Clinical Characteristics and Outcomes of Children With SARS-CoV-2 Infection During the Delta and Omicron Variant-Dominant Periods in Korea.

BACKGROUND: Data on the clinical characteristics of pediatric patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infection are limited. We aimed to evaluate the clinical features and outcomes of children with SARS-CoV-2 infection before and after omicron variant dominance in Korea. METHODS: A multicenter retrospective cohort study was conducted in hospitalized patients aged ≤ 18 years with laboratory-confirmed SARS-CoV-2 infection at five university hospitals in South Korea. The study periods were divided into the delta (from August 23, 2021 to January 2, 2022) and omicron (from January 30 to March 31, 2022). RESULTS: In total, 612 hospitalized patients were identified (211, delta; 401, omicron). During the omicron and delta periods, the proportions of individuals with serious illness (moderate, severe, and critical severity) were 21.2% and 11.8%, respectively (P = 0.034). Compared with the delta period, the proportions of patients with moderate illness increased significantly in the age groups of 0-4 years (14.2% vs. 3.4%) and 5-11 years (18.6% vs. 4.2%) during the omicron period. During the two periods, the proportions of patients with complex chronic diseases (delta, 16.0% vs. 4.3%, P = 0.040; omicron, 27.1% vs. 12.7%; P = 0.002), respiratory diseases except for asthma (delta, 8.0% vs. 0.0%, P = 0.013; omicron, 9.4% vs. 1.6%; P = 0.001), and neurologic diseases (delta, 28.0% vs. 3.2%, P < 0.001; omicron, 40.0% vs. 5.1%, P < 0.001) were significantly higher in patients with serious illness than in those with non-serious illness. During the delta period, the risk for serious illness was higher among patients with obesity (adjusted odds ratio [aOR], 8.18; 95% confidence interval [CI], 2.80-27.36) and neurologic diseases (aOR, 39.43; 95% CI, 6.90-268.3) and aged 12-18 years (aOR, 3.92; 95% CI, 1.46-10.85). However, the presence of neurologic disease (aOR, 9.80; 95% CI, 4.50-22.57) was the only risk factor for serious illness during the omicron period. During the omicron period, the proportions of patients with croup (11.0% vs. 0.5%) and seizures (13.2% vs. 2.8%) increased significantly compared with the delta period. CONCLUSION: Compared with the delta period, the proportions of young children and patients with complex comorbidities were higher during the omicron period in Korea. Patients with complex chronic diseases, especially neurologic diseases, had a high risk of severe coronavirus disease 2019 in the two distinct variant-dominant periods.

Change in Severity and Clinical Manifestation of MIS-C Over SARS-CoV-2 Variant Outbreaks in Korea.

BACKGROUND: There is difference in the incidence of multi-system inflammatory syndrome in children (MIS-C) in patients with different variants of severe acute respiratory syndrome coronavirus 2, however, little is known about the epidemiology in Asian countries. We investigated and compared the epidemiology of the MIS-C during omicron-dominant period with that of previous periods in South Korea. METHODS: We obtained clinical, epidemiological and laboratory data on MIS-C cases from national MIS-C surveillance in South Korea. We defined pre-delta period as January 2020-May 2021; delta period as June 2021-December 2021; and omicron period as January 2022-April 2022. We describe the clinical characteristics and outcomes of MIS-C patients by period. RESULTS: A total of 91 cases were assessed to be MIS-C cases. Number of MIS-C cases have increased from six cases during pre-delta period to 66 cases during omicron period, while the incidence rate (the number of MIS-C cases per 100,000 cases of reported coronavirus disease 2019) has decreased from 38.5 cases per 100,000 (95% confidence interval [CI], 14.1-83.9) during pre-delta period to 1.6 cases per 100,000 (95% CI, 1.2-2.0) during omicron periods. During pre-delta period, 66.7% and 100% had hypotension and gastrointestinal involvement, respectively; while during omicron period, 12.1% and 6.1% had such clinical manifestations. Fifty percent of pre-delta MIS-C patients were taken intensive care unit (ICU) cares, while 10.6% of patients during omicron periods were in ICUs. CONCLUSION: Omicron period were associated with less severe clinical manifestation compared to pre-delta and delta periods. Although incidence rate of MIS-C was lower for the omicron period than pre-delta and delta periods, number of patients reported with MIS-C may pose a substantial clinical burden.

A Report on a Nationwide Surveillance System for Pediatric Acute Hepatitis of Unknown Etiology in Korea.

BACKGROUND: Several cases of pediatric acute hepatitis of unknown etiology related to adenoviral infections have been reported in Europe since January 2022. The aim of this study was to compare the incidence, severity, possible etiology, and prognosis of the disease with those in the past in Korea. METHODS: The surveillance group collected data between May and November 2022 using a surveillance system. Acute hepatitis of unknown etiology was defined in patients aged < 16 years with a serum transaminase level > 500 IU/L, not due to hepatitis A-E or other underlying causes. For comparison, data from 18 university hospitals were retrospectively collected as a control group between January 2021 and April 2022. RESULTS: We enrolled 270 patients (mean age, 5 years). The most common symptom was fever. However, the incidence was similar between 2021 and 2022. Liver function test results, number of patients with acute liver failure (ALF), liver transplantation (LT), death, and adenovirus detection rates did not differ between the two groups. None of the adenovirus-positive patients in either group experienced ALF, LT, or death. In the surveillance group, adenovirus-associated virus-2 was detected in four patients, one of whom underwent LT. Patients with an unknown etiology showed significantly higher bilirubin levels, a lower platelet count, and a higher LT rate than patients with a possible etiology. CONCLUSION: The incidence of pediatric acute hepatitis of unknown etiology and adenovirus detection rate have not increased in Korea.

Twenty-Five Year Trend Change in the Etiology of Pediatric Invasive Bacterial Infections in Korea, 1996-2020.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic has contributed to the change in the epidemiology of many infectious diseases. This study aimed to establish the pre-pandemic epidemiology of pediatric invasive bacterial infection (IBI). METHODS: A retrospective multicenter-based surveillance for pediatric IBIs has been maintained from 1996 to 2020 in Korea. IBIs caused by eight bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pyogenes, Listeria monocytogenes, and Salmonella species) in immunocompetent children > 3 months of age were collected at 29 centers. The annual trend in the proportion of IBIs by each pathogen was analyzed. RESULTS: A total of 2,195 episodes were identified during the 25-year period between 1996 and 2020. S. pneumoniae (42.4%), S. aureus (22.1%), and Salmonella species (21.0%) were common in children 3 to 59 months of age. In children ≥ 5 years of age, S. aureus (58.1%), followed by Salmonella species (14.8%) and S. pneumoniae (12.2%) were common. Excluding the year 2020, there was a trend toward a decrease in the relative proportions of S. pneumoniae (rs = -0.430, P = 0.036), H. influenzae (rs = -0.922, P < 0.001), while trend toward an increase in the relative proportion of S. aureus (rs = 0.850, P < 0.001), S. agalactiae (rs = 0.615, P = 0.001), and S. pyogenes (rs = 0.554, P = 0.005). CONCLUSION: In the proportion of IBIs over a 24-year period between 1996 and 2019, we observed a decreasing trend for S. pneumoniae and H. influenzae and an increasing trend for S. aureus, S. agalactiae, and S. pyogenes in children > 3 months of age. These findings can be used as the baseline data to navigate the trend in the epidemiology of pediatric IBI in the post COVID-19 era.

Professional Status of Infectious Disease Specialists in Korea: A Nationwide Survey.

BACKGROUND: Infectious disease (ID) specialists are skilled facilitators of medical consultation who promote better outcomes in patient survival, antibiotic stewardship as well as healthcare safety in pandemic response. This study aimed to assess the working status of ID specialists and identify problems faced by ID professionals in Korea. METHODS: This was a nationwide cross-sectional study in Korea. An online-based survey was conducted over 11 days (from December 17-27, 2020), targeting all active adult (n = 281) and pediatric (n = 71) ID specialists in Korea (N = 352). Questions regarding the practice areas of the specialists were divided into five categories: 1) clinical practices of outpatient care, inpatient care, and consultations; 2) infection control; 3) antibiotic stewardship; 4) research; and 5) education and training. We investigated the weekly time-use patterns for these areas of practice. RESULTS: Of the 352 ID specialists, 195 (55.4%; 51.2% [144/281] adult and 71.8% [51/71] pediatric ID specialists) responded in the survey. Moreover, 144 (73.8%) of the total respondents were involved in all practice categories investigated. The most common practice area was outpatient service (93.8%), followed by consultation (91.3%) and inpatient service (87.7%). Specialists worked a median of 61 (interquartile range: 54-71) hours weekly: patient care, 29 (14-37) hours; research 11 (5-19) hours; infection control 4 (2-10) hours; antibiotic stewardship, 3 (1-5) hours; and education/training, 2 (2-6) hours. CONCLUSION: ID specialists in Korea simultaneously undertake multiple tasks and work long hours, highlighting the need for training and employing more ID specialists.

SARS-CoV-2-Naïve Korean Children and Adolescents Hospitalized With COVID-19 in 2021.

BACKGROUND: The risk of severe outcomes with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta variant remains low in children and adolescents, but less is known about its effect on the SARS-CoV-2-naïve population. This study evaluated clinical manifestations and risk factors for moderate-to-critical coronavirus disease 2019 (COVID-19) in mostly SARS-CoV-2-naïve children and adolescents in 2021. METHODS: This multicenter retrospective study included patients aged 0-18 years who were hospitalized with COVID-19 at 8 referring hospitals in South Korea during the predelta-predominant and delta-predominant periods in 2021. Each case was labeled as either hospitalization with medical needs or for isolation. Severity was categorized as mild, moderate, severe, or critical with regard to pneumonia presence and illness severity. RESULTS: Among 753 cases, most (99.5%) had no prior history of COVID-19 or vaccination against COVID-19. The proportions of hospitalization with medical needs (3.5% vs. 19.7%), moderate illness (0.9% vs. 4.0%), and severe/critical illness (0.8% vs. 5.3%) increased during delta predominance. The risk of moderate-to-critical COVID-19 among hospitalizations with medical needs was higher among patients aged 12-18 years (adjusted odds ratio [aOR], 4.1; 95% confidence interval [CI], 1.5-11.8) and with obesity (aOR, 6.9; 95% CI, 2.4-19.6) but not among patients infected during delta predominance. However, children with obesity experienced more severe COVID-19 during delta predominance (aOR, 6.1; 95% CI, 1.2-29.6). CONCLUSION: Despite its similar severity among most SARS-CoV-2-naïve children and adolescents, the delta variant may affect COVID-19 severity in those with high-risk underlying medical conditions. Underlying conditions, particularly obesity, may cause severe COVID-19 in children and adolescents, warranting strong consideration for vaccinating high-risk children.

Surveillance of COVID-19-Associated Multisystem Inflammatory Syndrome in Children, South Korea.

A concerning development during the coronavirus disease pandemic has been multisystem inflammatory syndrome in children. Reports of this condition in East Asia have been limited. In South Korea, 3 cases were reported to the national surveillance system for multisystem inflammatory syndrome in children. All case-patients were hospitalized and survived with no major disease sequelae.

Efficacy of tetracyclines and fluoroquinolones for the treatment of macrolide-refractory Mycoplasma pneumoniae pneumonia in children: a systematic review and meta-analysis.

BACKGROUND: Mycoplasma pneumoniae is a common pathogen that causes community-acquired pneumonia in school-age children. Macrolides are considered a first-line treatment for M. pneumoniae infection in children, but macrolide-refractory M. pneumoniae (MRMP) strains have become more common. In this study, we assessed the efficacy of tetracyclines and fluoroquinolones in MRMP treatment in children through a systematic review and meta-analysis. METHODS: Two reviewers individually searched 10 electronic databases (Medline/Pubmed, Embase, the Cochrane Library, and core Korean, Chinese, and Japanese journals) for papers published from January 1, 1990 to March 8, 2018. The following data for each treatment group were extracted from the selected studies: intervention (tetracyclines and fluoroquinolones/comparator), patient characteristics (age and sex), and outcomes (fever duration, hospital stay length, treatment success rate, and defervescence rates 24, 48, and 72 h after starting treatment). RESULTS: Eight studies involving 537 participants were included. Fever duration and hospital stay length were shorter in the tetracycline group than in the macrolide group (weighted mean difference [WMD] = - 1.45, 95% confidence interval [CI]: - 2.55 to - 0.36, P = 0.009; and WMD = - 3.33, 95% CI: - 4.32 to - 2.35, P < 0.00001, respectively). The therapeutic efficacy was significantly higher in the tetracycline group than in the macrolide group (odds ratio [OR]: 8.80, 95% CI: 3.12-24.82). With regard to defervescence rate, patients in the tetracycline group showed significant improvement compared to those in the macrolide group (defervescence rate after 24 h, OR: 5.34, 95% CI: 1.81-15.75; after 48 h, OR 18.37, 95% CI: 8.87-38.03; and after 72 h, OR: 40.77, 95% CI: 6.15-270.12). There were no differences in fever improvement within 24 h in patients in the fluoroquinolone group compared to those in the macrolide group (OR: 1.11, 95% CI: 0.25-5.00), although the defervescence rate was higher after 48 h in the fluoroquinolone group (OR: 2.78, 95% CI: 1.41-5.51). CONCLUSION: Tetracyclines may shorten fever duration and hospital stay length in patients with MRMP infection. Fluoroquinolones may achieve defervescence within 48 h in patients with MRMP infection. However, these results should be carefully interpreted as only a small number of studies were included, and they were heterogeneous.

Immunogenicity and Safety of a Newly Developed Tetanus-Diphtheria Toxoid (Td) in Healthy Korean Adolescents: a Multi-center, Randomized, Double-blind, Active-Controlled Phase 3 Trial.

BACKGROUND: Although the combination tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) is recommended at adolescence in developed countries, the tetanus and diphtheria toxoid vaccine (Td), which is less costly, is recommended instead in some parts of the world. A new Td, BR-TD-1001, was developed by a Korean manufacturer for distribution to endemic regions and for use in the initial step of novel Tdap development. METHODS: This phase 3, randomized, double-blind, multi-center trial, conducted in Korea, aimed to evaluate the immunogenicity and safety of BR-TD-1001. Healthy children aged 10 to 12 years were randomized 1:1 to receive either BR-TD-1001 or the control Td (Td-pur, GlaxoSmithKline). Antibodies were measured using enzyme-linked immunosorbent assay. RESULTS: A total of 218 subjects (BR-TD-1001, n = 108; control, n = 110) were enrolled and included in the safety analysis. Vaccine-mediated antibody responses were similar in both groups. We confirmed the non-inferiority of BR-TD-1001 against the control, Td; 100% of both groups achieved seroprotection against diphtheria and tetanus. Furthermore, there was no significant difference between groups in the proportion of participants who demonstrated boost responses against diphtheria and tetanus toxoids. The incidence of solicited local and systemic adverse events (AEs), unsolicited AEs, and serious AEs did not differ significantly between groups. CONCLUSION: The BR-TD-1001 satisfied the immunological non-inferiority criterion against diphtheria and tetanus, with a clinically acceptable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04618939.

Evaluation of Waning Immunity at 6 Months after Both Trivalent and Quadrivalent Influenza Vaccination in Korean Children Aged 6-35 Months.

BACKGROUND: The titer of influenza vaccine-induced antibodies declines over time, and younger children have lower immunogenicity and shorter duration of immunity. This study aimed to compare persistence of antibody at 6 months after influenza vaccination according to influenza virus strains, vaccine type, antigen dose, and primed status in children aged 6 to 35 months. METHODS: A total 124 healthy children aged 6 to 35 months were enrolled from September to December 2016 at 10 hospitals in Korea and randomly assigned to either a full dose of quadrivalent influenza vaccine or a half dose of trivalent influenza vaccine with Victoria B strain group. Hemagglutination inhibition antibody titers (that measure the seroprotection rates) were assessed for the recommended influenza strains at 6 months post vaccination. RESULTS: The seroprotection rates at 6 months for strains A (H1N1), A (H3N2), B/Yamagata, and B/Victoria were 88.7%, 97.4%, 36.6%, and 27.6%, respectively. The seroprotection rates for A (H1N1), A (H3N2) and B (Victoria) were 91.4%, 98.7% and 27.5% in a full dose of quadrivalent vaccine vs. 83.7%, 94.6% and 27.9% in a half dose trivalent vaccine, respectively. The seroprotection rate for the B (Yamagata) strain was 23.8% in the quadrivalent group and 14.0% in the trivalent group. CONCLUSION: Persistence of antibodies at 6 months was more favorable against the influenza A strains than against the B strains. Persistence of antibodies to additional B strain at 6 months was superior in the quadrivalent vaccine group. The immunity of primed children with different B strains was not superior to that of the unprimed group with another B strain.

Erratum: Addition of a Co-Author: Etiology of Invasive Bacterial Infections in Immunocompetent Children in Korea (2006-2010): a Retrospective Multicenter Study.

This corrects the article on e45 in vol. 33, PMID: 29349940.

Clonal Expansion of Macrolide-Resistant Sequence Type 3 Mycoplasma pneumoniae, South Korea.

To investigate the genetic background for the emergence of macrolide resistance, we characterized the genetic features of Mycoplasma pneumoniae using multilocus sequence typing. Of the 146 M. pneumoniae strains collected during the 5 consecutive outbreaks of M. pneumoniae pneumonia during 2000-2016 in South Korea, macrolide resistance increased from 0% in the first outbreak to 84.4% in the fifth. Among the 8 sequence types (STs) identified, ST3 (74.7%) was the most prevalent, followed by ST14 (15.1%). Macrolide-susceptible strains comprised 8 different STs, and all macrolide-resistant strains were ST3 (98.3%) except 1 with ST14. The proportion of macrolide-resistant strains in ST3 remained 2.2% (1/46) until the 2006-2007 outbreak and then markedly increased to 82.6% (19/23) during the 2010-2012 outbreak and 95.0% (38/40) during the 2014-2016 outbreak. The findings demonstrated that clonal expansion of ST3 M. pneumoniae was associated with the increase in macrolide resistance in South Korea.

Genetic structures of invasive Streptococcus pneumoniae isolates from Korean children obtained between 1995 and 2013.

BACKGROUND: Understanding the population genetics of pneumococci will allow detection of changes in the prevalence of circulating genotypes and evidence for capsular switching. We aimed to analyze the genetic structure of invasive pneumococcal isolates obtained from children before and after the use of pneumococcal conjugate vaccines (PCVs) in Korea. METHODS: A total of 285 invasive pneumococcal isolates were analyzed using serotyping, multilocus sequence typing, and antimicrobial susceptibility testing. We classified the isolation year to pre-PCV7 (1995-2003; n = 70), post-PCV7 (2004-2010; n = 142), and post-PCV13 (2011-2013; n = 73) periods. RESULTS: Of the 10 clonal complexes (CCs), antibiotic-resistant international clones, CC320 (31.6%), CC81 (14.7%), and CC166 (6.7%) were the main complexes. Serotype 19A was the main serotype of CC320 throughout the periods. Serotypes of CC81 mainly comprised of 23F (53.3%) in pre-PCV7 period and replaced by non-vaccine types (NVTs; 6C [10%], 13 [30%], 15A [40%], and 15B/C [20%]) in post-PCV13 period. The main serotype responsible for CC166 also changed from 9 V (80%) in pre-PCV7 to NVT 11A (50%) in post-PCV13 periods. Non-susceptibility to penicillin (42.3%) was the highest in CC320, increasing from 0 to 76%. CONCLUSION: The genetic structures of invasive pneumococcal isolates in Korean children have changed concomitantly with serotype after the implementation of PCVs.

Safety and Immunogenicity of an Egg-Cultivated Quadrivalent Inactivated Split-virion Influenza Vaccine (GC3110A) in Healthy Korean Children: a Randomized, Double-blinded, Active-controlled Phase III Study.

BACKGROUND: The frequency with which the 2 B lineages have been found to cocirculate in a season has been on the rise, which has spurred the need for a quadrivalent influenza vaccine (QIV) to protect against both B lineages. The World Health Organization (WHO) recommended that QIV include both B lineages beginning in the 2013-2014 flu season. This study was conducted to evaluate the immunogenicity and safety of an egg-cultivated QIV in healthy Korean children and adolescents aged ≥ 6 months to < 19 years. METHODS: A total of 528 subjects were randomized 4:1 to receive either a QIV (GC3110A) or a trivalent influenza vaccine. Hemagglutination inhibition antibody responses were assessed 28 days after the last dose. Safety was also evaluated. RESULTS: The proportion of subjects in the GC3110A group who achieved seroconversion was confirmed to exceed 40% across all age groups. The proportion of subjects aged ≥ 6 months to < 3 years in the GC3110A group who achieved seroprotection failed to meet the Ministry of Food and Drug Safety (MFDS) standard of 70%. Potential causes may include the small number of subjects, as well as the small dosage. However, results pertaining to the other age groups satisfied the MFDS standard. The safety profile was also comparable to that of the control. CONCLUSION: The new quadrivalent split influenza vaccine may offer broader protection to children and adolescents aged ≥ 3 years to < 19 years of age against both influenza B lineages than the existing trivalent influenza vaccines (Registered at the ClinicalTrials.gov NCT02541253).

Current Status of Pediatric Critical Care in Korea: Results of 2015 National Survey.

BACKGROUND: The aim of this study was to describe the structure, organization, management, and staffing of pediatric critical care (PCC) in Korea. METHODS: We directed a questionnaire survey for all Upper Grade General Hospitals (n = 43) in Korea in 2015. The first questionnaire was mainly about structure, organization, and staffing and responses were obtained from 32 hospitals. The second questionnaire was mainly about patients and management. Responses to second questionnaire were obtained from 18 hospitals. RESULTS: Twelve from 32 Upper Grade General Hospitals had pediatric intensive care units (PICUs) and 11 of them had the PICU which was exclusive for children. Total number of PICU beds in Korea was 113. The ratio of the number of PICU beds to the number of children was 1:77,460 in Korea and this ratio is lower than that of other developed countries. The mean number of beds in the PICUs was 9.4 ± 9.3 (range, 2-30). There were 16 medical doctors who were assigned for PCC and only 5 of them were full time pediatric intensivists. In the 18 Upper Grade General Hospitals that responded to the second questionnaire survey, there were 97 patients in the PICUs with an average number of 5.7 ± 7.2 (range, 0-22) on the survey day. The mean age of the patients was 3.4 ± 5.6 years. The mean length of hospital stay was 82 ± 271 days. The mean Pediatric Risk of Mortality score III was 9.4 ± 7.8 at the time of admission to the PICUs. CONCLUSION: There is a considerable shortage of PICU beds compared to those in developed countries. In addition, the proportion of PICUs with PCC specialists is much lower than those in the US and European countries.

Etiology of Invasive Bacterial Infections in Immunocompetent Children in Korea (2006-2010): a Retrospective Multicenter Study.

BACKGROUND: Invasive bacterial infections in apparently immunocompetent children were retrospectively analyzed to figure causative bacterial organisms in Korea. METHODS: A total of 947 cases from 25 university hospitals were identified from 2006 to 2010 as a continuance of a previous 10-year period study from 1996 to 2005. RESULTS: Escherichia coli (41.3%), Streptococcus agalactiae (27.7%), and Staphylococcus aureus (27.1%) were the most common pathogens in infants < 3 months of age. S. agalactiae was the most prevalent cause of meningitis and pneumonia and E. coli was the major cause of bacteremia without localizing signs in this group. In children 3 to 59 months of age, Streptococcus pneumoniae (54.2%), S. aureus (20.5%), and Salmonella spp. (14.4%) were the most common pathogens. S. pneumoniae was the leading cause of pneumonia (86.0%), meningitis (65.0%), and bacteremia without localizing signs (49.0%) in this group. In children ≥ 5 years of age, S. aureus (62.8%) was the predominant pathogen, followed by Salmonella species (12.4%) and S. pneumoniae (11.5%). Salmonella species (43.0%) was the most common cause of bacteremia without localizing signs in this group. The relative proportion of S. aureus increased significantly over the 15-year period (1996-2010) in children ≥ 3 months of age (P < 0.001), while that of Haemophilus influenzae decreased significantly in both < 3 months of age group (P = 0.036) and ≥ 3 months of age groups (P < 0.001). CONCLUSION: S. agalactiae, E. coli, S. pneumoniae, and S. aureus are common etiologic agents of invasive bacterial infections in Korean children.

Radiologic findings as a determinant and no effect of macrolide resistance on clinical course of Mycoplasma pneumoniae pneumonia.

BACKGROUND: With the emergence of macrolide resistance, concerns about the efficacy of macrolides for the treatment of Mycoplasma pneumoniae (MP) pneumonia in children have been raised. This study aimed to determine the effect of macrolide resistance on the outcome of children who were hospitalized with MP pneumonia. METHODS: Between 2010 and 2015, we performed culture of MP from nasopharyngeal samples obtained from children who were hospitalized with pneumonia at five hospitals in Korea. Macrolide resistance was determined by the analysis of 23S rRNA gene transition and the minimal inhibitory concentrations of four macrolides. Medical records were reviewed to analyze the clinical response to treatment with macrolides. RESULTS: MP was detected in 116 (4.8%) of the 2436 children with pneumonia. MP pneumonia was prevalent in 2011 and 2015. Of the 116 patients with MP pneumonia, 82 (70.7%) were macrolide-resistant. There were no differences in the age distribution, total duration of fever, and chest x-ray patterns between the macrolide-susceptible and macrolide-resistant groups. After macrolide initiation, mean days to defervescence were longer in the macrolide-resistant group than in macrolide-susceptible group (5.7 days vs. 4.1 days, P = 0.021). However, logistic regression analysis revealed that the presence of extrapulmonary signs (P = 0.039), homogeneous lobar consolidation (P = 0.004), or parapneumonic effusion (P < 0.001) were associated with fever duration of ≥7 days after the initiation of macrolides, regardless of macrolide resistance. CONCLUSIONS: This study demonstrated that fever duration in MP pneumonia was determined by the radiologic findings of chest x-ray, not by the presence of macrolide resistance. The results highlight the need for future studies to assess therapeutic benefit from macrolides in the treatment of children with MP pneumonia.

The Rate of Drug-Resistant Tuberculosis in Korean Children and Adolescents Since 2007.

The incidence of drug-resistant tuberculosis (DR-TB) in pediatric populations is a critical indicator of national TB management and treatment strategies. Limited data exist regarding the rate of pediatric DR-TB. In this study, we aimed to analyze the status of DR-TB in Korean children from 2007 to 2013. We analyzed specimens submitted to the Korean Institute of Tuberculosis using Mycobacterium tuberculosis culture and drug susceptibility tests (DSTs) from January 2007 through December 2013. Specimens from patients ≤ 19 years of age were included. Among the 2,690 cases, 297 cases were excluded because of insufficient data, leaving 2,393 cases for the final analysis. In total, resistance to one or more TB drugs was 13.5%. The resistance rates of each of the drugs were as follows: isoniazid (INH) 10.2%, rifampin (RFP) 5.1%, ethambutol (EMB) 3.7%, and pyrazinamide (PZA) 3.1%. The resistance rate of multidrug-resistant TB (MDR-TB) was 4.2%, and that of extensively drug-resistant TB (XDR-TB) was 0.8%. The overall drug resistance rate demonstrated significant increase throughout the study period (P < 0.001) but showed no significant difference compared to previous study from 1999 to 2007. The drug resistance rate of PZA in ≤ 15 years of age group was significantly greater than that of > 15 years (P < 0.001). The drug resistance rate has increased throughout the study period.

A Survey of Parental Perception and Pattern of Action in Response to Influenza-like Illness in Their Children: Including Healthcare Use and Vaccination in Korea.

Seasonal influenza is a significant cause of morbidity and mortality of children in Korea. However, few data are available on parental perception and action toward childhood influenza. This study aimed to characterize parental perception and patterns of action in response to influenza and influenza-like illnesses (ILIs), including vaccination and healthcare use. This prospective study involved a random survey of parents whose children were aged 6-59 months. The survey was conducted in October 2014. The study included 638 parents of 824 children younger than 6 years. Most parental information of influenza came from mass media (28.2%) and social media (15.5%). The factor that most often motivated parents to vaccinate their children against influenza was promotion of the government or mass media (36.6%). Negative predictors of immunization included safety concerns about influenza vaccination (28.1%) and mistrust in the vaccine's effectiveness (23.3%). Therefore, correct information about influenza and vaccination from mass media will be one of the cornerstones for implementing a successful childhood immunization program and reducing morbidity and mortality in Korea. Furthermore, to enroll younger children in vaccination programs, and to minimize coverage gaps, public concerns about vaccine safety should be resolved. The demographic data in the present study will be used to provide a deeper insight into a parental perception and will help health care providers increase influenza immunization rate.

The priming effect of previous natural pandemic H1N1 infection on the immunogenicity to subsequent 2010-2011 influenza vaccination in children: a prospective cohort study.

BACKGROUND: The effect of previous natural pandemic H1N1 (H1N1 pdm09) influenza infection on the immunogenicity to subsequent inactivated influenza vaccination in children has not been well studied. We aimed to evaluate the effect of H1N1 pdm09 natural infection and vaccination on the immunogenicity to subsequent 2010-2011 seasonal inactivated influenza vaccination in children. METHODS: From October 2010 to May 2011, we conducted an open-label, multi-center study in children aged 6 months -18 years in Korea. We measured antibody titers with a hemagglutination-inhibition (HI) assay at baseline, 1 month, and 6 months after vaccination with trivalent split or subunit vaccines containing H1N1 pdm, A/H3N2, and B. The subjects were classified into 4 groups depending on the presence of laboratory-confirmed H1N1 pdm09 infection and/or vaccination in the 2009-2010 season; Group I: vaccination (-)/infection(-), Group II: vaccination (-)/infection(+), Group III: vaccination (+)/infection(-), Group IV: vaccination (+)/infection(+). RESULTS: Among the subjects in group I, 47 subjects who had a baseline titer >1:10 were considered to have an asymptomatic infection. They were included into the final group II (n = 80). We defined the new group II as the infection-primed (IP) group and group III as the vaccine-primed (VP) group. Seroconversion rate (57.5 % vs 35.9 %, p = 0.001), seroprotection rate at 6 months after vaccination (70.8 % vs 61.8 %, p = 0.032), and GMT at 1 month after vaccination (129.9 vs 66.5, p = 0.002) were significantly higher in the IP group than in the VP group. In the 9-18 year-old group, seroconversion rate and immunogenicity at 1 and 6 months were significantly higher in the IP group than in the VP group. However in the 1-7 year-old age group, there was no significant difference between the two groups. CONCLUSIONS: Previous H1N1 pdm09 infection appears to have positive effects on immunogenicity of subsequent inactivated influenza vaccines against H1N1 pdm09 in older children.