Seroepidemiology of Hepatitis Viruses and Hepatitis B Genotypes of Female Marriage Immigrants in Korea.

PURPOSE: The Korean society has moved rapidly toward becoming a multicultural society. This study aimed to estimate the seroprevalence of hepatitis viruses and investigate hepatitis B virus (HBV) genotypic diversity in female marriage immigrants. MATERIALS AND METHODS: Screening program was conducted at support centers for multicultural families in 21 administrative districts in Korea between July 2011 and January 2017. A total of 963 female marriage immigrants were included in this study. Blood samples were tested for hepatitis viral markers and HBV genotype. RESULTS: Subjects' median age was 33 years (20-40 years), and they originated from nine countries including Vietnam (n=422, 43.8%), China (n=311, 32.3%), the Philippines (n=85, 8.8%), Cambodia (n=58, 6.0%), and Japan (n=39, 4.0%). About 30% (n=288) of subjects required hepatitis A vaccination. HBsAg positive rate was 5.4% (n=52). Positive HBsAg results were the highest in subjects from Southeast Asia (6.6%, n=38). Anti-HBs positive rate was 60.4% (n=582). About 34% (n=329) of subjects who were negative for anti-HBs and HBsAg required HBV vaccinations. Genotypes B and C were found in 54.6% (n=12) and 45.4% (n=10) of the 22 subjects with HBV, in whom genotypes were tested. Eight (0.8%) subjects were positive for anti-HCV. Positive anti-HCV results were the highest in subjects from Central Asia (7.9%, n=3). CONCLUSION: Testing for hepatitis viral marker (hepatitis A virus IgG and HBsAg/anti-HBs) is needed for female marriage immigrants. Especially, HBV genotype B is different from genotype C of Koreans. Therefore, interest and attention to vaccination programs for female marriage immigrants are necessary for both clinicians and public health institutes.

Behavioural and neuropsychiatric disturbance in three clinical subtypes of frontotemporal dementia: A Clinical Research Center for Dementia of South Korea-FTD Study.

OBJECTIVES: To characterise the behavioural and neuropsychiatric disturbances of patients with three clinical subtypes of frontotemporal dementia (FTD): behavioural variant FTD (bvFTD), semantic dementia (SD) and progressive non-fluent aphasia (PNFA). METHODS: Consecutive series of 66 patients with bvFTD, 58 patients with SD and 21 patients with PNFA were compared using the Frontal Behavioural Inventory (FBI) and the Neuropsychiatric Inventory (NPI). RESULTS: Patients with bvFTD had more behavioural and neuropsychiatric disturbances than patients with PNFA based on the total scores of FBI and NPI. When comparing subtotal and item scores of FBI and NPI, there were some significant differences among three clinical subtypes of FTD. CONCLUSION: There are some distinct patterns of behavioural and neuropsychiatric disturbance among three clinical subtypes of FTD.

Effect of galantamine on attention in patients with Alzheimer's disease combined with cerebrovascular disease.

AIM: Patients with Alzheimer's disease (AD) and cerebrovascular disease (CVD) show greater attentional deficits compared with AD patients without CVD. The aim of the present study was to investigate the effect of galantamine on attention in AD patients with CVD. METHODS: In this open trial, 1512 patients with AD and CVD were recruited from 71 nationwide hospitals. The patients were given galantamine for 16 weeks. The primary outcome measure was the score on the Attention Questionnaire Scale (AQS), which measures the patients' attention in their daily lives. The secondary outcome measures were the scores on the Korean Mini-Mental State Examination, the Clinical Dementia Rating scale and the Global Deterioration Scale. Efficacy measures were calculated both at baseline and at the end of the treatment (week 16). RESULTS: The responders rate on the AQS (change of the AQS from baseline >0) was 60.6% in AD patients with CVD. At the end of the treatment, both the AQS (15.0 ± 5.7 vs 16.3 ± 5.8, P < 0.001) and the Korean Mini-Mental State Examination scores (17.8 ± 4.8 vs 18.1 ± 5.1, P < 0.001) showed a significant improvement relative to the baseline performance. The Clinical Dementia Rating (1.25 ± 0.59 vs 1.22 ± 0.63 P = 0.025) and Global Deterioration Scale (3.82 ± 0.94 vs 3.76 ± 0.96, P = 0.002) scores also showed a significant decrease at the end of the treatment. CONCLUSIONS: Galantamine is effective in improving attention in the daily lives of AD patients with CVD. Geriatr Gerontol Int 2017; 17: 1661-1668.

Therapeutic drug monitoring and safety of intravenous voriconazole formulated with sulfobutylether ß-cyclodextrin in haematological patients with renal impairment.

Because of concerns about accumulation of cyclodextrin, oral voriconazole is recommended for patients with renal impairment. However, intravenous voriconazole may occasionally be imperative in critically ill patients with life-threatening invasive aspergillosis. We investigated the clinical effects of intravenous voriconazole formulated with sulfobutylether ß-cyclodextrin (SBECD) in patients with renal impairment. A prospective observational study was conducted on 25 adult patients with haematological malignancies who were treated with intravenous voriconazole for invasive aspergillosis. Among them, seven patients had a baseline creatinine clearance (CrCl) <50 ml min(-1) (case). Although voriconazole trough concentrations were significantly higher in cases (5.84 mg l(-1) ) than controls (2.28 mg l(-1) ), the proportion of concentrations within the target range did not differ between two groups (4/7 and 12/18, respectively; P = 0.658). The frequency of severe adverse events in cases (3/7) was comparable to that of controls (4/18; P = 0.355). No patients showed significant deterioration in renal function after the voriconazole therapy even in patients with renal impairment. Although CrCl <50 ml min(-1) was associated with higher voriconazole concentrations, its clinical impact remains unclear. SBECD-formulated intravenous voriconazole did not lead to a higher incidence of severe adverse events including nephrotoxicity in haematological patients with CrCl <50 ml min(-1) .

Prolonged entecavir therapy is not effective for HBeAg seroconversion in treatment-naive chronic hepatitis B patients with a partial virological response.

The aims of this study were to investigate the efficacy of prolonged entecavir (ETV) therapy in treatment-naive chronic hepatitis B (CHB) patients and to determine whether continuous ETV therapy is feasible to achieve HBeAg seroconversion, particularly in patients with partial virological response (PVR). A total of 142 treatment-naive patients with CHB were enrolled. The mean duration of treatment was 65 (range, 26 to 90) months, and 86 patients (60.6%) were HBeAg positive. PVR was defined as detectable hepatitis B virus (HBV) DNA (>116 copies/ml) at year 1. The cumulative incidence of virological response (VR) increased from 54.9% at year 1 to 98.2% at year 7. HBeAg positivity (odds ratio [OR], 4.146; P = 0.001) and initial alanine aminotransferase (ALT) (OR, 0.997; P = 0.004) were independent risk factors for PVR. Among the 64 patients with PVR, 47 patients (73.4%) achieved VR within 4 years after prolonged ETV therapy without treatment adaptation. Three patients (2.1%) experienced virological breakthrough and HBV variants with genotypic resistance. The cumulative rate of HBeAg seroconversion was significantly higher in the patients with VR than in the patients with PVR (P = 0.018). None of the PVR patients with HBV DNA at ≥5,000 copies/ml at year 1 ever experienced HBeAg seroconversion. Multivariate analysis identified VR at year 1 as the only determinant of HBeAg seroconversion (hazard ratio [HR], 3.009; P = 0.010). In conclusion, although there were patients with PVR, prolonged ETV therapy showed excellent VR, with only 2.1% emergence of viral resistance during a 7-year follow-up. However, to achieve HBeAg seroconversion, drug modification is needed for HBeAg-positive patients with PVR (especially those with HBV DNA at ≥5,000 copies/ml at year 1).

Bilateral psoas muscle abscess associated with emphysematous cystitis.

Psoas muscle abscess associated with emphysematous urinary tract infection is very rare. There were very few reports about urinary tract infections such as renal abscess, perinephric abscess, and emphysematous pyelonephritis complicated with psoas muscle abscess; however, psoas muscle abscess associated with emphysematous cystitis has not yet been reported. Here, we report a case of bilateral posas muscle abscess following emphysematous cystitis in an 81-year-old nondiabetic man, who was treated successfully with prolonged antibiotic therapy and supportive care. Early recognition of psoas muscle abscess can prevent aggressive interventional procedure and warrant good prognosis.

Long-term outcomes of two rescue therapies in lamivudine-refractory patients with chronic hepatitis B: combined lamivudine and adefovir, and 1-mg entecavir.

BACKGROUND/AIMS: Adefovir (ADV) and lamivudine (LAM) combination therapy (ADV+LAM) has been a useful option for patients with LAM-resistant (LAM-r) chronic hepatitis B (CHB). However, the long-term outcomes of LAM+ADV and 1-mg entecavir (ETV) rescue therapies have still been limited. The aim of this study was to determine the long-term outcomes of these two rescue therapies. METHODS: Sixty patients with LAM-r CHB underwent rescue therapy with LAM+ADV (n=36) or 1-mg ETV (n=24). We determined the duration of rescue therapy, timing and type of mutation, undetectable serum hepatitis B virus (HBV) DNA by PCR (lower limitation of detection, < 140 copies/mL), biochemical response (alanine aminotransferase < 40 IU/mL), and the incidence of hepatitis B virus e antigen (HBeAg) seroconversion and virologic breakthrough. RESULTS: Baseline characteristics did not differ between the two therapy groups. The duration of rescue therapy was 56 months (range, 14-100 months) in the ADV+LAM group and 42 months (range, 12-73 months) in the ETV group (P=0.036). The cumulative rates of HBV DNA undetectability and HBeAg seroconversion up to 6 years were 88.6% and 43.0%, respectively, in the ADV+LAM group, and 45.8% and 31.8% in the ETV group. The rate of virologic breakthrough and resistance was 14.4% in the ADV+LAM group and 71.9% in the ETV group (P=0.001). CONCLUSIONS: Combination of LAM and ADV therapy for up to 6 years achieved modest rates of virological suppression and resistance. ETV is not an optimal therapy because the risk of viral breakthrough to ETV increases over time.

Epidemiology and clinical features of bloodstream infections in hematology wards: one year experience at the catholic blood and marrow transplantation center.

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 coli 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. coli 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. coli was the most common causative BSI organism in hematologic wards followed by viridians streptococci and K. pneumoniae.

Impact of vancomycin resistance on mortality in neutropenic patients with enterococcal bloodstream infection: a retrospective study.

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.

Posaconazole treatment in Korea: single-center experience over 5 years.

PURPOSE: Posaconazole is a second-generation triazole with a broad spectrum. However, there is a lack of data to support a significant role for posaconazole in the treatment of invasive fungal infection (IFI), especially in Korea. Until recently, posaconazole was available only through the Korean Orphan Drug Center. This study was designed to review the use of posaconazole at a single-center in Korea. MATERIALS AND METHODS: Data from patients who received posaconazole treatment at Catholic Blood and Marrow Transplantation Center were retrospectively reviewed between January 2007 and September 2012. RESULTS: A total of 11 cases (3 males and 8 females, median age 52 years) received posaconazole. Five patients were given the drug for mucormycosis, two for invasive aspergillosis, and four for unspecified IFI for which galactomannan (GM) assays were negative. The treatment duration ranged from 4-250 days. Three patients received posaconazole for management refractory IFI, two for intolerance of previous antifungal therapy, and six for long-term maintenance treatment. The overall successful response rate to posaconazole was 55% (six of eleven patients). Five of eleven patients died during the study period. However, only one death was attributed to the progression of IFI. None of the patients discontinued posaconazole therapy due to adverse events. CONCLUSION: Posaconazole is an attractive oral antifungal agent for salvage treatment of IFI, particularly upon diagnosis of mucormycosis or in cases in which mucormycosis cannot be ruled out due to a negative GM.

Clinical characteristics and the usefulness of the QuantiFERON-TB Gold In-Tube test in hematologic patients with hepatic or splenic lesions.

BACKGROUND/AIMS: Hepatic or splenic lesions in hematologic patients are not defined well because they are not easy to evaluate due to limitations of invasive procedures. Management typically depends on the clinical diagnosis with few microbiological data. METHODS: We reviewed the medical records of consecutive hematologic patients with hepatic or splenic lesions in the infectious diseases unit from April 2009 to December 2010 at the Catholic Hematopoietic Stem Cell Transplantation Center in Korea. RESULTS: Twenty-six patients were identified. Their mean age was 46.0 ± 14.7 years, and 16 (61.5%) were male. Underlying diseases were acute myelogenous leukemia (n = 15, 57.7%) and myelodysplastic syndrome (n = 6, 23.1%). Among the nine nontuberculous infectious lesions, two bacterial, six fungal, and one combined infection were identified. The numbers of confirmed, probable, and possible tuberculosis (TB) cases were one, three, and four, respectively. Two patients had concurrent pulmonary TB. QuantiFERON-TB Gold In-Tube (QFT-GIT, Cellestis Ltd.) was positive in seven cases, among which six were diagnosed with TB. The sensitivity and specificity of QFT-GIT were 75% and 81.3%. Nine (34.6%) were defined as noninfectious causes. CONCLUSIONS: Causes of hepatic or splenic lesion in hematologic patients were diverse including TB, non-TB organisms, and noninfectious origins. TB should be considered for patients not responding to antibacterial or antifungal drugs, even in the absence of direct microbiological evidence. QFT-GIT may be useful for a differential diagnosis of hepatosplenic lesions in hematologic patients.

Sternal osteomyelitis with a mediastinal abscess caused by Gemella morbillorum following blunt force trauma.

Infections caused by Gemella morbillorum are uncommon. This organism is primarily associated with endocarditis and bacteremia and rarely with spondylodiscitis, arthritis, hepatic abscesses and meningitis. Sternal osteomyelitis caused by G. morbillorum has not yet been reported. We herein present a case of sternal osteomyelitis with a mediastinal abscess caused by G. morbillorum that occurred in a 74-year-old diabetic patient following blunt force trauma to the anterior chest wall. The patient was treated successfully with surgical excision and prolonged antibiotic treatment. Early recognition and timely intervention are important for managing life-threatening osteomyelitis of the sternum.

Clinical Impact of Cytochrome P450 2C19 Genotype on the Treatment of Invasive Aspergillosis under Routine Therapeutic Drug Monitoring of Voriconazole in a Korean Population.

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.

Escherichia coli and Klebsiella pneumoniae bacteremia in patients with neutropenic fever: factors associated with extended-spectrum ß-lactamase production and its impact on outcome.

Escherichia coli and Klebsiella pneumoniae are main pathogens in neutropenic fever even if the proportion of Gram-positive cocci is increasing. Extended-spectrum ß-lactamases (ESBL)-producing organisms are an emerging problem in nosocomial infection. Nevertheless, until now, information about risk factors for the acquisition and clinical outcomes of bacteremia due to ESBL-producing organisms is limited in neutropenic patients. From medical records collected between January 2007 and December 2008, we identified a total of 101 consecutive patients who developed bacteremia due to E. coli (n = 87) or K. pneumoniae (n = 14). Twenty-six (26 %) cases of bacteremia were caused by ESBL-producing organisms. A hospital stay of >2 weeks during the 3 months preceding bacteremia [adjusted odds ratio (OR), 5.887; 95 % confidence interval (CI), 1.572-22.041] and the use of broad-spectrum cephalosporins in the 4 weeks prior to bacteremia (adjusted OR, 6.186; 95 % CI, 1.616-23.683) were significantly related to the acquisition of ESBL. Twenty-four (92 %) of the ESBL-producing organisms were susceptible to either piperacillin-tazobactam or amikacin. Aminoglycosides (amikacin or isepamicin) were the main appropriate antimicrobial agents used against the ESBL-producing isolates during the initial empirical treatment (16/22, 73 %). However, the 30-day mortality rates for ESBL bacteremia and non-ESBL bacteremia were not significantly different (15 vs 5 %; p = 0.199). As alternatives to carbapenem, piperacillin-tazobactam plus amikacin or isepamicin combinations may be effective empirical therapeutic options for patients with neutropenic fever who are at high risk of developing bacteremia with ESBL-producing pathogens.

Prognosis of invasive pulmonary aspergillosis in patients with hematologic diseases in Korea.

BACKGROUND: The aim of this study was to investigate therapeutic outcomes and assess factors associated with therapeutic outcomes in hematologic patients with invasive pulmonary aspergillosis (IPA). METHODS: We analyzed all consecutive cases of IPA in adults with hematologic diseases from January 2008 to January 2009 at a Catholic Hematopoietic Stem Cell Transplantation (HSCT) Center in Seoul, Korea. RESULTS: A total of 54 patients were identified. Underlying diseases were acute myelogenous leukemia (n=25), acute lymphoblastic leukemia (n=10), myelodysplastic syndrome (n=7), chronic myelogenous leukemia (n=3), multiple myeloma (n=3), severe aplastic anemia (n=2) and other hematologic diseases (n=4). Twenty six patients (48.2%) were assessed as having a favorable response, of which 16 patients (29.6%) showed complete response. Overall 12-week mortality and IPA attributable mortality were 38.9% (n=21) and 33.3% (n=18), respectively. In multivariate analysis, uncontrolled underlying disease (odds ratio [OR], 7.31; 95% confidence interval [CI], 1.49~35.94; p=0.014) was associated with an unfavorable response, and for 12-week mortality, uncontrolled underlying disease (OR, 11.79; 95% CI, 1.49~93.46; p=0.020) and hypoalbuminemia (OR, 9.89; 95% CI, 1.42~68.99; p=0.021) were significantly poor prognostic factors. CONCLUSION: IPA still remains as a poor therapeutic outcome, especially in patients with refractory hematologic diseases.

Molecular epidemiology of extended-spectrum ß-lactamase-producing Escherichia coli in the community and hospital in Korea: emergence of ST131 producing CTX-M-15.

BACKGROUND: The prevalence of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli has been increased not only in the hospital but also in the community worldwide. This study was aimed to characterize ESBL- producing E. coli isolates and to investigate the molecular epidemiology of community isolates in comparison with hospital isolates at a single center in Korea. METHODS: A total of 142 ESBL-producing E. coli isolates were collected at Daejeon St Mary's Hospital in Korea from January 2008 to September 2009. The ESBLs were characterized by PCR sequencing using specific primers. The genetic relatedness was determined by pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). RESULTS: Of 142 isolates, 139 were positive for CTX-M type ESBLs; CTX-M-14 (n = 69, 49.6 %), CTX-M-15 (n = 53, 38.1 %) and both CTX-M-14 and -15 (n = 17, 12.2 %). CTX-M-14 and CTX-M-15 were detected in both community and hospital isolates whereas isolates producing both CTX-M14 and-15 were mainly identified in the hospital. CTX-M producing E. coli isolates were genetically heterogeneous, revealing 75 distinct PFGE types. By MLST, 21 distinctive STs including 5 major STs (ST131, ST405, ST38, ST10, and ST648) were identified. Major STs were distributed in both community and hospital isolates, and ST131 was the predominant clone regardless of the locations of acquisition. No specific major STs were confined to a single type of ESBLs. However, ST131 clones were significantly associated with CTX-M-15 and the majority of them were multidrug-resistant. Distinctively, we identified a hospital epidemic caused by the dissemination of an epidemic strain, ST131-PFGE type 10, characterized by multidrug resistance and co-producing both CTX-Ms with OXA-1 or TEM-1b. CONCLUSIONS: The epidemiology of ESBL-producing E. coli is a complex and evolving phenomenon attributed to the horizontal transfer of genetic elements and clonal spread of major clones, predominantly ST131. The multidrug resistant ST131 clone producing CTX-M-15 has emerged as a major clone in both the community and hospital, suggesting the widespread of this epidemic clone in Korea.

Real-time nucleic acid sequence-based amplification to predict the clinical outcome of invasive aspergillosis.

Monitoring the response to therapy for invasive aspergillosis (IA) is essential for the management of patients with hematologic diseases. We evaluated the correlation between the outcome of real-time nucleic acid sequence-based amplification (RTi-NASBA) for Aspergillus 18S rRNA and the clinical outcome of IA. A total of 157 serum samples from 29 patients with IA were tested for RTi-NASBA. The treatment response and mortality were compared with the NASBA outcome (whether the NASBA value was converted to negative or not) at 12 weeks after the start of antifungal therapy. At 12 weeks, there was a moderate correlation between the treatment failure and persistently positive NASBA (κ = 0.482; P = 0.019). Deaths attributable to IA were more prevalent in patients without negative conversion of NASBA than in those with negative conversion (50% vs 5%; P = 0.013). Significant factors of treatment failure at 12 weeks were the status of hematologic disease (nonremission; P = 0.041) and the NASBA outcome (failure of negative conversion; P = 0.024). Survival was significantly better in patients with negative conversion of NASBA than those with persistently positive values (P = 0.036). This study suggests that the serial monitoring of RTi-NASBA could be useful for prediction of the clinical outcome in hematologic patients with IA.

Voriconazole-related severe adverse events: clinical application of therapeutic drug monitoring in Korean patients.

BACKGROUND: Voriconazole is a triazole agent with excellent antifungal activity against Aspergillus species. However, despite its potential advantages, the occurrence of unpredictable toxicities might be critical in immunocompromised patients. The aim of this study was to analyze risk factors for voriconazole-related severe adverse events (SAEs). METHODS: This prospective observational study was conducted in Korean patients with hematological malignancies and invasive aspergillosis on intravenous voriconazole therapy between June 2008 and April 2009. RESULTS: Of the 25 patients enrolled, eight (32%) showed voriconazole-related SAEs, which included hepatotoxicities (n=5), cardiac tachyarrhythmias (n=2), and neurotoxicity (n=1). Sex, age, underlying hematological malignancies, voriconazole dose, the co-administration of a proton pump inhibitor, and CYP2C19 genotype were not found to be related to the occurrence of SAEs. However, trough plasma concentrations of voriconazole were found to be significantly higher in the patients with an SAE: median 6.32 mg/l (interquartile range (IQR) 2.86-9.71 mg/l) vs. median 2.15 mg/l (IQR 0.92-4.00 mg/l); p=0.011. Receiver operating characteristic curve analysis identified a cut-off trough concentration for SAEs of 5.83 mg/l (sensitivity 62.5% and specificity 94.1%). Furthermore, multivariate analysis showed that a trough concentration of ≥ 5.83mg/l was the only significant independent risk factor of an SAE. CONCLUSIONS: This study shows that therapeutic drug monitoring is indicated in patients with a voriconazole-related SAE and that dose adjustment is required if the trough concentration of voriconazole exceeds 5.83 mg/l.