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 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.

A Case of Lyme Disease Complicated with Atrioventricular Block in a 13-year-old Boy

Lyme disease is a common vector-borne disease caused by Borrelia burgdorferi. Erythema migrans represents the most common manifestation during the early phase of this disease;however, systemic manifestations involving the nervous system, joints, or heart are known to occur. We report a case of Lyme disease accompanied by cardiac complications in a 13-year-old Korean male adolescent. The patient developed annular erythematous lesions on his lower extremities after a field trip during his visit to Connecticut, USA, for a boarding school camp, and his skin lesions were consistent with erythema migrans. Indirect immunofluorescence assay and Western blot analysis for Lyme immunoglobulin M showed positive results. Electrocardiography revealed a first-degree atrioventricular block, and he was diagnosed with Lyme carditis and received a 4-week course of oral doxycycline. Follow-up electrocardiography performed a week later revealed normal findings, and the patient showed an uneventful recovery. Lyme carditis often presents as an asymptomatic heart block that can progress to an advanced heart block; however, this condition is reversible with appropriate antibiotic treatment.

A Case of Lyme Disease Complicated with Atrioventricular Block in a 13-year-old Boy

Lyme disease is a common vector-borne disease caused by Borrelia burgdorferi. Erythema migrans represents the most common manifestation during the early phase of this disease;however, systemic manifestations involving the nervous system, joints, or heart are known to occur. We report a case of Lyme disease accompanied by cardiac complications in a 13-year-old Korean male adolescent. The patient developed annular erythematous lesions on his lower extremities after a field trip during his visit to Connecticut, USA, for a boarding school camp, and his skin lesions were consistent with erythema migrans. Indirect immunofluorescence assay and Western blot analysis for Lyme immunoglobulin M showed positive results. Electrocardiography revealed a first-degree atrioventricular block, and he was diagnosed with Lyme carditis and received a 4-week course of oral doxycycline. Follow-up electrocardiography performed a week later revealed normal findings, and the patient showed an uneventful recovery. Lyme carditis often presents as an asymptomatic heart block that can progress to an advanced heart block; however, this condition is reversible with appropriate antibiotic treatment.

Mycobacterium bovis Osteitis Following Immunization with Bacille Calmette-Guérin (BCG) in Korea

BACKGROUND: Mycobacterium bovis Bacille Calmette-Guérin (BCG) osteitis, a rare complication of BCG vaccination, has not been well investigated in Korea. This study aimed to evaluate the clinical characteristics of BCG osteitis during the recent 10 years in Korea. METHODS: Children diagnosed with BCG osteitis at the Seoul National University Children's Hospital from January 2007 to March 2018 were included. M. bovis BCG was confirmed by multiplex polymerase chain reaction (PCR) in the affected bone. BCG immunization status and clinical information were reviewed retrospectively. RESULTS: Twenty-one patients were diagnosed with BCG osteitis and their median symptom onset from BCG vaccination was 13.8 months (range, 6.0–32.5). Sixteen children (76.2%) received Tokyo-172 vaccine by percutaneous multiple puncture method, while four (19.0%) and one (4.8%) received intradermal Tokyo-172 and Danish strain, respectively. Common presenting symptoms were swelling (76.2%), limited movement of the affected site (63.2%), and pain (61.9%) while fever was only accompanied in 19.0%. Femur (33.3%) and the tarsal bones (23.8%) were the most frequently involved sites; and demarcated osteolytic lesions (63.1%) and cortical breakages (42.1%) were observed on plain radiographs. Surgical drainage was performed in 90.5%, and 33.3% of them required repeated surgical interventions due to persistent symptoms. Antituberculosis medications were administered for a median duration of 12 months (range, 12–31). Most patients recovered without evident sequelae. CONCLUSION: Highly suspecting BCG osteitis based on clinical manifestations is important for prompt management. A comprehensive national surveillance system is needed to understand the exact incidence of serious adverse reactions following BCG vaccination and establish safe vaccination policy in Korea.

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

The authors regret that one co-author (Kyung-Hyo Kim) was missing in the article.

One-year antibody persistence and safety of a 4-dose schedule of MenACWY-CRM in healthy infants from South Korea

PURPOSE: Results from a post-marketing study to generate evidence on 1-year antibody persistence and safety following vaccination of infants from South Korea with the quadrivalent meningococcal conjugate vaccine MenACWY-CRM. MATERIALS AND METHODS: In this phase IV, open-label, multi-center study (NCT02446691), 128 infants received MenACWY-CRM at ages 2, 4, 6, and 12 months. One-year antibody persistence following the full vaccination course was evaluated (primary objective) for the four meningococcal serogroups (Men) by serum bactericidal activity assay using human or rabbit complement (hSBA/rSBA). Immune responses at 1-month post-vaccination and safety were also assessed. RESULTS: The percentage of children with hSBA titers ≥8 ranged between 94% (MenA) and 100% (MenY/W) 1-month post-vaccination, and from 39% (MenA) to 89% (MenY) 1-year post-vaccination. At least 99% and 92% of children had rSBA titers ≥8 and ≥128 against each meningococcal serogroup, 1-month post-vaccination. One-year post-vaccination, the percentage of children with rSBA titers ≥8 and ≥128 ranged from 54% (MenC) to 99% (MenA) and from 30% (MenC) to 98% (MenA). Geometric mean titers declined from 1-month to 1-year post-vaccination, when they varied between 6.8 (MenA) and 53.6 (MenW) by hSBA and between 17.2 (MenC) and 2,269.5 (MenA) by rSBA. At least one solicited and unsolicited adverse event was reported for 79% and 66% of children. Of 36 serious adverse events reported, none were vaccination-related. CONCLUSION: Antibody persistence (hSBA/rSBA titers ≥8) was determined in 39%–99% of children 1 year after a 4-dose MenACWY-CRM series during infancy, with an acceptable clinical safety profile.

Will a Quadrivalent Vaccine Solve the Problem of Influenza B Mismatches?

No abstract available.

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.

Epidemiology and Clinical Characteristics of Parainfluenza Virus Type 4 in Korean Children: a Single Center Study, 2015–2017

PURPOSE: We aimed to identify the epidemiology and the clinical characteristics of human parainfluenza virus type 4 (HPIV-4) infection compared to HPIVs 1–3 infections in Korean children. METHODS: We reviewed medical records of children with HPIV infection who visited Seoul National University Children's Hospital from 2015 to 2017. Detection of respiratory viruses was performed using real time-polymerase chain reaction (rt-PCR), which could differentiate HPIVs 1–4. Diagnosis was classified as a febrile illness, upper respiratory tract infection (URI), croup, bronchiolitis, or pneumonia. The epidemiology, demographic features, and clinical characteristics among HPIV types were compared. The clinical data were analyzed only for the previously healthy children. RESULTS: Of the 472 children diagnosed with HPIV infection, 108 (22.9%) were previously healthy: 24 (22.2%), 19 (17.6%), 39 (36.1%), and 26 (24.1%) in HPIV types 1, 2, 3, and 4, respectively. The median age of children with HPIV-4 infection was 11 (0–195) months: the proportion of children aged 0.05). CONCLUSIONS: We observed seasonal peak of HPIV-4 infection in 2015 and 2017. HPIV-4 was a common respiratory pathogen causing lower respiratory tract infection in hospitalized children.

Bacterial Infections after Liver Transplantation in Children: Single Center Study for 16 Years

PURPOSE: Survival after liver transplantation (LT) has improved over the years, but infection is still a major complication. We aimed to identify the characteristics of bacterial infections in pediatric LT recipients. METHODS: This study is a retrospective review of 189 consecutive children undergoing LT between 2000 and 2015 at a single center. In this study, the incidence of infection was determined for the following periods: within 1 month, between 1–5 months, and between 6–12 months. Patients who underwent liver transplants more than once or multiple organ transplants were excluded. RESULTS: All patients had received postoperative antibiotic for 3 days. Only the maintenance immunosuppression with oral tacrolimus and steroids were performed. As a result, 132 bacterial infections developed in 87 (46.0%) patients (0.70 events per person-year). Bacterial infections occurred most frequently within the first month (n=84, 63.6%) after LT. In the pathogens, Staphylococcus aureus (15.2%), Enterococcus species (15.2%), and Klebsiella species (13.6%) were most common. Regarding the organ infected, bloodstream was most common (n=39, 29.5%), followed by peritoneum (n=28, 21.2%), urinary tract (n=25, 18.9%), and lungs (n=20, 15.2%). We changed prophylactic antibiotics from ampicillin-sulbactam to piperacillin-tazobactam at 2011, October, there were no significant effects in the prevalence of antibiotics resistant bacterial infections. The 1-year mortality was 9.0% (n=17), in which 41.2% (n=7) was attributable to bacterial infection; septicemia (n=4), pneumonia (n=2), and peritonitis (n=1). CONCLUSIONS: The incidence and type of bacterial infectious complications after LT in pediatric patients were similar to those of previous studies. Bacterial complications affecting mortality occur within 6 months after transplantation, so proper prophylaxis and treatment in this period may improve the prognosis of LT.

Etiology of Bacteremia in Children with Hemato-oncologic Diseases from a Single Center from 2011 to 2015

PURPOSE: The aim of this study was to identify the pathogens of blood stream infection (BSI) in children with hemato-oncologic disorders, to analyze susceptibility patterns of microorganisms to guide empirical antimicrobial therapy, and to compare temporal trends of the pathogen and antimicrobial susceptibility with those of previous studies. METHODS: We retrospectively analyzed the medical records of children with hemato-oncologic disorders whose blood culture grew pathogens at the Seoul National University Children's Hospital between 2011 and 2015. RESULTS: A total of 167 patients developed 221 episodes of bacteremia. Among 229 pathogens, gram-negative bacteria (GNB) accounted for 69.0% (64.0% in 2002 to 2005, 63.4% in 2006 to 2010); gram-positive bacteria (GPB) accounted for 28.8% (31.3% in 2002 to 2005, 34.6% in 2006 to 2010); and fungus accounted for 2.2%. Among GNB, Klebsiella species (53.2%, 84/158) and Escherichia coli (19.6%, 31/158) were common. Staphylococcus aureus (48.5%, 32/66) and viridans streptococci (21.2%, 14/66) were frequently isolated among GPB. The susceptibilities of oxacillin and vancomycin in GPB were 54.8% and 96.9% (51.5% and 95.5% in 2002 to 2005; 34.1% and 90.5% in 2006 to 2010), respectively, whereas in GNB, the susceptibilities of cefotaxime, piperacillin/tazobactam, and imipenem were 73.2%, 77.2%, and 92.6% (75.9%, 82.8%, and 93.4% in 2002 to 2005; 62.8%, 82.9%, 93.8% and in 2006 to 2010), respectively. There were no significant differences in the proportion of etiologic agents or the antimicrobial susceptibilities between the current study and that of the previous two studies from 2002 to 2010. Overall fatality rate was 13.1%. CONCLUSIONS: GNB predominated in BSI among children with hemato-oncologic disorders. The etiology of bacteremia and antimicrobial susceptibility were comparable to those of the previous studies. Thus, piperacillin/tazobactam can be used as the initial empirical antimicrobial agent in febrile neutropenia.

Blackwater Fever Followed by Severe Falciparum Malaria in a Child

Blackwater fever is a serious clinical syndrome manifested by acute intravascular hemolysis, fever, and the passage of black or red urine, which is classically associated with falciparum malaria and irregular administration of quinine. In Korea, Plasmodium vivax is the only endemic malaria circulating; a number of imported cases of falciparum malaria have been reported in patients following return from international travel to a malaria endemic area. Therefore, it is important for health care professionals including pediatricians to be aware of the falciparum malaria and its clinical courses. Herein, we report a case of a 14-year-old girl with severe falciparum malaria that was complicated by blackwater fever.

Changes in the Serotype Distribution among Antibiotic Resistant Carriage Streptococcus pneumoniae Isolates in Children after the Introduction of the Extended-Valency Pneumococcal Conjugate Vaccine

This study investigated the serotype distribution and antimicrobial resistance of 3,820 nasopharyngeal Streptococcus pneumoniae isolates from infants and children who presented with respiratory symptoms at Seoul National University Children's Hospital from July 2010 to June 2015 after the introduction of the extended-valency pneumococcal conjugate vaccines (PCVs). Serotypes and antimicrobial susceptibility were determined using the Quellung reaction and E-test, respectively. S. pneumoniae was isolated from 397 (10.4%) specimens. The most common serotypes were 19A (14.0%), 23A (12.8%), 15B/C (10.7%), 11A (10.1%), 6C (7.8%), and 6A (6.3%) among the typeable pneumococci (n = 335). The PCV serotype proportions significantly decreased (59.1% in 2010/11 to 17.0% in 2014/15, P < 0.001), whereas the non-PCV serotype proportions significantly increased (40.9% in 2010/11 to 83.0% in 2014/15, P < 0.001). The non-susceptibility rates for penicillin (oral), penicillin (parenteral, non-meningitis), cefotaxime, and erythromycin were 97.8%, 22.8%, 27.7%, and 95.5%, respectively. The proportions of PCV serotypes responsible for non-susceptibility to penicillin (parenteral, non-meningitis) and multidrug resistance significantly decreased (80.8% to 21.1%, P < 0.001 and 64.3% to 12.3%, P < 0.001, respectively), whereas the non-PCV serotype proportions significantly increased (19.2% to 78.9%, P < 0.001 and 35.7% to 87.7%, P < 0.001, respectively). Serotypes 23A and 15B/C demonstrated significant proportional increase among the antibiotics resistant strains. Thus, the PCV serotype proportions decreased and the non-PCV serotype proportions increased among nasopharyngeal carriage pneumococci after the introduction of extended-valency PCVs in Korea. Antimicrobial non-susceptibility rates for penicillin and erythromycin remain high despite the decrease in the proportion of PCV serotypes responsible for antimicrobial resistance over time.

Early Changes in the Serotype Distribution of Invasive Pneumococcal Isolates from Children after the Introduction of Extended-valent Pneumococcal Conjugate Vaccines in Korea, 2011-2013

This study was performed to measure early changes in the serotype distribution of pneumococci isolated from children with invasive disease during the 3-year period following the introduction of 10- and 13-valent pneumococcal conjugate vaccines (PCVs) in Korea. From January 2011 to December 2013 at 25 hospitals located throughout Korea, pneumococci were isolated among children who had invasive pneumococcal disease (IPD). Serotypes were determined using the Quellung reaction, and the change in serotype distribution was analyzed. Seventy-five cases of IPD were included. Eighty percent of patients were aged 3-59 months, and 32% had a comorbidity that increased the risk of pneumococcal infection. The most common serotypes were 19A (32.0%), 10A (8.0%), and 15C (6.7%). The PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, and 6A) accounted for 14.7% of the total isolates and the PCV13 minus PCV7 types (1, 3, 5, 7F and 19A) accounted for 32.0% of the total isolates. Serotype 19A was the only serotype in the PCV13 minus PCV7 group. The proportion of serotype 19A showed decreasing tendency from 37.5% in 2011 to 22.2% in 2013 (P = 0.309), while the proportion of non-PCV13 types showed increasing tendency from 45.8% in 2011 to 72.2% in 2013 (P = 0.108). Shortly after the introduction of extended-valent PCVs in Korea, serotype 19A continued to be the most common serotype causing IPD in children. Subsequently, the proportion of 19A decreased, and non-vaccine serotypes emerged as an important cause of IPD. The impact of extended-valent vaccines must be continuously monitored.

The Immunogenicity and Safety of a Combined DTaP-IPV//Hib Vaccine Compared with Individual DTaP-IPV and Hib (PRP~T) Vaccines: a Randomized Clinical Trial in South Korean Infants

Recommended infant vaccination in Korea includes DTaP-IPV and Hib vaccines administered as separate injections. In this randomized, open, controlled study we assessed the non-inferiority of immunogenicity of DTaP-IPV//Hib pentavalent combination vaccine (Pentaxim™) compared with licensed DTaP-IPV and Hib (PRP~T) vaccines. We enrolled 418 healthy Korean infants to receive either separate DTaP-IPV and Hib vaccines (n = 206) or the pentavalent DTaP-IPV//Hib (n = 208) vaccine at 2, 4, 6 months of age. Antibodies to all components were measured before the first vaccination and one month after the third, and safety was assessed after each vaccination including recording of reactions by parents. We confirmed the non-inferiority of DTaP-IPV//Hib compared with DTaP-IPV and Hib vaccines; 100% of both groups achieved seroprotection against D, T, IPV and PRP~T, and 97.5%-99.0% demonstrated seroresponses to pertussis antigens. Antibody levels were similar in both groups, except for those to the Hib component, PRP~T. In separate and combined groups geometric mean concentrations of anti-PRP~T antibodies were 23.9 and 11.0 µg/mL, respectively, but 98.3% and 97.4% had titers ≥ 1 µg/mL, indicative of long-term protection. All vaccines were well tolerated, with no vaccine-related serious adverse event. Both groups had similar safety profiles, but the combined vaccine group had fewer injection site reactions. The immunological non-inferiority and similar safety profile of DTaP-IPV//Hib vaccine to separate DTaP-IPV and Hib vaccines, with the advantage of fewer injections and injection site reactions, supports the licensure and incorporation of DTaP-IPV//Hib into the Korean national vaccination schedule (Clinical trial registry, NCT01214889).

Human Parechovirus as an Important Cause of Central Nervous System Infection in Childhood

PURPOSE: Human parechovirus (HPeV) is an increasingly recognized pathogenic cause of central nervous system (CNS) infection in neonates. However, HPeV infections have not been studied in older children. This study determined the prevalence and clinical features of HPeV CNS infection in children in Korea. METHODS: Reverse transcription polymerase chain reaction assays were performed using HPeV-specific, 5′ untranslated, region-targeted primers to detect HPeV in cerebrospinal fluid (CSF) samples from children presenting with fever or neurologic symptoms from January 1, 2013, to July 31, 2014. HPeV genotyping was performed by sequencing the viral protein 3/1 region. Clinical and laboratory data were retrospectively abstracted from medical records and compared with those of enterovirus (EV)-positive patients from the same period. RESULTS: Of 102 CSF samples, six (5.9%) were positive for HPeV; two of 21 EV-positive samples were co-infected with HPeV. All samples were genotype HPeV3. Two HPeV-positive patients were <3 months of age and four others were over 1 year old. While HPeV-positive infants under 1 year of age presented with sepsis-like illness without definite neurologic abnormalities, HPeV-positive children over 1 year of age presented with fever and neurologic symptoms such as seizures, loss of consciousness, and gait disturbance. The CSF findings of HPeV-positive patients were mostly within the normal range, whereas most (73.7%) EV-positive patients had pleocytosis. CONCLUSIONS: Although HPeV is typically associated with disease in young infants, the results of this study suggest that HPeV is an emerging pathogen of CNS infection with neurologic symptoms in older childhood.

Post-exposure Prophylaxis against Varicella Zoster Virus in Hospitalized Children after Inadvertent Exposure

PURPOSE: This study described the post-exposure prophylaxis (PEP) and secondary varicella infection in children inadvertently exposed to varicella zoster virus (VZV) in the hospital. METHODS: We retrospectively analyzed data from patients with VZV infection who were initially not properly isolated, as well as children exposed to VZV at the Seoul National University Children's Hospital between January 2010 and December 2015. The PEP measures were determined by the presence of immunity to VZV and immunocompromising conditions. Patient clinical information was reviewed via medical records. RESULTS: Among 147 children hospitalized between 2010 and 2015, 13 inadvertent exposures were notified due to VZV infection. Five index children had a history of VZV vaccination. Eighty-six children were exposed in multi-occupancy rooms and 62.8% (54/86) were immune to VZV. The PEP measures administered to 27 exposed patients included varicella zoster immunoglobulin and VZV vaccination. Four children developed secondary varicella, which was linked to a single index patient, including one child who did not receive PEP and three of the 27 children who received PEP. The rates of secondary varicella and prophylaxis failure were 4.7% (4/85) and 11.1% (3/27), respectively. The secondary varicella rates were 1.9% (1/54) and 9.7% (3/31) among immunocompetent and immunocompromised children, respectively. CONCLUSIONS: Delayed diagnosis of VZV infection can lead to unexpected exposure and place susceptible children and immunocompromised patients at risk for developing varicella. The appropriateness of the current PEP strategy based on VZV immunity may require re-evaluation.

Evaluation of Timeliness of Palivizumab Immunoprophylaxis Based on the Epidemic Period of Respiratory Syncytial Virus: 22 Year Experience in a Single Center

PURPOSE: This study aimed to analyze the epidemic period of RSV infection and evaluate the appropriate time of palivizumab immunoprophylaxis. METHODS: From January 1991 to July 2012, nasopharyngeal (NP) aspirates were obtained from patients who visited Seoul National University Children's Hospital for respiratory symptoms. NP samples were used to detect respiratory viruses. Among them, we analyzed the positive number and detection rate of RSV infection in two-week interval. The beginning of RSV season was defined when RSV positive number was more than 4 and RSV detection rate was over 10%. From January 2007 to March 2014, we analyzed the starting time of palivizumab immunoprophylaxis for the infants at high risk. RESULTS: The RSV detection rate was 2,013/21,698 (9.69%) over 22 years. The median RSV season was from 2nd-3rd week of October to 1st- 2nd week of February. The earliest starting week was the 3rd week of July in year 2001, and the latest end week was the 3rd week of May in year 1990. Palivizumab immunoprophylaxis was initiated most frequently at the 3rd week of October (18.7%). However, the percentage of starting palivizumab on the 1st week of September has increased from 3.8% in the year 2007 to 14.1% in 2013. CONCLUSIONS: The year to year variability of RSV season exists. The starting time of palivizumab immunoprophylaxis should be adjusted based on the season of RSV epidemic.

Voriconazole Therapeutic Drug Monitoring is Necessary for Children with Invasive Fungal Infection / 소아감염

PURPOSE: To determine the clinical significance of voriconazole therapeutic drug monitoring (TDM) in the pediatric population. METHODS: Twenty-eight patients with invasive fungal infections administered with voriconazole from July 2010 to June 2012 were investigated retrospectively. Fourteen received TDM, and 143 trough concentrations were analyzed. All 28 patients were assessed for adverse events and treatment response six weeks into treatment, and at the end. RESULTS: Out of 143 samples, 53.1% were within therapeutic range (1.0-5.5 mg/L). Patients administered with the same loading (6 mg/kg/dose) and maintenance (4 mg/kg/dose) dosages prior to initial TDM showed highly variable drug levels. Adverse events occurred in 9 of 14 patients (64.3%) in both the TDM and non-TDM group. In the TDM group, voriconazole-related encephalopathy (n=2, 14.3%) and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation (n=8, 57.1%) occurred with serum levels in the toxic range (>5.5 mg/L), whereas blurred-vision (n=2, 14.3%) occurred within the therapeutic range (1.18 mg/L and 3.9 mg/L). The frequency of voriconazole discontinuation due to adverse events was lower in the TDM group (0.0% vs. 18.2%, P=0.481). Overall, 57.2% of the patients in the TDM group versus 14.3% in the non-TDM group showed clinical response after 6 weeks (P=0.055), whereas 21.4% in the TDM group versus 14.3% in the non-TDM group showed response at final outcome (P=0.664). In the TDM group, >67.0% of the serum levels were within therapeutic range for the first 6 weeks; however 45.5% were within therapeutic range for the entire duration. CONCLUSION: Routine TDM is recommended for optimizing the therapeutic effects of voriconazole.

Association between Respiratory Virus Infection and Pneumococcal Colonization in Children / 소아감염

PURPOSE: This study aimed to investigate the association between respiratory virus infection and pneumococcal colonization in children. METHODS: From May 2009 to June 2010, nasopharyngeal (NP) aspirates were obtained from patients under 18 years old who visited Seoul National University Children's Hospital for respiratory symptoms. NP samples were used to detect respiratory viruses (influenza virus A and B, parainfluenza virus 1, 2 and 3, respiratory syncytial virus A and B, adenovirus, rhinovirus A/B, human metapneumovirus, human coronavirus 229E/NL63 and OC43/HKU1) by RT-PCR and pneumococcus by culture. RESULTS: Median age of the patients was 27 months old. A total of 1,367 NP aspirates were tested for respiratory viruses and pneumococcus. Pneumococcus was isolated from 228 (16.7%) of samples and respiratory viruses were detected from 731 (53.5%). Common viruses were rhinovirus (18.4%), respiratory syncytial virus (RSV) A (10.6%), adenovirus (6.9%), influenza virus A (6.8%). Pneumococcal isolation rate was significantly higher in the cases of positive virus detection than negative detection [21.3% (156/731) vs. 11.3% (72/636), P<0.001]. For individual viruses, pneumococcal isolation rate was positively associated with detection of influenza virus A [24.7% (23/93) vs 16.1% (205/1274), P=0.001], RSV A [28.3% (41/145) vs 15.3% (187/1222), P=0.001], RSV B [31.3% (10/32) vs 16.3% (218/1335), P=0.042], rhinovirus A/B [22.6% (57/252) vs 15.3% (171/1115), P=0.010]. CONCLUSION: The study revealed that pneumococcal isolation from NP aspirates is related with respiratory virus detection. The result of this study could be used to investigate how respiratory viruses and pneumococcus cause clinical diseases.