Clinical characteristics and outcomes of children with COVID-19 in pediatric intensive care units during the Omicron wave in Taiwan.

BACKGROUND: Since April 2022, the SARS-CoV-2 Omicron variant has caused a notable increase in pediatric COVID-19 cases in Taiwan. During the acute phase of infection, some children required admissions to pediatric intensive care units (PICU). This study aimed to analyze their clinical presentations and outcomes while exploring associated factors. METHODS: Medical records were retrospectively collected from patients with COVID-19 (aged <18 years) admitted to our PICU from April 2022-March 2023. Early stage is defined as the period without adequate vaccination and treatment guidelines for children from April-June 2022, and the remaining months are referred to as late stage. Clinical characteristics and outcomes were compared between patients in early and late stages. RESULTS: We enrolled 78 children with COVID-19, with a median length of stay (LOS) in PICU of 3 days and a 5% mortality rate. Patients admitted during the early stage had lower vaccination rates (7% vs. 50%), higher pediatric logistic organ dysfunction scores (2 vs. 0.1), and longer LOS in the PICU (6 vs. 2 days) than those admitted during the late stage. Multivariate analysis identified admission during the early stage as a risk factor for prolonged LOS (>7 days) in the PICU (odds ratio: 3.65, p = 0.047). CONCLUSION: Without available vaccinations and suitable treatment guidelines, children with COVID-19 tended to have more severe illness and prolonged LOS in the PICU. These observations highlight the importance of vaccinations and familiarity of medical providers with adequate management of this newly-emerging infectious disease.

Clinical manifestations and risk factors of shock in children with multisystem inflammatory syndrome.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a novel disease associated with COVID-19. The COVID-19 epidemic peaked in May 2022 in Taiwan, and we encountered our first case of MIS-C in late May 2022. We aimed to present patients' clinical manifestations and identify risk factors for shock. METHODS: We included patients diagnosed with MIS-C at two medical centers from May 2022 to August 2022. We separated those patients into two groups according to whether they experienced shock. We collected demographic, clinical manifestation, and laboratory data of the patients and performed statistical analysis between the two groups. RESULTS: We enrolled 28 patients, including 13 (46 %) with shock and 15 (54 %) without shock. The median age was 6.4 years (IQR: 1.9-7.5). In single variable analysis, patients with shock tended to be older, had more neurological symptoms, more conjunctivitis and strawberry tongue, lower lymphocyte count, lower platelet counts, and higher C-reactive protein, higher procalcitonin, higher ferritin, and higher D-dimer levels than those without shock. The area under the ROC curve that used procalcitonin to be the risk factor of shock with MIS-C was 0.815 (95 % CI 0.644 to 0.987). The cutoff value obtained by ROC analysis of procalcitonin was 1.68 ng/mL. With this cutoff, the test characteristics of procalcitonin were as follows: sensitivity 77 %, specificity 93 %, positive predictive value 91 %, negative predictive value 82 %. Multivariable analysis revealed that procalcitonin was the only independent risk factor of shock with MIS-C on admission (OR, 26.00, 95 % CI, 1.01-668.89). CONCLUSIONS: MIS-C patients with high initial procalcitonin levels have higher risks of experiencing shock and may need ICU admission.

High incidence of cerebrovascular lesions on magnetic resonance imaging in pediatric COVID-19 during omicron outbreak - A retrospective case series.

BACKGROUND: The incidence of pediatric hospitalizations has significantly increased since the spread of the omicron variant of COVID-19. Changes of characteristics in respiratory and neurological symptoms have been reported. We performed a retrospective, cross-sectional study to characterize the MRI change in children with an emphasis on the change of cerebral vasculatures. METHODS: We retrospectively collected clinical and MRI data of 31 pediatric patients with neurological symptoms during the acute infection and abnormalities on MRI during the outbreak of omicron variant from April 2022 to June 2022 in Taiwan. The clinical manifestations and MRI abnormalities were collected and proportion of patients with vascular abnormalities was calculated. RESULTS: Among 31 pediatric patients with post-COVID-19 neurological symptoms, MRI abnormalities were observed in 15 (48.4%), predominantly encephalitis/encephalopathy (73.3%). Notable MRI findings included focal diffusion-weighted imaging (DWI) hyperintensity in cerebral cortex and thalamus, diffuse cortical T2/DWI hyperintensity, and lesions in the medulla, pons, cerebellum, and splenium of corpus callosum. Vascular abnormalities were seen in 12 (80%) patients with MRI abnormalities, mainly affecting the middle cerebral arteries. The spectrum of neurological manifestations ranged from seizures to Alice in Wonderland syndrome, underscoring the diverse impact of COVID-19 on pediatric patients. CONCLUSION: A high proportion of vascular abnormalities was observed in pediatric patients with neurological involvements, suggesting that vascular involvement is an important mechanism of neurological manifestations in omicron variant infection.

Multicenter registry of multisystem inflammatory syndrome in children (MIS-C) and Paired comparison with Kawasaki disease.

OBJECTIVES: This study aimed to identify clinical characteristics to differentiate multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) in Taiwan, an island with a delayed cluster of MIS-C and a high incidence of KD. Additionally, we studied risk factors for developing severe complications in patients with MIS-C. METHODS: We conducted a retrospective, multicenter, cohort, and observational study that linked data on patients with MIS-C between May and December 2022 and patients with KD between 2019 and 2021 from 12 medical centers. Hemodynamic compromise, defined as the need for inotropic support or fluid challenge, was recorded in patients with MIS-C. We also evaluated maximal coronary Z-scores before treatment and one month after disease onset. RESULTS: A total of 83 patients with MIS-C and 466 patients with KD were recruited. A 1:1 age and gender-matched comparison of 68 MIS-C and KD pairs showed that MIS-C patients had a lower percentage of positive BCG red halos, lower leukocyte/platelet counts, more gastrointestinal symptoms, and a higher risk of hemodynamic compromise. In Taiwan, 38.6% of MIS-C patients experienced hemodynamic compromise, with presence of conjunctivitis and elevated levels of procalcitonin (>1.62 ng/mL) identified as independent risk factors. CONCLUSIONS: We identified two independent risk factors associated with hemodynamic compromise in MIS-C patients. The comparison between matched MIS-C and KD patients highlighted significant differences in clinical presentations, like BCG red halos, which may aid in the differential diagnosis of the two disease entities, especially in regions with a high incidence rate of KD.

An Elastic Organic Crystal Enables Macroscopic Photoinduced Crystal Elongation.

Among the various types of photomechanical deformations of organic crystals, photoinduced elongation of millimeter-scale crystals has yet to be demonstrated. Here we report that the millimeter-sized crystalline rods of an anthracene-pentiptycene hybrid organic π-system (1) are highly elastic and able to elongate up to 21.6% or 0.40 mm without fragmentation upon undergoing [4 + 4] photodimerization reactions. Both the mechanical and photomechanical effects reveal a strong cohesion of the system, even at the interface of 1 and its photodimer 2 and under the conditions of randomized molecular packing, representing a new class of mechanically adaptive organic crystals.

Application of nested multiplex polymerase chain reaction respiratory and pneumonia panels in children with severe community-acquired pneumonia.

Community-acquired pneumonia (CAP) is a serious clinical concern. A lack of accurate diagnosis could hinder pathogen-directed therapeutic strategies. To solve this problem, we evaluated clinical application of nested multiplex polymerase chain reaction (PCR) in children with severe CAP. We prospectively enrolled 60 children with severe CAP requiring intensive care between December 2019 and November 2021 at a tertiary medical center. Nested multiplex PCR respiratory panel (RP) and pneumonia panel (PP) were performed on upper and lower respiratory tract specimens. We integrated standard-of-care tests and quantitative PCR for validation. The combination of RP, PP, and standard-of-care tests could detect at least one pathogen in 98% of cases and the mixed viral-bacterial detection rate was 65%. The positive percent agreement (PPA), and negative percent agreement (NPA) for RP were 94% and 99%; the PPA and NPA for PP were 89% and 98%. The distribution of pathogens was similar in the upper and lower respiratory tracts, and the DNA or RNA copies of pathogens in the lower respiratory tract were equal to or higher than those in the upper respiratory tract. PP detected bacterial pathogens in 40 (67%) cases, and clinicians tended to increase bacterial diagnosis and escalate antimicrobial therapy for them. RP and PP had satisfactory performance to help pediatricians make pathogenic diagnoses and establish therapy earlier. The pathogens in the upper respiratory tract had predictive diagnostic values for lower respiratory tract infections in children with severe CAP.

The impact of the coronavirus disease 2019 epidemic and national public restrictions on Pediatric Intensive Care Units in Taiwan.

BACKGROUND/PURPOSE: Coronavirus disease 2019 (COVID-19) pandemic challenges pediatric health globally by limited medical accessibility. In response to COVID-19 epidemic in Taiwan, public restrictions were applied and the Level 3 alert was announced from May to July in 2021 for local outbreak. This study aims to analyze patients' clinical features and outcomes in the pediatric intensive care unit (PICU) during the COVID-19 epidemic with the Level 3 alert in Taiwan. METHODS: Medical records were retrospectively collected in patients admitted to the PICU of National Taiwan University Children's Hospital from May to July 2021 (Level 3 alert) and May to July 2019 and 2020 (control periods). Clinical characteristics and outcomes were compared between patients in the period with the Level 3 alert and control periods. RESULTS: During the study period, PICU monthly admissions significantly decreased in the Level 3 alert period and were negatively correlated with monthly newly confirmed COVID-19 cases. Patients admitted during the Level 3 alert were older, had higher disease severity, lower proportion of cardiovascular disease, and higher proportion of hematology-oncology diseases than those in the control group. After adjusting for the above factors, admission during Level 3 alert was an independent factor for higher mortality rate and prolonged length of stay (>14 days) in the PICU. CONCLUSION: During the COVID-19 epidemic with strict public restrictions, critically ill patients admitted to the PICU decreased but had increased disease severity, prolonged length of stay in the PICU, and higher mortality, reflecting the impact of quarantine and limited medical access.

Viral dynamics of SARS-CoV-2 Omicron infections in a previously low COVID-19 prevalence region: Effects of vaccination status, antiviral agents, and age.

BACKGROUND: In Taiwan, the prevalence of COVID-19 was low before April 2022. The low SARS-CoV-2 seroprevalence in the population of Taiwan provides an opportunity for comparison with fewer confounding factors than other populations globally. Cycle threshold (Ct) value is an easily accessible method for modeling SARS-CoV-2 dynamics. In this study, we used clinical samples collected from hospitalized patients to explore the Ct value dynamics of the Omicron variant infection. METHODS: From Jan 2022 to May 2022, we retrospectively included hospitalized patients tested positive by nasopharyngeal SARS-CoV-2 PCR. We categorized the test-positive subjects into different groups according to age, vaccination status, and use of antiviral agents. To investigate the nonlinear relationship between symptom onset days and Ct value, a fractional polynomial model was applied to draw a regression line. RESULTS: We collected 1718 SARS-CoV-2 viral samples from 812 individuals. The Ct values of unvaccinated individuals were lower than those of vaccinated persons from Day 4 to Day 10 after symptom onset. The Ct value increased more rapidly in those individuals with antiviral drug treatment from Day 2 to Day 7. In elderly individuals, the Ct values increased slowly from Day 5 to Day 10, and the increasing trend was unique compared with that in children and adults. CONCLUSION: Our study demonstrated the primary viral infection dynamics of the Omicron variant in hospitalized patients. Vaccination significantly affected viral dynamics, and antiviral agents modified viral dynamics irrespective of vaccination status. In elderly individuals, viral clearance is slower than that in adults and children.

Impact of pneumococcal conjugate vaccination on hospitalized childhood pneumonia in Taiwan.

BACKGROUND: A national 13-valent pneumococcal conjugate vaccine (PCV13) catch-up program among children aged 2-5 years in 2013, before routine infant immunization in 2015, successfully reduced serotype 19A-related invasive pneumococcal diseases in Taiwan. We aimed to investigate its impact on hospitalized childhood pneumonia. METHODS: We analyzed the National Health Insurance Research Database, 2001-2017, for hospitalized children aged <18 years with the diagnoses of all-cause pneumonia, lobar/pneumococcal pneumonia, and pneumococcal parapneumonic diseases. The study period was divided into 2001-2005 (pre-PCV), 2006-2012 (private sectors), and 2013-2017 (universal PCV13 vaccination). RESULTS: On pneumococcal parapneumonic diseases, the national PCV13 vaccination program was associated with an immediate decline in 2-4-year-old children and significant decreasing trends in all ages. The incidence rate ratios of 2016-2017/2011-2012 were 0.16 (95% confidence interval [CI], 0.06-0.40) and 0.18 (95% CI, 0.13-0.23) in children aged < 2 and 2-4 years, respectively. We observed an increase of lobar/pneumococcal pneumonia cases after an early decline. The intensive/invasive medical needs and the fatality of all-cause pneumonia decreased significantly in children of all ages. CONCLUSIONS: Pneumococcal parapneumonic diseases and the disease burden of lobar/pneumococcal pneumonia and lower respiratory tract infections declined after the national PCV13 vaccination program. IMPACT: The impact study of the PCV13 immunization program on childhood pneumonia in Asian countries remained limited. The unique PCV13 immunization program in Taiwan, catch-up before primary infantile series, reduced severe childhood pneumococcal pneumonia at 5 years post PCV13. The intensive and invasive medical needs and fatality of all-cause pneumonia decreased significantly in children of all ages. We observed an increase in lobar/pneumococcal pneumonia after an early decline.

Comparisons of the clinical and mycological characteristics of pediatric candidemia.

BACKGROUND/PURPOSE: Invasive candidiasis is a severe infectious disease that could lead to mortality in critically ill children. METHODS: We collected data regarding demographics, underlying diseases, predisposing factors, outcomes for pediatric patients with candidemia at a medical centre in Taiwan from 2011 to 2017. RESULTS: Fifty-eight patients with 60 candidemia episodes were diagnosed. The 3 most common species were Candida albicans (42%), Candida parapsilosis (25%) and Candida tropicalis (23%). C. parapsilosis predominantly infected infants and neonates (median age: 0.8 years, range: 0.1-14.5). Cases with C. tropicalis had significantly higher rates of multidrug resistance (p = 0.011) and disseminated candidiasis (p = 0.025) compared with other cases. The all-cause mortality rate was 43%, and the candidemia-related mortality rate was 29%. Pediatric sequential organ failure assessment score >8 [adjusted odds ratio (aOR) 66.2, 95% CI 4.03-1088.5] and posaconazole resistance (aOR 33.57, 95% CI 1.61-700.3) were the most significant risk factors associated with candidemia-related mortality, whereas treatment with effective antifungal agents within 48 h (aOR 0.07, 95% CI 0.01-0.9) was the only significant protective factor. CONCLUSION: Candidemia-related mortality was related to azole resistance; therefore, empirical therapy with echinocandin or amphotericin B is recommended pending species and susceptibility results.

Children with Mycoplasma pneumoniae infection in Taiwan: Changes in molecular characteristics and clinical outcomes.

BACKGROUND: Mycoplasma pneumoniae is a pathogen that causes respiratory diseases in children. Infections caused by M. pneumoniae are usually self-limited but occasionally can be severe. We observed emerging cases of severe mycoplasma infection requiring extracorporeal membrane oxygenation (ECMO). Thus, we investigated chronological changes in the molecular features of the M. pneumoniae and its clinical impacts among the pediatric population. METHODS: From 2011 to 2019, respiratory samples were collected from patients younger than 18 years old with pneumonia in a tertiary children's hospital. Focused multiple-locus variable number of tandem repeats analysis (MLVA) typing was performed on samples positive for M. pneumoniae in 2016 and 2019. Clinical data from the patients' electronic medical records were collected. We described the annual trend of macrolide resistance and MLVA type and analyzed the associations between clinical manifestations and MLVA types. RESULTS: The percentage of macrolide-resistant (MLR) M. pneumoniae gradually increased from 22% (27/122) in 2015 to 70% (82/117) in 2019. Among the MLRM. pneumoniae, the predominant strain shifted from type P (31% [13/42]) to type A (40% [19/46]). The demographics, initial presentations, and clinical courses of the subjects with MLRM. pneumoniae did not differ significantly between 2011 and 2019. However, in 2019, two fulminant cases requiring venovenous ECMO were observed, which indicates that more attention to the clinical severity of MLRM. pneumoniae infections is warranted. CONCLUSION: Obtaining accurate information on macrolide susceptibility is crucial for physicians to initiate appropriate antibiotic treatment in a timely fashion. Although we could not identify significant differences among mycoplasma pneumonias caused by different MLVAs over a span of 9 years, the emergence of severe mycoplasma infections requiring ECMO was clinically significant, and further monitoring was required.

Clinical characteristics of influenza with or without Streptococcus pneumoniae co-infection in children.

BACKGROUND/PURPOSE: Influenza is frequently complicated with bacterial co-infection. This study aimed to disclose the significance of Streptococcus pneumoniae co-infection in children with influenza. METHODS: We retrospectively reviewed medical records of pediatric patients hospitalized for influenza with or without pneumococcal co-infection at the National Taiwan University Hospital from 2007 to 2019. Clinical characteristics and outcomes were compared between patients with and without S. pneumoniae co-infection. RESULTS: There were 558 children hospitalized for influenza: 494 had influenza alone whereas 64 had S. pneumoniae co-infection. Patients with S. pneumoniae co-infection had older ages, lower SpO2, higher C-Reactive Protein (CRP), lower serum sodium, lower platelet counts, more chest radiograph findings of patch and consolidation on admission, longer hospitalization, more intensive care, longer intensive care unit (ICU) stay, more mechanical ventilation, more inotropes/vasopressors use, more surgical interventions including video-assisted thoracoscopic surgery (VATS) and extracorporeal membrane oxygenation (ECMO), and higher case-fatality rate. CONCLUSION: Compared to influenza alone, patients with S. pneumoniae co-infection had more morbidities and mortalities. Pneumococcal co-infection is considered when influenza patients have lower SpO2, lower platelet counts, higher CRP, lower serum sodium, and more radiographic patches and consolidations on admission.

RSV pneumonia with or without bacterial co-infection among healthy children.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of childhood pneumonia, but there is limited understanding of whether bacterial co-infections affect clinical severity. METHODS: We conducted a retrospective cohort study at National Taiwan University Hospital from 2010 to 2019 to compare clinical characteristics and outcomes between RSV with and without bacterial co-infection in children without underlying diseases, including length of hospital stay, intensive care unit (ICU) admission, ventilator use, and death. RESULTS: Among 620 inpatients with RSV pneumonia, the median age was 1.33 months (interquartile range, 0.67-2 years); 239 (38.6%) under 1 year old; 366 (59.0%) males; 201 (32.4%) co-infected with bacteria. The three most common bacteria are Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae. The annually seasonal analysis showed that spring and autumn were peak seasons, and September was the peak month. Compared with single RSV infection, children with bacterial co-infection were younger (p = 0.021), had longer hospital stay (p < 0.001), needed more ICU care (p = 0.02), had higher levels of C-reactive protein (p = 0.009) and more frequent hyponatremia (p = 0.013). Overall, younger age, bacterial co-infection (especially S. aureus), thrombocytosis, and lower hemoglobin level were associated with the risk of requiring ICU care. CONCLUSION: RSV related bacterial co-infections were not uncommon and assoicated with ICU admission, especially for young children, and more attention should be given. For empirical antibacterial treatment, high-dose amoxicillin-clavulanic acid or ampicillin-sulbactam was recommended for non-severe cases; vancomycin and third-generation cephalosporins were suggested for critically ill patients requiring ICU care.

Clinical characteristics of recurrent pneumonia in children with or without underlying diseases.

BACKGROUND: Recurrent pneumonia is uncommon in children and few studies investigate the clinical impact of underlying diseases on this issue. This study aimed to explore the difference in clinical manifestations, pathogens, and prognosis of recurrent pneumonia in children with or without underlying diseases. METHODS: We conducted a retrospective study of pediatric recurrent pneumonia from 2007 to 2019 in National Taiwan University Hospital. Patients under the age of 18 who had two or more episodes of pneumonia in a year were included, and the minimum interval of two pneumonia episodes was more than one month. Aspiration pneumonia was excluded. Demographic and clinical characteristics of patients were collected and compared. RESULTS: Among 8508 children with pneumonia, 802 (9.4%) of them had recurrent pneumonia. Among these 802 patients, 655 (81.7%) had underlying diseases including neurological disorders (N = 252, 38.5%), allergy (N = 211, 32.2%), and cardiovascular diseases (N = 193, 29.5%). Children without underlying diseases had more viral bronchopneumonia (p < 0.001). Children with underlying diseases were more likely to acquire Staphylococcus aureus (p = 0.001), and gram-negative bacteriae, more pneumonia episodes (3 vs 2, p < 0.001), a longer hospital stay (median: 7 vs. 4 days, p < 0.001), a higher ICU rate (28.8% vs 3.59%, p < 0.001), and a higher case-fatality rate (5.19% vs 0%, p < 0.001) than those without underlying diseases. CONCLUSION: Children with underlying diseases, prone to have recurrent pneumonia and more susceptible to resistant microorganisms, had more severe diseases and poorer clinical outcomes. Therefore, more attention may be paid on clinical severity and the therapeutic plan.

Severe Mycoplasma pneumoniae pneumonia requiring intensive care in children, 2010-2019.

BACKGROUND/PURPOSE: Despite the high prevalence of Mycoplasma pneumoniae infections, reports on severe life-threatening M. pneumoniae pneumonia (MPP) in children are limited. METHODS: We retrospectively enrolled pediatric patients with PCR-positive MPP requiring ICU admission in a children's hospital in Taipei, Taiwan from Jun 2010 to October 2019. Clinical manifestations and laboratory data of severe MPP were analyzed. Macrolide susceptibility was determined by genotyping, and its relationship with clinical manifestations was also analyzed. RESULTS: Approximately 5% (34/658) children hospitalized for MPP required ICU admission. Compared with non-ICU cases (n = 291), ICU cases (n = 34) were associated with more underlying conditions, more pleural effusion, longer fever duration, longer hospital stay, the requirement of second-line antibiotic treatment, and delayed effective and second-line antibiotic treatment. Macrolide resistance was similar in ICU and non-ICU groups (53% vs 53%; p = 0.986). In severe MPP, patients requiring endotracheal intubation were associated with more septic shock, empyema, ARDS, prolonged fever after effective antibiotic treatment, delayed second-line and effective antibiotic treatment. In 18 of the 22 patients with pleural fluid analysis, the pleural effusion was alkaline (pH > 7.7) and lymphocyte-predominant. CONCLUSION: M. pneumoniae infection can cause severe life-threatening pneumonia in children. Delayed effective and second-line antibiotic treatments are associated with severe life-threatening MPP.

Clinical features of tuberculosis and Bacillus Calmette-Guérin (BCG) -associated adverse effects in children: A 12-year study.

PURPOSE: To investigate the clinical feature of tuberculosis and BCG adverse effects in children and to examine whether delayed BCG vaccination changes the incidence of BCG osteomyelitis. METHODS: We analyzed patients younger than 18 years with tuberculosis or BCG-associated adverse effects from 2008 to 2019. We compared their clinical features, laboratory tests and outcomes. RESULTS: Totally 137 patients were collected, with 27% of pulmonary tuberculosis (PTB), 31% of extrapulmonary tuberculosis (EPTB) and 42% of BCG-associated adverse effects. The median age was older in PTB than EPTB group (17.1 vs 15.4 years; p = 0.015). More patients in EPTB group had fever than PTB group (55% vs 25%; p = 0.008). Compared with exclusively EPTB, more patients in EPTB plus PTB group had fever (78% vs 38%; p = 0.009), and had more systemic symptoms (67% vs 25%; p = 0.007), lower absolute lymphocyte count (1230 vs 1850/µL; p = 0.033), higher CRP level (5.62 vs 2.21 mg/dL; p = 0.024) and longer hospital stay (20 vs 11 days; p = 0.031). In BCG osteomyelitis group, the median time interval from vaccination to diagnosis was 16.4 months (IQR 15.0-20.2). Age at vaccination, either at birth or 5-8 month-old, did not affect the proportion of BCG osteomyelitis among children with BCG-associated adverse effects. CONCLUSION: Children with EPTB plus PTB had more fever, lower lymphocyte count and higher CRP. The median time interval from vaccination to diagnosis of BCG osteomyelitis was 16.4 months and the proportion of BCG osteomyelitis among children with BCG-associated adverse effects was not affected by delayed vaccination in this study.

Clinical features and risk factors associated with bacteremia of nontyphoidal salmonellosis in pediatric patients, 2010-2018.

BACKGROUND/PURPOSE(S): This study aimed to investigate clinical features and antimicrobial susceptibility of inpatient children with nontyphoidal salmonellosis from 2010 to 2018. METHODS: We retrospectively collected pediatric patients with nontyphoidal Salmonella infection confirmed by positive cultures in a tertiary medical center in Taiwan from 2010 to 2018. Patients' characteristics, clinical manifestations, and laboratory data were collected. Serogroup category and antimicrobial susceptibility were also analyzed. RESULTS: Of total 569 isolates, ampicillin resistant rate was 53% in average, third-generation cephalosporin resistant rate was 6.7%, ciprofloxacin resistant rate was 9% and trimethoprim-sulfamethoxazole resistant rate was 30%. Compared to the resistant rates in 2010, the resistance rate of third generation cephalosporin was significantly higher (3.4% vs. 11%, p = 0.003) but that of ciprofloxacin was significantly lower (20% vs. 11%, p < 0.001) in 2018. Among 297 inpatients with nontyphoidal salmonellosis, Group D (38%) was the most common in the bacteremia patients whereas Group B (48%) was the most common in the non-bacteremia patients. Among 244 immunocompetent inpatients with community-acquired salmonellosis, the bacteremia patients had significantly longer fever duration and diarrhea duration before hospitalization (p < 0.001), and significant higher rate of anemia (p = 0.028) due to either thalassemia trait or prolonged disease course than the non-bacteremia patients. CONCLUSION: Third-generation cephalosporin was still the drug of choice for nontyphoidal Salmonella infection in children though the resistant rate increased progressively. Significant risk factors associated with bacteremia were longer fever and diarrhea duration and anemia due to either thalassemia trait or prolonged disease course in immunocompetent children.

Cost-effectiveness evaluation of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine for children in Taiwan.

BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) and non-typeable Haemophilus influenzae (NTHi) are substantial contributors to morbidity and mortality of diseases including invasive pneumococcal diseases (IPDs), pneumonia and acute otitis media (AOM) worldwide. In Taiwan, 10-valent pneumococcal polysaccharide and NTHi protein D conjugate vaccine (PHiD-CV) and 13-valent pneumococcal conjugate vaccine (PCV13) are licensed in children against pneumococcal disease. In addition to S. pneumoniae, clinical trials suggest efficacy of PHiD-CV against NTHi AOM. This study aims at evaluating the cost-effectiveness of a 2 + 1 schedule of PHiD-CV vs. PCV13 2 + 1 in the universal mass vaccination program of infants in Taiwan. METHODS: A published Markov cohort model was adapted to simulate the epidemiological burden of IPD, pneumonia and AOM for a birth cohort in Taiwan over 10 years. The probability of entering a specific health state was based on the incidence rate of the diseases. Only direct medical costs were included, and costs and outcomes were discounted annually. Vaccine efficacy assumptions were based on published data and validated by a panel of independent experts. Clinical, epidemiological, and serotype distribution data were based on locally published data or the National Health Insurance Research Database. Price parity of vaccines was assumed. Published pneumococcal disease-related disutility weights were used due to lack of local data. Incremental cost-effectiveness ratio was calculated and benchmarked against the recommended threshold in Taiwan. Extensive one-way sensitivity analysis, alternative scenarios and probabilistic sensitivity analysis were performed to test the robustness of the results. RESULTS: PHiD-CV would potentially reduce the number of NTHi-related AOM cases substantially and prevent comparable IPD and pneumonia-related cases and deaths compared to PCV13. Over a 10-year horizon, PHiD-CV is estimated to dominate PCV13, saving 6.7 million New Taiwan Dollars (NTD) and saving 21 quality-adjusted life years. The result was robust over a wide range of sensitivity analyses. The dominance of PHiD-CV was demonstrated in 90.5% of the simulations. CONCLUSIONS: PHiD-CV 2 + 1 would provide comparable prevention of IPD, pneumonia cases and additional reduction of NTHi-AOM cases, and is considered dominant compared with PCV13 2 + 1 in Taiwan.

Multiple-locus variable-number tandem-repeat analysis (MLVA) of macrolide-susceptible and -resistant Mycoplasma pneumoniae in children in Taiwan.

BACKGROUND/PURPOSE: To date, molecular typing studies on Mycoplasma pneumoniae are limited. We evaluated the molecular types of Mycoplasma pneumoniae in pediatric patients in Taiwan in 2016. METHODS: We used real-time quantitative PCR on respiratory specimens to identify M. pneumoniae in children with community-acquired pneumonia. The domain V of their 23S rRNA were sequenced for detection of macrolide-resistant point mutations. Molecular typing with multiple locus variable-number tandem repeat analysis (MLVA) was done for both macrolide-susceptible and -resistance M. pneumoniae samples. RESULTS: M. pneumoniae was detected in 22% (180/826) respiratory samples during the study period. Among all M. pneumoniae-positive samples, 24% (43/180) had harbored macrolide-resistant genotypes, and 86% (37/43) of them were A2063G mutation. Forty-two macrolide-resistant strains and 20 randomly selected macrolide-susceptible strains underwent MLVA profiling. MLVA 4-5-7-2 was the most frequent type (32/62, 52%), followed by 4-5-7-3 (17/62, 27%) and 1-5-6-2 (9/62, 15%). There was a strong association between MLVA 4-5-7-2 and macrolide resistance (p < 0.001). In contrast, M 4-5-7-3 and 1-5-6-2 were related to macrolide susceptibility (p < 0.001, and p = 0.025, respectively). CONCLUSION: Macrolide resistance was relatively low (24%) in this age group in 2016 in Taiwan, and A2063G was the dominant point mutation. MLVA 4-5-7-2 was associated with macrolide resistance.

Pediatric parapneumonic effusion before and after national pneumococcal vaccination programs in Taiwan.

BACKGROUND: Reports on the effectiveness of pneumococcal conjugate vaccines (PCVs) on pediatric parapneumonic effusion are limited. We report the changes in cases and etiologies of pediatric parapneumonic effusion in a children's hospital before and after national PCV13 vaccination programs. METHODS: We screened medical records of children 0-18 years admitted to the National Taiwan University Hospital with diagnoses of lobar pneumonia and parapneumonic effusion between 2008 and 2017. Patients with effusion analyses were included. Results of blood, pleural fluid, and respiratory specimens surveyed as standard care were analyzed. RESULTS: Diagnostic testing revealed at least a pathogen in 85% of 202 children with lobar pneumonia and parapneumonic effusion. After national PCV13 immunization, pneumococcal empyema decreased by 72% among 2- to 5-year olds. Mycoplasma pneumoniae was the second most common etiology. There were marked differences in effusion characteristics, metabolic, and respiratory parameters between children infected with pneumococcus and M. pneumoniae. CONCLUSION: The effectiveness of the national PCV13 immunization programs on pneumococcal empyema was evident and remained substantial after 4 years in Taiwan. Continuous surveillance is important to monitor the emergence of other pathogens including non-PCV serotypes and M. pneumoniae.