Yun Kyung Kim

Bloodstream Infections by Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae in Children: Epidemiology and Clinical Outcome

ABSTRACT To determine the epidemiologic features and clinical outcomes of bloodstream infections caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolates, cases of bacteremia caused by these organisms in children were analyzed retrospectively. Among the 157 blood isolates recovered from 1993 to 1998 at the Seoul National University Childrens Hospital, the prevalence of ESBL production was 17.9% among the E. coli isolates and 52.9% among the K. pneumoniae isolates. The commonest ESBLs were SHV-2a and TEM-52. A novel ESBL, TEM-88, was identified. Pulsed-field gel electrophoresis analysis of the ESBL-producing organisms showed extensive diversity in clonality. The medical records of 142 episodes were reviewed. The risk factors for bloodstream infection with ESBL-producing organisms were prior hospitalization, prior use of oxyimino-cephalosporins, and admission to an intensive care unit within the previous month. There was no difference in clinical severity between patients infected with ESBL-producing strains (the ESBL group) and those infected with ESBL-nonproducing strains (the non-ESBL group) at the time of presentation. However, the overall fatality rate for the ESBL group was significantly higher than that for the non-ESBL group: 12 of 45 (26.7%) versus 5 of 87 (5.7%) (P = 0.001). In a subset analysis of patients treated with extended-spectrum cephalosporins with or without an aminoglycoside, favorable response rates were significantly higher in the non-ESBL group at the 3rd day (6 of 17 versus 33 of 51; P = 0.035), the 5th day (6 of 17 versus 36 of 50; P < 0.05), and the end of therapy (9 of 17 versus 47 of 50; P < 0.001). In conclusion, the ESBL production of the infecting organisms has a significant impact on the clinical course and survival of pediatric patients with bacteremia caused by E. coli and K. pneumoniae.

Genome Type Analysis of Adenovirus Types 3 and 7 Isolated during Successive Outbreaks of Lower Respiratory Tract Infections in Children

ABSTRACT Adenovirus is an important cause of respiratory infections in infants and children. Fifty-one serotypes have been identified, and adenovirus type 3 (Ad3) and Ad7 have often been associated with outbreaks of severe respiratory tract infections. Each serotype can be further divided into genome types based on the patterns of digestion of their DNAs with restriction enzymes. DNA restriction analysis was performed with 56 strains of Ad3 and 98 strains of Ad7 by using 12 restriction enzymes recognizing 6 bp (BamHI, BclI, BglI, BglII, BstEII, EcoRI, HindIII, HpaI, SalI, SmaI, XbaI, and XhoI). The virus strains were isolated during outbreaks of lower respiratory tract infections in children during an 11-year period from 1990 to 2000 in Seoul, Korea. Among the Ad3 strains, seven genome types were identified; Ad3a and six novel types (Ad3a13, Ad3a14, Ad3a15, Ad3a16, Ad3a17, and Ad3a18). Multiple genome types cocirculated during outbreaks, and some of these were isolated during the 11-year observation period, while others were restricted to particular outbreaks. For Ad7, two genome types, Ad7d and Ad7l, the latter of which is a novel genome type, were identified. A shift in genome types occurred from Ad7d to Ad7l during successive outbreaks. Mortality was 3.6% among children with Ad3 infections and 18% among children infected with either of the Ad7 genome types. In conclusion, the data confirm that Ad3 genome types are more diverse than those of Ad7 and suggest that shifts of genome types may occur during successive outbreaks of Ad3 and Ad7.

The Causative Organisms of Bacterial Meningitis in Korean Children in 1996-2005

Bacterial meningitis remains a serious cause of morbidity and mortality in childhood, despite the availability of effective vaccines against Haemophilus influenzae type b (Hib) or Streptococcus pneumoniae. The purpose of this study was to analyze data on bacterial meningitis cases in Korea from 1996 through 2005. The information of all hospitalized bacteria-proven meningitis cases was obtained from 17 university hospitals nationwide. A total of 402 cases were identified. Of these, 125 (29.9%) cases were neonates. Streptococcus agalactiae was the most common bacteria responsible for 99 (24.6%) of all cases regardless of age, followed by S. pneumoniae for 91 (22.6%) and H. influenzae for 67 (16.7%) patients. The common etiology beyond the neonatal period was S. pneumoniae for 91 (33.0%) followed by H. influenzae for 63 (22.8%) patients. The overall case fatality rate was 9.4%, which was similar with that in 1986-1995. In conclusion, S. agalactiae, S. pneumoniae and H. influenzae were important etiologic agents of bacterial meningitis in children in the last 10 yrs. It is required to establish the preventive strategy of the three bacteria. The nationwide epidemiologic study should be continued to evaluate immunization strategy and efficacy.

High Prevalence of Extended-Spectrum β-Lactamase-Producing Strains among Blood Isolates of Enterobacter spp. Collected in a Tertiary Hospital during an 8-Year Period and Their Antimicrobial Susceptibility Patterns

ABSTRACT Of 72 blood isolates of Enterobacter spp. collected over an 8-year period, 50% (36 of 72) were derepressed or partially derepressed AmpC mutants. The extended-spectrum β-lactamase (ESBL) production rate was 43% (31 of 72 isolates), and 67.3% (31 of 46) of extended-spectrum cephalosporin-resistant strains produced ESBLs. Thus, a confirmatory test for ESBL production is necessary for extended-spectrum cephalosporin-resistant Enterobacter spp.

Safety and immunogenicity of an inactivated split-virus influenza A/H1N1 vaccine in healthy children from 6 months to <18 years of age: a prospective, open-label, multi-center trial.

This study was conducted to determine the immunogenicity and safety of an inactivated split-virus influenza A/H1N1 vaccine in healthy Korean children from 6 months to <18 years of age. The immunization schedule consisted of two vaccinations, 21 days apart. The unadjuvanted vaccine contained 7.5microg (subjects 6 months to <3 years of age) or 15microg (subjects 3 to <18 years of age) of hemagglutinin antigen per dose. A total of 251 subjects were enrolled and 248 and 242 subjects, respectively, were included in the post-first dose and post-second dose immunogenicity evaluations conducted on a per protocol basis. By day 21, after the first dose, hemagglutination-inhibition titers of 1:40 or more were observed in 5.9% of subjects 6 months to <3 years of age, 34.9% of subjects 3 to <9 years of age and 81.4% of subjects 9-18 years of age. By day 21 after the second dose, the titer had been achieved 55.9%, 69.5% and 90.5%, respectively. No vaccination-related serious adverse events were observed. A single 15-microg dose of vaccine was highly immunogenic in subjects equal to or more than 9 years of age. However, a two-dose regimen is needed to produce potentially protective antibody titers in younger children.

Human metapneumovirus-associated lower respiratory tract infections in Korean infants and young children

To define the role of human metapneumovirus (hMPV) in previously healthy Korean children, a retrospective study was done on 166 children with lower respiratory tract infections and on their stored nasal aspirates. The hMPV gene was detected by reverse transcriptase-polymerase chain reaction. Twenty-six of 166 individuals tested positive for hMPV. The clinical diagnoses of hMPV infection were pneumonia in 15 children and bronchiolitis in 11 children.

Response to primary and booster vaccination with 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine in Korean infants.

Background: This randomized single-blind study in Korea evaluated noninferiority of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) versus the 7-valent pneumococcal conjugate vaccine (7vCRM) when both were coadministered with H. influenzae type b (Hib) conjugate vaccine, as opposed to coadministration with diphtheria-tetanus-acellular pertussis-based combination vaccines in previous studies. Methods: Infants received 3 primary doses at 2, 4, and 6 months and a booster dose at 12 to 18 months of PHiD-CV (N = 374) or 7vCRM (N = 129), both coadministered with Hib vaccine. Immune responses were measured 1 month postdose 3 and postbooster using 22F-inhibition enzyme-linked immunosorbent assay and functional opsonophagocytic activity assay. Results: PHiD-CV-induced antibody responses against each of the vaccine pneumococcal serotypes and protein D. Noninferiority to 7vCRM was demonstrated for all 10 PHiD-CV serotypes in terms of percentages of subjects reaching an antibody concentration ≥0.2 &mgr;g/mL after primary vaccination. Postprimary and postbooster, percentages of subjects with antibody concentration ≥0.2 &mgr;g/mL or opsonophagocytic activity titer ≥8 were generally consistent between groups for each pneumococcal serotype common to both vaccines. The safety and reactogenicity profiles of PHiD-CV and 7vCRM were generally comparable after both primary and booster vaccination. Conclusions: In this Korean study, 3-dose PHiD-CV priming followed by a booster dose was immunogenic for all 10 vaccine pneumococcal serotypes and protein D. Noninferiority to 7vCRM in terms of enzyme-linked immunosorbent assay threshold responses postpriming was demonstrated. The safety and reactogenicity profiles of both vaccines when coadministered with Hib vaccine were generally comparable.

Serotype distribution and antibiotic resistance of Streptococcus pneumoniae isolated from invasive infections after optional use of the 7-valent conjugate vaccine in Korea, 2006-2010

This study examined the serotype distribution and antimicrobial resistance of pneumococcal isolates from invasive infections in children between 2006 and 2010, when the 7-valent pneumococcal conjugate vaccine (PCV7) was offered as an optional vaccine in Korea. Among 140 isolates collected from 8 centers, the common serotypes were 19A (22.9%), 19 F (12.1%), and 6B (8.6%). Between 2006 and 2010, PCV7 serotypes decreased from 62.5% to 21.4% (P = 0.002), whereas three 13-valent pneumococcal conjugate vaccine (PCV13)-specific serotypes (3, 6A, and 19A) increased from 18.8% to 42.9% (P = 0.016). Among 102 multidrug-resistant isolates, the proportion of PCV7 serotypes decreased from 65.2% to 21.7% (P = 0.001), and 3 PCV13-specific serotypes increased from 17.4% to 47.8% (P = 0.008). Optional PCV7 vaccination has influenced the proportion of PCV7 serotypes in Korea, resulting in a decrease, whereas the proportions of 3 PCV13-specific serotypes, particularly 19A, have increased.

Current status and clinical presentations of invasive neonatal Group B streptococcal infections in Korea

Background:  Group B streptococcus (GBS) is the most common cause of invasive neonatal infections in developed countries. The incidence of early‐onset GBS disease in Korea is known to be much lower than that in other developed countries; however neonatal GBS disease has been frequently reported in recent years in Korea. This retrospective study sought to determine the current status and clinical presentation of neonatal GBS disease in Korea.

Varicella and Varicella Vaccination in South Korea

ABSTRACT With continuing occurrence of varicella despite increasing vaccine coverage for the past 20 years, a case-based study, a case-control study, and an immunogenicity and safety study were conducted to address the impact of varicella vaccination in South Korea. Varicella patients under the age of 16 years were enrolled for the case-based study. For the case-control study, varicella patients between 12 months and 15 years of age were enrolled with one control matched for each patient. For the immunogenicity and safety study, otherwise healthy children from 12 to 24 months old were immunized with Suduvax (Green Cross, South Korea). Fluorescent antibody to membrane antigen (FAMA) varicella-zoster virus (VZV) antibody was measured before and 6 weeks after immunization. In the case-based study, the median age of the patients was 4 years. Among 152 patients between 1 and 15 years of age, 139 children received varicella vaccine and all had breakthrough infections. Clinical courses were not ameliorated in vaccinated patients, but more vaccinated patients received outpatient rather than inpatient care. In the case-control study, the adjusted overall effectiveness of varicella vaccination was 54%. In the immunogenicity and safety study, the seroconversion rate and geometric mean titer for FAMA antibody were 76.67% and 5.31. Even with increasing varicella vaccine uptake, we illustrate no upward age shift in the peak incidence, a high proportion of breakthrough disease, almost no amelioration in disease presentation by vaccination, and insufficient immunogenicity of domestic varicella vaccine. There is need to improve the varicella vaccine used in South Korea.