Building nomogram plots for predicting urinary tract infections in children less than three years of age.

BACKGROUND AND PURPOSE: Urinary tract infections (UTIs) are the most common bacterial infection in young children. This study aimed to formulate nomogram plots for clinicians to predict UTIs in children aged <3 years by evaluating the risk factors for UTIs in these children. METHODS: This retrospective study was conducted at a tertiary medical center from December 2017 to November 2020. Children less than three years of age were eligible for the study if they had undergone both urine culture and urinalysis during the study period. Mixed-effects logistic regression models with a stepwise procedure were used to determine the relationship between outcome (positive/negative UTI) and covariates of interest (e.g., weight percentile, laboratory) for each patient. Nomogram plots were constructed on the basis of significant factors. We repeated the analysis thrice to adapt it to three different medical settings: medical centers, regional hospitals, and local clinics. RESULTS: In the medical center setting, the two most significant factors were urine leukocyte count ≥100 (OR =8.87; 95% CI (Confidence Interval), 4.135-19.027) and urine nitrite level (OR =8.809; 95% CI, 5.009-15.489). The two factors showed similar significance at the regional hospital and local clinic settings. Abnormal renal echo findings were positively correlated with UTI in the medical center setting (OR =2.534; 95% CI 1.757-3.655). Three nomogram plots for the prediction of UTIs were drawn for medical centers, regional hospitals, and local clinics. CONCLUSION: Using the three nomogram plots, frontline doctors can formulate the probabilities of pediatric UTIs for better decision-making.

Etiology, clinical features, management, and outcomes of skin and soft tissue infections in hospitalized children: A 10-year review.

PURPOSE: This study aimed to describe the etiology, clinical features, hospital course, and outcomes of hospitalized children with skin and soft tissue infections (SSTIs) and to test if clinical and laboratory variables at admission could differentiate between community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and community-acquired methicillin-sensitive S. aureus (CA-MSSA). METHODS: We reviewed the clinical, laboratory, treatment, and outcome data for children hospitalized with SSTIs, aged 0-18 years at MacKay Children's Hospital between 2010 and 2019. Multivariable logistic regression was used to identify independent predictors of CA-MRSA and CA-MSSA SSTIs. RESULTS: A total of 1631 patients were enrolled. Erysipelas/cellulitis (73.8%) was the most common pediatric SSTI type, followed by acute lymphadenitis (13.6%) and abscess/furuncle/carbuncle (8.6%). Among the 639 culture-positive isolates (purulent SSTIs), 142 (22.2%) were CA-MSSA and 363 (56.8%) were CA-MRSA. The age group 0-1 month (OR, 6.52; 95% CI 1.09-38.92; P = 0.04) and local lymph node reaction (OR, 2.47; 95% CI 1.004-6.08; P = 0.049) were independent factors for differentiating children with CA-MSSA from those with CA-MRSA SSTIs. MRSA isolates in our cohort were highly susceptible to glycopeptides (100%), linezolid (100%), daptomycin (100%), and sulfamethoxazole/trimethoprim (98.6%) but were significantly less susceptible to clindamycin compared with MSSA (34.2% vs. 78.2%, P < 0.001). CONCLUSION: S. aureus is the leading pathogen of culture-proven SSTIs in hospitalized children with MRSA accounting for more than half. Determining the optimal empirical antibiotics in CA-SSTIs may rely on the patient's age, disease severity, and local epidemiologic data.

Reducing catheter related bloodstream infection risk of infant with a prophylactic antibiotic therapy before removing peripherally inserted central catheter: A retrospective study.

PURPOSE: This study examined the efficacy of prescribing antibiotics, specifically a single dose of vancomycin, in reducing the incidence of culture-positive and culture-negative sepsis prior to the removal of peripherally inserted central catheters (PICCs). MATERIALS AND METHODS: We retrospectively reviewed charts of infants who had PICCs in a tertiary level hospital during the period from 2010 to 2019. The incidence of post-catheter removal clinical sepsis between the groups with or without antibiotics was compared. The antibiotic group was defined by receiving a single dose of vancomycin or any other antibiotic prior to line removal. RESULTS: We enrolled 585 PICC removal episodes in 546 infants for analysis. Antibiotics were given prior to removal in 257 cases (43.9%) and not given prior to removal in 328 cases (56.1%). There were 13 episodes of post-catheter removal clinical sepsis detected within 72 h (2.2%), 2 of which were culture-positive (0.3%). A 9.3-fold decrease in the odds for clinical sepsis was observed in the antibiotic group (p = 0.01). The incidence of post-catheter removal sepsis was decreased by a single prophylactic dose of vancomycin (p = 0.02), whereas the use of other antibiotics showed no effect (p = 0.35). Logistic regression analysis demonstrated that comorbidities with gastrointestinal diseases (p = 0.01), PICC insertion sites in the scalp and neck (p = 0.04), and no vancomycin administration prior to line removal (p = 0.02) were independent risk factors for subsequent clinical sepsis. CONCLUSION: A single prophylactic dose of vancomycin prior to PICC line removal might reduce clinical sepsis events in infants.

Prediction of Coronary Artery Aneurysms in Children With Kawasaki Disease Before Starting Initial Treatment.

Background: Precisely predicting coronary artery aneurysms (CAAs) remains a clinical challenge. We aimed to investigate whether coronary dimensions adjusted for body surface area (Z scores) on baseline echocardiography and clinical variables before primary treatment could predict the presence of late CAAs. Methods: We conducted a retrospective study including children hospitalized for Kawasaki disease and received intravenous immunoglobulin within 10 days of illness. We defined late CAAs as a maximum Z score (Zmax) ≥2.5 of the left main, right, or left anterior descending coronary artery at 11-60 days of illness. Associations between late CAAs and clinical parameters and baseline maximum Z scores were analyzed. Results: Among the 314 included children, 31 (9.9%) had late CAAs. Male, higher C-reactive protein, and higher baseline Zmax were risk factors of late CAAs. Late CAAs were significantly associated with baseline Zmax ≥2.0 vs. <2.0 (25 [32.5%] vs. 6 [2.5%], P < 0.001). The odds ratio for late CAAs among the patients with baseline Zmax ≥2.0 vs. <2.0 was 18.5 (95% confidence interval, 7.23 to 47.41, P < 0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of baseline Zmax ≥2.0 for the presence of later CAAs were 80.6, 81.6, 32.5, and 97.5%, respectively. Conclusions: Findings from this study suggest that Zmax ≥2.0 of coronary arteries on baseline echocardiography may be used to predict children at a high risk of late CAAs and allow for targeted early intensification therapy.

To mix or not to mix? A rapid systematic review of heterologous prime-boost covid-19 vaccination.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has had an enormous impact worldwide, and vaccination is believed to be the method that will control the pandemic. Several types of vaccines developed using different platforms have been authorized, but the immunogenicity and reactogenicity of heterologous prime-boost vaccination with different vaccines remain largely unclear. AREAS COVERED: Electronic databases including PubMed, Embase, medRxiv, Research Square, and SSRN were searched to investigate the immunogenicity and reactogenicity associated with heterologous vaccination.As of 30 June 2021, four trials including 1,862 participants were identified. Heterologous administration of BNT162b2 (BNT) in ChAdOx1 (ChAd)-primed participants (ChAd/BNT) showed noninferior immunogenicity to homologous BNT administration (both prime and booster were BNT vaccines, BNT/BNT) with tolerable reactogenicity and higher T cell responses. Compared with homologous ChAdOX1 vaccination (ChAd/ChAd), heterologous ChAd/BNT was found to elicit higher immunogenicity (ChAd/BNT vs. ChAd/ChAd, antibody titer ratio: 9.2). EXPERT OPINION: Our systematic review found robust immunogenicity and tolerable reactogenicity of heterologous administration of a BNT162b2 boost in ChAdOx1-primed participants. An additional benefit of stronger T cellular immunity was also observed. Heterologous vaccination is a reasonable and feasible strategy to combat COVID-19. Further studies are warranted to confirm the benefits and identify the optimal combinations, doses, and intervals.

Inoculation Age of Bacillus Calmette-Guérin Tokyo-172 Strain and Vaccine-related Adverse Reactions in Taiwan Birth Cohort of 2012-2017.

BACKGROUND: In 2016 in Taiwan, inoculation with the Bacillus Calmette-Guérin (BCG) Tokyo-172 vaccine was postponed from 24 hours after birth to 5-8 months of age. We reviewed BCG-induced adverse reactions reported to the Vaccine Injury Compensation Program (VICP) to identify differences between early and delayed BCG inoculation. METHODS: Clinical presentations of BCG-related adverse reactions reported to VICP for the 2012-2017 birth cohort were reviewed until the end of 2019. The correlations between inoculation age and complications were evaluated. RESULTS: We analyzed 233 BCG adverse reactions, including regional lymphadenitis (33.9%), injection site reactions (35.2%), osteitis/osteomyelitis (27.9%), and distant soft tissue infections (3.0%). The incidence of osteitis/osteomyelitis was lower when vaccination was done after 5 months of age (relative risk [RR], 0.32; 95% confidence interval [CI], .16-.64). Injection site reactions (RR, 8.82; 95% CI, 5.04-15.44) and lymphadenitis (RR, 2.24; 95% CI, 1.44-3.45) were significantly more common in vaccinees older than 5 months. Shorter onset durations of mild adverse reactions (lymphadenitis and injection site reactions) were reported in vaccinees older than 5 months, while no statistical significance was found regarding osteitis/osteomyelitis. CONCLUSIONS: Osteomyelitis and distant soft tissue infection may occur less frequently when BCG inoculation occurs after 5 months of age, although mild adverse reactions can be more frequent, symptom onset times can be shortened. As few severe reactions might occur more than 2 years after BCG inoculation and the policy of delayed BCG inoculation was implemented in 2016, a longer observational period is needed to clarify the exact severe complications decrement.

Efficacy of clarithromycin-naproxen-oseltamivir combination therapy versus oseltamivir alone in hospitalized pediatric influenza patients.

PURPOSE: This study aimed to compare the safety and efficacy of clarithromycin-naproxen-oseltamivir combination therapy to that of oseltamivir therapy alone in hospitalized pediatric influenza patients. METHODS: This prospective, single-blind study included children aged 1-18 years hospitalized with influenza, in MacKay Children's Hospital, Taiwan, between December 2017 and December 2019. The primary outcomes were the time to defervescence and decrease of the Pediatric Respiratory Severity Score (PRESS) during hospitalization. The secondary outcomes were serial changes in virus titers, measured using real-time polymerase chain reaction. RESULTS: Fifty-four patients were enrolled (28 in the control group and 26 in the combination group) in total. There were no differences in the patients' baseline characteristics between the groups. The time to defervescence was significantly shorter in the combination group than the oseltamivir group (13.2 h vs. 32.1 h, p = 0.002). The decrease in the virus titer from days 1-3 (log Δ13) was more pronounced in the combination group than the oseltamivir group. (39% vs. 19%, p = 0.001). There were no differences in adverse effects such as vomiting, diarrhea, and abdominal pain during the study or within 30 days after antiviral therapy. CONCLUSION: The clarithromycin-naproxen-oseltamivir combination group experienced a more rapid defervescence and a more rapid decline of influenza virus titer than the group treated with oseltamivir alone. Further consideration should be given to whether the overall benefits of combination therapy in hospitalized pediatric influenza patients outweigh the risks.

Validation of genome-wide associated variants for Kawasaki disease in a Taiwanese case-control sample.

Kawasaki disease (KD) is an acute febrile systemic vasculitis of unknown etiology that affects infants and young children. Considerable evidence supports the hypothesis that there is a genetic basis for KD susceptibility. Genome-wide association studies (GWAS) have identified several genetic variants associated with KD. This study aims to replicate three novel KD-associated single nucleotide polymorphisms (SNPs), identified by GWAS in Japanese, in a Taiwanese population. Associations between these SNPs and development of coronary artery lesions (CALs) were also investigated. The rs2254546 A/G, rs2857151 A/G, and rs4813003 C/T SNPs were genotyped in 681 children with KD and 563 ethnically-matched healthy controls using TaqMan Assay or DNA sequencing. We found rs2254546 and rs4813003 SNPs were significantly associated with KD (G allele, odds ratio [OR] = 1.54, P = 1.0 × 10-5; C allele, OR = 1.32, P = 8.1 × 10-4). However, no evidence for associations with CAL development was observed. Our study successfully validates associations of the rs2254546 and rs4813003 SNPs with KD in a Taiwanese population. Further functional studies of the SNPs are important in understanding the pathogenesis of KD.

Clinical features of neonatal listeriosis in Taiwan: A hospital-based study.

BACKGROUND: Neonatal listeriosis is a major cause of mortality in newborn; however, there is limited information about this disease in Taiwan. The aim of our study was to identify the outcome determinants, clinical features, and incidence of pregnancy-associated listeriosis, which includes both neonatal and maternal listeriosis. METHODS: We retrospectively analyzed the medical records of neonatal and maternal patients with pregnancy-associated listeriosis at two hospitals in Taiwan from January 2000 to December 2018. Listeriosis was indicated by positive Listeria monocytogenes culture. RESULTS: Our study examined 18 neonates and 19 mothers. The neonatal and fetal death rate was 24%. All five cases of fetal losses or neonatal deaths occurred before 29 weeks of gestational age. The annual incidence of confirmed neonatal listeriosis increased significantly from 0.94/10,000 neonatal inpatients in 2000-2011 to 5.45/10,000 neonatal inpatients in 2012-2018 (p = 0.026). Clinical presentations of neonatal listeriosis included respiratory distress (85%), leukocytosis or leukopenia (77%), bandemia (69%), thrombocytopenia (77%), hypocalcemia (100%) and elevated C-reactive protein (CRP) levels (92%). Lower gestation correlated with a higher fatality rate (p = 0.002). Among the maternal cases investigated, 67% had a diagnosis of listeriosis, and 72% presented with fever. However, only 21% of the 19 mothers received complete antepartum ampicillin treatment. CONCLUSIONS: The incidence of neonatal listeriosis is increasing, especially in preterm neonates. Maternal listeriosis should be adequately treated with appropriate empirical antibiotics.

Respiratory tract infections in children with tracheostomy.

BACKGROUND: Children with tracheostomy are at increased risk for respiratory tract infections, yet the risk involved in tracheostomy related infections is unclear. METHODS: We conducted a retrospective review of the medical records of children who underwent tracheostomy between January 2002 and December 2016 at a teaching hospital in Taipei. Demographics, underlying disease, indication for tracheostomy, laboratory data and management, and long-term outcome data were collected. Infection episodes were grouped into definite, possible, non-bacterial pneumonia, and local infection groups. RESULTS: Ninety patients were enrolled. Forty-two (46.7%) patients had infections that required hospitalization. Definite bacterial pneumonia accounted for 12 (8.5%) episodes, 113 episodes (80.1%) were possible bacterial pneumonia, 12 (8.5%) were non-bacterial pneumonia, and 4 (2.8%) were local infections. Patients with definite and possible bacterial pneumonia were found to have a longer hospital duration than patients with non-bacterial pneumonia (p=0.024), with mean hospitalization stays of 8.83±5.59 days and 5.67±2.55 days, respectively. The median duration from tracheostomy to bacterial pneumonia was 1.78 years (range, 0.04- 11.38) whereas for the non-bacterial pneumonia group it was 0.57 years (range, 0.04-6.61). Cerebral palsy (CP) (adjusted odds ratio [AOR] 3.65; 95% confidence interval [CI]: 1.11-11.99; p=0.033) and gastroesophageal reflux disease (GERD) (AOR 2.84; 95% CI: 1.09-7.38; p=0.033) were independently associated with respiratory tract infections in these children. CONCLUSION: In this study, CP and GERD were associated with infections in children with tracheostomy. Bacterial and non-bacterial pneumonia are difficult to differentiate clinically which may lead to unnecessary antibiotics use.

Predictive value of Thomsen-Friedenreich antigen activation for Streptococcus pneumoniae infection and severity in pediatric lobar pneumonia.

BACKGROUND: Most cases of complicated pneumonia in children are caused by pneumococcal infections. Thomsen-Friedenreich antigen (TA) is present on erythrocytes, platelets and glomeruli, and it can be activated during pneumococcal infection. The aim of this study was to investigate the predictive value of TA activation for pneumococcal infection and association with the severity of complicated pneumonia. MATERIALS AND METHODS: Patients with lobar pneumonia were routinely tested for TA at the Department of Pediatrics, Mackay Memorial Hospital from January 2010 to December 2015. We retrospectively reviewed and analyzed their charts and data including age, sex, etiology of infection, chest tube insertion or video-assisted thoracoscopic surgery, length of hospital stay, TA activation, white blood cell count and level of C reactive protein. RESULTS: A total of 142 children with lobar pneumonia were enrolled, including 35 with empyema, 31 with effusion, 11 with necrotizing pneumonia and four with lung abscess. Streptococcus pneumoniae was the most commonly identified pathogen. Twenty-two patients (15.4%) had activated TA, all of whom were infected with S. pneumoniae. TA activation had 100% specificity and 100% positive predictive value for pneumococcal infection. In the multivariate analysis in lobar pneumonia, TA activation (OR, 15.8; 95% CI, 3.0-83.5; p = 0.001), duration of fever before admission (OR, 1.2; 95% CI, 1.1-1.5; p = 0.013) and initial CRP level (OR, 1.1; 95% CI, 1.0-1.1; p = 0.004) were independent predictors of empyema. CONCLUSIONS: TA activation is a specific marker for pneumococcal pneumonia and might indicate higher risk for complicated pneumonia.

The epidemiology of non-typhoidal Salmonella gastroenteritis and Campylobacter gastroenteritis in pediatric inpatients in northern Taiwan.

BACKGROUND: Campylobacter and Non-typhoidal Salmonella (NTS) are the two most common bacterial pathogens associated with acute gastroenteritis in children. This study aims to elucidate the epidemiology of Campylobacter and NTS gastroenteritis and develop a scoring system to differentiate them. MATERIALS AND METHODS: This retrospective study enrolled 886 children ≤18 years of age, hospitalized due to acute gastroenteritis with stool culture-proven Campylobacter or NTS infection from July 2012 to December 2015. Pearson's chi-square test and multivariate logistic regression were used to compare clinical manifestations and laboratory data. Receiver operating characteristic curves were plotted to evaluate the scoring system. RESULTS: Seasonality was found in NTS gastroenteritis from May to September, but no seasonality in Campylobacter gastroenteritis. Campylobacter jejuni and Salmonella serogroup B were the most common pathogens. The median ages were 68.2 and 18.5 months and the incidence rates of bacteremia were 0.6% and 7.1% in the Campylobacter and NTS groups, respectively. Salmonella serogroup C2 infection had the highest risk of bacteremia (OR: 5.9, 95% CI: 2.8-12.7, p < 0.001). Multivariate analysis showed significant differences in sex, age, fever, dehydration, immature WBC, CRP and Na between the two groups. A score of ≥2 points indicated Campylobacter gastroenteritis, with sensitivity 75%, specificity 77%. The positive and negative predictive values were of 73.3% and 93.9% after validation. CONCLUSION: Campylobacter gastroenteritis is associated with older age and male sex, while NTS gastroenteritis is associated with moderate to severe dehydration and bacteremia. Salmonella serogroup C2 infection has the highest risk of bacteremia.

Epidemiology and antimicrobial susceptibility of non-typeable Haemophilus influenzae in otitis media in Taiwanese children.

BACKGROUND: Concerns about non-typeable Haemophilus influenzae (NTHi) in otitis media (OM) have grown after the introduction of pneumococcal conjugate vaccine (PCV). We aim to better understand the clinical role of NTHi in pediatric OM. METHODS: Middle ear fluid samples from children <18 years with OM were obtained from 2010 to 2015. For culture-positive episodes (Streptococcus pneumoniae, H. influenzae, Moraxella catarrhalis, and Streptococcus pyogenes), patients' demographic and clinical information were reviewed and analyzed. RESULTS: A total of 783 episodes were included with 31.8% of isolates as positive. S. pneumoniae was recovered in 69.4%, NTHi in 24.6%, M. catarrhalis in 5.6%, and S. pyogenes in 4.0% of culture-positive episodes. The proportion of pneumococcal OM has declined since 2012 (P for trend <0.005), but NTHi OM rose simultaneously (P for trend = 0.009). Factors associated with increased risk of NTHi infection included less spontaneous otorrhea (OR 0.15, 95% CI 0.06-0.39, P < 0.001), absence of fever (OR 0.30, 95% CI 0.14-0.66, P = 0.003), concurrent sinusitis (OR 2.91, 95% CI 1.36-6.20, P = 0.006), previous ventilation tube insertion (OR 12.02, 95% CI 3.15-45.92, P < 0.001) and recurrent OM (OR 3.43, 95% CI 1.01-11.71, P = 0.049). The susceptibility of NTHi to amoxicillin/clavulanate was 82.0%. CONCLUSIONS: NTHi OM has trended upward in the post-PCV era. Concurrent sinusitis, previous ventilation tube insertion, and recurrent OM were associated with NTHi OM implicated a correlation between NTHi and complex OM. In consideration of NTHi infection, we suggest amoxicillin/clavulanate as the first-line therapy for OM among Taiwanese children.

Clinical Manifestations, Management, and Outcomes of Osteitis/Osteomyelitis Caused by Mycobacterium bovis Bacillus Calmette-Guérin in Children: Comparison by Site(s) of Affected Bones.

OBJECTIVE: To evaluate the clinical manifestations, management, and outcomes of Mycobacterium bovis Bacillus Calmette-Guérin (BCG) osteitis/osteomyelitis. STUDY DESIGN: We reviewed 71 cases of BCG osteitis/osteomyelitis registered in Taiwan's vaccine injury compensation program (VICP) in 1998-2014. Demographic, clinical, laboratory, treatment, and outcome data were compared according to site(s) of infection. RESULTS: Involvement of a long bone of the lower extremity was present in 36.6% of the children, followed by foot bone (23.9%), rib or sternum (15.5%), upper extremity long bone (9.9%), hand bone (7%), multiple bones (4.2%), and vertebrae (2.8%). Children with lower extremity long bone involvement had a longer interval from receipt of BCG vaccine to presentation (median, 16.0 months; P = .02), and those with foot bone infection had higher rates of swelling (94.1%; P = .02) and local tenderness (76.5%; P = .004). Surgical intervention was performed in 70 children, with no significant difference in the number of procedures by site (median, 1.0 procedure per patient). Among the 70 children who received antimicrobial therapy, those with vertebral and multifocal infections had a longer duration of treatment (P < .001) and/or second-line antituberculosis medications (P = .002). Three children with vertebral and multifocal infections had major sequelae with kyphosis or leg length discrepancy. Outcomes were good for children with involvement of the ribs, sternum, and peripheral bones without multifocal involvement. The average time for functional recovery was 6.2 ± 3.9 months. CONCLUSION: Children with BCG osteitis/osteomyelitis in different bones had distinct presentations and outcomes. Pediatricians should consider BCG bone infection in young vaccinated children with insidious onset of signs and symptoms, and consider affected site(s) in the management plan.

Acute otitis media caused by Streptococcus pneumoniae serotype 19A ST320 clone: epidemiological and clinical characteristics.

BACKGROUND: Streptococcus pneumoniae serotype 19A ST320, a highly multiresistant and virulent clone, has emerged as a common pathogen causing acute otitis media (AOM) in children. METHODS: Patients aged 0-18 years with AOM who presented at Mackay Memorial Hospital, Taipei, Taiwan were prospectively enrolled between December 1, 2009, and November 30, 2012. For each patient, a specimen of middle-ear fluid was obtained and cultured. S. pneumoniae isolates were tested by serotyping, antibiotic-resistance profiling, and multilocus sequence typing. Demographic characteristics and clinical history of patients with pneumococcal AOM were recorded. RESULTS: Pneumococcal AOM was observed in 108 (24.8%) of 436 episodes. One hundred and four isolates of S. pneumoniae were available for study. The most common serotypes were 19A (67 isolates, 64.4%), followed by 19F (16 isolates, 15.4%), and 3 (7 isolates, 6.7%). Among the 85 sequence-typed isolates, Serotype 19A ST320 (50, 58.8%) was the most frequent. Children with AOM caused by Serotype 19A ST320 were younger (33.9 ± 21.4 months vs. 46.7 ± 35.9 months, p = 0.04) and had a higher rate of spontaneous rupture of the tympanic membrane (64.0% vs. 40%, p = 0.05) than those caused by isolates of other sequence types. Serotype 19A ST320 caused 90% of AOM episodes in children aged ≤ 12 months and had had higher resistance rates to penicillin according to meningeal breakpoints (p = 0.011), amoxicillin (p < 0.001) and trimethoprim/sulfamethoxazol (p < 0.001). CONCLUSIONS: It is better to use pneumococcal conjugate vaccine effective against Serotype 19A in early infancy to prevent the first and subsequent episodes of AOM in children in Taiwan.

Redistribution of Streptococcus pneumoniae Serotypes After Nationwide 13-valent Pneumococcal Conjugate Vaccine Program in Children in Northern Taiwan.

BACKGROUND: After the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) against Streptococcus pneumoniae, public health officials in Taiwan monitored a decline in circulating vaccine serotypes and the emergence of nonvaccine serotypes in children with invasive pneumococcal disease. A gradually expanded PCV13 national immunization program was launched in 2013 in Taiwan. Here, we evaluate the changes in the distribution of pneumococcal serotypes and antimicrobial nonsusceptibility in children during the evolution of vaccination policy. METHODS: S. pneumoniae isolates from children with pneumococcal disease were collected and serotyped from 2010 to 2015 in northern Taiwan. PCVs were administered at the recipients' expense between 2010 and 2012, and then PCV13 was partially reimbursed by the government beginning in 2013. The distribution and diversity of serotypes were analyzed along with their antimicrobial susceptibilities. RESULTS: Among a total of 498 isolates, the proportion of invasive pneumococcal disease isolates declined (47.1%-10.6%) during the study period, and serotype diversity increased after 2011. Between 2010 and 2012, the dominant serotypes were 19A, 19F, 3, 6B and 14, and serotype 19A rose from 44.1% to 57.5%. Serotypes 19A, 15A, 19F and 15B were more prevalent from 2013 to 2015, and serotype 19A decreased from 42.1% to 4.5%. Serotypes 19F and 15A became the most commonly detected serotypes in 2015. Overall, PCV13 additional serotypes were reduced by 80% (P < 0.0001) but nonvaccine serotypes increased from 8.8% to 51.5% (P < 0.0001). CONCLUSIONS: The step-by-step PCV13 national immunization program is effective against pneumococcal disease in Taiwanese children, mainly by reducing PCV13 additional serotypes.

Risk factor analysis and molecular epidemiology of respiratory adenovirus infections among children in northern Taiwan, 2009-2013.

BACKGROUND/PURPOSE: Respiratory infections caused by human adenoviruses (HAdV) are worldwide, and have significantly increased recently in Taiwan. This study aimed to clarify the molecular epidemiology and risk factors of HAdV severe infections and pneumonia among Taiwanese children. METHODS: Patients with HAdV infections and hospitalized in a medical center between 2009 and 2013 were divided into severe or nonsevere HAdV infections based on whether or not they received intensive care. HAdV pneumonia was identified for comparison. The HAdV genotype was determined by sequencing the partial hexon and fiber genes. The nucleotide sequences were compared by phylogenetic analysis. RESULTS: The 176 patients (97 boys, 79 girls) had a median age of 3.7 years. The HAdV infections circulated year-round. HAdV B3 (54.5%) was the most common genotype, followed by HAdV C2 (21%), HAdV E4 (8%), and HAdV B7 (6.8%). Thirty-two patients needed intensive care. In multivariate analysis, the risk factors for severe HAdV infections were underlying neurologic diseases [odds ratio (OR): 164.9; p < 0.001], prematurity (OR: 10.9; p = 0.042), and HAdV B7 (OR: 39.5; p = 0.011). Twenty-nine patients had HAdV pneumonia. Patients with underlying neurologic diseases (OR 76.8; p < 0.001), airway anomaly (OR 15.1; p = 0.033), chronic lung diseases (OR 12.5; p = 0.047), weight < 3rd percentile (OR 5.5; p = 0.027), and HAdV B7 (OR 4.2; p = 0.002) had higher incidences of pneumonia. Four with underlying neurologic diseases died of acute respiratory distress syndrome. CONCLUSION: HAdV infections circulate all year-round. HAdV B7 is strongly related to severe infections and pneumonia. Underlying neurologic diseases and prematurity are risk factors for severe HAdV infections.

Vancomycin dosing and target attainment in children.

BACKGROUND/PURPOSE: The aim of this study is to determine the best dosing strategy for vancomycin by studying the associated factors and examining correlations between the area under the plasma concentration-time curve (AUC) values and trough concentrations in children. METHODS: Children aged 3 months to 18 years were included if they received vancomycin for more than three doses between January 1, 2010 and December 31, 2012 and had one or more serum vancomycin trough concentrations. Vancomycin clearance (CL) was calculated using the following model: CL = 0.248*Wt0.75*(0.48/serum creatinine)0.361*[ln (age)/7.8]0.995. The AUC (mg-h/L) was calculated by 24-hour dose (mg/kg/d)/CL(L/h). The value of AUC divided by the minimum inhibitory concentration (MIC) of vancomycin was AUC/MIC. RESULTS: A total of 218 children were included. The mean age was 6.0 ± 5.1 years and the mean body weight was 20 ± 11.7 kg. Vancomycin trough concentrations were moderately correlated with AUC values (r2 = 0.232, p < 0.01). Dosing of 15 mg/kg/dose q6h produced significantly higher AUC values (p < 0.001) and vancomycin trough concentrations (p < 0.001) compared to dosing of 10 mg/kg/dose q6h. In children receiving a 10-mg/kg/dose q6h, 5.6% (5/90) achieved the target trough concentrations of 15-20 µg/mL and 9.5% (5/90) achieved the goal AUC/MIC ≥ 400. In children receiving a 15-mg/kg/dose q6h, 13% (6/46) achieved the target trough concentrations of 15-20 µg/mL, whereas 54.3% (25/46) achieved the goal AUC/MIC ≥ 400. CONCLUSION: A 15-mg/kg/dose q6h compared to a 10-mg/kg/dose q6h is more likely to achieve target trough concentrations of 15-20 µg/mL and the goal AUC/MIC ≥ 400.