Diastolic/systolic blood pressure ratio for predicting febrile children with sepsis and progress to septic shock in the emergency department.

OBJECTIVE: Given the scarcity of studies analyzing the clinical predictors of pediatric septic cases that would progress to septic shock, this study aimed to determine strong predictors for pediatric emergency department (PED) patients with sepsis at risk for septic shock and mortality. METHODS: We conducted chart reviews of patients with ≥ 2 age-adjusted quick Sequential Organ Failure Assessment score (qSOFA) criteria to recognize patients with an infectious disease in two tertiary PEDs between January 1, 2021, and April 30, 2022. The age range of included patients was 1 month to 18 years. The primary outcome was development of septic shock within 48 h of PED attendance. The secondary outcome was sepsis-related 28-day mortality. Initial important variables in the PED and hemodynamics with the highest and lowest values during the first 24 h of admission were also analyzed. RESULTS: Overall, 417 patients were admitted because of sepsis and met the eligibility criteria for the study. Forty-nine cases progressed to septic shock within 48 h after admission and 368 were discharged without progression. General demographics, laboratory data, and hemodynamics were analyzed by multivariate analysis. Only the minimum diastolic blood pressure/systolic blood pressure ratio (D/S ratio) during the first 24 h after admission remained as an independent predictor of progression to septic shock and 28-day mortality. The best cutoff values of the D/S ratio for predicting septic shock and 28-day mortality were 0.52 and 0.47, respectively. CONCLUSIONS: The D/S ratio is a practical bedside scoring system in the PED and had good discriminative ability in predicting the progression of septic shock and in-hospital mortality in PED patients. Further validation is essential in other settings.

Clinical manifestations and microbiological features between indigenous and imported enteric fever in Taiwan, 2010-2020.

Previous studies had showed that indigenous clones of Salmonella Typhi and S. Paratyphi were originally imported from other countries in Taiwan. We presented the clinical manifestations and laboratory findings of indigenous and imported enteric fever cases in Taiwan in the current decade. We retrospectively reviewed typhoid and paratyphoid fever cases in two medical centers of Chang Gung Memorial Hospitals in 2010-2020. A total of 37 enteric fever cases including 24 typhoid fever and 13 paratyphoid fever were recorded. There were 20 indigenous cases, 16 imported cases, and one indetermined case. Splenomegaly and hepatitis were more frequent in typhoid fever than in paratyphoid fever (P < 0.05). Imported cases had more ciprofloxacin non-susceptibility rate (8/16, 50.0%) than indigenous cases (2/20, 10%). Indigenous ciprofloxacin non-susceptible S. Typhi isolates were found in 2018. One indigenous S. Paratyphi B isolate was multi-drug resistant (MDR) to chloramphenicol, ampicillin, and trimethoprim/sulfamethoxazole.

C-Reactive Protein Concentration Can Help to Identify Bacteremia in Children Visiting the Emergency Department: A Single Medical Center Experience.

BACKGROUND: For febrile children who are evaluated in a pediatric emergency department (PED), blood culture can be considered the laboratory criterion standard to detect bacteremia. However, high rates of negative, false-positive, or contaminated blood cultures in children often result in this testing being noncontributory. This study determined the factors associated with true-positive blood cultures in children. METHODS: This retrospective study was conducted at a tertiary medical center's PED. The blood culture use reports were prepared by an infectious disease specialist and were classified as bacteremia, nonbacteremia, and contamination. RESULTS: We registered a total of 239,459 PED visits during the 8-year period, and 21,841 blood culture samples were taken. Of the laboratory test studies, higher C-reactive protein (CRP) levels and lower hemoglobin levels were observed in the bacteremia group compared with other groups (all P < 0.001). The cut-off value calculated for each age group was adjusted for better clinical usage and significantly improved the blood culture clinical utility documented in the following age groups: 0 to 1 years (CRP level = 30 mg/L, odds ratio [OR] = 5.4, P < 0.001), 1 to 3 years (CRP level = 45 mg/L, OR = 3.7, P < 0.001), and 12 to 18 years (CRP level = 50 mg/L, OR = 6.3, P = 0.006). Using the CRP cut-off value established in this study, we could reduce the blood culture samples in the PED by 14,108 (64.6%). CONCLUSIONS: This study provides new evidence that CRP may be a useful indicator for blood culture sampling in certain age groups and may help improve the efficiency of blood culture in the PED.

Risk factors of Omicron variant associated acute encephalitis/encephalopathy in children.

BACKGROUND: Outbreak of Omicron BA.2 in Taiwan led to an increased number of acute encephalitis/encephalopathy cases in children and several fatal cases drew public attention. In pre-Omicron period, pediatric cases of COVID-19-associated acute encephalitis have been reported and during Omicron epidemic, febrile convulsions, encephalitis were mentioned more frequently. The outcome of patients with neurological complications was worse. However, few studies investigated the risk factors, pathophysiology and prognosis of COVID-19-associated encephalitis/encephalopathy. Here, we describe the presentation of pediatric cases of COVID-19-associated acute encephalitis/encephalopathy and explore the associated risk factors. METHODS: Pediatric patients with confirmed SARS-CoV-2 infections were prospectively enrolled at admission at Chang Gung Memorial Hospital between April and August 2022. Patients were categorized into groups of acute encephalitis/encephalopathy, febrile convulsions or mild disease. Demographic descriptions, clinical manifestations and laboratory data were collected. RESULTS: Of 288 acute COVID-19 patients, there were 38 (13.2%) acute encephalitis/encephalopathy, 40 (13.9%) febrile convulsions, and 210 (72.9%) mild disease. Among acute encephalitis/encephalopathy group, the mean age was 68.3 ± 45.0 months. The common neurological symptoms were lethargy (65.8%), seizures (52.6%), and impaired consciousness (34.2%). Over 3 years old (adjusted odds ratio [aOR]: 7.57, p < 0.001), absolute neutrophil count ≥3150/µL (aOR: 5.46, p = 0.008), and procalcitonin ≥0.5 ng/mL (aOR: 4.32, p = 0.021) were independent factors for acute encephalitis/encephalopathy. CONCLUSIONS: Most cases of COVID-19-associated acute encephalitis/encephalopathy showed no evidence of direct viral invasion but associations with older age, increased peripheral neutrophil, and serum procalcitonin. These findings may imply the neutrophil-mediated systemic inflammatory response plays an important role on central nerve system, leading to cerebral dysfunction.

Ecthyma Gangrenosum Secondary to Methicillin-Sensitive Staphylococcus aureus in an Atopic Child with Transient Neutropenia: A Case Report and Review of the Literature.

In addition to Pseudomonas aeruginosa, other organisms including Staphylococcus aureus have been reported to have associations with ecthyma gangrenosum (EG). There are very limited reports of Staphylococcus aureus EG causing systemic symptoms in an immunocompetent child. We present the case of an atopic child with transient neutropenia developing characteristic skin lesions of EG. Culture of the skin wounds yielded methicillin-susceptible Staphylococcus aureus (MSSA), and incisional biopsy of the skin lesions revealed aggregates of Gram-positive cocci at the subepidermal area and necrotic vasculitis but without perivascular bacterial invasion. In the literature review, seven cases of Staphylococcus aureus EG were reported, and only two were pediatric cases. From this case, we emphasize the importance of early culturing for microorganisms in cases presenting with EG. When toxin-mediated systemic symptoms accompany EG-like skin lesions, MSSA should be considered in an atopic child with transient neutropenia.

Incidence rates, emerging serotypes and genotypes, and antimicrobial susceptibility of pneumococcal disease in Taiwan: A multi-center clinical microbiological study after PCV13 implementation.

Objectives The multi-center clinical microbiological study in Taiwan aimed to evaluate the impact of childhood PCV13 immunization on pneumococcal disease, and the magnitude of serotype replacement in invasive and non-invasive pneumococcal disease among all age groups. Methods The study of culture-confirmed pneumococcal disease (CCPD) was conducted at four hospitals across Taiwan in 2015-2018. Pneumococcal pneumonia was defined as clinical diagnosis with positive sputum or bronchoalveolar lavage culture. Serotyping, multi-locus sequence typing, and antimicrobial susceptibility testing for penicillin and ceftriaxone were performed. Results A total of 1413 CCPD cases were identified. Invasive pneumococcal disease (IPD) accounted for 13.4% (190/1413) of CCPD. PCV7-type CCPD incidence declined among all age groups between 2015 and 2018. In adults aged 50-64 years, PCV7-type pneumococcal pneumonia incidence in 2018 was 72% lower than that in 2015, and all pneumococcal pneumonia incidence was 35% lower than that in 2015. In children, CCPD incidence was higher in 2018 than in 2015 (IRR 1.75 for age < 5 years, IRR 1.56 for age 5-17 years). Incidence of CCPD caused by non-PCV13-types, mainly 15A and 23A, increased significantly in those younger than 50 years. Serotypes 19A and 19F constituted the largest clonal complex, CC236/320 (n = 280, 19.8%). The rates of penicillin and ceftriaxone non-susceptibility were higher in PCV13-type isolates. Conclusions Childhood PCV13 immunization exerted an indirect protection to vaccine serotype clinically defined non-bacteremic pneumococcal pneumonia among adults, especially those between 50 and 64 years of age. Emerging non-PCV13 serotypes mainly caused non-invasive mucosal disease among children.

Clonal spread of macrolide-resistant Mycoplasma pneumoniae sequence type-3 and type-17 with recombination on non-P1 adhesin among children in Taiwan.

OBJECTIVES: Mycoplasma pneumoniae is currently the most commonly detected bacterial cause of childhood community-acquired pneumonia in several countries. Of note, clonal expansion of macrolide-resistant ST3 occurred in Japan and South Korea. An alarming surge in macrolide resistance complicates the treatment of pneumonia. We aimed to evaluate the clinical manifestation and clonal relatedness of M. pneumoniae circulating among children in Taiwan. METHODS: We prospectively enrolled 626 children with radiologically confirmed pneumonia between 2017 and 2019. An M. pneumoniae infection was suspected on clinical grounds, and tested by real-time PCR and oropharyngeal swab cultures. We used multilocus sequence typing and whole-genome sequencing to characterize the genetic features of M. pneumoniae. RESULTS: A total of 226 children with M. pneumoniae pneumonia were enrolled. Macrolide resistance was found in 77% (174/226) of patients. Multi-locus sequence typing revealed that ST3 (n = 93) and its single-locus variant ST17 (n = 84) were the predominant clones among macrolide-resistant strains. ST17 presented clinical characteristics comparable to its ancestor ST3. On multivariate analysis, macrolide resistance (OR 3.5; 95% CI 1.4-8.5; p 0.007) was independently associated with fever >72 hours after macrolide treatment. By whole-genome sequencing, prediction analysis of recombination sites revealed one recombination site in ST3 and ST17 compared with M29 (a macrolide-sensitive ST3 strain isolated from China in 2005) containing cytadhesin MgpC-like protein, RepMP4 and RepMP5. ST17 had another recombination site containing an adhesin and RepMP2/3. CONCLUSIONS: In addition to macrolide resistance, ST3 and its ST17 variant might evolve through recombination between repetitive sequences and non-P1 cytadhesins for persistent circulation in Taiwan.

Divergent serotype distribution between children with otitis media and those without in the pneumococcal conjugate vaccine era.

We investigated pneumococcal carriage between children ≦5 years old with otitis media (OM) and those without. Non-PCV13 serotypes were common in both groups; 19A remained the second most common serotype among children with OM despite high PCV13 coverage. This is important when considering a schedule with reduced vaccine doses or reduced valency, and the modification of pneumococcal immunization schedule should be followed up closely to monitor the result of protection against pneumococcal infections.

Risk factors for and molecular characteristics of methicillin-resistant Staphylococcus aureus nasal colonization among healthy children in southern Taiwan, 2005-2010.

BACKGROUND/PURPOSE: Nasal colonization of Staphylococcus aureus is a well-defined risk factor for subsequent infection. This study investigated the prevalence of methicillin-resistant S. aureus (MRSA) in southern Taiwan and aimed to identify the host factors for S. aureus colonization and the virulence factor of Panton-Valentine Leukocidin (PVL) genes. METHODS: In a hospital-based study in Kaohsiung from Oct. 2005 to Dec. 2010, we performed nasal swab in the healthy children aged 2-60 months. We examined the relationship between the demographic characteristics and S. aureus nasal colonization. MRSA isolates were further analyzed for antimicrobial susceptibility and molecular characteristics. RESULTS: Among 3020 healthy children, 840 (27.8%) children had S. aureus nasal colonization. Of 840 isolates, 246 (29.3%) isolates were MRSA. MRSA colonization was significantly associated with age 2-6 months, day care attendance, and influenza vaccination. Breastfeeding was a protective factor against MRSA colonization. Most MRSA isolates were susceptible to trimethoprim-sulfamethoxazole and doxycycline. Ninety-four percent of MRSA isolates carried either type IV staphylococcal cassette chromosome mec (SCCmec) or SCCmec VT and 87% belonged to the local community strains, namely clonal complex 59/SCCmec IV or VT. MRSA isolates with PVL-negative was associated with children with passive smoking. CONCLUSIONS: Between 2005 and 2010, 27.8% and 8.14% of healthy children in southern Taiwan had nasal carriage of S. aureus and MRSA, respectively. Most MRSA isolates were local community strains. Several demographic factors associated with nasal MRSA colonization were identified.

Evaluation of the impact of 13-valent pneumococcal conjugate vaccine immunization in children by surveillance of culture-confirmed pneumococcal disease: A prospective clinical microbiological study.

The study aimed to investigate the impact of 13-valent pneumococcal conjugate vaccine (PCV13) immunization on the overall pneumococcal disease in children in Taiwan by surveillance of culture-confirmed pneumococcal disease (CCPD). This study was conducted in a medical center from 2012 to 2016. Clinical isolates of Streptococcus pneumoniae were prospectively collected from pediatric patients. Serotyping, multi-locus sequence typing, and antimicrobial susceptibility testing were performed. A total of 473 patients with CCPD, including 58 with invasive pneumococcal disease (IPD), were identified. The incidence of CCPD per 10,000 admissions decreased from 71.7 in 2012 to 27.0 in 2016. The proportion of additional PCV13 serotypes significantly decreased from 52.0% in 2012 to 21.7% in 2015 but increased slightly to 26.7% because of serotype 19A in 2016 (P < 0.0001). The proportion of non-vaccine serotypes (NVTs) increased significantly from 18.4% in 2012 to 66.7% in 2016, but the increase of the incidence of CCPD caused by NVTs was not considered significant (P = 0.0885). Genotyping identified predominant clones, ST6315A, ST8315B, and ST166/33823A, for major NVTs. The penicillin non-susceptibility of PCV13 serotypes was significantly higher than that of NVTs (P < 0.0001). Surveillance of CCPD appears superior to IPD alone for evaluation of the overall impact of pneumococcal immunization. Serotype replacement occurred quickly after the use of PCV13, while the incidence of NVT infection did not show a significant increase in children over the years. The gradual introduction of PCV13 into national immunization program is effective in reducing overall pneumococcal disease in children.

Clinical features and dynamic ordinary laboratory tests differentiating dengue fever from other febrile illnesses in children.

BACKGROUND: Dengue fever is not easily to be diagnosed before presentation of the classic symptoms. The study aimed to investigate the clinical features and dynamic laboratory tests in pediatric patients to facilitate dengue diagnosis. METHODS: This retrospective study examined the medical records of all pediatric patients who were clinically suspected to have dengue from June to December 2014. Laboratory-positive dengue cases were confirmed by detecting non-structural protein NS1, reverse transcription-polymerase chain reaction of dengue virus, and dengue-specific IgM seroconversion. RESULTS: Of the 317 pediatric cases clinically suspected of dengue, 205 were laboratory-positive and 112 were laboratory-negative. In laboratory-positive cases, the most common clinical manifestation was skin rash in 156 (76.1%). Leukopenia occurred on days 1-5; thrombocytopenia, on days 2-7; prolonged activated partial thromboplastin time (aPTT), on days 1-4; and elevated transaminase levels, on days 3-11; and low CRP, on days 0-14. The specificity and positive predictive value (PPV) of combining of rash, itching and petechiae increased up to 100%. The PPV of combining of leukopenia, thrombocytopenia, and elevated transaminase levels reached 100% on day 2 as well as days 6-8. CONCLUSION: Leukopenia, thrombocytopenia, elevated aPTT, elevated transaminase levels, and low CRP could be used to differentiate dengue fever from other febrile illnesses. During dengue epidemics, combinations of the symptoms and laboratory findings are helpful to physicians for accurate diagnosis of dengue fever.

Rebound Thymic Hyperplasia after Chemotherapy in Children with Lymphoma.

BACKGROUND: Development of mediastinal masses after completion of chemotherapy in pediatric patients with malignant lymphoma is worrisome and challenging to clinicians. METHODS: We performed a retrospective review of 67 patients with lymphoma treated at our hospital from January 1, 2001 to June 1, 2013. Patients who received at least two chest computed tomography (CT) examinations after complete remission (CR) was achieved were further analyzed. Gallium-67 scans and positron emission tomography (PET) were recorded and compared between these patients. RESULTS: Sixty-two of 67 patients reached CR, of whom 31 (22 male, 9 female) were patients that received at least two chest CT examinations after CR. Rebound thymic hyperplasia (RTH) was diagnosed in 21/31 patients (67.7%), including 14/23 (60.9%) and seven out of eight (87.5%) with non-Hodgkin's lymphoma and Hodgkin's lymphoma, respectively. Ages ranged from 3 years to 18 years (median 10 years). Increased radioactivity uptake of the anterior mediastinum in gallium scans was found in nine out of 20 patients (45%) with thymic rebound. PET was performed in six out of 21 patients. Increased fluorodeoxyglucose (FDG)-avid uptake in the anterior mediastinum was observed in four of six patients (66.7%) by PET. One patient received thymectomy. No patients with RTH had lymphoma relapse within the median follow-up period (5 years). Relapse was statistically significantly different (p = 0.001) between patients with and without RTH. CONCLUSION: RTH developed in 67.7% of pediatric patients with lymphoma in CR after chemotherapy. The association of RTH development and lowered relapse rates has yet to be determined. Awareness of this phenomenon is important in the prevention of unnecessary surgical intervention or chemotherapy.