killing slopes until 8 hours. After the 24 hours of experiments, OD of GEN would be advantageous not only in having more reductions in colony counts, but also suppressing the development of resistance or SCVs for 48 hours.

Characteristics of Cytomegalovirus Diseases among Hematopoietic Stem Cell Transplant Recipients : A 10-year Experience at an University Hospital in Korea

BACKGROUND: Studies on cytomegalovirus (CMV) diseases in Korean hematopoietic stem cell transplant (HSCT) recipients are lacking and do not reflect the recent trends of advances and changes. Therefore, we tried to analyze the clinical features of CMV diseases in HSCT recipients over the past 10 years at a tertiary university hospital in Korea. METHODS: Retrospective review of medical records was done for all adult HSCT patients who received transplant at the Catholic HSCT Center from January 1998 to January 2008. RESULTS: Forty-four cases (2.2%) of CMV diseases were identified. CMV pneumonia was diagnosed in 17 patients, retinitis in 16 patients, enterocolitis in 7 patients, esophagitis 1 patient, gastritis in 1 patient, duodenitis in 1 patient, and hepatitis in 1 patient. The median onset of symptom was 90 days after transplantation. Late CMV diseases accounted for 47.7%. CMV related death varied from 0 to 58.8% according to the involved organ. CMV retinitis was diagnosed relatively later in the course of transplantation mostly in patients who had chronic graft versus host disease (GVHD). On the contrary, CMV enterocolitis mainly occurred in patients who suffered from acute GVHD. The overall concurrent CMV reactivation was documented to be 63.6%; the concurrent CMV reactivation was observed only in 37.5% of patients with retinitis. CONCLUSIONS: We observed some differences in the pattern of CMV disease manifestation according to the involved organ and reconfirmed the fact that CMV pneumonia is the most common and fatal disease in HSCT recipients. Additionally, CMV retinitis was not uncommon in HSCT recipients. Since specific marker does not exist in predicting retinitis, regular ocular examination should be done thoroughly, especially in patients with chronic GVHD.

Characteristics of Cytomegalovirus Diseases among Hematopoietic Stem Cell Transplant Recipients : A 10-year Experience at an University Hospital in Korea

BACKGROUND: Studies on cytomegalovirus (CMV) diseases in Korean hematopoietic stem cell transplant (HSCT) recipients are lacking and do not reflect the recent trends of advances and changes. Therefore, we tried to analyze the clinical features of CMV diseases in HSCT recipients over the past 10 years at a tertiary university hospital in Korea. METHODS: Retrospective review of medical records was done for all adult HSCT patients who received transplant at the Catholic HSCT Center from January 1998 to January 2008. RESULTS: Forty-four cases (2.2%) of CMV diseases were identified. CMV pneumonia was diagnosed in 17 patients, retinitis in 16 patients, enterocolitis in 7 patients, esophagitis 1 patient, gastritis in 1 patient, duodenitis in 1 patient, and hepatitis in 1 patient. The median onset of symptom was 90 days after transplantation. Late CMV diseases accounted for 47.7%. CMV related death varied from 0 to 58.8% according to the involved organ. CMV retinitis was diagnosed relatively later in the course of transplantation mostly in patients who had chronic graft versus host disease (GVHD). On the contrary, CMV enterocolitis mainly occurred in patients who suffered from acute GVHD. The overall concurrent CMV reactivation was documented to be 63.6%; the concurrent CMV reactivation was observed only in 37.5% of patients with retinitis. CONCLUSIONS: We observed some differences in the pattern of CMV disease manifestation according to the involved organ and reconfirmed the fact that CMV pneumonia is the most common and fatal disease in HSCT recipients. Additionally, CMV retinitis was not uncommon in HSCT recipients. Since specific marker does not exist in predicting retinitis, regular ocular examination should be done thoroughly, especially in patients with chronic GVHD.

Comparison of Quantitative Cytomegalovirus Real-time PCR in Whole Blood and pp65 Antigenemia Assay: Clinical Utility of CMV Real-time PCR in Hematopoietic Stem Cell Transplant Recipients

Successful preemptive therapy for cytomegalovirus (CMV) infection in transplant patients depends on the availability of sensitive, specific, and timely diagnostic tests for CMV infection. Although the pp65 antigenemia assay has been widely used for this purpose, real-time quantification of CMV DNA has recently been recognized as an alternative diagnostic approach. However, the guidelines for antiviral therapy based on real-time quantitative polymerase chain reaction (RQ-PCR) have yet to be established. From November 2004 to March 2005, a total of 555 whole blood samples from 131 hematopoietic stem cell transplant (HSCT) recipients were prospectively collected. RQ-PCR was conducted using an Artus(R) CMV LC PCR kit (QIAGEN). Both qualitative and quantitative correlations were drawn between the two methods. Exposure to the antiviral agent influenced the results of the two assays. Additionally, the discrepancy was observed at low levels of antigenemia and CMV DNA load. Via ROC curve analysis, the tentative cutoff value for preemptive therapy was determined to be approximately 2x10(4) copies/mL (sensitivity, 80.0%; specificity, 50.0%) in the high risk patients, and approximately 3x10(4) copies/mL (sensitivity, 90.0%; specificity, 70.0%) in the patients at low risk for CMV disease. Further study to validate the optimal cutoff value for the initiation of preemptive therapy is currently underway.

Three cases of ciprofloxacin treatment failure in imported typhoid fever / 대한내과학회지

Recently, the role of ciprofloxacin in the empirical treatment of typhoid fever has been limited with the increased incidence of nalidixic acid-resistant Salmonella enterica serovar Typhi in South-central and Southeast Asia, as well as multidrug-resistant strains. We experienced three cases of imported typhoid fever that did not respond to ciprofloxacin. All of the blood isolates were susceptible to ciprofloxacin in vitro, but the patients failed to achieve clinical improvement with ciprofloxacin and were treated with ceftriaxone or azithromycin. Although nalidixic acid-resistant strains may be reported as susceptible to ciprofloxacin on disk diffusion tests, they frequently show a poor clinical response to ciprofloxacin because of the increased minimum inhibitory concentration of ciprofloxacin. Therefore, if clinical improvement is delayed or fails with ciprofloxacin, imported typhoid fever from South-central or Southeast Asia should be considered as being due to nalidixic acid-resistant strains and should be treated with high-dose ciprofloxacin, ceftriaxone, or azithromycin.

Comparison of Real-time PCR Methods and pp65 Antigenemia Assay to Detect Cytomegalovirus Reactivation in Hematopoietic Stem Cell Transplantation

Human cytomegalovirus (HCMV) is a common human pathogen that causes morbidity and mortality in hematopoietic stem cell transplantation (HSCT) recipients. Early diagnosis of HCMV infection or reactivation, and setting threshold values for effective pre-emptive therapies, are required for appropriate HCMV disease prevention in HSCT recipients. We compared the HCMV infections detected by the two methods, LightCycler-based PCR (LC PCR) and in-house immediate early protein PCR (in-house IE PCR) with the results of a pp65 antigenemia assay as the reference. The sensitivity and specificity for the in-house IE PCR were 79.3% and 72.7%, respectively, and 82.9% and 40.7%, respectively, for the LC PCR. The correlation between the HCMV viral load and pp65 antigenemia in HSCT recipients was r=0.603 with in-house IE PCR and r=0.525 with LC PCR. The discordant results between methods and relatively low (r) values suggest that we need more study to set threshold values according to the using methods with clinical outcome.

A Case of Perianal Abscess due to Panton-Valentine Leukocidin Positive Community-Associated Methicillin-Resistant Staphylococcus aureus : Report in Korea and Literature Review from the Far East

Community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) with Panton-Valentine leukocidin (PVL) genes have recently emerged worldwide, but infections due to PVL carrying CA-MRSA strains have never been reported in Korea. We report a case of extensive perianal abscess due to PVL+ CA-MRSA in a 76-year-old Korean female patient, of which genetic background was very close to USA300. It belonged to staphylococcal cassette chromosome mec element (SCCmec) type IV, ST8 of multilocus sequence typing (MLST), type 1 spa type, and accessory gene regulator locus (agr) group I. Comprehensive literature reviews from the Far East showed molecular characteristics were diverse and PVL genes were infrequently found than in western countries.

A Case of Pneumatosis Cystoides Intestinalis in an Allogenic Stem Cell Transplant Recipient Who had Bronchiolitis Obliterans and Pulmonary Infection by Mycobacterium abscessus

Hematopoietic stem cell transplantation (HSCT) can cause various complications involving lung, liver, intestine and other organs. Chemotherapy, radiation therapy, and graft-versus-host disease (GVHD) may injure the cells in the intestinal mucosa of HSCT recipients. Pneumatosis cystoides intestinalis (PI) is a condition that presence of air in the bowel wall is demonstrated by radiologic or pathologic tests. It is one of the infrequent complications after HSCT and is associated with several medical and surgical conditions. However its pathogenesis and definite etiologic factors are still unknown. Here, we present a case of PI in a HSCT recipient, who was diagnosed of bronchiolitis obliterance accompanied with chronic GVHD and pulmonary disease caused by Mycobacterium abscessus.

Comparison of Real-time PCR Methods and pp65 Antigenemia Assay to Detect Cytomegalovirus Reactivation in Hematopoietic Stem Cell Transplantation

Human cytomegalovirus (HCMV) is a common human pathogen that causes morbidity and mortality in hematopoietic stem cell transplantation (HSCT) recipients. Early diagnosis of HCMV infection or reactivation, and setting threshold values for effective pre-emptive therapies, are required for appropriate HCMV disease prevention in HSCT recipients. We compared the HCMV infections detected by the two methods, LightCycler-based PCR (LC PCR) and in-house immediate early protein PCR (in-house IE PCR) with the results of a pp65 antigenemia assay as the reference. The sensitivity and specificity for the in-house IE PCR were 79.3% and 72.7%, respectively, and 82.9% and 40.7%, respectively, for the LC PCR. The correlation between the HCMV viral load and pp65 antigenemia in HSCT recipients was r=0.603 with in-house IE PCR and r=0.525 with LC PCR. The discordant results between methods and relatively low (r) values suggest that we need more study to set threshold values according to the using methods with clinical outcome.

A Case of Perianal Abscess due to Panton-Valentine Leukocidin Positive Community-Associated Methicillin-Resistant Staphylococcus aureus : Report in Korea and Literature Review from the Far East

Community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) with Panton-Valentine leukocidin (PVL) genes have recently emerged worldwide, but infections due to PVL carrying CA-MRSA strains have never been reported in Korea. We report a case of extensive perianal abscess due to PVL+ CA-MRSA in a 76-year-old Korean female patient, of which genetic background was very close to USA300. It belonged to staphylococcal cassette chromosome mec element (SCCmec) type IV, ST8 of multilocus sequence typing (MLST), type 1 spa type, and accessory gene regulator locus (agr) group I. Comprehensive literature reviews from the Far East showed molecular characteristics were diverse and PVL genes were infrequently found than in western countries.

A Case of Pneumatosis Cystoides Intestinalis in an Allogenic Stem Cell Transplant Recipient Who had Bronchiolitis Obliterans and Pulmonary Infection by Mycobacterium abscessus

Hematopoietic stem cell transplantation (HSCT) can cause various complications involving lung, liver, intestine and other organs. Chemotherapy, radiation therapy, and graft-versus-host disease (GVHD) may injure the cells in the intestinal mucosa of HSCT recipients. Pneumatosis cystoides intestinalis (PI) is a condition that presence of air in the bowel wall is demonstrated by radiologic or pathologic tests. It is one of the infrequent complications after HSCT and is associated with several medical and surgical conditions. However its pathogenesis and definite etiologic factors are still unknown. Here, we present a case of PI in a HSCT recipient, who was diagnosed of bronchiolitis obliterance accompanied with chronic GVHD and pulmonary disease caused by Mycobacterium abscessus.

Current Antimicrobial Usage for the Management of Neutropenic Fever in Korea: A Nationwide Survey

A nationwide questionnaire-based survey was performed to evaluate the current clinical practices for the management of neutropenic fever in hematology units and hematopoietic stem cell transplantation (HSCT) centers throughout Korea. A 86.9% response rate was obtained from a total of 46 doctors and practical policies of the 33 sites were analysed. Approximately 42.4% and 84.8% of the sites responded that they used oral fluoroquinolone as prophylaxis for neutropenic patients receiving chemotherapy and HSCT, respectively. Additionally, 42.4% of the sites responded that they used antifungal prophylaxis in the chemotherapy groups whereas 90.9% of the sites responded that they used antifungal prophylaxis in HSCT recipients. Approximately half of the responding sites prescribed combination regimen with 3rd or 4th cephalosporin plus aminoglycoside as a first-line therapy. Most of the sites considered persistent fever for 2-4 days or aggravated clinical symptoms for 1-2 days as failure of the first-line regimen, and they changed antibiotics to second- line regimens that varied widely among the sites. Twenty-seven sites (84.4%) responded that they considered adding an antifungal agent when fever persisted for 5-7 days despite antibacterial therapy. Amphotericin B deoxycholate was preferred as a first-line antifungal, which was probably due to the limitations of the national health insurance system. The role of oral antibiotics in the management of neutropenic fever still accounted for a small portion. To the best of our knowledge, this survey is the first report to examine the practical policies currently in place for the management of neutropenic fever in Korea and the results of this survey may help to establish a Korean guideline in the future.

Effects of Antifungal Agents on the Production of Cytokines from Macrophages Stimulated by Aspergillus fumigatus conidia

BACKGROUND: We wanted to evaluate the immunomodulatory effect of three antifungal agents, amphotericin B (AmB), micafungin (MF), itraconazole (ITZ), in the aspect of cytokine production and expression of nuclear factor-kappaB (NF-kappaB) in the Aspergillus fumigatus conidia treated-RAW264.7 cells, a murine alveolar macrophage cell line. MATERIALS AND METHODS: We evaluated cytotoxic effect of antifungal agents using commercial cell proliferation assay. Tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 production according to stimulation (control, A. fumigatus conidia only, conidia + antifungal drug, conidia + antifungal drug + G(M)-CSF) was evaluated and compared each using commercial ELISA method. NF-kappaB activation was evaluated by western blot analysis. RESULTS: AmB, MF, ITZ showed dose-dependent cytotoxic effect on the tested cells. Stimulation of cells by A. fumigatus conidia induced TNF-alpha production. Pretreatment of AmB at concentration not affecting cellular survival did not change the production of TNF-alpha compared to conidia treated cells, but pretreament of MF or ITZ showed reduced amount of TNF-alpha production compared to conidia treated cells. AmB also showed synergistic effect on TNF-alpha production when simultaneously treated with GM-CSF. IL-10 production was markedly increased when the cells were treated with AmB with conidia. MF and ITZ induced less increase of IL-10 production than AmB. AmB also showed synergistic effect on the production of IL-10 when treated with GM-CSF simultaneously. A. fumigatus conidia enhanced expression of NF-kappaB. The degree of NF-kappaB expression was associated with the amount of TNF-alpha and IL-10 produced. CONCLUSION: The antifungal agents we used in this experiment showed that decreased TNF-alpha production and increased IL-10 production from the RAW264.7 cells stimulated by A. fumigatus conidia after pretreatment of antifungal agents. But more studies, such as the association between immunomodulatory effect, antifungal activity and difference of signal pathway of cellular activation according to drugs should be performed.

Distribution of Human Cytomegalovirus gB Genotypes and Its Association with Diseases in Hematopoietic Stem Cell Transplant Recipients in Korea; A Preliminary Report

BACKGROUND: Human cytomegalovirus (HCMV) glycoprotein B (gB) is the major envelope glycoprotein, encoded by the UL55 gene. Based on sequence variation in the UL55 gene, HCMV can be classified into four gB genotypes. Previous studies have suggested an association between HCMV gB genotypes and clinical outcome in the immunocompromised hosts. The goal of this study was to determine the distribution of HCMV gB genotypes and the effect of gB genotype in the developement of HCMV diseases in hematopoietic stem cell transplant (HSCT) recipients in Korea. MATERIALS AND METHODS: DNA was extracted from 94 blood specimen of 52 allogeneic HSCT recipients with HCMV infection. HCMV gB genotype was determined using polymerase chain reaction to amplify a region of UL55, followed by restriction fragment length polymorphism (RFLP) analysis based on RsaI and HinfI digestion. RESULTS: The distribution of gB types were as follows: gB1, 73.1% (38/52) of patients; gB2, 13.5% (7/52); gB3, 1.9% (1/52) and mixed infection (gB1 and gB2), 9.6% (5/52). While gB4 was not detected, a new genotype (described as gB7 by Trincado et al, 2000) was identified on the basis of their RFLP pattern. During average 708 days' follow up period, HCMV diseases developed in 5 patients. All of them had gB1 genotype. There was no statistically significant association between the incidence of HCMV diseases and the gB genotypes. Re-infection with gB1 strain was detected in one patient who had been previously infected with gB2. This episode was associated with fever, elevated liver enzyme and positive antigenemia. CONCLUSION: HCMV gB1 was the dominant genotype and no gB4 was detected in allogeneic HSCT recipients in Korea, which is an unique pattern compared with the previous reports. Although we can not find significant association between the HCMV diseases and the gB genotypes, genotyping of HCMV will serve in the study of pathogenesis and transmission of this virus in transplant patients. Further study is underway with large study population.

A Case of Subacute Infective Endocarditis Caused by Arcanobacterium haemolyticum in a Patient with Mitral Valve Prolapse

Recently, we experienced a case of subacute infective endocarditis caused by A. haemolyticum on mitral valve prolapse complicated with systemic emboli, which was successfully treated with antibiotics and valve replacement surgery. To our knowledge, this is the first report to address infective endocarditis caused by A. haemolyticum in a immunocompetent patient who had mitral valve prolapse and survived with successful treatment. Greater awareness of this uncommon organism is needed to make an accurate diagnosis and perform a better clinical management in the early stage of the disease. Recommendation for the treatment of septic A. haemolyticum infections has not been established. Therefore, the treatment should be based on clinical experiences and in vitro susceptibility profiles of the individual strain. The site of infection as well as antimicrobial susceptibility profiles should be considered for appropriate antibiotics choice and decision to perform a surgical intervention.

Effects of Antifungal Agents on the Production of Cytokines from Macrophages Stimulated by Aspergillus fumigatus conidia

BACKGROUND: We wanted to evaluate the immunomodulatory effect of three antifungal agents, amphotericin B (AmB), micafungin (MF), itraconazole (ITZ), in the aspect of cytokine production and expression of nuclear factor-kappaB (NF-kappaB) in the Aspergillus fumigatus conidia treated-RAW264.7 cells, a murine alveolar macrophage cell line. MATERIALS AND METHODS: We evaluated cytotoxic effect of antifungal agents using commercial cell proliferation assay. Tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 production according to stimulation (control, A. fumigatus conidia only, conidia + antifungal drug, conidia + antifungal drug + G(M)-CSF) was evaluated and compared each using commercial ELISA method. NF-kappaB activation was evaluated by western blot analysis. RESULTS: AmB, MF, ITZ showed dose-dependent cytotoxic effect on the tested cells. Stimulation of cells by A. fumigatus conidia induced TNF-alpha production. Pretreatment of AmB at concentration not affecting cellular survival did not change the production of TNF-alpha compared to conidia treated cells, but pretreament of MF or ITZ showed reduced amount of TNF-alpha production compared to conidia treated cells. AmB also showed synergistic effect on TNF-alpha production when simultaneously treated with GM-CSF. IL-10 production was markedly increased when the cells were treated with AmB with conidia. MF and ITZ induced less increase of IL-10 production than AmB. AmB also showed synergistic effect on the production of IL-10 when treated with GM-CSF simultaneously. A. fumigatus conidia enhanced expression of NF-kappaB. The degree of NF-kappaB expression was associated with the amount of TNF-alpha and IL-10 produced. CONCLUSION: The antifungal agents we used in this experiment showed that decreased TNF-alpha production and increased IL-10 production from the RAW264.7 cells stimulated by A. fumigatus conidia after pretreatment of antifungal agents. But more studies, such as the association between immunomodulatory effect, antifungal activity and difference of signal pathway of cellular activation according to drugs should be performed.

Distribution of Human Cytomegalovirus gB Genotypes and Its Association with Diseases in Hematopoietic Stem Cell Transplant Recipients in Korea; A Preliminary Report

BACKGROUND: Human cytomegalovirus (HCMV) glycoprotein B (gB) is the major envelope glycoprotein, encoded by the UL55 gene. Based on sequence variation in the UL55 gene, HCMV can be classified into four gB genotypes. Previous studies have suggested an association between HCMV gB genotypes and clinical outcome in the immunocompromised hosts. The goal of this study was to determine the distribution of HCMV gB genotypes and the effect of gB genotype in the developement of HCMV diseases in hematopoietic stem cell transplant (HSCT) recipients in Korea. MATERIALS AND METHODS: DNA was extracted from 94 blood specimen of 52 allogeneic HSCT recipients with HCMV infection. HCMV gB genotype was determined using polymerase chain reaction to amplify a region of UL55, followed by restriction fragment length polymorphism (RFLP) analysis based on RsaI and HinfI digestion. RESULTS: The distribution of gB types were as follows: gB1, 73.1% (38/52) of patients; gB2, 13.5% (7/52); gB3, 1.9% (1/52) and mixed infection (gB1 and gB2), 9.6% (5/52). While gB4 was not detected, a new genotype (described as gB7 by Trincado et al, 2000) was identified on the basis of their RFLP pattern. During average 708 days' follow up period, HCMV diseases developed in 5 patients. All of them had gB1 genotype. There was no statistically significant association between the incidence of HCMV diseases and the gB genotypes. Re-infection with gB1 strain was detected in one patient who had been previously infected with gB2. This episode was associated with fever, elevated liver enzyme and positive antigenemia. CONCLUSION: HCMV gB1 was the dominant genotype and no gB4 was detected in allogeneic HSCT recipients in Korea, which is an unique pattern compared with the previous reports. Although we can not find significant association between the HCMV diseases and the gB genotypes, genotyping of HCMV will serve in the study of pathogenesis and transmission of this virus in transplant patients. Further study is underway with large study population.