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배경: Systemic corticosteroids have become the standard of care for patients with severe to critical coronavirus disease 2019 (COVID-19). However, the real-world efficacy and safety outcomes of a higher dose of corticosteroids remain uncertain. This study aimed to determine the impact of higher dose corticosteroids on the survival and development of COVID-19-associated pulmonary aspergillosis (CAPA). 방법: We conducted a nationwide, population-based study using the National Health Information Database between January 2020 and June 2021. Adult patients with severe to critical COVID-19 were enrolled. The high-dose corticosteroid group included patients who received more than 60 mg of dexamethasone or an equivalent dose over 10 days. Analyses were performed using both a propensity-score matched cohort and an entire cohort. 결과: During the study period, 102,304 patients were screened, 10,417 met the eligibility criteria, and 2,457 were successfully matched. High-dose corticosteroid use significantly reduced all-cause mortality at 28 days (hazard ratios [HRs], 0.543; confidence intervals [CIs], 0.475–0.619), but increased the risk of CAPA (HRs, 5.824; CIs, 2.260–15.008). As a prespecified exploratory outcome, all-cause mortality at 90 days was lower and mechanical ventilation (MV) free days at 28 days were longer in the high-dose corticosteroid group (all p < 0.05). However, there was no difference in the rate of MV applying at 28 days, and all-cause mortality according to the development of CAPA. 결론: Among patients with severe to critical COVID-19, higher dose corticosteroids resulted in a decrease in all-cause mortality at 28 and 90 days but the risk of CAPA development increased. Clinical awareness and active surveillance for CAPA should be needed to avoid associated unfavorable outcomes. [ABSTRACT FROM AUTHOR]

배경 Fusarium is a filamentous fungus, found in soil, water and plants. Fusarium is mostly harmless but some species cause opportunistic infection in the setting of immunosuppression. Disseminated Fusarium infection is fatal in neutropenic host, antifungal susceptibility is not well established, and some species are known to be resistant to all available antifungal agents. 방법 We retrospectively reviewed the electronical medical record of patients with culture-proven Fusarium infections at Seoul St Mary’s hospital from October 2012 through December 2021. Invasive fusariosis was defined according to the consensus of invasive fungal disease published in 2019 by the European Organization for Research and Treatment of Cancer and the Mycoses Study Group. 결과 We identified 19 cases of hematologic malignancy patients with invasive fusariosis. We found 12 cases of Fusarium fungemia. In the other 7 cases, Fusarium was isolated from specimen other than blood, such as anterior chamber aspiration, paranasal sinus, skin and sputum, and those cases were accom- panied with sign of infection attributable to Fusarium. The median age of patients was 57 years, 68.4% (13 cases) were male. The most common underlying hematologic disease was acute myeloid leukemia (63.2%, 12 cases). Among 19 cases, 57.9% (11 cases) were due to Fusarium solani, and 36.7 % (7 cases) were associated with non-solani Fusarium. Seven patients were coinfected with other fungi, mainly Aspergillus (31.6%, 6 cases). Overall mortality rate was 78.9% (15 cases), in which 26.3% (5 cases) were associated with fusariosis. We tested the minimum inhibitory concentrations (MIC) of antifungal agents in 8 available clinical isolates. For Fusarium solani species, MIC ranges were 4~16 ㎍/㎖ for voriconazole, 8~64 ㎍/㎖ for isavuconazium, and 1~32 ㎍/㎖ for amphotericin B. In non-solani Fusarium species, MIC ranges were 1~32 ㎍/㎖ for voriconazole, 2~64 ㎍/㎖ for isavuconazium and 2~4 ㎍/㎖ for amphotericin B. The activity of posaconazole was shown to be limited in both Fusarium solani and non-solani Fusarium species with an MIC50 of 64 ㎍/㎖. 결론 Invasive fusariosis is a life-threatening infection to immunocompromised host. Fusarium exhibits high MIC to antifungal agents. Further study with large number of patients and clinical isolates is necessary [ABSTRACT FROM AUTHOR]

배경: Letermovir is used for cytomegalovirus (CMV) prophylaxis in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Letermovir should be initiated on D0~28 in CMV-seropositive recipient with undetectable plasma CMV DNA within 5 days, until D100 after HSCT. We evaluate the impact of early letermovir prophylaxis on the incidence of clinically significant CMV infection (CS-CMVi). 방법: Retrospective review was performed for allo-HSCT recipients from NOV 2020 to OCT 2021 at Seoul St. Mary’s Hospital. Blood CMV RQ-PCR was checked biweekly during hospitalization and at every visit after discharge. CS-CMVi, CMV end-organ disease, CMV blips were evaluated at week 24 after HSCT. We compared incidence of CS-CMVi in early prophylaxis group (D0~D3) with late prophylaxis group (D4~D28). 결과: A total of 358 patients underwent allo-HSCT, of which 306 received letermovir prophylaxis. Among 306 patients, 145 (47.4%) had high risk of CMV reactivation, and 206 patients (67.3%) started letermovir prophylaxis at D0~D3 after HSCT. The median day of letermovir initiation in our study was day 2 (range 0~27). At week 24, there were 96 patients (31.4%) with CS-CMVi, 20 (6.5%) had CMV end organ disease, and CMV blips were observed in 64 (20.9%) patients. In high risk group (n=145), CS-CMVi was developed in 30/96 (31.2%) and 20/49 (40.8%) of patients (p=0.289) in early and late prophylaxis group, respectively. CMV-related mortality was 1.0% at week 24. 결론: Letermovir prophylaxis is effective in preventing CMV infection in seropositive allo-HSCT recipients. Early initiation of letermovir did not have significant difference in incidence of CS-CMVi compared to late prophylaxis. However early prophylaxis showed lower incidence in high risk group. Further studies are needed for longer follow up duration, including timing of prophylaxis according to risk of CMV reactivation. [ABSTRACT FROM AUTHOR]

Dasatinib, a tyrosine kinase inhibitor, is widely used for patients with chronic myeloid leukemia and Philadelphia chromosome- positive acute lymphoblastic leukemia. Although the drug has a potent immunosuppressive effect, infectious complications during dasatinib treatment have been reported rarely. We describe five patients who developed cytomegalovirus (CMV) colitis during dasatinib treatment, in whom the colitis was initially confused with other causes. The patients, three with chronic myeloid leukemia, and two with acute lymphoblastic leukemia, were diagnosed with CMV colitis based on endoscopic and histologic findings. The patients who examined blood CMV polymerase chain reaction were all positive. The patients received antiviral therapy in the form of either ganciclovir or valganciclovir, and the overall treatment outcome was fair. These cases suggest that physicians should consider the possibility of CMV reactivation when treating diarrhea and/or hematochezia in patients on dasatinib. [ABSTRACT FROM AUTHOR]

Non-tuberculous mycobacterial (NTM) disease is a relatively rare cause of neutropenic fever in patients with hematologic malignancies. During the neutropenic period, performing invasive procedures for microbiological or pathological confirmation is difficult. In addition, the optimal treatment duration for NTM disease in patients with leukemia, especially prior to stem cell transplantation (SCT), has not been documented. Therefore, we report a case of pneumonia with necrotizing lymphadenitis caused by Mycobacterium kansasii diagnosed during chemotherapy being performed for acute myeloid leukemia. The radiologic findings were similar to those of invasive fungal pneumonia; however, a bronchoalveolar washing fluid culture confirmed that the pathogen was M. kansasii. After 70 days from starting NTM treatment, allogeneic SCT was performed without any complications. The patient fully recovered after 12 months of NTM treatment, and neither reactivation of M. kansasii infection nor related complications were reported. [ABSTRACT FROM AUTHOR]

배경: Invasive mucormycosis (IM) are increasing worldwide according to the profound immune suppression and use of broad spectrum antifungal agents. The aim of this study was to determine the characteristics of IM, and also analyzed clinical courses and outcomes of patients with hematologic diseases. 방법: We retrospectively reviewed all consecutive proven or probable (PP-) IM cases between Jan. 2011 and Mar. 2022 in a cohort of invasive fungal diseases (IFDs) at Seoul St. Mary’s Hospital, Seoul, Korea. 결과: During the study period, a total of 44 cases of PP-IM were identified. Median age was 55 year-old and 59% were male. Most common underlying diseases were acute myelogenous leukemia (n=17), followed by acute lymphocytic leukemia (n=9). Primary infection site was lung (n=30), followed by paranasal sinus (n=8), intestines (n=4), and skin and soft tissue (n=2). Disseminated infection was found in 27% of patients. Anti-mold active antifungal agents were administered in 23% of patients with median duration of 32 (range 13–95) days prior to the diagnosis of IM. There were 16 isolates from 15 culture-positive PP-IM patients; Rhizopus sp. (n=4), Rhizomucor sp. (n=4), Cunninghamella sp. (n=3), Paecilomyces sp. (n=3), Lichthemia sp. (n=2). Coinfection with PP-invasive aspergillosis (IA) was found in 25% of patients. Surgery was performed concurrently in 75% of patients. Survival rate at 100-d was 66%. Surgery was performed in 42% and 86% in deceased and survivor group at 6-wks, respectively. Fifteen patients received subsequent chemotherapy (CTx) or hematopoietic cell transplantation (HCT) after the diagnosis of IM. Among them, 11 were survived, while four patients died from infectious complication other than IFD. Two patients started CTx within one month from the surgical resection of pulmonary IM, who recovered without any complications. 결론: IM shows high mortality rate. IM and IA coinfection is not rare. In cases with successful surgical resection of IM, subsequent CTx or HCT can be considered. [ABSTRACT FROM AUTHOR]

Background: Stenotrophomonas maltophilia causes serious infections in immunocompromised hosts. Here, we analyzed the clinical characteristics of S. maltophilia bloodstream infection (BSI) in patients with hematologic malignancies and evaluated in vitro synergistic effects of antimicrobial combinations. Methods: We retrospectively reviewed all consecutive episodes of S. maltophilia BSIs in adult hematologic patients from June 2009 to May 2014, with in vitro susceptibility and synergy tests using high-throughput bioluminescence assay performed for available clinical isolates. Results: Among 11,004 admissions during 5-year period, 31 cases were identified as S. maltophilia BSIs. The incidence rate of S. maltophilia BSI was 0.134 cases/1,000 patient-days. Overall and attributable mortality of S. maltophilia BSI was 64.5% and 38.7%, respectively. Severe neutropenia (adjusted hazard ratio [HR] 5.24, p =0.013), shock at the onset of BSI (adjusted HR 6.05, p <0.001), and pneumonia (adjusted HR 3.15, p =0.017) were independent risk factors for mortality. In vitro susceptibilities to ceftazidime, levofloxacin, ticarcillin-clavulanic acid (TIM) and trimethoprim-sulfamethoxazole (SXT) were 11.1%, 44.0%, 40.7%, and 88.9%, respectively. MIC50/MIC90 for moxifloxacin and tigecycline were 1/4 mg/L and 4/8 mg/L. The 50% and 90% fractional inhibitory concentrations (FIC50/FIC90) of clinical isolates against a combination of SXT and TIM were 0.500/0.750. For SXT plus levofloxacin or moxifloxacin, FIC50/FIC90 were 0.625/1.000 and 0.625/0.625, respectively. Conclusion: S. maltophilia BSIs show high mortality, which is related to severe neutropenia, shock, and S. maltophilia pneumonia. Based upon drug susceptibility testing, the primary treatment of choice for S. maltophilia BSIs should be SXT in hematologic patients, rather than quinolones, with combination therapies including SXT serving as a feasible treatment option. [ABSTRACT FROM AUTHOR]

Human infection caused by Shewanella algae is rare, which usually occurred after direct contact with seawater or ingestion of raw seafood in the immunocompromised host. There have been anecdotal reports about Shewanella infections in human, but their pathogenic role and microbiologic data are limited. Here, we report a fatal case of spontaneous bacterial peritonitis with bacteremia due to S. algae in a 57-year-old male with liver cirrhosis who had no history of exposure to seawater or raw seafood. Polymicrobial infection with Streptococcus mitis and Escherichia coli was combined and the patient died in spite of early appropriate antimicrobial therapy and early goal-directed therapy for sepsis. [ABSTRACT FROM AUTHOR]

Most cases of gas gangrene caused by Clostridium species begin with trauma-related injuries but in rare cases, spontaneous gas gangrene (SGG) can occur when patients have conditions such as advanced malignancy, diabetes, or immunosuppression. Clostridium perfringens, a rare cause of SGG, exists as normal flora of skin and intestines of human. Adequate antibiotics with surgical debridement of infected tissue is the only curative therapeutic management. Mortality rate among adults is reported range of 67-100% and majority of deaths are occurred within 24 hours of onset. We experienced a case of SGG on the trunk, buttock and thigh in a neutropenic patient with acute lymphoblastic leukemia. His clinical course was rapid and fatal during pre-engraftment neutropenic period of allogeneic stem cell transplantation. [ABSTRACT FROM AUTHOR]

Sepsis remains a leading cause of death in critically ill patients, despite efforts to improve patient outcome. Thus far, no magic drugs exist for severe sepsis and septic shock. Instead, early diagnosis and prompt initial management such as early goal-directed therapy are key to improve sepsis outcome. For early detection of sepsis, biological markers (biomarkers) can help clinicians to distinguish infection from host response to inflammation. Ideally, biomarkers can be used for risk stratification, diagnosis, monitoring of treatment responses, and outcome prediction. More than 170 biomarkers have been identified as useful for evaluating sepsis, including C-reactive protein, procalcitonin, various cytokines, and cell surface markers. Recently, studies have reported on the usefulness of biomarker-guided antibiotic stewardships. However, the other side of these numerous biomarkers is that no novel single laboratory marker can diagnose, predict, and track the treatment of sepsis. The purpose of this review is to summarize several key biomarkers from recent sepsis studies [ABSTRACT FROM AUTHOR]

Background Vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI) is generally associated with the delayed administration of adequate antibiotics. The identification of risk factors and outcomes of VRE BSI is necessary for establishing strategies for managing neutropenic fever in patients with hematological malignancies. Methods We retrospectively analysed consecutive cases of enterococcal BSI in patients with neutropenia after chemotherapy or stem cell transplantation between July 2009 and December 2011 at a single center. Results During the 30-month period, among 1,587 neutropenic patients, the incidence rate of enterococcal BSI was 1.76 cases per 1,000 person-days. Of the 91 enterococcal BSIs, there were 24 cases of VRE. VRE BSI was associated with E. faecium infection (P < .001), prolonged hospitalization (P = .025) and delayed administration (⩾48 hours after the febrile episode) of adequate antibiotics (P = .002). The attributable mortality was 17% and 9% for VRE and vancomycin-susceptible Enterococcus (VSE), respectively (P = .447). The 30-day crude mortality was 27% and 23% for VRE and VSE, respectively (OR 1.38, 95% CI 0.53- 3.59; P = .059). Only SAPS-II was an independent predictive factor for death (adjusted OR 1.12, 95% CI 1.08-1.17; P < .001). Conclusions In conclusion, vancomycin resistance showed some trend towards increasing 30-day mortality, but is not statistically significant despite the delayed use of adequate antibiotics (⩾48 hours). Only underlying severity of medical condition predicts poor outcome in a relatively homogeneous group of neutropenic patients. [ABSTRACT FROM AUTHOR]

배경 Rapid and accurate detection of bacterial pathogen is crusial to make shorten time to proper antibacterial therapy especially in immunocompromised host. The aim of this study was to evaluate the performance of newly developed multiplex ligation-dependent probe amplification (MLPA) and capillary electrophoresis (CE) based single-strand conformation polymorphism (SSCP) system to detect bacteria from blood of febrile neutropenic patients. 방법 This was a prospective study performed at Catholic Hematology Hospital between Jan. to Sep. 2017. The MLPA-CE-SSCP system, previously designed to target several major Gram positive and negative bacterial species (nuc and mecA for Staphylococcus aureus; lytA for Streptococcus pneumoniae; sodA and vanA for Enterococcus faecium; uidA and lacY for Shigella species and/or Escherichia coli; phoE for Klebsiella pneumoniae; ecfX for Pseudomonas aeruginosa; ompA for Acinetobacter baumannii) and resistance genes (blaTEM, blaSHV, blaCTX-M group 1, blaIMP, and blaNDM-1) were tested for blood sampled simultaneously with blood culture. 결과 Among 540 blood samples obtained peripherally or centrally from 283 febrile episodes in 104 patients, bacteremia was identified from 126 samples through automated culture system. Among them, 88 pathogens from 87 samples corresponded to MLPA targets; E. coli (n=50) was the most common (ESBL E. coli, n=17), followed by 16 K. pneumoniae (ESBL K. pneumoniae, n=4), 9 E. faecium (vancomycin-resistant, n=3), 6 P. aeruginosa, 5 S. aureus (methicillin-susceptible, n=5), 1 S. pneumoniae, and 1 A. baumannii. Positive predictive value (PPV) and false positive (FP) proportion of MLPA-CE-SSCP method was 85.1% and 14.9%, respectively. FP samples (n=13) were all in the following cases; follow-up blood culture after the previous (≤7 days) bacteremia (n=6), positive in another simultaneous set of blood cultures (n=5), or during ciprofloxacin prophylaxis (n=2). Sensitivity, specificity, and negative predictive value (NPV) of MLPA-CE-SSCP method was 84.1%, 97.1%, and 96.9%. The concordance rate and NPV for detecting resistance was 77.2% and 100%, respectively. Time to final result was shorter (≤ 8h) than automated system (median 47h 30m; range 25h 7m-152h 49m). 결론 The newly MLPA-CE-SSCP system could help early detection of clinically important bacterial pathogen and common resistance in febrile neutropenic patients. Further improvement and optimization are needed for wide use of nucleic acid detection methods in clinical fields. [ABSTRACT FROM AUTHOR]

Schizophyllum commune is a mold in phylum Basidiomycota and is an uncommon human pathogen. Sinusitis and allergic bronchopulmonary mycosis are the two major diseases caused by S. commune. Although there have been several reports of invasive fungal diseases, most of them were invasive sinusitis. We present a case of invasive fungal pneumonia due to S. commune, developed in a patient with acute myeloid leukemia presenting neutropenic fever. The diagnosis was made by characteristic macroscopic and microscopic findings of fungal isolate and was confirmed via sequencing of internal transcribed spacer region. The patient was improved after 8 weeks of antifungal therapy based on the susceptibility result. We propose that S. commune should be considered as an emerging pathogen of invasive fungal pneumonia when a patient is under immunocompromised state. We also reviewed global literatures focused on the invasive fungal diseases caused by S. commune. [ABSTRACT FROM AUTHOR]

배경: Candidemia is the most common form of invasive candidiasis and is still associated with high mortality rates in immunocompromised patients. It is known that the distribution of Candida species can be varied according to the region and patient group. Recently, active antifungal prophylaxis has been increased in patients with hematologic diseases, which might influence the characteristics of candidemia. Therefore, we aimed to assess the characteristics of candidemia including species distribution, antifungal resistance, and outcomes of patients. 방법: A retrospective data review was performed at the Catholic Hematology Hospital from August 2011 to November 2021. Candidemia was defined as at least one positive blood culture for Candida sp. Different episodes of candidemia in the same patient were counted independently. Only the initial Candida isolate was included within an episode. Two or more documented species of Candida were all counted independently. 결과: A total of 155 candidemia episodes were identified from 150 patients and demographics are shown in Table 1. 62 Patients (41.3%) were neutropenic state (ANC <500cells/µL) when diagnosed as candidemia and catheter-related origin was the most common secondary cause with 46 patients (30.7%). Candida species found are reported in Table 2, 38 cases (24.5%) of candidemia were caused by C. albicans and 117 cases (75.5%) by non-albicans species. Among non-Candida albicans sp., C. tropicalis was most common (36.8%). Most common species was C. tropicalis (36.8%), followed by C. albicans (24.5%), C. glabrata (15.5%), C. krusei (10.3%). The results of antifungal susceptibility are shown in Table 3. Overall mortality rate at 28-day was 40%. 결론: In this study, C. tropicalis is the most common species in patients with hematologic disease and non-albicans Candida sp. accounted for three-fourths of candidemia. Mortality rate is still high despite treatment and appropriate treatment strategy should be decided regarding the distribution and resistance pattern. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 46 year young woman suffering from acute myeloid leukemia who was admitted for the treatment of grade III acute graft-versus-host disease (GVHD). Topics discussed includes fluconazole treatment during which extracellular and intracellular budding yeast cells were fortuitously identified on peripheral blood smear, diagnosis and antifungal treatment's impact on prognosis of candidemia in immunocompromised patients.

배경 Prolonged use of antibiotics and mucosal injury by intensive chemotherapy are important risk factors for Enterococcal infection in patients with acute leukemia. This study aimed to identify the changes in the epidemiology of Enterococcal bloodstream infection (BSI) and to investigate the impact of Enterococcal BSI on long-term outcome in patients with acute leukemia. 방법 All adult acute leukemia patients diagnosed with Enterococcal BSI (N = 512) between 2014 to 2018 at the Catholic Hematology Hospital were retrospectively reviewed. During the study period, the new institutional strategy of restricting fluoroquinolone prophylaxis and saving carbapenem applied since OCT 2016. The incidence rate was assessed with antibiotics consumption and multivariable models were used to estimate the impact of vancomycin-resistant Enterococcal BSI on the outcome. 결과 During the study period, 512 Enterococcal BSI cases were identified in 433 patients: 172 (33.6%) were vancomycin-resistant Enterococcus (VRE). There was no difference in baseline characteristics between VRE and vancomycin-susceptible Enterococcus BSI. The incidence rate of VRE decreased for 6 months after the strategy change (39.2% vs 12.2%, Odds ratio [OR]=0.312, 95% confidence interval [CI], 0.116-0.843, p=0.018). However, the incidence rate showed increasing trend with the increased use of total antibiotics consumption. VRE BSI was associated with higher 100-day mortality than VSE BSI after adjusting for covariates (hazard ratio [HR]=1.477; 95% CI, 1.027-2.125, p=0.035), but there was no difference in long-term outcome at one year. In multivariable models, high-risk groups such as 60 years or older, advanced stage of disease, polymicrobial BSI, high Pitt bacteremia score, and BSI complications in hematopoietic cell transplantation recipient were strongly associated with worse overall mortality at one year (p<0.05 for all variables). 결론 The incidence of Enterococcal BSI is closely related to the total antibiotics consumption and it has a worse impact on the long-term outcome in high-risk groups. Restricting the use of prophylactic fluoroquinolone and carbapenem alone is not sufficient to reduce total antibiotics consumption but also Enterococcal BSI. Multidisciplinary interventions to reduce the overall use of antibiotics are needed. [ABSTRACT FROM AUTHOR]

Lateral flow assays (LFAs) have emerged as indispensable tools for point-of-care testing during the pandemic era. However, the interpretation of results through unassisted visual inspection by untrained individuals poses inherent limitations. In our study, we propose a novel approach that combines computer vision (CV) and lightweight machine learning (ML) to overcome these limitations and significantly enhance the performance of LFAs. By incorporating CV-assisted analysis into the LFA assay, we achieved a remarkable three-fold improvement in analytical sensitivity for detecting Influenza A and for SARS-CoV-2 detection. The obtained R² values reached approximately 0.95, respectively, demonstrating the effectiveness of our approach. Moreover, the integration of CV techniques with LFAs resulted in a substantial amplification of the colorimetric signal specifically for COVID-19 positive patient samples. Our proposed approach, which incorporates a simple machine learning algorithm, provides substantial enhancements in assay sensitivity, improving diagnostic efficacy and accessibility of point-of-care testing without requiring significant additional resources. Moreover, the simplicity of the machine learning algorithm enables its standalone use on a mobile phone, further enhancing its practicality for point-of-care testing. [ABSTRACT FROM AUTHOR]

배경 Varicella-Zoster virus (VZV) reactivation is one of the most frequent opportunistic infections after allogeneic hematopoietic stem cell transplantation (HSCT). To prevent VZV reactivation, acyclovir prophylaxis have been administered. Although incidence of VZV reactivation decreased after acyclovir prophylaxis, there is no consensus regarding dose and duration of therapy, also adverse drug reactions (ADRs). In this study, we analyzed allogeneic HSCT recipients with acyclovir prophylaxis to establish dosing regimens and duration for VZV prevention. 방법 We retrospectively reviewed medical records until June 30, 2020 of patients who underwent allogeneic HSCT between January 2018 and March 2019. Patients aged ≥17 years and with hematologic malignancies were included. Acyclovir was given 800 mg/d orally until 1 year after transplantation. Half-dose reduction was done if ADRs occured, such as neutropenia, thrombocytopenia, kidney injury, and liver injury. Early withdrawal was done if there were death, relapse of underlying malignancy, or severe ADRs. 결과 Among 383 eligible patients, 69 (18%) had VZV reactivation. 2 of 69 VZV reactivated (2%) had 2 episodes. 199 patients (52%) fulfilled 1-year prophylaxis. 108 patients (28%) had reduced dose of acyclovir. The reasons of dose reduction were neutropenia (36, 33%), thrombocytopenia (8, 7%), acute kidney injury (AKI) (52, 48%), hepatic injury (2, 2%), multiple reasons (2, 2%), and other (5, 5%). 7 of 69 VZV reactivation (10%) got reactivation while taking acyclovir, 3 of them took immunosuppressive therapy (IST) at reactivation. Cumulative incidence of VZV reactivation was 8.22±1.61% at 1 year after HSCT, and 31.52±3.53% at 2 years. There were no statistically significant differences of incidence between full dose (8.29±1.94% at 1 year, 25.4±5.49% at 2 years) and reduced dose groups (8.02±2.91% at 1 year, 25.4±5.49% at 2 years, p=0.742). In 199 patients fulfilled 1-year-prophylaxis, 42 (21%) had VZV reactivation. 8 of them had IST at reactivation. 결론 The incidence of VZV reactivation was reduced during prophylaxis, but increased stiffly after 1-year of prophylaxis. Further research is needed to determine whether to prolong the duration of prophylaxis. There was no statistically significant differences of VZV reactivation incidence between full dose and reduced dose of acyclovir. Therefore, when ADRs were suspected, reduced dose of acyclovir (400mg/day) could be used effectively for prophylaxis of VZV reactivation. [ABSTRACT FROM AUTHOR]

Primary sternal osteomyelitis (PSO) is a rare condition that may develop without any contiguous focus of infection. Due to the rarity of the disease, early diagnosis and appropriate treatment are often delayed. Herein, we describe a patient with PSO caused by Staphylococcus aureus that presented with chest pain and fever. The patient had no predisposing factors for sternal osteomyelitis. The chest pain was thought to be non-cardiogenic, as electrocardiography and cardiac enzyme did not reveal ischemic changes when he visited the emergency room. After blood culture revealed the presence of S. aureus, every effort was made to identify the primary focus of infection. Bone scan and magnetic resonance imaging revealed osteomyelitis with soft tissue inflammation around the sternum. After 8 weeks of antibiotics treatment, the patient recovered without any complications. [ABSTRACT FROM AUTHOR]

Background: Carbapenemase-producing Enterobacteriaceae (CPE) are Gram-negative bacteria with increasing prevalence of infection worldwide. In Korea, 25 cases of CPE isolates were reported by the Korea Centers for Disease Control and Prevention in 2011. Most CPE cases were detected mainly at tertiary referral hospitals. We analyzed the prevalence and risk factors for carbapenem-resistant Enterobacteriaceae (CRE) in a mid-sized community-based hospital in Korea. Materials and Methods: We retrospectively analyzed all consecutive episodes of Enterobacteriaceae in a mid-sized community-based hospital from January 2013 to February 2014. CRE was defined as organisms of Enterobacteriaceae showing decreased susceptibility to carbapenems. Risk factors for CRE were evaluated by a case–double control design. Carbapenemase was confirmed for CRE using a combined disc test. Results: During 229,710 patient-days, 2,510 Enterobacteriaceae isolates were obtained. A total of 41 (1.6%) CRE isolates were enrolled in the study period. Thirteen species (31.7%) were Enterobacter aerogenes, 8 (19.5%) Klebsiella pneumoniae, 5 (12.2%) Enterobacter cloacae, and 15 other species of Enterobacteriaceae, respectively. Among the 41 isolates, only one (2.4%) E. aerogenes isolate belonged to CPE. For evaluation of risk factors, a total of 111 patients were enrolled and this included 37 patients in the CRE group, 37 in control group I (identical species), and 37 in control group II (different species). Based on multivariate analysis, regularly visiting the outpatient clinic was a risk factor for CRE acquisition in the control group I (P = 0.003), while vascular catheter and Charlson comorbidity index score ≥ 3 were risk factors in control group II (P = 0.010 and 0.011, each). Patients with CRE were more likely to experience a reduced level of consciousness, use a vasopressor, be under intensive care, and suffer from acute kidney injury. However, CRE was not an independent predictor of mortality compared with both control groups. Conclusion: In conclusion, the prevalence of CRE was higher than expected in a mid-sized community-based hospital in Korea. CRE should be considered when patients have a vascular catheter, high comorbidity score, and regular visits to the outpatient clinic. This study suggests the need for appropriate prevention efforts and constant attention to CRE infection control in a mid-sized community-based hospital. [ABSTRACT FROM AUTHOR]

Background: Patients with hematologic diseases are at high risk of bloodstream infections (BSIs). This study aimed to analyze clinical features and distributions of microorganisms in patients with hematologic diseases presenting at a tertiary care university-affiliated hospital in Korea. Materials and Methods: We retrospectively reviewed all BSI episodes recorded in patient medical records at two hematologic wards of the Catholic Hematology Hospital from January to December 2020. Our aim was to analyze demographic and clinical characteristics relevant to BSIs. We also described the antimicrobial resistance patterns of the major pathogens identified in this study, and evaluated risk factors for extended-spectrum beta-lactamase (ESBL) production in Enterobacteriaceae isolates and for vancomycin resistance in enterococcal isolates. Results: A total of 380 BSI episodes were identified in 334 patients over the course of 1 year (monomicrobial BSI episodes, 86.1%; polymicrobial BSI episodes, 13.9%). Gram-negative bacteria accounted for 242 isolates (54.8%). The most frequently isolated Gram-negative bacteria isolates were Escherichia coli (107 [24.2%]) followed by Klebsiella spp. (72 [16.3%]), Pseudomonas spp. (21 [4.8%]), and Enterobacter spp. (12 [2.7%]). The most commonly identified Gram-positive bacteria were Enterococcus spp. (72 [16.3%]) followed by viridans streptococci (54 [12.2%]), coagulase-negative staphylococci (CoNS) (24 [5.4%]), and Corynebacterium spp. (22 [5.0%]). ESBL-producing Enterobacteriaceae accounted for 25.1% of the total distribution. Among 54 Enterococcus faecium isolates, 100.0% were resistant to ampicillin and 55.6% showed resistance to vancomycin, while 100.0% (n = 12) of Enterococcus faecalis isolates were susceptible to ampicillin and vancomycin, respectively. Use of ciprofloxacin prophylaxis (odds ratio: 5.20; 95% confidence interval: 1.11 - 24.34; P = 0.04) was an independent risk factor for ESBL production in Enterobacteriaceae BSIs. Conclusion: Compared with the results of a previous study conducted at the same institution, our findings demonstrated that Gram-negative bacteria remained dominant pathogens in BSIs occurring in patients with hematologic diseases. Our findings also demonstrated a comparatively decreased prevalence of ESBL-producing Enterobacteriaceae in the evaluated BSIs. However, the prevalence of enterococcal BSIs had not decreased, and the proportion of vancomycin-resistant Enterococcus isolates from E. faecium BSIs had increased. In addition, we found that ciprofloxacin prophylaxis was statistically significantly associated with ESBL production in Enterobacteriaceae BSIs. We conclude that, in order to avoid critical complications and to reduce the burden of antimicrobial-resistant organisms in patients with hematologic diseases, it is necessary to conduct periodic examinations evaluating changes in BSI epidemiology within a single medical center. [ABSTRACT FROM AUTHOR]

배경 Immunocompromised patients with hematologic malignancies are at high risk of mortality from bloodstream infections (BSIs). The aim of this study is to analyze clinical features and distribution of micro- organisms isolated from the bloodstream infection episodes in patients with hematologic malignancies at a tertiary care university hospital in Republic of Korea over one year. 방법 We retrospectively reviewed all consecutive episodes of bloodstream infections including the medical re- cords to analyze demographic and clinical characteristics from January 2020 to December 2020 from two hematologic wards at the Catholic Medical Center. 결과 380 bloodstream infection episodes were identified from 334 patients over one year. 184 (48.4%) were male patients, and median age was 53 (18-78). 367 (96.6%) of the BSI episodes occurred at neutropenic state, and the median CRP level was 14.7 mg/dL (0.83-45.17). 40 (10.5%) cases required ICU care, and 36 (9.5%) cases developed septic shock. 71 (18.7%) cases used prophylactic ciprofloxacin before the onset of BSI. Polymicrobial BSI accounted for 53 (13.9%) cases, and in-hospital and/or 28-day mortality were 50 (13.2%) episodes. Gram-negative bacteria predominated (54.8%) with Escherichia coli (24.2%) and Klebsiella spp. (16.3%) as the most common pathogens. Enterococcus spp. (16.3%) and Viridans streptococci (12.2%) were the most common gram-positive bacteria (44.3%) isolated from the bloodstream infection episodes. 결론 Gram-negative bacteria were dominant causative BSI organisms in patients with hematologic malig- nancies, Escherichia coli being the leading pathogen of all. Most of the patients had neutropenia at the onset of BSI. [ABSTRACT FROM AUTHOR]

The ichroma Chikungunya virus (CHIKV) IgG/IgM (Boditech Med Inc., Chuncheon, Korea) is a newly developed rapid lateral flow immunoassay for detection of anti- CHIKV-IgG/IgM. This study conducted with thirty-six anti-CHIKV IgG positive sera, 57 anti-CHIKV IgM positive sera and 163 anti-CHIKV IgG/IgM negative sera which were confirmed by commercial enzyme-linked immunosorbent assays (ELISAs) (Inbios CHIKjj Detect™ IgM Capture ELISA, Inbios CHIKjj Detect™ IgG ELISA (InBios International Inc., Seattle, WA, USA), Anti-CHIKV ELISA (IgM), Anti- CHIKV ELISA (IgG) (Euroimmun, Lübeck, Germany)). The ichroma detected all 36 anti-CHIKV IgG and 57 anti-CHIKV IgM positivity (100% sensitivity). For 163 anti-CHIKV IgG/IgM negative sera, the ichroma showed one false positive for IgM (99.4% specificity). The ichroma showed no cross-reactivity and no interference. The ichroma demonstrated good diagnostic performance compared to the current ELISAs. [ABSTRACT FROM AUTHOR]

BACKGROUND: Recently, Citrobacter freundii bacteremia outbreak in a neonatal intensive care unit has attracted public attention in Korea. However, Citrobacter bacteremia is uncommon and usually occurs in patients with underlying diseases such as malignancy and hepatobiliary diseases. Increase in resistance and emerging of multidrug resistance among Citrobacter species have gradually been reported. The aim of this study was to investigate the clinical characteristics and outcome of C. freundii and non-freundii bacteremia and antimicrobial susceptibility trends. MATERIALS AND METHODS: We reviewed the medical records of patients with Citrobacter bacteremia at St. Mary's Hospital, from 2007 to 2017. RESULTS: A total of 43 patients with a median age of 72 (24-93) years was identified and 90.7% of them had comorbidities. Twenty-nine (67.4%) patients had C. freundii bacteremia while 14 had non-freundii bacteremia (six of C. braakii, five of C. koseri, two of C. amalonaticus and one of C. youngae). A total of 26 (51.2%) patients had community-acquired infection and intra-abdominal infection including hepatobiliary tract was the most common portal of entry (24/43, 55.8%). Moreover, hepatobiliary tract was the leading primary site of nosocomial infection (9/17, 52.9%). Polymicrobial bacteremia was observed in 21 (48.8%) patients. The percentages of Citrobacter species susceptible to ampicillin, amikacin, aztreonam, cefazolin, cefoxitin, cefotaxime, cefepime, piperacillin-tazobactam, ciprofloxacin, and imipenem were 9.5%, 97.6%, 73.8%, 9.5%, 14.3%, 71.4%, 92.9%, 83.3%, 83.3% and 100%, respectively. The resistance rate did not increase during the study period. Of 39 patients treated with antibiotics, 36 (92.3%) received appropriate empirical antibiotics. Overall mortality was 18.6%. High Charlson comorbidity index and Pitt bacteremia score were significant risk factors for death in univariate analysis and showed trends in the multivariate analysis. No significant difference in clinical features and antimicrobial susceptibility rate was observed between C. freundii and non-freundii bacteremia. CONCLUSION: Citrobacter bacteremia was predominant in the elderly with comorbidities, while no pediatric case was observed. Hepatobiliary tract is the leading primary focus of bacteremia both in community-acquired and nosocomial infection. The rate of susceptibility to antibiotics has not changed in the last 11 years [ABSTRACT FROM AUTHOR]

Animal models are essential to studies of infectious diseases. The use of mice to test bacterial infection has been extensively reported. However, methods applied to clinical isolates, particularly for carbapenem-resistant bacteria, must be tailored according to the infection models and bacteria used. In this study, we infected 6-week-old female BALB/c mice intraperitoneally with different strains of resistant bacteria plus 3% hog gastric mucin. This method was found to be efficient and readily applicable for investigation of carbapenem-resisant Gram-negative pathogens (e.g., Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii) detected in Korea. [ABSTRACT FROM AUTHOR]

배경: Due to the conventional poliovirus neutralization test (cPNT) limitation, there are some difficulties in assessing the efficacy of the poliovirus (PV) vaccine. Therefore, an alternative method, such as the pseudovirus neutralization test (pPNT), should be necessary. We aim to produce serotype 1, 2 & 3 of poliovirus pseudovirus for pPNT method that correlates with the conventional PV neutralization test (cPNT). 방법: We synthesized genetically the viral capsids of serotype 1, 2, & 3 of the wild or vaccine strain (Mahoney, MEF-1, Saukett, Sabin 1, 2, and 3 strain), and cloned the viral capsid gene (VP1-4) conjugated with AcGFP into pcDNA 4.0 vector. Also, we constructed the viral replicon vector (pGEM) including the 5` UTR and 3`UTR region conjugated with firefly luciferase (Fluc). We produced RNA transcripts by RiboMAX T7 kit from the linearized poliovirus replicon plasmid. 결과: We transfected PV-capsid expression plasmid of each serotypes into the 293FT cell, and in vitro RNA transcript was also transfected in the capsid-expressing cell. Each pseudovirus was extracted from cell lysates after the observation of the cytopathic effect and confirmed by Western blot with anti-poliovirus antibodies. We confirmed the titer of pseudovirus after infection in RD cell by luciferase activity (the RLU value). With the final concentration of 400 IU/5 Ol, we performed the neutralization test with WHO international standard anti-poliovirus serum Types 1, 2 and 3 (82/585), and it was observed that there were no the cross-reactivity among each serotypes. 결론: We showed that the produced pseudoviruses in this study could be available as an alternative for the neutralization test with an advantage in safety. And luciferase reporter in the replicon could provide the infectivity in the susceptible cell, expecting neutralization profiles of pseudovirus in human serums. [ABSTRACT FROM AUTHOR]

With the rise in multidrug-resistant (MDR) bacterial infections, there has been increasing interest in combinations of ≥2 antimicrobial agents with synergistic effects. We established an MDR bacterial strain library to screen for in vitro antimicrobial synergy by using a broth microdilution checkerboard method and highthroughput luciferase-based bacterial cell viability assay. In total, 39 MDR bacterial strains, including 23 carbapenem-resistant gram-negative bacteria, 9 vancomycin-intermediate Staphylococcus aureus, and 7 vancomycin-resistant Enterococcus faecalis, were used to screen for potential antimicrobial synergies. Synergies were more frequently identified with combinations of imipenem plus trimethoprim-sulfamethoxazole for carbapenem-resistant Acinetobacter baumannii in the library. To verify this finding, we tested 34 A. baumannii clinical isolates resistant to both imipenem and trimethoprim-sulfamethoxazole by the checkerboard method. The imipenem plus trimethoprim-sulfamethoxazole combination showed synergy in the treatment of 21 (62%) of the clinical isolates. The results indicate that pilot screening for antimicrobial synergy in the MDR bacterial strain library could be valuable in the selection of combination therapeutic regimens to treat MDR bacterial infections. Further studies are warranted to determine whether this screening system can be useful to screen for the combined effects of conventional antimicrobials and new-generation antimicrobials or nonantimicrobials. [ABSTRACT FROM AUTHOR]

Background: Genetic polymorphisms of cytochrome P450 enzymes, especially CYP2C19 influence voriconazole pharmacokinetics. However, the impact of CYP2C19 genetic polymorphisms on the therapeutic efficacy and toxicity of voriconazole therapy are not well established. Materials and Methods: In this prospective observational study, we analyzed all consecutive adult patients with hematologic diseases who were treated for invasive aspergillosis (IA) with voriconazole between January 2011 and June 2012. CYP2C19 genotype and routine therapeutic drug monitoring of voriconazole were performed. The target range for voriconazole trough levels was 1-5.5 mg/L. Results: A total of 104 consecutive patients were enrolled, including 39 homozygous extensive metabolizers (EMs, 38%), 50 heterozygous extensive metabolizers (HEMs, 48%), and 15 poor metabolizers (PMs, 14%). The initial voriconazole trough levels were 1.8, 2.7, and 3.2 mg/L in EMs, HEMs, and PMs, respectively (P = 0.068). Out-of-range initial trough levels were most frequently observed in EMs (46%) followed by HEMs (26%) and PMs (0%) (P = 0.001). The frequency of initial trough levels < 1 mg/L but not > 5.5 mg/L differed significantly among the 3 groups (P = 0.005). However, treatment response, all-cause and IA-attributable mortality, and the occurrence of voriconazole-related adverse events did not differ significantly among the 3 groups (P = 0.399, P = 0.412, P = 0.317, and P = 0.518, respectively). Conclusions: While none of the initial voriconazole trough levels in PMs was outside the target range, subtherapeutic initial trough levels were frequent in EMs. Although there was no significant relationship between CYP2C19 genotype and either the clinical outcomes of IA or toxicity of voriconazole, further large-scale multicenter studies using clinical data from homogeneous populations are required. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the clinical features and epidemiology of bloodstream infections (BSIs) in 2 distinctive hematological wards of the Catholic Blood and Marrow Transplantation (BMT) center. Materials and Methods: We retrospectively reviewed the medical data of patients who developed BSIs from June 2009 to May 2010 in 2 hematologic wards at the Catholic BMT center. Ward A is a 44-bed unit mainly conducting conventional high dose chemotherapy and ward B is a 23-bed unit exclusively conducting BMT. Results: Overall, 222 BSI episodes were developed from 159 patients. Acute myeloid leukemia in ward A and multiple myeloma in ward B were more frequent than in ward B and A, respectively. Sex, age, presence of neutropenia, shock, Pitt bacteremia score, type of central catheter, level of C-reactive protein, duration of admission days, type of BSI, overall mortality and distribution of organisms were not different between the 2 wards. There were 202 monomicrobial and 20 polymicrobial BSI episodes, including 2 fungemia episodes. The incidence rate of overall BSIs per 1,000 patient-days was higher in ward A than in ward B (incidence rate ratio 2.88, 95% confidence interval 1.97-4.22, P<0.001). Among 243 organisms isolated, the number of gram positives, gram negatives and fungi were 122, 119 and 2, respectively. Escherichia coil was the most common organism in both ward A and B (27.6% and 42.4%), followed by viridians streptococci (18.6% and 15.2%) and Klebsiella pneumoniae (13.3% and 9.0%). Extended spectrum beta-lactamase (ESBL) producers accounted for 31.9% (23/72) of E. coil and 71.0% (22/31) of K. pneumoniae. Out of 19 Enterococcus faecium, 7 isolates (36.8%) were resistant to vancomycin. The crude mortality rates at 7 and 30 days after each BSI episode were 4.5% (10/222) and 13.1% (29/222), and were significantly higher in the patients with shock compared with those without shock (20.5% vs. 1.1%, P<0.001 and 38.5% vs. 7.7%, P<0.001, respectively). Conclusions: The incidence rate of BSIs was higher in patients receiving chemotherapy than those receiving BMT, but the distribution of organisms was not different between the 2 wards. E. coil was the most common causative BSI organism in hematologic wards followed by viridians streptococci and K. pneumoniae. [ABSTRACT FROM AUTHOR]