[Show abstract][Hide abstract] ABSTRACT: Mycoplasma pneumoniae is responsible for approximately 20% to 30% of community-acquired pneumonia, and is well known for its diverse extrapulmonary manifestations. However, acute necrotizing pancreatits is an extremely rare extrapulmonary manifestation of M. pneumoniae infection. A 6-year-old girl was admitted due to abdominal pain, vomiting, fever, and confused mentality. Acute necrotizing pancreatitis was diagnosed according to symptoms, laboratory test results, and abdominal computed tomography scans. M. pneumoniae infection was diagnosed by a 4-fold increase in antibodies to M. pneumoniae between acute and convalescent sera by particle agglutination antibody assay. No other etiologic factors or pathogens were detected. Despite the occurrence of a large infected pseudocyst during the course, the patient was able to discharge without morbidity by early aggressive supportive care. This is the first case in Korea of a child with acute necrotizing pancreatitis associated with M. pneumoniae infection.
[Show abstract][Hide abstract] ABSTRACT: Neurologic complications are serious complications after hematopoietic stem cell transplantation (HSCT) and significantly contribute to morbidity and mortality. The purpose of this study was to investigate the clinical features and prognosis in pediatric patients who had neurologic complications after allogeneic HSCT. We retrospectively reviewed the medical records of children and adolescents (19 years old or younger) who underwent allogeneic HSCT at our institution from 2000 to 2012. A total of 383 patients underwent 430 allogeneic transplants. Among them, 73 episodes of neurologic complications occurred in 70 patients. The cumulative incidence of neurologic complications at day 400 was 20.0%. Almost two-thirds of the episodes (63.0%, 46/73) occurred within day 100 after transplantation. Calcineurin inhibitor (CNI)-related neurotoxicity was observed as the most common cause of neurotoxicity (47.9%, 35/73) and was significantly associated with earlier onset-neurologic complications, seizure, and tremor. It also showed a significant association with lower probability of headache, abnormality of cranial nerve, and neurologic sequelae. In a multivariate analysis, days to neutrophil engraftment after HSCT, extensive chronic graft-versus-host disease (GVHD) and the existence of neurologic sequelae were identified as risk factors for mortality in patients who had neurologic complications (HR 1.08, 95% CI 1.02 to 1.15, P = .011, HR 5.98, 95% CI 1.71 to 20.90, P = .005, HR 4.37, 95% CI 1.12 to 17.05, P = .034, respectively). However, there was no significant difference in the 5-year overall survival between the patients who had neurologic complications without sequelae and the patients who did not have any neurologic complications (57.3% versus 61.8%, P = .906). In conclusion, we found that the major significant risk factors for mortality in pediatric recipients with neurologic complications were the existence of neurologic sequelae and extensive chronic GVHD.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2015; 21(6). DOI:10.1016/j.bbmt.2015.02.007 · 3.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Although mouse brain-derived, inactivated Japanese encephalitis vaccines (JE-MBs) have been successfully used for a long time, potential rare neurological complications have prompted the development of a Vero cell culture-derived inactivated vaccine (JE-VC). In a phase III clinical study, we aimed to compare the safety and immunogenicity of a JE-VC, KD-287 with a JE-MB, JEV-GCC, in children. Methods: In this multicenter, double-blinded, randomized controlled trial, the study population consisted of 205 healthy Korean children aged 12-23 months. Each subject was subcutaneously vaccinated with either KD-287 or JEV-GCC twice at an interval of 2 weeks and then vaccinated once 12 months after the second vaccination. Neutralizing antibodies were measured by the plaque reduction neutralization test using the homologous and heterologous, as a post hoc analysis, challenge virus strains. Results: The three-dose regimen of KD-287 showed a comparable safety profile with JEV-GCC except higher incidence of fever after the first dose (30.4% and 14.7%, respectively). Most of the fever was mild degree (61.3% and 66.7%, respectively). KD-287 fulfilled the non-inferiority criteria for seroconversion rate (SCR) and geometric mean titer (GMT) of the neutralizing antibody, which were the primary endpoints, at 4 weeks after the third vaccination (95% CI: -1.00, 3.10 for the SCR difference and 10.8, 17.6 for the GMT ratio). The SCRs of KD-287 were all 100% and the GMTs were higher in the KD-287 group than in the JEV-GCC group after the second vaccination and before and after the third vaccination (GMT ratio: 5.59, 20.13, and 13.79, respectively, p < 0.001 in all). GMTs were higher in the KD-287 group in the heterologous analysis also (GMT ratio: 4.05, 5.15, and 4.19, respectively, p < 0.001 in all).
[Show abstract][Hide abstract] ABSTRACT: Abstract Objective: To investigate changes in the etiologic microorganisms causing early-onset neonatal sepsis (EONS) in preterm labor (PTL) or preterm premature rupture of membranes (pPROM) cases over the past 16 years and to analyze the associated factors. Methods: We included consecutive singleton pregnancies delivered before 34 weeks due to PTL or pPROM. The etiologic microorganisms causing EONS in PTL and pPROM cases were compared between period 1 (1996 to 2004) and period 2 (2005 to 2012). Results: There was no difference in the incidence of Gram-positive bacteria causing EONS between period 1 and 2, either in PTL (2.0% vs 2.1%, p = 1.0) or in pPROM (1.5% vs 1.6%, p = 1.0). However, the incidence of EONS caused by Gram-negative bacteria was significantly increased in pPROM (0.6% vs 2.7%, p = 0.040) during period 2, compared to period 1; but not in PTL (0.3% vs 1.2%, p = 0.211). Multivariable analysis revealed that a prolonged ROM-to-delivery interval (>7days) was significantly associated with EONS caused by Gram-negative bacteria in pPROM (odds ratio: 6.6, 95% confidence interval: 1.4-31.8, p = 0.018). Conclusions: The etiologic microorganisms causing EONS have changed over the past 16 years in pPROM cases but not in PTL cases.
Journal of Maternal-Fetal and Neonatal Medicine 10/2014; 28(16):1-24. DOI:10.3109/14767058.2014.972928 · 1.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic granulomatous disease (CGD) is a rare immunodeficiency disease, which is characterized by the lack of a functional nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in phagocytes. The disease presents leukocytosis, anemia, hypergammaglobulinemia, and granuloma formation of the skin, lung, or lymph nodes. The mutation of the CYBB gene encoding gp91phox, located on chromosome Xp21.1 is one of the causes of CGD. We report a patient with X-linked CGD who carried a novel mutation, a c.1133A>G (paAsp378Gly) missense mutation, in the CYBB gene.
[Show abstract][Hide abstract] ABSTRACT: 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 3 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.
[Show abstract][Hide abstract] ABSTRACT: Rubinstein-Taybi syndrome (RTS) is a multiple congenital anomaly syndrome characterized by facial abnormalities, broad thumbs and toes, and mental retardation. RTS is known to be caused by the disruption, either by point mutations or microdeletions, of the human CREB-binding protein (CREBBP) gene on 16p13.3. Gross rearrangements involving 16p13.3, such as translocations or inversions, have rarely been reported in RTS. A 3-month-old boy with a phenotype typical of RTS was referred for genetic diagnosis. Cytogenetic analysis revealed a novel reciprocal translocation: t(1;16)(p36.2;p13.3). Gene dosage analysis for the CREBBP gene was performed using multiple ligation-dependent probe amplification (MLPA) and revealed heterozygous deletion of the whole CREBBP gene. Genome-wide single nucleotide polymorphism (SNP)-array confirmed the deletion and also indicated large genomic deletions in both 1p36.2 and 16p13.3. To the best of our knowledge, this is the first report of characterization of the genomic dosage imbalances in RTS by SNP-array.
Annals of clinical and laboratory science 11/2013; 43(4):450-6. · 0.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:QuantiFERON-TB Gold In-Tube (QFT-G IT; Cellestis Inc., Valencia, CA, USA) is one of the Interferon-gamma Release Assays (IGRAs) that are promising tools for diagnosing active or latent Mycobacterium tuberculosis infection. We investigated the clinical and laboratory factors that affect the rate of indeterminate QFT-G IT test results. We also suggest the workflow strategy to achieve optimized test results using QFT-G IT for the diagnosis of active TB or LTBI.Methods:We performed statistical analysis using data from review of medical records, retrospectively. The first phase included 683 QFT-G IT test results from 676 patients tested from January 2008 to May 2008, and the second phase included additional 663 QFT-G IT test results from 653 patients tested from January 2008 to December 2008 at Samsung Medical Center, a tertiary care hospital in South Korea.Results:Immunosuppressive drug therapy, underlying diseases, bed-ridden status, and hypoalbuminemia were significantly associated with an indeterminate QFT-G IT test result. With the reduction in incubation delay from an average of 9.82 hours to an average of 2.70 hours during the test procedure by making changes in the workflow, the frequency of indeterminate QFT-G IT test results was significantly reduced from 11.4% to 2.7%. However, if there was a more than 6 hours of incubation delay, the frequency of indeterminate QFT-G IT test results was increased in a statistically significant manner.Conclusion:This study demonstrates that not only the clinicopathological factors, but also the laboratory factor such as incubation delay affects significantly on the rate of indeterminate QFT-G IT test results, and hence optimization of the test procedure may contribute to the reduction in the rate of indeterminate QFT-G IT test results that delay the diagnosis of TB.
[Show abstract][Hide abstract] ABSTRACT: Background: Ventilator-associated pneumonia (VAP) is a serious threat in critically ill pediatric patients. Data regarding associated VAP caused by Stenotrophomonas maltophilia in pediatric population is limited.
Methods: A retrospective chart review was performed in pediatric patients 18 years old or younger who developed the first episode of S. maltophilia associated VAP at Samsung Medical Center, Seoul Korea from January 2008 to December 2012.
Results: A total of 45 patients were identified with VAP caused by S. maltophilia. Median age was 1.9 years (range, 0.1 to 18.8 years) and 24 patients were male (53.3%). Underlying illnesses were hematologic oncologic malignancy (n=14, 31.1%28.9%), cardiologic diseases (n=13, 28.97%), neurologic diseases (n=9, 20.0%), pulmonary diseases (n=5, 11.1%), and others (n=4, 8.9%). The median duration of ventilator treatment before VAP was 21 days (range, 3-255 days). Two patients also developed S. maltophilia bacteremia (4.4%). Overall mortality at 30 days was 6.7%.
Conclusion: S. maltophilia should be also considered as a possible pathogen for VAP in critically ill pediatric patients. Empiric antibiotic choice should include agents that are active against S. maltophila in patients who are deteriorating on broad spectrum beta-lactam antimicrobial agents.
IDWeek 2013 Meeting of the Infectious Diseases Society of America; 10/2013
[Show abstract][Hide abstract] ABSTRACT: Background:
Ciprofloxacin is not approved in children under 18 years old due to its potential musculoskeletal adverse effects. However, it is widely prescribed in the pediatric patients. We conducted a retrospective multicenter study to evaluate the prescription pattern of ciprofloxacin and to review any reported adverse events in Korean children.
A retrospective review was performed in patients younger than 18 years old who received ciprofloxacin in 7 university hospitals in Korea from January 2006 to December 2011.
A total of 729 patients were identified. The median age was 15.9 years (range, 0.1-17.9); 18 patients (2.5%) were under 2 years old, 77 (10.6%) 2-9 years, 143 (19.6%) 10-14 years, and 491 (67.4%) 15-17 years. Two-hundred sixty-nine (36.9%) patients had comorbid medical conditions. Ciprofloxacin was given as the first-line antimicrobial agent in 480 (65.8%) patients. Clinical diagnoses at the time of ciprofloxacin prescription were gastroenteritis (325, 44.6%), urinary tract infections (159, 21.8%), abscess or skin and soft tissue infections (65, 8.9%) and pneumonia (55, 7.5%). There were 22 bacteremia cases (3.0%). Ciprofloxacin was prescribed mostly by emergency care physicians (207, 28.4%), internal medicine physicians (187, 25.7%) and pediatricians (153, 21.0%). The use of ciprofloxacin based on culture results was observed in only 26.1% of total patients (190/729); 43.8% by pediatricians vs. 21.4% by non-pediatric physicians (P<0.0001). Adverse events after use of ciprofloxacin were observed in 15 patients (2.1%): four with hypersensitivity, six with gastrointestinal complaints, one with headache, one with EKG abnormality and three others. There was no musculoskeletal complication reported.
This is the first multicenter study to evaluate the prescription pattern and safety of ciprofloxacin in Korean children. We found that ciprofloxacin was frequently prescribed in children as an empiric antibiotic choice in many unapproved indications and musculoskeletal adverse event was not reported in any of these patients. There is a need for systematic monitoring for the appropriate use of ciprofloxacin and development of musculoskeletal complication in Korean children.
IDWeek 2013 Meeting of the Infectious Diseases Society of America; 10/2013
[Show abstract][Hide abstract] ABSTRACT: We describe three children with urinary tract abnormalities and large numbers of S. pneumoniae in their urine, along with a brief review of previously reported cases. These findings strongly suggest that S. pneumoniae is a uropathogen, especially in children with urinary tract abnormalities.
[Show abstract][Hide abstract] ABSTRACT: This article contains the recommended immunization schedule by the Committee on Infectious Diseases of the Korean Pediatric Society, updated in March 2013, when Haemophilus influenzae type b vaccine is now included in the National Immunization Program in Korea. It also includes catch-up immunization schedule for children and adolescents who are behind the recommended schedule. These schedules are a minor revision of the corresponding parts of Immunization Guideline, 7th edition, of the Korean Pediatric Society, released in 2012. Pediatricians should be aware of these schedules to provide adequate immunization to Korean children and adolescents.
Korean Journal of Pediatrics 06/2013; 56(6):231-234. DOI:10.3345/kjp.2013.56.6.231
[Show abstract][Hide abstract] ABSTRACT: Fluoroquinolones are an important class of antibiotics that are widely used in adult patients because of their broad spectrum of activity, good tissue penetration, and oral bioavailability. However, fluoroquinolone use in children is limited because juvenile animals developed arthropathy in previous experiments on fluoroquinolone use. Indications for fluoroquinolone use in patients younger than 18 years, as stated by the U.S. Food and Drug Administration, include treatment of complicated urinary tract infections and postexposure treatment for inhalation anthrax. In Korea, the systemic use of fluoroquinolones has not been approved in children younger than 18 years. Although concerns remain regarding the adverse musculoskeletal effects of fluoroquinolones in children, their use in the pediatric population has increased in many circumstances. While pediatricians should be aware of the indications and adverse effects of fluoroquinolones, recent studies have shown that the risk for musculoskeletal complications in children did not significantly increase following fluoroquinolone treatment. In addition, fluoroquinolones may be particularly helpful in treating multidrug-resistant infections that have not responded to standard antibiotic therapy in immunocompromised patients. In the present article, we provide an updated review on the safety and current recommendations for using fluoroquinolones in children.
Korean Journal of Pediatrics 05/2013; 56(5):196-201. DOI:10.3345/kjp.2013.56.5.196
[Show abstract][Hide abstract] ABSTRACT: Background:
Invasive aspergillosis (IA) is a major cause of morbidity and mortality in immunocompromised children. We investigated the usefulness of an Aspergillus galactomannan (GM) antigen assay as a diagnostic tool for IA in pediatric cancer patients and hematopoietic cell transplantation (HCT) recipients.
The GM antigen assay results were analyzed in 749 blood samples from 99 patients. A GM index (GMI) greater than or equal to 0.5 on at least two separate occasions was considered positive. A review of the clinical data was performed for subjects with proven or probable IA.
Twenty-one of 23 patients with proven or probable IA had positive GM antigen test results (91.3% sensitivity, 95% CI 71.9-98.9; 81.7% specificity, 95% CI 69.6-90.5; P < 0.0001). The false-positive rate was 18.3%. Being younger than 3 years of age, having a solid tumor, and receiving HCT within 4 weeks of the test were statistically significant factors for causing false-positive results (P < 0.05). Among the 23 patients with IA (six proven, 17 probable), 16 (69.6%) had hematological malignancies, five (22.7%) had solid tumors, and two (8.7%) had primary immunodeficiency. Nineteen patients (82.6%) received HCT. The most common clinical site of IA was the lungs (91.3%), and consolidation was the most frequent finding in chest CT scans (36.8%). The mortality at 12 weeks was 43.5%.
Having a positive GM assay at least twice is useful in diagnosing IA in pediatric patients with cancer and HCT recipients.
[Show abstract][Hide abstract] ABSTRACT: We report a case of the isolation of the Aspergillus versicolor complex, initially misidentified by morphological characteristics as the Scopulariopsis species, from a homograft with a bicuspidalized pulmonary valve. An eighteen-month-old female, who had critical pulmonary stenosis, underwent pulmonary valve replacement. On postoperative day 8, she developed a fever, which did not respond to empiric broad-spectrum antibiotics. While no definitive source was identified, a filamentous fungus was isolated from the thawed homograft tissue culture prior to implantation on the operation day. The colonies were powdery green with white edges on Sabouraud dextrose agar. Microscopic examination showed septate hyphae with branched conidiophores and chains of spiny conidia, which suggested Scopulariopsis species. After direct sequencing of the internal transcribed spacer (ITS) regions, the fungus was identified as the A. versicolor complex. To our knowledge, the isolation of the A. versicolor complex from a homograft valve has not been previously described. This case shows that laboratory staff should be aware that microscopic morphology of the A. versicolor complex can resemble that of a number of other genera, including Scopulariopsis species.
[Show abstract][Hide abstract] ABSTRACT: Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) now provides an important alternative diagnostic modality in patients with intrathoracic tuberculosis lymphadenopathy. The procedure is well tolerated in the outpatient setting, provides access to the mediastinal and hilar lymph node locations commonly in tuberculosis and also allows bronchial washing to be performed at the same procedure. However, there is no report of EBUS-TBNA applied to children to diagnose tuberculosis. We report a case of EBUS-TBNA applied to children who had intrathoracic tuberculosis lymphadenopathy.
Korean Journal of Pediatric Infectious Diseases 01/2013; 20(3).
[Show abstract][Hide abstract] ABSTRACT: Voriconazole is the drug of choice for invasive aspergillosis (IA) and drug levels are influenced by interactions with other drugs and genetic predisposition. We performed a retrospective analysis of voriconazole drug levels and investigated the adequacy of drug levels in pediatric cancer patients and hematopoietic cell transplant (HCT) recipients with IA.
Trough serum concentrations of voriconazole in patients younger than 19 years during a 30-month period were analyzed. The therapeutic range was determined as 1–6 µg/ml.
A total of 193 voriconazole measurements at steady-state [86 on intravenous (IV) and 107 on oral (PO) doses] were obtained from 27 patients (median age 12.2 years). On the first monitoring, 19 patients (70.4%) achieved the therapeutic range. However, only 10 patients (37.0%) achieved the therapeutic range on second monitoring. Sixty-four percent of the total measurements were within the therapeutic range: 66.3% of IV and 61.7% of PO. A significant correlation between oral doses and trough levels of voriconazole was observed in patients ≤6 years old (Spearman's rank correlation coefficient = 0.4819, P = 0.027). Patients aged ≤6 years needed a significantly higher median dose of PO voriconazole to maintain therapeutic trough levels compared to older patient groups (8.9 vs. 4.2 mg/kg/dose, P < 0.001). Voriconazole level <1 µg/ml was more frequently observed in patients with treatment failure at week 6 of voriconazole therapy (failure vs. success, 42.1% vs. 19.7%; P = 0.012).
Serum concentrations of voriconazole in children were variable, depending on the patient's age and route of administration. Continuous and careful drug level monitoring should be performed. Pediatr Blood Cancer 2013; 60: 82–87.