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Background: Influenza imposes a significant healthcare burden in Korea, leading the government to initiate a national immunization program. Previous studies on vaccine effectiveness (VE) were limited to single-season estimation in Korea., Methods: This multicenter prospective cohort study enrolled patients with influenza-like illnesses at 10 medical centers in Korea from 2011 to 2021. The demographic and clinical data were collected from questionnaire surveys and electronic medical records. Using a test-negative design, we aimed to investigate the effectiveness of a seasonal influenza vaccine for antigenic matching of the vaccine and circulating viral strains over 10 seasons., Results: Overall, 5322 adults aged ≥65 years were enrolled. Only three (33.3 %) of nine seasons showed >70 % antigenic match between vaccine and circulating strains. Influenza VE was significantly variable by season, ranging from -46.9 % (95 %confidence interval [CI]: -127.6-5.2) in the 2011/12 season to 47.7 % (95 %CI: 22.6-64.7) in the 2016/17 season. A significant difference was observed in the VE depending on whether the vaccine strains matched with epidemic strains: 28.8 % (95 %CI: 8.8-44.8) in matched seasons versus -12.0 % (95 %CI: -30.0-3.7) in mismatched seasons. Across the study period, influenza-related hospitalizations were reduced by 13.6 % (95 %CI: 0.7-24.8) with vaccination. In a subgroup analysis, the VE against influenza-related hospitalization was 48.4 % (95 %CI 29.6-62.2) in A/H3N2 dominant seasons and 53.8 % (95 %CI: -73.4-87.7) in A/H1N1 dominant seasons, respectively., Conclusion: Influenza vaccine mismatch was frequent over the study period, leading to negligibly low VE in mismatched seasons. Influenza vaccination reduces the risk of influenza-related hospitalizations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hee Jin Cheong reports financial support was provided by Korea University College of Medicine. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

As coronavirus disease-2019 (COVID-19) becomes an endemic disease, the virus continues to evolve and become immunologically distinct from previous strains. Immune imprinting has raised concerns about bivalent mRNA vaccines containing both ancestral virus and Omicron variant. To increase efficacy against the predominant strains as of the second half of 2023, the updated vaccine formulation contained only the mRNA of XBB.1.5 sublineage. We conducted a multicenter, test-negative, case-control study to estimate XBB.1.5 monovalent vaccine effectiveness (VE) and present the results of an interim analysis with data collected in November 2023. Patients who underwent COVID-19 testing at eight university hospitals were included and matched based on age (19-49, 50-64, and ≥65 years) and sex in a 1:1 ratio. VE was calculated using the adjusted odds ratio derived from multivariable logistic regression. Of the 992 patients included, 49 (5.3%) received the XBB.1.5 monovalent vaccine at least 7 days before COVID-19 testing. Patients with COVID-19 (cases) were less likely to have received the XBB.1.5 monovalent vaccine (case 3.5% vs. control 7.2%, p=0.019) and to have a history of COVID-19 within 6 months (2.2% vs. 4.6%, p=0.068). In contrast, patients with COVID-19 were more likely to be healthcare workers (8.2% vs. 3.0%, p=0.001) and to have chronic neurological diseases (16.7% vs. 11.9%, p=0.048). The adjusted VE of the XBB.1.5 monovalent mRNA vaccine was 56.8% (95% confidence interval: 18.7-77.9%). XBB.1.5 monovalent mRNA vaccine provided significant protection against COVID-19 in the first one to two months after vaccination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nham, Sohn, Choi, Wie, Lee, Lee, Jeong, Eom, Choi, Seong, Yoon, Noh, Song, Cheong and Kim.)

In the 2023-2024 season, the influenza epidemic in South Korea peaked earlier than in recent years. In this study, we aimed to estimate the interim vaccine effectiveness (VE) of the influenza vaccination to prevent influenza during the early season. From November 1, 2023, to December 31, 2023, we enrolled 2,632 subjects with influenza-like illness from eight hospitals participating in hospital-based influenza morbidity and mortality surveillance. A retrospective test-negative case-control study was conducted to estimate the VE. The results showed an adjusted VE of 22.5% (95% confidence interval [CI], 6.6 to 35.8) for the total population. The adjusted VE was 22.3% (95% CI, 6.1 to 35.7) for influenza A and 9.4% (95% CI, -51.3 to 45.7) for influenza A/H1N1. Full results of the analysis will be reported., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: Bivalent booster mRNA vaccines containing the omicron-variant strains have been introduced worldwide in the autumn of 2022. Nevertheless, the omicron subvariants evoked another large coronavirus disease 2019 (COVID-19) pandemic wave in late 2022 and early 2023., Methods: A retrospective, test-negative, case-control study was conducted to estimate the vaccine effectiveness (VE) of bivalent COVID-19 vaccines in 8 university hospitals between January and February 2023. The case and control groups were divided based on nasopharyngeal COVID-19 real-time polymerase chain reaction results and matched based on age, sex, hospital, and date (week) of the test performed. The VE of the BA.1- or BA.4/BA.5-based mRNA vaccines were estimated. VE was calculated using the 1-adjusted odds ratio from multivariable logistic regression., Results: In total, 949 patients and 947 controls were enrolled in this study. VE for the BA.4/BA.5-based bivalent mRNA vaccine was 43% (95% confidence interval [CI], 17, 61%). In subgroup analysis based on age and underlying medical conditions, BA.4/BA.5-based bivalent mRNA vaccine was effective against old adults aged ≥ 65-years (VE, 55%; 95% CI, 23, 73%) and individuals with comorbidities (VE, 54%; 95% CI, 23, 73%). In comparison, the BA.1-based bivalent mRNA vaccine did not demonstrate statistically significant effectiveness (VE, 25%; 95% CI, -8, 49%)., Conclusion: The BA.4/BA.5-based bivalent mRNA booster vaccine provided significant protection against COVID-19 in the Korean adults, especially in the older adults aged ≥ 65 years and in individuals with underlying medical conditions., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Social isolation and control owing to coronavirus disease 2019 (COVID-19) are easing; however, concerns regarding new infectious diseases have not disappeared. Given epidemic experiences such as severe acute respiratory syndrome (SARS), the influenza pandemic, Middle East respiratory syndrome (MERS), and COVID-19, it is necessary to prepare for the outbreak of new infectious diseases and situations in which large-scale vaccinations are required. Although the development of vaccines against COVID-19 has contributed greatly to overcoming the pandemic, concerning vaccine side effects from the general public, including medical personnel, and decreased confidence in vaccine efficacy and side effects, present many challenges in promoting and educating vaccinations for new infectious diseases in the future. In addition to plans to develop vaccines for the outbreak of new infectious diseases, education and promotion plans are necessary to administer the latest developments of vaccines to the general public. Moreover, efforts are needed to secure the necessity, legitimacy, and evidence for rapid vaccination on a large scale at the national level. It is also necessary to carefully prepare scientific bases and explanatory statements so that the general public can easily understand them. This study aimed to establish vaccine strategies and vaccination education plans for new infectious diseases that may occur in the future. Many ways to promote vaccination to the general public and healthcare workers should be prepared to ensure that the latest vaccines against new infectious diseases are administered safely. Thus, education and promotion of vaccine efficacy and safety based on specific data from clinical studies are necessary., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Purpose: This study aimed to examine the changes in the characteristics of community-onset fluoroquinolone-resistant (FQ-R) Escherichia coli isolates causing community-acquired acute pyelonephritis (APN) in South Korea., Methods: Blood or urine samples were prospectively collected from patients aged ≥15 years with community-acquired APN who were admitted to one of the eight Korean hospitals included in this study between September 2017 and August 2018. Phylogenetic typing, multilocus sequence typing, and molecular characterization of β-lactamase resistance and plasmid-mediated quinolone resistance (PMQR) determinants were performed. The data were compared with those from a previous study with the same design conducted in 2010-2011., Results: A total of 300 and 346 isolates were identified in 2010-2011 and 2017-2018, respectively. Among them, 76 (22.0%) and 77 (25.7%) FQ-R isolates were identified in 2010-2011 and 2017-2018, respectively. A significantly higher antimicrobial resistance against third-to fourth-generation cephalosporins, including cefotaxime (23.9% vs. 77.9%, P < 0.001), were observed among FQ-R isolates in 2017-2018 than among those in 2010-2011. A higher proportion of ST131 isolates (27.6% vs. 66.2%, P < 0.001), as well as isolates that had extended-spectrum β-lactamase (ESBL)/plasmid-mediated AmpC β-lactamase (PABL) (23.7% vs. 79.2%, P < 0.001), was observed in 2017-2018 than in 2010-2011. Further, more PMQR determinants (11.8% vs. 40.8%, P < 0.001) were observed in 2017-2018 than in 2010-2011., Conclusions: Among uropathogenic FQ-R E. coli isolates in South Korea, the prevalence of ST131 and the proportion of isolates containing ESBL and/or PMQR determinants have increased., Competing Interests: Declaration of competing interest None declared., (Copyright © 2022. Published by Elsevier B.V.)

Background: Inappropriate use of antibiotics not only increases antibiotic resistance as collateral damage but also increases clinical failure rates and medical costs. The purpose of this study was to determine the relationship between the appropriateness of antibiotic prescription and outcomes of community-acquired acute pyelonephritis (CA-APN)., Methods: A multicenter prospective cohort study was conducted at eight hospitals in Korea between September 2017 and August 2018. All hospitalized patients aged ≥ 19 years who were diagnosed with CA-APN on admission were recruited. The appropriateness of empirical and definitive antibiotics, as well as the appropriateness of antibiotic treatment duration and route of administration, was evaluated in accordance with the guideline and expert opinions. Clinical outcomes and medical costs were compared between patients who were administered antibiotics 'appropriately' and 'inappropriately.', Results: A total of 397 and 318 patients were eligible for the analysis of the appropriateness of empirical and definitive antibiotics, respectively. Of them, 10 (2.5%) and 18 (5.7%) were administered 'inappropriately' empirical and definitive antibiotics, respectively. Of the 119 patients whose use of both empirical and definitive antibiotics was classified as 'optimal,' 57 (47.9%) received antibiotics over a longer duration than that recommended; 67 (56.3%) did not change to oral antibiotics on day 7 of hospitalization, even after stabilization of the clinical symptoms. Patients who were administered empirical antibiotics 'appropriately' had shorter hospitalization days (8 vs. 10 days, P = 0.001) and lower medical costs (2381.9 vs. 3235.9 USD, P = 0.002) than those who were administered them 'inappropriately.' Similar findings were observed for patients administered both empirical and definitive antibiotics 'appropriately' and those administered either empirical or definitive antibiotics 'inappropriately'., Conclusions: Appropriate use of antibiotics leads to better outcomes, including reduced hospitalization duration and medical costs., (© 2022. The Author(s).)

Background: Community-acquired acute pyelonephritis (CA-APN) is relatively rare in men. This study aimed to compare the clinical characteristics of CA-APN between male and female patients., Methods: We prospectively collected the clinical and microbiological data of hospitalized CA-APN patients aged ≥19 years in South Korea from March 2010 to February 2011 in 11 hospitals and from September 2017 to August 2018 in 8 hospitals. Only the first episodes of APN of each patient during the study period were included., Results: From 2010 to 2011, 573 patients from 11 hospitals were recruited, and from 2017 to 2018, 340 patients were recruited from 8 hospitals. Among them, 5.9% (54/913) were male. Male patients were older (66.0 ± 15.2 vs. 55.3 ± 19.0 years, P < 0.001), had a higher Charlson comorbidity index (1.3 ± 1.5 vs. 0.7 ± 1.2, P = 0.027), and had a higher proportion of structural problems in the urinary tract (40.7% vs. 6.1%, P < 0.001) than female patients. Moreover, the total duration of antibiotic treatment was longer (21.8 ± 17.8 d vs. 17.3 ± 9.4 d, P = 0.001) and the proportion of carbapenem usage was higher (24.1% vs. 9.5%, P = 0.001) in men than in women. Male patients were hospitalized for longer durations than female patients (median, 10 d vs. 7 d, P < 0.001)., Conclusions: Male CA-APN patients were older and had more comorbidities than female CA-APN patients. In addition, male patients received antibiotic treatment for a longer duration than female patients., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The purpose of this study was to determine whether the fluoroquinolone (FQ) minimum inhibitory concentration (MIC) for the causative agent Escherichia coli influences the clinical response of FQ treatment at 72 h in patients with community-acquired acute pyelonephritis (CA-APN). We prospectively collected the clinical data of women with CA-APN from 11 university hospitals from March 2010 to February 2012 as well as E. coli isolates from the urine or blood. In total, 78 patients included in this study received FQ during the initial 72 h, and the causative E. coli was detected. The clinical response at 72 h was significantly higher in patients with a levofloxacin MIC ≤ 16 mg/L than in those with an MIC > 16 mg/L (70.4% vs. 28.6%, p = 0.038). No difference was observed in clinical response at 72 h based on ciprofloxacin MIC. To summarize, FQ can be an effective treatment option for CA-APN when levofloxacin MIC against E. coli is ≤16 mg/L.

Background: After pandemic, A(H1N1)pdm09 is generally known to be associated with younger adults' infection and greater severity than seasonal A(H3N2) but some inconsistences between recent studies exist., Objectives: We aimed to compare the epidemiology and clinical outcomes of A(H1N1)pdm09 and A(H3N2) to verify and consolidate about the knowledge of known differences of subtypes., Methods: Data were retrospectively collected from the hospital-based influenza morbidity and mortality surveillance in South Korea in nine tertiary care hospitals, from August 31, 2014, to August 25, 2018. Patients with H1N1pdm09 or H3N2 infection admitted in the emergency room or ward were recruited., Results: A total of 1747 patients had influenza A and were divided into two groups those with A(H1N1)pdm09 (n = 240) and those with A(H3N2) (n = 1507). A(H1N1)pdm09 group had younger age (mean age ± standard deviation 50.0 ± 18.8 in H1N1 vs 53.4 ± 21.1 in H3N2, P = .030), lower influenza vaccination (27.9% vs 43.9%, P < .001) and pneumococcal vaccination rates (41.0% vs 51.9%, P < .001), and fewer underlying diseases (67.5% vs 74.0%, P = .035) than the A(H3N2) group. Influenza A subtypes were not associated with pneumonia risk (adjusted odds ratios [AOR] of A(H1N1)pdm09: 0.7 [95% confidence interval [CI]: 0.4-1.2, P = .172]) and in-hospital mortality (hazard ratio (HR) of A(H1N1)pdm09: 1.0 (95% CI: 0.3-3.1, P = .983)). Influenza vaccination reduced in-hospital mortality in hospitalized patients (HR: 0.3 (95% CI: 0.1-0.7), P = .005)., Conclusions: A(H1N1)pdm09 infection was more common in younger patients without significant difference in pneumonia risk and in-hospital mortality between subtypes. Influenza vaccination was associated with reduced in-hospital mortality., (© 2020 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

This study examined changes in the clinical characteristics of community-acquired acute pyelonephritis (CA-APN) in South Korea between the period 2010-2011 and 2017-2018. We recruited all CA-APN patients aged ≥19 years who visited eight hospitals in South Korea from September 2017 to August 2018, prospectively. Data collected were compared with those from the previous study in 2010-2012, with the same design and participation from 11 hospitals. A total of 617 patients were enrolled and compared to 818 patients' data collected in 2010-2011. Escherichia coli was the most common causative pathogen of CA-APN in both periods (87.3% vs. 86.5%, p = 0.680). E. coli isolates showed significantly higher antimicrobial resistance against fluoroquinolone (32.0% vs. 21.6%, p < 0.001), cefotaxime (33.6% vs. 8.3%, p < 0.001), and trimethoprim/sulfamethoxazole (37.5% vs. 29.2%, p = 0.013) in 2017-2018 than in 2010-2011. Total duration of antibiotic treatment increased from 16.55 ± 9.68 days in 2010-2011 to 19.12 ± 9.90 days in 2017-2018 ( p < 0.001); the duration of carbapenem usage increased from 0.59 ± 2.87 days in 2010-2011 to 1.79 ± 4.89 days in 2010-2011 ( p < 0.001). The median hospitalization was higher for patients in 2017-2018 than in 2010-2011 (9 vs. 7 days, p < 0.001). In conclusion, antimicrobial resistance of E. coli to almost all antibiotic classes, especially third generation cephalosporin, increased significantly in CA-APN in South Korea. Consequently, total duration of antibiotic treatment, including carbapenem usage, increased.

Background: Escherichia coli is the predominant causative pathogen for community-acquired urinary tract infections (UTIs), and the increase in fluoroquinolone-resistant E. coli is of great concern in Korea. The objectives of this study were to investigate the genotypic characteristics and molecular epidemiology of ciprofloxacin-resistant (CIP-R) E. coli isolated from community-acquired UTIs in Korea., Materials and Methods: E. coli samples isolated from the blood or urine were collected from patients with community-acquired acute pyelonephritis aged 15 years and more who were admitted to 12 Korean hospitals from 1st April 2010 to 29th February 2012. Phylogenetic typing, multilocus sequence typing, and molecular characterization of β-lactamase and plasmid-mediated quinolone resistance determinants were performed for CIP-R E. coli isolates., Results: A total of 569 E. coli isolates were collected, and 122 (21.4%) isolates were CIP-R isolates. The most prevalent sequence type (ST) was ST131 (28.7%, 35/122), followed by ST393 (14.7%, 18/122), ST1193 (13.1%, 16/122), ST38 (9.0%, 11/122), and ST405 (8.2%, 10/122). The antimicrobial resistance rates of ST131 to cefepime (22.9%, 8/35), ST38 to gentamicin (100%, 11/11), and ST405 to cefotaxime (66.7%, 6/9) were significantly higher than the resistance rates of all other STs combined. Notably, 40% (4/10) of ST405 clones produced extended-spectrum β-lactamases and were co-resistant to trimethoprim/sulfamethoxazole. aac(6')-1b-cr (20%, 7/35) and CTX-M-14 (40%, 4/10) were more frequently observed in ST131 and ST405 compared with other clones, respectively., Conclusions: Among the CIP-R uropathogenic E. coli isolates in this study, ST131, ST38, and ST405 were specifically associated with antimicrobial resistance., Competing Interests: No conflicts of interest., (Copyright © 2020 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Background: Annually, about 80% of the Korean elderly aged ≥65 years receive influenza vaccination. Repeated annual vaccination has been suggested as an important factor of poor influenza vaccine effectiveness (VE), though reported conflicting results., Methods: During the consecutive A/H3N2-dominant influenza seasons between 2012 and 2015, we comparatively evaluated the VE (repeated vs. current season only) against laboratory-confirmed influenza, pneumonia and hospitalization in the elderly aged ≥65 years with influenza-like illness (ILI). Clinical and demographic data were collected prospectively, and vaccination status of prior and current seasons was verified using the immunization registry data of Korean Centers for Disease Control and Prevention., Results: During the first A/H3N2-dominant season in 2012-2013, influenza vaccine showed statistically significant effectiveness against influenza A infection only and when vaccinated in the current season only (VE 53%, 95% CI 15-77). In the latter two seasons (2013-2015 years), the adjusted VE for influenza A was indistinguishable between repeated vaccination and vaccination in the current season only., Conclusion: During consecutive influenza A/H3N2 epidemics, poor influenza vaccine effectiveness may be more pronounced among the elderly population with a high annual vaccine uptake rate., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Scrub typhus, a mite-borne disease caused by bites of Orientia tsutsugamushi -infected chiggers, is endemic in Asia-Pacific countries. In Korea, it is a seasonal disease prevalent in autumn and one of the important causes of acute undifferentiated febrile illness. The purpose of this study was to identify the risk factors for the prediction of the severe clinical course of scrub typhus and to investigate the differences in the clinical and laboratory findings of hospitalized elderly and non-elderly patients with scrub typhus., Materials and Methods: This study retrospectively reviewed the medical records of patients diagnosed with scrub typhus., Results: A total of 710 patients were enrolled and 43.9% of them were elderly patients. The number of patients with complicated scrub typhus was 168 (23.7%) and the most common complication of severe scrub typhus was hepatic dysfunction (10.7%) followed by pneumonia (7.2%), acute kidney injury (4.9%) and shock (2.4%). Blood urea nitrogen ≥20 mg/dL, adenosine deaminase (ADA) ≥100 IU/L, pulmonary edema or pleural effusion, lactate dehydrogenase ≥500 U/L, alkaline phosphatase ≥400 IU/L, ferritin ≥500 ng/mL and absence of skin rash were independently associated with severe scrub typhus. There was no significant difference in the incidence of complicated scrub typhus between elderly and non-elderly patients. Absence of skin rash, pulmonary edema, pleural effusion, serum creatinine ≥1.5 mg/dL, total bilirubin ≥1.5 mg/dL, ADA ≥100 IU/L and ferritin ≥500 ng/mL were significantly associated with a longer hospitalization (≥10 days)., Conclusion: The several independent predictors of complicated scrub typhus were identified in this study. Absence of skin rash, the increased levels of serum ADA and ferritin were identified as the predictors of complicated scrub typhus, which were also associated with a prolonged hospitalization., Competing Interests: No conflicts of interest., (Copyright © 2019 by The Korean Society of Infectious Diseases and Korean Society for Antimicrobial Therapy.)

Background: This study was conducted to assess the immunogenicity and safety of GC1107 (adult tetanus diphtheria [Td] vaccine). The primary goal was to evaluate the non-inferiority of the immunogenicity of GC1107 compared to the control vaccine. Additionally, the safety profiles of GC1107 and the control vaccine were compared., Methods: The subjects were adults ≥ 18 years old who were not injected with Td or adult tetanus-diphtheria-pertussis (TdaP) vaccine within the recent 5 years. A total of 253 subjects were enrolled and randomized to either the GC1107 group or the control group. For immunogenicity assessment, blood samples were collected at baseline and 28 days after vaccination and antibody titer of diphtheria and tetanus were assessed., Results: The seroprotection rates of diphtheria and tetanus were 89.76% and 91.34%, respectively, in the GC1107 group, and 87.80% and 86.99% in the control group. The geometric mean titer (GMT) of the anti-diphtheria antibody increased after vaccination in both groups, showing no significant difference between the groups ( P = 0.139). The anti-tetanus GMTs after vaccination also showed comparable increases in both groups, and showed no significant difference ( P = 0.860). In the safety evaluation, solicited local adverse reactions occurred in 81.2% of the subjects in the GC1107 group and in 86.4% of the subjects in the control group. Solicited systemic adverse events occurred in 33.2% of the subjects in the GC1107 group and in 47.2% of the subjects in the control group, which did not reach statistical significance., Conclusion: This phase III study demonstrated non-inferiority in immunogenicity and comparable safety of GC1107 compared with the control Td vaccine., Trial Registration: ClinicalTrials.gov Identifier: NCT02361866., Competing Interests: Disclosure: The authors have no potential conflicts of interest to disclose.

Two antigenically distinct influenza B lineage viruses (Yamagata/Victoria) have been co-circulating globally since the mid-1980s. The quadrivalent influenza vaccine (QIV) may provide better protection against unpredictable B strains. We conducted a randomized, double-blind, phase III trial to evaluate the immunogenicity and safety of an egg-based inactivated, split-virion QIV (GC3110A). Subjects aged ≥ 19 years were randomized 2:1:1 to be vaccinated with QIV- GC3110A, trivalent influenza vaccine (TIV) containing the Yamagata lineage strain (TIV-Yamagata), or TIV containing the Victoria lineage strain (TIV-Victoria). Hemagglutination inhibition assays were performed 21 days post-vaccination. Solicited/unsolicited adverse events (AEs) were assessed within 21 days after vaccination, while serious AEs were reported up to six months after vaccination. A total of 1,299 were randomized to receive QIV-GC3110A (648 subjects), TIV-Yamagata (325 subjects), or TIV-Victoria (326 subjects). Compared to the TIVs, the QIV-GC3110A met the non-inferiority criteria for all four subtype/lineage strains with respect to the geometric mean titer (GMT) ratio and the difference of seroconversion rate. The safety profiles of QIV-GC3110A were consistent with those of TIV. In conclusion, QIV-GC3110A is safe, immunogenic, and comparable to strain-matched TIV.

Background: Influenza and pneumonia are leading causes of morbidity and mortality among the elderly. Although vaccination is a main strategy to prevent these infectious diseases, concerns remain with respect to vaccine effectiveness., Methods: During three influenza seasons (2014-2015, 2015-2016 and 2016-2017), we evaluated the effectiveness of the influenza and pneumococcal vaccines against pneumonia and acute exacerbation of cardiopulmonary diseases among the elderly aged ≥65 years with influenza-like illness (ILI). Demographic and clinical data were collected prospectively., Results: Among 2,119 enrolled cases, 1,302 (61.4%) and 871 (41.1%) received the influenza vaccine and 23-valent pneumococcal polysaccharide vaccine (PPV23), respectively. During an A/H3N2-dominant season with poor influenza vaccine effectiveness (2014-2015 season), neither the influenza vaccine nor PPV23 showed significant effectiveness against pneumonia or acute exacerbation of cardiopulmonary diseases. During seasons with good influenza vaccine effectiveness (2015-2016 and 2016-2017 seasons), the influenza vaccine was effective in preventing pneumonia, but PPV23 was not. In particular, the influenza vaccine was effective in preventing acute exacerbation of heart diseases (75.0%) during the A/H1N1-dominant 2015-2016 season., Conclusion: The influenza vaccine was effective in preventing pneumonia only during vaccine-matched seasons with good effectiveness against circulating influenza viruses. In addition, the influenza vaccine was cardio-protective during a vaccine-matched A/H1N1-dominant season., Competing Interests: The authors have declared that no competing interests exist.

We aimed to characterize the lineages of influenza B viruses obtained from clinical specimens during the 2007-2014 seasons in South Korea. RT-PCR for the partial hemagglutinin gene of influenza B virus was performed on laboratory-confirmed influenza B samples from the 2007-2008 season to 2013-2014 season. A phylogenetic tree was generated, and current influenza vaccine strains for the Northern Hemisphere were used as representative strains of Victoria and Yamagata lineages. A total of 571 influenza B virus sequences were analyzed. During the 2009-2010 season, most of the circulating influenza B viruses matched the vaccine strain; 91.0% (91/100) of viruses belonged to the Victoria lineage. In the 2007-2008, 2011-2012, and 2013-2014 seasons, co-circulation of each influenza B lineage was found with a match ratio to the vaccine strain of 53.2% (42/79), 40.9% (63/154), and 58.3% (134/230), respectively. Overall, 41.7% (238/571) of the circulating influenza B viruses belonged to the lineage mismatching the vaccine strain. During the seven influenza seasons, influenza B epidemics were substantial in four seasons in South Korea. Significant mismatches of the vaccine and lineage of the circulating influenza B viruses were found. The current trivalent influenza vaccine may not be fully suitable for effective protection against influenza B., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The influenza virus is reportedly associated with 3-5 million cases of severe illness and 250 000-500 000 deaths annually worldwide., Objectives: We investigated the variation of influenza A virus in Korea and examined the association with death., Methods: A total of 13 620 cases were enrolled in the Hospital-based Influenza Morbidity & Mortality surveillance system in Korea during 2011-2016. Among these cases, a total of 4725 were diagnosed with influenza using RT-PCR (influenza A; n = 3696, influenza B; n = 928, co-infection; n = 101). We used 254 viral sequences from the 3696 influenza A cases for phylogenetic analysis using the BioEdit and MEGA 6.06 programs., Results: We found that the sequences of A/H3N2 in the 2011-2012 season belong to subgroup 3C.1, whereas the sequences in the 2012-2013 season pertain to subgroup 3C.2. The sequences in the 2013-2014 and 2014-2015 seasons involve subgroups 3C.3a and 3C.2a. The A/H1N1pdm09 subtype belongs to subgroup 6 and contains two clusters. In addition, sequence analysis confirmed the several substitutions of internal genes and gene substitutions associated with drug resistance (I222V in NA and S31N in M2) in the fatal cases. While statistical analysis found no significant associations between genetic differences in the viruses and mortality, mortality was associated with certain host factors, such as chronic lung disease., Conclusions: In conclusion, influenza A virus clade changes occurred in Korea during the 2011-2016 seasons. These data, along with antigenic analysis, can aid in selecting effective vaccine strains. We confirmed that fatality in influenza A cases was related to underlying patient diseases, such as chronic lung disease, and further studies are needed to confirm associations between mortality and viral genetic substitutions., (© 2018 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Urinary tract infections (UTIs) are infectious diseases that commonly occur in communities. Although several international guidelines for the management of UTIs have been available, clinical characteristics, etiology and antimicrobial susceptibility patterns may differ from country to country. This work represents an update of the 2011 Korean guideline for UTIs. The current guideline was developed by the update and adaptation method. This clinical practice guideline provides recommendations for the diagnosis and management of UTIs, including asymptomatic bacteriuria, acute uncomplicated cystitis, acute uncomplicated pyelonephritis, complicated pyelonephritis related to urinary tract obstruction, and acute bacterial prostatitis. This guideline targets community-acquired UTIs occurring among adult patients. Healthcare-associated UTIs, catheter-associated UTIs, and infections in immunocompromised patients were not included in this guideline., Competing Interests: No conflicts of interest., (Copyright © 2018 by The Korean Society of Infectious Diseases and Korean Society for Chemotherapy.)

Since 2013, the Hospital-based Influenza Morbidity and Mortality (HIMM) surveillance system began a H7N9 influenza surveillance scheme for returning travelers in addition to pre-existing emergency room (ER)-based influenza-like illness (ILI) surveillance and severe acute respiratory infection (SARI) surveillance. Although limited to eastern China, avian A/H7N9 influenza virus is considered to have the highest pandemic potential among currently circulating influenza viruses. During the study period between October 1st, 2013 and April 30th, 2016, 11 cases presented with ILI within seven days of travel return. These patients visited China, Hong Kong, or neighboring Southeast Asian countries, but none of them visited a livestock market. Seasonal influenza virus (54.5%, 6 among 11) was the most common cause of ILI among returning travelers, and avian A/H7N9 influenza virus was not detected during the study period., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2018 The Korean Academy of Medical Sciences.)

To evaluate the frequency and appropriateness of indwelling urinary catheters (IUC) use and the incidence of catheter-associated urinary tract infections (CA-UTI), and explore the risk factors for CA-UTI in hospitals as a whole, we conducted a study. This study was divided into two parts; a point-prevalence study on Dec 12th 2012 and a prospective cohort study from Dec 13th 2012 to Jan 9th 2013 were performed in six hospitals in Korea. All hospitalized patients with newly-placed IUCs were enrolled and monitored weekly for 28 days after IUC placement. In the point-prevalence study, the IUCs were present in median 14.9/100 hospitalized patients (1Q 14, 3Q 16) across the six hospitals. In the prospective cohort study, the median IUC-days per patient was 5 (1Q 3, 3Q 10) and the median CA-UTI prevalence per 1,000 catheter days was 1.9 (1Q 0.7, 3Q 3.8) with significant inter-hospital variation. The proportion of patients with inappropriate IUC maintenance increased with number of IUC-days (8.5% on day 7, 9.4% on day 14, 16.3% on day 21, and 23.1% on day 28). Urinary output monitoring (23/36, 63.9%) was the most common indication for inappropriate use after 1 week of ICU placement. In multivariate analysis, IUC-days was significantly associated with the development of CA-UTI (odds ratio 1.122, 95% confidence interval 1.074-1.173, P< 0.001). IUC-days and CA-UTI rates vary between hospitals. IUC-days is a risk factor for CA-UTI, and is correlated with inappropriate use.

Background: Renal disease is one of the leading causes of morbidity and mortality among people infected with human immunodeficiency virus (HIV). However, there are very few published studies about renal insufficiency in HIV-infected persons in Asia, especially in South Korea., Materials and Methods: A cross-sectional study was performed to investigate the prevalence and risk factors of renal insufficiency, defined as <60 mL/min/1.73 m², in subjects in the Korea HIV/AIDS Cohort Study enrolled from 19 institutions between December 2006 and July 2013. Data at entry into the cohort were analyzed., Results: Of 454 enrolled subjects, 24 (5.3%) showed renal insufficiency at entry into the cohort. The mean age of patients in the renal insufficiency group was 5.28 years and the majority were male subjects (91.7%). All the patients were receiving antiretroviral agents, mostly protease inhibitor-based regimens (76.4%), for an average of 19 months. In univariate analysis, older age (P = 0.002), diabetes mellitus (DM) (P = 0.0002), unknown route of transmission (P = 0.007), and taking indinavir (P = 0.0022) were associated with renal insufficiency. In multivariable analysis, older age [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.03-1.12, P = 0.002], DM [OR 3.03, 95% CI 1.17-7.82, P = 0.022], unknown route of transmission [OR 6.15, 95% CI 1.77-21.33, P = 0.004], and taking indinavir [OR 3.07, 95% CI 1.17-8.05, P = 0.023] were independent risk factors of renal insufficiency., Conclusion: The prevalence of renal insufficiency in HIV-infected subjects in this study was relatively low, similar to that in other countries. Aging, DM, and taking indinavir were significantly associated with decreased glomerular filtration rate. Furthermore, unknown route of transmission was an independent risk factor, which was interpreted as a reflection of patient compliance. Further studies on the incidence and risk factors of renal insufficiency during HIV infection using follow-up cohort data are necessary., Competing Interests: No conflicts of interest., (Copyright © 2017 by The Korean Society of Infectious Diseases and Korean Society for Chemotherapy)

Background: The influenza B virus has two lineages; Yamagata and Victoria. The two lineages are antigenically distinct and it is difficult to expect cross-protection between the lineages. Actually, the mismatch between circulating influenza B viruses and vaccine strains has been occurred frequently. The cell-culture system for the production of influenza vaccine can contribute to improve vaccine strain selection and expand vaccine supplies. We investigated the immunogenicity and safety of cell culture-derived quadrivalent inactivated influenza vaccine (NBP607-QIV) in adults and elderly subjects., Methods: A randomized controlled phase III trial was undertaken in 10 university hospitals in the Republic of Korea (Clinical trial Number-NCT02467842). Adults (aged 19-59 years) and elderly subjects (aged ≥60 years) were randomly assigned in a 2:1:1 ratio to NBP607-QIV versus cell culture-based trivalent inactivated influenza vaccine-Yamagata (NBP607-Y) and cell culture-based trivalent inactivated influenza vaccine-Victoria (NBP607-V). Immunogenicity was assessed 3 weeks after vaccination by hemagglutination inhibition assay. Safety was assessed for 6 months post-vaccination: solicited adverse events (AEs) for 7 days, unsolicited AEs for 21 days and serious adverse events (SAEs) for 6 months. AEs were sub-classified as adverse drug reactions (ADRs) according to the causality., Results: A total of 1,503 participants were randomly assigned to NBP607-QIV (n = 752), NBP607-Y (n = 373) and NBP607-V (n = 378). The seroconversion rates of NBP607-QIV were 52.4%, 51.2%, 43.7% and 55.8% against A/H1N1, A/H3N2, B/Yamagata and B/Victoria, respectively. Non-inferiority against shared strains and superiority against alternate-lineage B strains were demonstrated for NBP607-QIV vs. NBP607-Y and NBP607-V. A total of 730 reactions occurred in 324 (43.1%) subjects of NBP607-QIV group. Majority of ADRs was solicited (99.2%) and mild (90.3%) in intensity. In adults (aged 19-59 years), solicited local AEs were slightly more frequent in NBP607-QIV group than NBP607-Y or NBP607-V group (40.9%, 33.4% and 32.5%, respectively). One SAE was observed among NBP607-QIV group, which was considered to be unrelated to the study vaccine within 3 weeks of vaccination and no vaccine-related SAEs were reported up to 6 months after vaccination., Conclusions: NBP607-QIV is a safe, well-tolerated and immunogenic influenza vaccine in Korean adults and elderly subjects.

In the 2016-2017 season, the A(H3N2) influenza epidemic presented an unusual early peak pattern compared with past seasons in South Korea. The interim vaccine effectiveness (VE) of influenza vaccination in preventing laboratory-confirmed influenza was estimated using test-negative design through the tertiary hospital-based influenza surveillance system in South Korea. From 1 September, 2016 to 7 January, 2017, adjusted VE of influenza vaccination in preventing laboratory-confirmed A(H3N2) was -52.1% (95% confidence interval [CI], -147.2 to 6.4); -70.0% (95% CI, -212.0 to 7.4) in 19-64 years and 4.3% (95% CI, -137.8 to 61.5) in the elderly. Circulating A(H3N2) viruses belonged to the three phylogenetic subclades of 3C.2a, differently to A/Hong Kong/4801/2014, the current vaccine strain. Amino acid substitutions in hemagglutinin of circulating viruses seem to contribute to low VE. In conclusion, interim VE analysis presented that the protection of laboratory-confirmed influenza by seasonal influenza vaccination did not show the statistical significance in South Korea in the 2016-2017 influenza season.

Considering the pandemic potential of avian influenza A/H5N1, development of an effective and well-tolerated vaccine is an essential part of pandemic preparedness plans. This phase III, randomized, double-blind study was conducted to assess the immunogenicity and safety profile of an alum-adjuvanted, whole virion, pre-pandemic influenza A/H5N1 vaccine (MG1109). Healthy individuals were randomly assigned, in a 3:1 ratio, to receive two doses of either MG1109 or placebo containing alum gel. Immunogenicity was determined by hemagglutination inhibition (HI) and microneutralization (MN) assays. Solicited and unsolicited adverse events were assessed after vaccination. Among 420 enrolled subjects, 418 were available for safety analysis, and 298 MG1109 recipients were available for per-protocol immunogenicity analyses. According to the HI assays, after two vaccine doses, all three of the Committee for Medicinal Products for Human Use (CHMP) criteria were met against the vaccine strain for all age groups: seroprotection rate = 74.8% (95% CI: 69.9 - 79.8), seroconversion rate = 67.8% (95% CI: 62.5-73.1), and geometric mean titer ratio (GMTR) = 5.9 (95% CI: 5.4 - 6.4). According to the MN assays, the GMTR was 2.4 (95% CI: 2.1 - 2.7) and 7.0 (95% CI: 6.3 - 7.9) three weeks after the first and second vaccine doses, respectively. Solicited local and systemic adverse events were mostly mild to moderate and were not significantly different between MG1109 and placebo recipients. In conclusion, two-dose administration of alum-adjuvanted H5N1 pre-pandemic influenza vaccine (MG1109) was highly immunogenic and tolerable in adults.

Background: This study was performed to investigate the disease burden of seasonal influenza in adults ≥20 years of age in Korea, based on surveillance data from the Hospital-based Influenza Morbidity & Mortality Surveillance (HIMM) network., Materials and Methods: The HIMM network is composed of two surveillance systems: emergency room-based and inpatients-based surveillance. A total of ten university hospitals all over the country are included in the surveillance network. The adult catchment population of the HIMM network was calculated by using the data of each hospital and the database of the Health Insurance Review and Assessment Service (HIRA) of Korea. The incidence rates of laboratory-confirmed medically-attended influenza, laboratory-confirmed influenza-related admission and laboratory-confirmed influenza-related death were calculated based on the catchment population. The socioeconomic burden of influenza was estimated using the human capital approach., Results: During the 2013-2014 influenza season, the calculated adult catchment population of the HIMM network was 1,380,000. The incidence of medically-attended laboratory-confirmed influenza infection was 242.8 per 100,000 adults. The incidence of laboratory-confirmed influenza-related admission was 57.9 per 100,000 adults. The incidence of laboratory-confirmed influenza-related death was 3.1 per 100,000 adults. The total socioeconomic cost of 2013-2014 seasonal influenza in Korean adult population was estimated as 125 million USD (1 USD = 1,100 KRW)., Conclusion: The disease burden of 2013-2014 seasonal influenza in Korean adult population is very high and indicates that more active prevention and control policies will be needed to decrease the burden. Additional researches will be needed to assess the burden of seasonal influenza in the Korean child population.

Background: The objective of this study was to examine the usefulness of blood cultures and radiologic imaging studies for developing therapeutic strategies in community-acquired acute pyelonephritis (CA-APN) patients., Materials and Methods: We prospectively collected the clinical data of CA-APN patients who visited 11 hospitals from March 2010 to February 2011., Results: Positive urine and blood cultures were obtained in 69.3% (568/820) and 42.7% (277/648), respectively, of a total of 827 CA-APN patients. Blood culture identified the urinary pathogen in 60 of 645 (9.3%) patients for whom both urine and blood cultures were performed; the organisms isolated from urine were inconsistent with those from blood in 11 and only blood cultures were positive in 49 patients. Final clinical failure was more common in the bacteremic patients than the non-bacteremic ones (8.0% vs. 2.7%, P = 0.003), as was hospital mortality (3.6% vs. 0.3%, P = 0.003). Likewise, durations of hospitalization and fever were significantly longer. Bacteremia was independent risk factor for mortality (OR 9.290, 1.145-75.392, P = 0.037). With regard to radiologic studies, the detection rate of APN was 84.4% (445/527) by abdominal computed tomography and 40% (72/180) by abdominal ultrasonography. Eighty-one of 683 patients (11.9%) were found to have renal abscess, perinephric abscess, urolithiasis, hydronephorosis/hydroureter or emphysematous cystitis, which could potentially impact on clinical management. Patients with Pitt score ≥ 1, flank pain or azotemia were significantly more likely to have such structural abnormalities., Conclusion: Blood cultures are clinically useful for diagnosis of CA-APN, and bacteremia is predictive factor for hospital mortality. Early radiologic imaging studies should be considered for CA-APN patients with Pitt scores ≥1, flank pain or azotemia., Competing Interests: No conflicts of interest, (Copyright © 2017 by The Korean Society of Infectious Diseases and Korean Society for Chemotherapy)

Background: Klebsiella pneumoniae with hypermucoviscosity (HM) phenotype is generally more virulent than HM-negative strains. The aim of this study was to investigate the prevalence of HM phenotype among urinary isolates and to compare the virulence factors, antimicrobial susceptibility patterns and clinical characteristics of HM-positive and -negative K. pneumoniae isolated from urine of hospitalized patients., Methods: From June to October 2013, a total of 81 non-repetitive K. pneumoniae strains were isolated from urine. HM phenotype was determined by a string test. The K1 and K2 genotypes, the allS, kfu, rmpA, rmpA2 and wabG, aerobactin gene were detected by polymerase chain reaction., Results: Of the 81 K. pneumoniae isolates, 12.3% produced a positive string test. The aerobactin (80.0%[8/10] vs. 15.5%[11/71], p = .0001), allS (40.0%[4/10] vs. 9.9%[7/71], p = .009), rmpA (70.0%[7/10] vs. 14.1%[10/71], p = .0001) and rmpA2 (60.0%[6/10] vs. 16.9%[12/71], p = .002) genes were more prevalent in HM positive than in HM negative strains. The K1 (20.0%[2/10) vs. 8.5%[6/71]] and K2 (30.0%[3/10] vs. 4.2%[3/71]) capsular serotypes were more common in HM strains than in non-HM strains (p = .0001). HM-positive K. pneumoniae isolates were more susceptible to amoxicillin/clavulanic acid (p = .02), cefazolin (p = .03), cefotaxime (p = .02) and ciprofloxacin (p = .03) than HM-negative isolates. Multivariate analysis showed that HM phenotype (OR, 23.87; 95% CI, 3.91-145.4, p < .01) and age >60 years (OR, 8.33; 95% CI, 1.25-55.31, p = .03) were significant risk factors for concurrent bacteraemia., Conclusion: Klebsiella pneumoniae with expression of HM phenotype isolated from urine were more likely to be associated with concurrent bacteraemia than isolates without the HM phenotype, and were more susceptible to antibiotics. Physicians have to be aware of the possibility of bacteraemia in patients with K. pneumoniae bacteriuria, especially if strains are HM positive and the patient is >60 years old.

Background: Concomitant administration of influenza and pneumococcal vaccines could be an efficient strategy to increase vaccine uptake among older adults. Nevertheless, immune interference and safety issues have been a concern when more than one vaccines are administered at the same time., Methods: Subjects aged ⩾60years were randomized in a 1:1:1 ratio to receive MF59-adjuvanted trivalent inactivated influenza vaccine (MF59-aTIV)+13-valent pneumococcal conjugate vaccine (PCV13) (Group 1), PCV13 alone (Group 2), or MF59-aTIV alone (Group 3). Hemagglutination inhibition (HI) and opsonophagocytic activity (OPA) assays were used to compare immunogenicity after single or concomitant vaccination., Results: A total of 1149 subjects (Group 1, N=373; Group 2, N=394; Group 3, N=382) were available for the assessment of immunogenicity and safety. All groups met immunogenicity criteria for the influenza vaccine in older adults with similar seroprotection rates, seroconversion rates, and geometric mean titer (GMT) fold-increases, irrespective of concomitant vaccination. For each pneumococcal serotype, OPA titers increased markedly after the PCV13 vaccination, irrespective of the concomitant influenza vaccination. After concomitant administration, the non-inferiority criteria of GMT ratios were met for all three influenza subtypes and 13 pneumococcal serotypes. No vaccine-related serious adverse events occurred., Conclusions: Concomitant MF59-aTIV and PCV13 administration showed no interference with antibody response and showed good safety profiles. (Clinical Trial Number - NCT02215863)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The World Health Organization recommends the surveillance of influenza-like illness (ILI) and severe acute respiratory infection (SARI) to respond effectively to both seasonal influenza epidemics and pandemics. In Korea, the "Hospital-based Influenza Morbidity and Mortality (HIMM)" surveillance system has been operated to monitor ILI and SARI occurrences., Materials and Methods: A multi-center prospective observational study was conducted. Adult patients with acute respiratory infection (ARI) were enrolled during the 2011-12, 2012-2013, and 2013-2014 influenza seasons at the 10 university hospitals using the HIMM surveillance system. With respect to SARI and pneumonia development, risk profiles were analyzed in patients with ARI in Korea., Results: A total of 5,459 cases were eligible for this analysis. Among 5,459 cases with ARI, 2,887 cases (52.9%) were identified that they had influenza infection. Among enrolled cases, 750 cases belonged to the SARI group, while 4,709 cases belonged to the non-SARI group. With respect to pneumonia development, 317 cases were accompanied by pneumonia, and 5,142 cases were not. Multivariate analyses revealed that the following factors were associated with an increased risk of SARI: Old age (≥65 years) (odds ratio [OR] 2.69, 95% confidence interval [CI] 2.2-3.32), chronic heart disease (CHD) (OR 2.24, 95% CI 1.68-2.98), cerebrovascular disease (CVD) (OR 1.49, 95% CI 1.05-2.10), chronic obstructive pulmonary disease (COPD) (OR 2.34, 95% CI 1.48-3.69), asthma (OR 2.33, 95% CI 1.62-3.36), chronic kidney disease (CKD) (OR 2.62, 95% CI 1.73-3.99), chronic liver disease (OR 1.71, 95% CI 1.04-2.81), and autoimmune diseases (OR 2.53, 1.57-4.08). Multivariate analyses revealed that the following factors were independent risk factors for pneumonia development: Old age (≥65 years) (OR 5.71, 95% CI 4.10-7.94), CHD (OR 1.54, 95% CI 1.07-2.22), COPD (OR 2.34, 95% CI 1.48-3.69), asthma (OR 2.33, 95% CI 1.62-3.36), CKD (OR 2.62, 95% CI 1.73-3.99), immunocompromised conditions (OR 3.12, 95% CI 1.47-6.62), and autoimmune diseases (OR 3.35, 95% CI 1.79-6.27). The risk of SARI and pneumonia was increased by the number of concurrent chronic medical conditions., Conclusion: The risk of SARI and pneumonia development among adult patient with ARI was significantly increased by the presence or number of concurrent chronic medical conditions in Korea., Competing Interests: No conflicts of interest.

Identification of mite and tick bite sites provides important clinical information. The predominant mite species in Korea associated with scrub typhus are Leptotrombidium pallidum and Leptotrombidium scutellare The most abundant tick species is Haemaphysalis longicornis To date, there has been no comparative study on preferred bite sites between mites and ticks in humans. This study included a review of medical records and a field study. For mite bite sites, eschars were checked on 506 patients with scrub typhus, confirmed by indirect immunofluorescence assay or nested polymerase chain reaction on the 56-kDa type-specific antigen gene of Orientia tsutsugamushi Tick bite sites were identified and marked on a diagram for 91 patients who experienced tick bites within the previous year through a field epidemiological investigation. The mite and tick bite sites in Koreans were compared. The most frequently observed mite bite sites were the anterior chest, including the axillae (29.1%) and the abdominal region, including the inguinal area (26.1%). Tick bite sites were most frequent on the lower extremities (33.0%), followed by the abdominal region, including the inguinal area (26.4%), and upper extremities (26.4%). The distribution was significantly different between mite and tick bite sites (P < 0.001). There was a statistically significant difference in the mite bite (P = 0.001), but not tick bite sites (P = 0.985), between men and women. This is the first report on the differences between tick and mite bite sites, and may help clinicians reach a rapid diagnosis of mite- or tick-borne infection., (© The American Society of Tropical Medicine and Hygiene.)

Background/aims: Efforts to decrease the use of extended-spectrum cephalosporins are required to prevent the selection and transmission of multi-drug resistant pathogens, such as extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. The objectives of this study were to assess the clinical efficacy of intravenous cefuroxime as an empirical antibiotic for the treatment of hospitalized women with acute pyelonephritis (APN) caused by Escherichia coli., Methods: We analyzed the clinical and microbiologic database of 328 hospitalized women with community-onset APN., Results: Of 328 women with APN, 22 patients had cefuroxime-resistant E. coli APN, and 306 patients had cefuroxime-susceptible E. coli APN. The early clinical success rates were significantly higher (p = 0.001) in the cefuroxime-susceptible group (90.8%, 278/306) than in the cefuroxime-resistant group (68.2%, 15/22) at 72 hours. The clinical cure rates at 4 to 14 days after completing antimicrobial therapy were not significantly different in the cefuroxime-resistant or -susceptible groups, with 88.2% (15/17) and 97.8% (223/228; p = 0.078), respectively. The microbiological cure rates were not significantly different and were 90.9% (10/11) and 93.4% (128/137), respectively (p = 0.550). The median duration of hospitalization in the cefuroxime-resistant and -susceptible groups was 10 days (interquartile range [IQR], 8 to 13) and 10 days (IQR, 8 to 14), respectively (p =0.319)., Conclusions: Cefuroxime, a second-generation cephalosporin, can be used for the initial empirical therapy of community-onset APN if tailored according to uropathogen identification and susceptibility results, especially in areas where the prevalence rate of ESBL-producing uropathogens is low.

Background: Cell culture-derived influenza vaccines (CCIVs) have several important advantages over egg-based influenza vaccines, including shorter production time, better preservation of wild-type virus antigenicity and large-scale production capacity., Methods: A randomized, double-blind, phase 3 trial was undertaken to evaluate the immunogenicity and safety of a novel cell culture-derived inactivated, subunit, trivalent influenza vaccine (NBP607, SK Chemicals, Seongnam, Korea) compared to the control vaccine (AgrippalS1, Novartis Vaccines and Diagnostics Srl, Siena, Italy) among healthy adults aged 19 years or older (Clinical trial Number-NCT02344134). Immunogenicity was determined at pre-vaccination, 1 month and 6 month post-vaccination by the hemagglutination inhibition assay. Solicited and unsolicited adverse events were assessed after vaccination., Results: A total of 1156 healthy subjects were recruited. NBP607 met all of the criteria of Committee for Medicinal Products for Human Use (CHMP) at 21 days post-vaccination. Contrary to NBP607, the control vaccine did not satisfy the seroconversion criteria for influenza B irrespective of age. Although the geometric mean titer for each influenza subtype declined gradually, seroprotection rate still remained ≥80% for all subtypes up to six month after NBP607 administration. NBP607 recipients met the seroprotection criteria for all three influenza subtypes up to 6 month post-vaccination. There was no significant difference in the occurrence of adverse events between the NBP607 and control groups., Conclusion: NBP607, a novel CCIV, showed excellent immunogenicity that lasted ≥6 months after vaccination and had tolerable safety profiles. In particular, NBP607 was more immunogenic against influenza B compared to the control, an egg-based subunit vaccine., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: This study examined the clinical effectiveness of parenteral cefuroxime and cefotaxime as empirical antibiotics for treating hospitalized women with uncomplicated acute pyelonephritis (APN)., Materials and Methods: This study was based on the clinical and microbiologic data of 255 hospitalized women with APN. Of these 255 women, 144 patients received cefuroxime and 111 received cefotaxime., Results: There were no marked differences in the demographic features, clinical characteristics, and treatment duration between the populations of the cefuroxime and cefotaxime groups. The rates of defervescence showed no significant differences in the two groups at 48, 72, 96, and 120 hours. The clinical cure rates observed at the follow-up visit 4 to 14 days after the completion of antimicrobial therapy were not statistically different between the cefuroxime and cefotaxime groups [94.9% (129 of 136) versus 98.0% (100 of 102), respectively; p=0.307], and the microbiological cure rates were also not significantly different [88.3% (91 of 103) versus 95.0% (76 of 80), respectively; p=0.186]. The median hospitalization periods in the cefuroxime and cefotaxime groups were 7 (6-8) and 7 (6-8) days (p=0.157), respectively. Microbiological success rates after 72-96 hours of initial antimicrobial therapy were also not statistically different in the cefuroxime and cefotaxime groups, 89.4% (110 of 123) versus 94.9% (93 of 98; p=0.140)., Conclusion: Cefuroxime, a second-generation cephalosporin, is an appropriate antibiotic option for the initial treatment of uncomplicated APN and its efficacy does not differ from cefotaxime, a third-generation cephalosporin, in the initial parenteral therapy for community-onset APN.

Invasive aspergillosis (IA), generally considered an opportunistic infection in immunocompromised hosts, is associated with high morbidity and mortality. IA commonly occurs in the respiratory tract with isolated reports of aspergillosis infection in the nasal sinuses, central nervous system, skin, liver, and urinary tract. Extra-pulmonary aspergillosis is usually observed in disseminated disease. To date, there are a few studies regarding primary and disseminated gastrointestinal (GI) aspergillosis in immunocompromised hosts. Only a few cases of primary GI aspergillosis in non-immunocompromised hosts have been reported; of these, almost all of them involved the upper GI tract. We describe a very rare case of IA involving the lower GI tract in the patient without classical risk factors that presented as multiple colon perforations and was successfully treated by surgery and antifungal treatment. We also review related literature and discuss the characteristics and risk factors of IA in the immunocompetent hosts without classical risk factors. This case that shows IA should be considered in critically ill patients, and that primary lower GI aspergillosis may also occur in the immunocompetent hosts without classical risk factors.

Background: AS03-adjuvanted H5N1 pandemic influenza vaccines have been assessed in an extensive clinical development program conducted in North America, Europe, and Asia including children from 6 months of age, adults, and elderly adults. We evaluated AS03-H5N1 in Korean adults 18 through 60 years of age., Methods: This Phase IV, randomized, study was conducted to assess the immunogenicity, reactogenicity, and safety of two doses (3.75μg of hemagglutinin antigen) of A/Indonesia/5/2005 (H5N1) adjuvanted with AS03 given 21 days apart in Korean adults. Antibody responses were assessed using hemagglutination-inhibition (HI) assays against the vaccine strain and a vaccine-heterologous strain (A/Vietnam/1194/2004) 21 days after the second dose. A control group (safety) received a licensed seasonal inactivated trivalent influenza vaccine (TIV). Reactogenicity was assessed for 7 days after each vaccination, and unsolicited adverse events were assessed for 182 days following vaccination in both study groups (NCT01730378)., Results: AS03-H5N1 was immunogenic and elicited robust HI antibody responses with seroconversion rates of 100% for the vaccine strain and 69.1% for the heterologous strain (N=81). HI antibody responses fulfilled the European licensure criteria for immunogenicity (primary endpoint). The incidence of local and systemic solicited adverse events (reactogenicity) was higher with AS03-H5N1 than TIV. There was no apparent difference in the rate of unsolicited adverse events in the AS03-H5N1 and TIV groups., Conclusion: The results indicate that AS03-H5N1 vaccine is immunogenic with reactogenicity and safety findings that are consistent with the established profile of AS03-H5N1 vaccine., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background/aims: Acute pyelonephritis (APN) is the most common cause of community-onset bacteremia in hospitalized elderly patients. The objectives of this study were to investigate the differences in the clinical and microbiological data of hospitalized elderly and non-elderly women with community-onset APN., Methods: Women with community-onset APN as a discharge diagnosis were identified from January 2004 to December 2013 using an electronic medical records system. We compared the clinical and microbiologic data in elderly and non-elderly women with community-onset APN due to Enterobacteriaceae., Results: Of the 1,134 women with community-onset APN caused by Enterobacteriaceae, 443 were elderly and 691 were non-elderly women. The elderly group had a lower frequency of upper and lower urinary tract symptoms/signs than the non-elderly. The incidence of bacteremia, extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, patients with a C-reactive protein (CRP) level ≥ 15 mg/dL, and patients with a leukocyte count ≥ 15,000/mm(3) in the blood, were significantly higher in the elderly group than in the non-elderly group. The proportion of patients requiring hospitalization for 10 days or more was significantly higher in the elderly group compared to the non-elderly group (51.5% vs. 26.2%, p < 0.001). The clinical cure rates at 4 to 14 days after the end of therapy were 98.3% (338/344) and 97.4% (519/533) in the elderly and non-elderly groups, respectively (p = 0.393)., Conclusions: Elderly women with APN exhibit higher serum CRP levels, a higher frequency of bacteremia, a higher proportion of ESBL-producing uropathogens, and require a longer hospitalization than non-elderly women, although these patients may not complain of typical urinary symptoms.

This study was performed to compare the therapeutic efficacy of cefuroxime with that of cefotaxime as initial antimicrobial therapies in women with complicated nonobstructive acute pyelonephritis (APN) caused by Enterobacteriaceae infections. The clinical characteristics and outcomes of a cefuroxime-treated group (n = 156) were compared with those of a cefotaxime-treated group (n = 166). Of these 322 women, 90 from each group were matched by propensity scores. The defervescence rates were not significantly different in the cefuroxime and cefotaxime groups at 72 h after the start of antimicrobial therapy (81.1% versus 78.9%, P = 0.709). The clinical and microbiological cure rates during the follow-up visits that were 4 to 14 days after the end of the antimicrobial therapies were not significantly different in the cefuroxime versus cefotaxime groups, which were 97.8% (87/89) versus 97.8% (87/89) (P > 0.999) and 89.5% (68/76) versus 90.7% (68/75) (P = 0.807), respectively. The median hospital stay duration and the median times to defervescence in the cefuroxime versus cefotaxime groups were 8 days (interquartile range [IQR], 7 to 10 days) versus 9 days (IQR, 7 to 11 days), respectively, and 55 h (IQR, 37 to 70 h) versus 55 h (IQR, 35 to 69 h), respectively. Bacteremia, extended-spectrum-β-lactamase-producing Enterobacteriaceae, C-reactive protein levels of ≥ 15 mg/dl, and white blood cell counts of ≥ 15,000/mm(3) of blood had independent effects on the rates of early clinical failure. Our data suggest that the effects of cefuroxime are not different from those of cefotaxime when they are used as an initial antimicrobial treatments for community-onset complicated nonobstructive APN in women., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Pneumonia and acute exacerbation of chronic illness are leading causes of influenza-related hospitalization. Therefore, influenza and pneumococcal vaccinations are strongly recommended for adults with comorbidities. Using a hospital-based influenza surveillance system, we performed a multicenter, prospective cohort study of patients visiting emergency rooms with influenza-like illness (ILI) during the influenza epidemic period in 2013 to 2014. Patients aged ≥ 19 years were enrolled, and clinical data were collected. Multivariate analyses were performed to estimate the effectiveness of influenza and pneumococcal vaccination in preventing pneumonia development and hospitalization. During study periods, 2,262 patients with ILI were registered. Among 2,217 patients with available vaccination records, 31.9% (707 patients) and 9.7% (216 patients) had received influenza and pneumococcal vaccines, respectively. Among patients who had been administered a pneumococcal vaccine, 94.4% had received the 23-valent polysaccharide vaccine (PPV23). The adjusted rates of effectiveness of the influenza vaccine for preventing pneumonia development and hospitalization were 64.0% (95% confidence interval [CI] = 29% to 81%) and 35.0% (95% CI = 12% to 52%), respectively. Pneumococcal vaccination did not reduce pneumonia development or hospitalization. In conclusion, influenza rather than PPV23 vaccination may reduce pneumonia development and hospitalization in patients with preceding ILI., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

A Gram-negative, yellow-pigmented, rod-shaped bacteria, designated M09-0166(T)and M09-1053 were isolated from human urine samples. 16S rRNA gene sequence analysis revealed that the isolates belong to the Myroides cluster and were closely related to Myroides phaeus DSM 23313(T) (96.3 %), Myroides odoratimimus KCTC 23053(T) (96.1 %), Myroides profundi KCTC 23066(T) (96.0 %), Myroides odoratus KCTC 23054(T) (95.4 %) and Myroides pelagicus KCTC 12661(T) (95.2 %). The major mena quinone was identified as MK-6. The major polar lipids were identified as phosphatidylethanolamine, amino lipids, and several unknown lipids, and the major fatty acids as iso-C15:0 and iso-C17:0 3-OH. Phenotypic and chemotaxonomic data supported the affiliation of the isolates with the genus Myroides and clearly indicated that two isolates represent novel species, for which the name Myroides injenensis sp. nov. (type strain, M09-0166(T) = KCTC 23367(T) = JCM 17451(T)) is proposed.

Aminoglycosides may serve as fluoroquinolone-sparing or cephalosporin-sparing agents if the clinical effectiveness of aminoglycoside monotherapy is demonstrated. The purposes of this study were to investigate the clinical efficacy of gentamicin as an initial empirical antimicrobial agent and to evaluate the effects of gentamicin resistance on clinical outcomes in women with complicated non-obstructive acute pyelonephritis (APN). Medical records of 1066 women with a diagnosis of APN were reviewed retrospectively. We enrolled 275 women with community-onset complicated non-obstructive APN due to Enterobacteriaceae who received gentamicin as their initial antibiotic. Of these 275 patients, 43 had gentamicin-resistant (GM-R) Enterobacteriaceae APN, and 232 had gentamicin-susceptible (GM-S) Enterobacteriaceae APN. The early clinical success rates were 67.4% (29/43) versus 89.7% (208/232) at 72 h in the GM-R versus the GM-S groups (p 0.001). The overall clinical cure rate was 100% (43/43) and 98.7% (229/232) in the GM-R and GM-S groups, respectively. The duration of hospital stay was significantly longer in the elderly, although there were no significant differences in the rates of early clinical success, final clinical cure, mortality, and time to fever clearance between the elderly and non-elderly groups. Resistance of Enterobacteriaceae to gentamicin, haematuria and serum C-reactive protein level≥20 mg/dL were independently associated with early clinical failure. Gentamicin can be an effective initial antibiotic option for empirical therapy in women with community-onset complicated APN who do not need urological interventional procedures. The use of gentamicin may contribute to a reduction of fluoroquinolone or broad-spectrum cephalosporin use in the treatment of complicated APN., (© 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.)

In patients with community-onset acute pyelonephritis (CO-APN), assessing the risk factors for poor clinical response after 72 h of antibiotic treatment (early clinical failure) is important. The objectives of this study were to define those risk factors, and to assess whether early clinical failure influences mortality and treatment outcomes. We prospectively collected the clinical and microbiological data of women with CO-APN in South Korea from March 2010 to February 2012. The numbers of cases in the early clinical success and early clinical failure groups were 840 (79.1%) and 222 (20.9%), respectively. Final clinical failure and mortality were higher in the early clinical failure group than in the early clinical success group (14.9% vs 2.3%, p <0.001; 6.8% vs 0.1%, p 0.001, respectively). In a multiple logistic regression model, the risk factors for early clinical failure among the total 1062 patients were diabetes mellitus (OR 1.5; 95% CI 1.1-2.1), chronic liver diseases (OR 3.3; 95% CI 1.6-6.7), malignancy (OR 2.2; 95% CI 1.1-4.4), Pitt score ≥2 (OR 2.5; 95% CI 1.6-3.8), presence of azotaemia (OR 1.8; 95% CI 1.2-2.7), white blood cell count ≥20 000/mm(3) (OR 2.5; 95% CI 1.6-4.0), serum C-reactive protein level ≥20 mg/dL (OR 1.7; 95% CI 1.2-2.4), and history of antibiotic usage within the previous year (OR 1.5; 95% CI 1.1-2.2). Analysing the subgroup of 743 patients with CO-APN due to Enterobacteriaceae, fluoroquinolone resistance of the uropathogen was another factor associated with early clinical failure (OR 1.7; 95% CI 1.1-2.5). Simple variables of underlying diseases, previous antibiotic usage and initial laboratory test outcomes can be used to decide on the direction of treatment in CO-APN., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

Objectives: Purpose of this study was to compare clinical characteristics and treatment outcomes in diabetic and non-diabetic women with community-acquired APN (CA-APN)., Methods: We prospectively collected and analyzed clinical data of women with CA-APN who attended 11 hospitals in South Korea from March 2010 to February 2012., Results: Of a total of 775 patients, 246 (31.7%) were diabetic and 529 (68.3%) non-diabetic. Fewer of the diabetic patients had flank pain (27.6% vs. 37.2% P = 0.009), symptoms of lower urinary tract infection (57.3% vs. 69.6% P = 0.001) and costovertebral angle tenderness (54.9% vs. 72.2% P < 0.001). However, more of them had C-reactive protein ≥20 mg/dL (40.7% vs. 27.4% P < 0.001), azotemia (29.3% vs. 13.4% P < 0.001) and bacteremia (53.7% vs. 38.2% P < 0.001). Final clinical failure rates and deaths did not differ between the two groups: 6.9% vs. 4.5%, P = 0.169; 2.0% vs. 1.7%, P = 0.747. However, hospitalization was longer in the diabetics than the non-diabetics (median 9.0 days vs. 7.0 days, P < 0.001). In logistic regression, diabetes was independently associated with longer hospitalization (OR 1.7, CI 1.1-2.7, P = 0.011), together with nausea/vomiting, history of admission within 1 year, bacteremia, azotemia, and dementia, as well as extended-spectrum β-lactamase (ESBL)-positivity and fluoroquinolone resistance of uropathogens., Conclusions: CA-APN patients with diabetes have more severe disease manifestations and require longer hospitalization than non-diabetic patients although their clinical findings are less clear than those of non-diabetic patients., (Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Spontaneous pneumothorax occurs in up to 35% of patients with Pneumocystis jirovecii pneumonia. However, spontaneous pneumomediastinum and pneumopericardium are uncommon complications in patients infected with human immunodeficiency virus, with no reported incidence rates, even among patients with acquired immunodeficiency syndrome (AIDS) and P. jirovecii pneumonia. We report a case of spontaneous pneumomediastinum, pneumopericardium, and pneumothorax with respiratory failure during treatment of P. jirovecii pneumonia in a patient with AIDS; the P. jirovecii infection was confirmed by performing methenamine silver staining of bronchoalveolar lavage specimens. This case suggests that spontaneous pneumomediastinum and pneumopericardium should be considered in patients with AIDS and P. jirovecii pneumonia.