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Background: Subdural empyema is one of the more serious complications of bacterial meningitis and therapeutic challenges to clinicians. We aimed to evaluate the clinical characteristics, treatment, and outcome of subdural empyema in neonates with bacterial meningitis. Methods: A retrospective cohort study was conducted in two medical centers in Taiwan that enrolled all cases of neonates with subdural empyema after bacterial meningitis between 2003 and 2020. Results: Subdural empyema was diagnosed in 27 of 153 (17.6%) neonates with acute bacterial meningitis compared with cases of meningitis without subdural empyema. The demographics and pathogen distributions were comparable between the study group and the controls, but neonates with subdural empyema were significantly more likely to have clinical manifestations of fever (85.2%) and seizure (81.5%) (both p values < 0.05). The cerebrospinal fluid results of neonates with subdural empyema showed significantly higher white blood cell counts, lower glucose levels and higher protein levels (p = 0.011, 0.003 and 0.006, respectively). Neonates with subdural empyema had a significantly higher rate of neurological complications, especially subdural effusions and periventricular leukomalacia. Although the final mortality rate was not increased in neonates with subdural empyema when compared with the controls, they were often treated much longer and had a high rate of long-term neurological sequelae. Conclusions: Subdural empyema is not uncommon in neonates with acute bacterial meningitis and was associated with a high risk of neurological complications, although it does not significantly increase the final mortality rate. Close monitoring of the occurrence of subdural empyema is required, and appropriate long-term antibiotic treatment after surgical intervention may lead to optimized outcomes. [ABSTRACT FROM AUTHOR]

Streptococcus agalactiae (Group B Streptococcus, GBS) is an important pathogen of bacterial meningitis in neonates. We aimed to investigate the clinical and genetic characteristics of neonatal GBS meningitis. All neonates with GBS meningitis at a tertiary level medical center in Taiwan between 2003 and 2020 were analyzed. Capsule serotyping, multilocus sequence typing, antimicrobial resistance, and whole-genome sequencing (WGS) were performed on the GBS isolates. We identified 48 neonates with GBS meningitis and 140 neonates with GBS sepsis. Neonates with GBS meningitis had significantly more severe clinical symptoms; thirty-seven neonates (77.8%) had neurological complications; seven (14.6%) neonates died; and 17 (41.5%) survivors had neurological sequelae at discharge. The most common serotypes that caused meningitis in neonates were type III (68.8%), Ia (20.8%), and Ib (8.3%). Sequence type (ST) is highly correlated with serotypes, and ST17/III GBS accounted for more than half of GBS meningitis cases (56.3%, n = 27), followed by ST19/Ia, ST23/Ia, and ST12/Ib. All GBS isolates were sensitive to ampicillin, but a high resistance rates of 72.3% and 70.7% to erythromycin and clindamycin, respectively, were noted in the cohort. The virulence and pilus genes varied greatly between different GBS serotypes. WGS analyses showed that the presence of PezT; BspC; and ICESag37 was likely associated with the occurrence of meningitis and was documented in 60.4%, 77.1%, and 52.1% of the GBS isolates that caused neonatal meningitis. We concluded that GBS meningitis can cause serious morbidity in neonates. Further experimental models are warranted to investigate the clinical and genetic relevance of GBS meningitis. Specific GBS strains that likely cause meningitis requires further investigation and clinical attention. [ABSTRACT FROM AUTHOR]

Background: We aimed to describe the clinical features of Gram-negative bacillary (GNB) meningitis in neonates and investigate the risk factors associated with final adverse outcomes of neonatal GNB meningitis. Methods: From 2003 to 2020, all neonates (aged ≤ 90 days old) with bacterial meningitis who were hospitalized in four tertiary-level neonatal intensive care units (NICUs) of two medical centers in Taiwan were enrolled. Neonates with GNB meningitis were compared with those with Streptococcus agalactiae (group B streptococcus, GBS) meningitis. Results: During the study period, a total of 153 neonates with bacterial meningitis were identified and enrolled. GNB and GBS accounted for 40.5% (n = 62) and 35.3% (n = 54) of all neonatal bacterial meningitis, respectively. In neonates with GNB meningitis, the final mortality rate was 6.5% (4 neonates died); 48 (77.4%) had neurological complications, and 26 (44.8%) of 58 survivors had neurological sequelae at discharge. Although the final outcomes were comparable between neonates with GNB meningitis and those with GBS meningitis, neonates with GNB meningitis were more likely to have more severe clinical manifestations initially and have ventriculomegaly at follow-up. After multivariate logistic regression analysis, neonates with seizure at onset, early onset sepsis, and requirement of surgical intervention for neurological complications were independently associated with final adverse outcomes. Conclusions: GNB meningitis was associated with a high risk of neurological complications and sequelae, although it did not significantly increase the final mortality rate. Close monitoring of the occurrence of neurological complications and advanced therapeutic strategies to optimize the outcomes are urgently needed in the future. [ABSTRACT FROM AUTHOR]

Background: Candida parapsilosis is the most common non-albicans candida species that causes invasive candidiasis, but little is known about its impacts on the outcomes of pediatric patients. We aimed to characterize the clinical characteristics, risk factors and outcomes of C. parapsilosis bloodstream infections (BSIs) in children. Methods: All pediatric patients with Candida parapsilosis BSIs between 2005 and 2020 from a medical center in Taiwan were enrolled and analyzed. The antifungal susceptibility, clinical manifestations, management and outcomes were investigated. Cases of Candida parapsilosis BSIs were compared between patients with C. albicans BSIs and other Candida spp. BSIs. Results: During the study period, 95 episodes (26.0% of total cases) of Candida parapsilosis BSIs were identified and analyzed. No significant difference was found between pediatric patients with C. parapsilosis BSIs and those with C. albicans BSIs in terms of patients' demographics, most chronic comorbidities or risk factors. Pediatric patients with C. parapsilosis BSIs were significantly more likely to have previous azole exposure and be on total parenteral nutrition than those with C. albicans BSIs (17.9 vs. 7.6% and 76.8 vs. 63.7%, p = 0.015 and 0.029, respectively). The duration of C. parapsilosis candidemia was relatively longer, and therefore patients often required a longer duration of antifungal treatment when compared with those of C. albicans candidemia, although the candidemia-attributable mortality rates were comparable. Of the C. parapsilosis isolates, 93.7% were susceptible to all antifungal agents, and delayed appropriate antifungal treatment was an independent factor in treatment failure. Conclusions: Pediatric patients with C. parapsilosis BSIs were more likely to have previous azole exposure and be on total parenteral nutrition, and the clinical significances included a longer duration of candidemia and patients often required a longer duration of antifungal treatment. [ABSTRACT FROM AUTHOR]

Background: Empiric antibiotics are often prescribed in critically ill and preterm neonates at birth until sepsis can be ruled out. Although the current guideline suggests narrow-spectrum antibiotics, an upgrade in antibiotics is common in the neonatal intensive care unit. The impacts of initial broad-spectrum antibiotics on the outcomes of critically ill neonates with respiratory failure requiring mechanical intubation have not been well studied. Methods: A total of 1162 neonates from a tertiary level neonatal intensive care unit (NICU) in Taiwan who were on mechanical ventilation for respiratory distress/failure at birth were enrolled, and neonates receiving ampicillin plus cefotaxime were compared with those receiving ampicillin plus gentamicin. Propensity score-matched analysis was used to investigate the effects of ampicillin plus cefotaxime on the outcomes of critically ill neonates. Results: Ampicillin plus cefotaxime was more frequently prescribed for intubated neonates with lower birth weight, higher severity of illness, and those with a high risk of early-onset sepsis. Only 11.1% of these neonates had blood culture-confirmed early-onset sepsis and/or congenital pneumonia. The use of ampicillin plus cefotaxime did not significantly contribute to improved outcomes among neonates with early-onset sepsis. After propensity score-matched analyses, the critically ill neonates receiving ampicillin plus cefotaxime had significantly worse outcomes than those receiving ampicillin plus gentamicin, including a higher risk of late-onset sepsis caused by multidrug-resistant pathogens (11.2% versus 7.1%, p = 0.027), longer duration of hospitalization (median [IQR], 86.5 [47–118.8] days versus 78 [45.0–106.0] days, p = 0.002), and a significantly higher risk of in-hospital mortality (14.2% versus 9.6%, p = 0.023). Conclusions: Ampicillin plus cefotaxime should not be routinely prescribed as the empiric antibiotics for critically ill neonates at birth because they were associated with a higher risk of infections caused by multidrug-resistant pathogens and final worse outcomes. [ABSTRACT FROM AUTHOR]

Background: Pediatricians face a therapeutic challenge when patients with Candida bloodstream infections (BSIs) simultaneously have positive bacterial culture. We aim to characterize the clinical characteristics of pediatric Candida BSIs complicated with mixed bacteremia and subsequent bacterial infections, risk factors and impacts on outcomes. Methods: All episodes of pediatric Candida BSIs between 2005 and 2020 from a medical center in Taiwan were reviewed. Mixed Candida/bacterial BSIs were defined as isolation of a bacterial pathogen from blood cultures obtained within 48 h before or after the onset of Candida BSI. The clinical features and impacts of mixed Candida/bacterial BSIs were investigated. Results: During the study period, 320 patients with a total of 365 episodes of Candida BSIs were identified and analyzed. Mixed Candida/bacterial BSIs were 35 episodes (9.6%). No significant difference was found between mixed Candida/bacterial BSIs and monomicrobial Candida BSIs in terms of patient demographics, Candida species distributions, most chronic comorbidities or risk factors. Patients with mixed Candida/bacterial BSIs were associated with a significantly higher risk of subsequent bacteremia (51.4% vs. 21.2%, p < 0.001) and a relatively higher candidemia-attributable mortality rate (37.2% vs. 22.4%, p = 0.061) than those with monomicrobial Candida BSIs. Mixed Candida/bacterial BSIs were not an independent risk factor of treatment failure or final mortality according to multivariate logistic regression analyses. Conclusions: The clinical significance of mixed Candida/bacterial BSIs in children included a longer duration of septic symptoms, significantly higher likelihood to have subsequent bacteremia, and relatively higher risk of candidemia attributable mortality. [ABSTRACT FROM AUTHOR]

Neonatal candidemia is associated with significant morbidities and a high mortality rate. We aimed to investigate the clinical characteristics of Candida bloodstream infections in neonates and the impact of therapeutic strategies on the outcomes. We identified all the neonates with candidemia from a medical center in Taiwan over an 18-year period (2003–2021) and analyzed them. Clinical isolates were confirmed by DNA sequencing, and antifungal susceptibility testing was performed. The prognostic factors associated with clinical treatment failure (30-day, all-cause mortality and persistent candidemia > 72 h after antifungal agents) and in-hospital mortality were analyzed using logistic regression modeling. A total of 123 neonates with 139 episodes of candidemia were included in the study. The median (IQR) gestational age and birth weight of the neonates with candidemia were 29.0 (26.0–35.0) weeks and 1104.0 (762.0–2055) g, respectively. The most common Candida spp. was Candida albicans (n = 57, 41.0%), followed by C. parapsilosis (n = 44, 31.7%), Candida guilliermondii (n = 12, 8.6%), and C. glabrata (n = 11, 7.9%). The overall susceptibility to fluconazole was 81.3%, and the resistant rates against other antifungal agents were less than 3%. The cumulative mortality rate at 7 and 30 days after the first episode of candidemia was 11.3% and 32.3%, respectively. The overall in-hospital mortality rate was 42.3%. The treatment outcomes did not change over the study period and were not affected by delayed initiation of antifungal agents. Multivariate analysis showed that delayed catheter removal (odds ratio [OR], 5.54; 95% confidence interval [CI]: 1.93–15.86, p = 0.001), septic shock (OR, 7.88; 95% CI: 2.83–21.93, p < 0.001), and multiple chronic comorbidities (OR, 8.71; 95% CI: 1.82–41.81, p = 0.007) were independently associated with the final in-hospital mortality. We concluded that the overall mortality of neonatal candidemia has remained consistently high over the past decade. Prompt early catheter removal and an aggressive treatment strategy for neonatal candidemia with septic shock would be critical to improving patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Asian infants are at a higher risk of having Hirschsprung’s disease (HD). Although HD is surgically correctable, serious and even lethal complications such as Hirschsprung’s-associated enterocolitis (HAEC) can still occur. The aim of this study was to investigate the risk factors of HAEC, and the clinical impacts of delayed diagnosis of HD in newborn infants. Patients and methods: By review of medical charts in a medical center in Taiwan, 51 cases of neonates with HD between 2002 and 2009 were collected. Patients were divided into two groups based on the time of initial diagnosis: Group I, diagnosis made within 1 week after birth, and Group II after 1 week. Clinical features including demographic distribution, presenting features of HD, short-term and long-term complications related to HD were compared between the two groups of patients. Results: There were 25 patients in Group I and 19 in Group II. Group II patients had more severe clinical signs and symptoms of HAEC than Group I patients. The incidence of preoperative HAEC was 12% in Group I and 63% in Group II (adjusted odds ratio = 12.81, confidence interval = 2.60–62.97). Patients with preoperative HAEC were more likely to develop adhesive bowel obstruction after operation (33% vs. 3%, p = 0.013) and failure to thrive (33% vs. 3%, p = 0.013). Also, patients with long-segment or total colonic aganglionosis were at risk of developing both postoperative HAEC (85% vs. 29%, p = 0.001) and failure to thrive (39% vs. 3%, p = 0.002). Conclusion: In our study, we found that delayed diagnosis of HD beyond 1 week after birth significantly increases the risk of serious complications in neonatal patients. Patients with long-segment or total colonic aganglionosis have higher risk of postoperative HAEC and failure to thrive. Patients with preoperative HAEC are more likely to have adhesive bowel obstruction and failure to thrive. [ABSTRACT FROM AUTHOR]

Background: Although significant advances have been made in perinatal care, retinopathy of prematurity (ROP) remains a serious complication in prematurely born individuals. There have been limited studies on ROP in Taiwan, and most of those existing reports are outdated. Methods: This retrospective study included 252 very-low-birth-weight (VLBW) infants admitted to the neonatal intensive care unit of Chang Gung Children’s Hospital over a 2-year period between July 2005 and June 2007. All infants were examined for ROP according to the guidelines published by the American Academy of Pediatrics. The relationship between clinical risk factors and the development of ROP was analyzed. Results: Of the 252 VLBW infants, 216 met the screening criteria. Of the 216, 99 (45.8%) had ROP. Compared with neonates born at 29 weeks of gestational age (GA) or later, those very premature infants of ≤25weeks’ and 26–28 weeks’ GA had increased odds ratios (OR) of 8.49 and 3.19, respectively, for the development of severe ROP. No ROP was detected in infants of greater than 33 weeks’ GA. The simultaneous presence of a low GA, low birth weight (LBW), lower Apgar scores, hypotension, patent ductus arteriosus, septicemia, intraventricular hemorrhage, ventilator dependence, and use of postnatal steroids was associated with severe ROP. Using multiple logistic regression analyses for ROP, only maternal preeclampsia [OR, 2.52; confidence interval (CI), 1.32–4.7]; duration of mechanical ventilation (OR, 1.06; CI, 1.04–1.08); and LBW (OR, 2.62; CI, 1.370–3.375) predicted the development of threshold ROP. Conclusion: The incidence of ROP among VLBW infants was 45.8%; 19.0% had severe ROP. Infants of lower GAs and/or with LBW, whose mother had preeclampsia or who had a long duration of mechanical ventilation are at risk for the development of threshold ROP. [ABSTRACT FROM AUTHOR]

Background: There is no national data on group B streptococcus (GBS) infection in Taiwan. We investigated incidence of maternal GBS colonization and neonatal GBS infection rate and clinical pictures of neonatal GBS infection to estimate the value of intrapartum chemoprophylactic strategy in Taiwan. Methods: From January 2004 to June 2005, a prospective study to estimate maternal colonization rate by maternal rectovaginal culture at six hospitals was conducted. Neonatal GBS infection rate based on inborn infants was calculated retrospectively from January 2001 to June 2005; clinical pictures of infants diagnosed with invasive GBS disease were reviewed. Results: Maternal colonization rate of GBS was around 20% at hospital base, incidence of neonatal GBS infection was 1 per 1000 live births of infants born at hospitals. There were 221 infants with GBS infection: in 142, the disease occurred within 7 days of birth (early-onset disease, EOD), and in 79, it developed later (late-onset disease). Infantile EOD was more often seen in mothers with premature rupture of membrane, often accompanied by respiratory failure necessitating ventilator support. Infants with late-onset disease often manifested fever, leukopenia, thrombocytopenia, and meningitis. Fifteen infants died, mostly of EOD type (12 of 15). Risk factors of mortality included rescue at delivery room, leukopenia, thrombocytopenia, sepsis, respiratory distress, persistent hypertension of newborn, respiratory failure needing intensive respiratory support (intermittent mandatory ventilator and high frequency oscillatory ventilator), surfactant use, shock, and congenital heart diseases. Conclusions: We concluded that universal maternal rectovaginal culture of GBS with intrapartum antibiotic prophylaxis is an urgent call to reduce EOD and mortality because of GBS infection in neonates in Taiwan. [ABSTRACT FROM AUTHOR]

Summary: Objectives: Listeria monocytogenes is an important pathogen in neonates in Western countries, with a fatality rate of 20–30%. There is limited information on neonatal listeriosis in Eastern countries. The purpose of this study was to delineate the occurrence and clinical picture of neonatal listeriosis in Taiwan. Methods: A questionnaire-based survey of all of the 17 medical centers in Taiwan was performed, and a literature review of neonatal listeriosis as reported in Taiwan from 1990 to 2007 was made. Results: A total of 14 cases (10 male, four female) of neonatal listeriosis were identified, including 11 found from the survey of four medical centers and another three collected from the literature review. Three were found to have occurred prior to 2000 and 11 were found to have occurred after 2000. The age of onset was less than 3 days in all cases. L. monocytogenes was identified from blood in 13, cerebrospinal fluid in four, and gastric aspirate in two. Half of the cases (7/14) had involvement of the central nervous system with pleocytosis and hypoglycorrhachia in cerebrospinal fluid, and three of them even developed hydrocephalus. The mortality rate was 29%. Conclusions: Our findings suggest that listeriosis may emerge as an important health threat among newborn infants in Taiwan. [Copyright &y& Elsevier]

Background: Neonatal sepsis contributes to great mortality and morbidity among very-low-birth-weight (VLBW) infants. Prevalence and pathogen distribution of sepsis in the neonatal intensive care units (NICUs) vary with time and geographic location. Such information serves as a guide for selection of empirical antibiotics coverage., Methods: This is a case series study performed by retrospective chart review of VLBW infants (birth body weight, BBW, <1500 g) in a medical center during a 5-year period from January 2005 to December 2009. Episodes of positive blood cultures, pathogen distribution and related clinical manifestations were described., Results: A total of 158 episodes of sepsis were identified from 1042 VLBW infants. Sepsis rate was 152 per 1000 live births. The vast majority of infections (60.7%) were caused by Gram-positive organisms [G(+)], and overall Coagulase-negative staphylococci (CoNS) (52.5%) were the most common pathogen identified. Prevalence for early-onset sepsis (EOS) was 1% and for late-onset sepsis (LOS) was 14.2%. Infants with EOS had a much higher case fatality rate than LOS (40% vs. 4.7%). Escherichia coli (40%) were the leading pathogen of EOS while CoNS (54.7%) was the leading pathogens of LOS. Overall, apnea and/or bradycardia and/or cyanosis (65.8%), poor activity (48.7%), and increased respiratory effort (43.0%) were the most common presenting features of sepsis., Conclusion: Unlike term infants, Gram-negative organism and E coli were the leading pathogen of EOS among VLBW infants. Judicious and timely use of antibiotic therapy is crucial in the care of VLBW infants., (Copyright © 2012. Published by Elsevier B.V.)

Background: "Late preterm" defines infants born at 34(0/7) through 36(6/7) weeks' gestation, which comprise a majority of preterm births. These infants were treated clinically as "near-term" in the past, but recent studies have implied increased morbidities that differentiate late preterm and term infants. The purpose of this study was to examine the prevalence and clinical complications that could be associated with late preterm birth, as compared to term., Methods: This was a retrospective cohort study that reviewed infants born in a medical center in Northern Taiwan during a 2-year period between 2008 and 2009. Maternal obstetrical factors, neonatal demographic distributions, and neonatal complications were compared between full-term and late preterm deliveries., Results: During the study period, there were 7998 live births in the institute, including 6507 term and 1491 preterm infants. Of the latter, there were 914 (61.3%) born after 34 weeks' gestation. The Neonatal Intensive Care Unit (NICU) (including a special care nursery) admission rate was higher in late preterm infants when compared to term (36% vs. 2%), and was 74%, 43%, and 21% in infants born at 34, 35, and 36 weeks' gestation, respectively. Compared with term infants, late-preterm infants had longer hospital stay if admitted to NICU (including special care nursery) (17 days vs. 10 days), and they were associated with increased risk of neonatal morbidities, including respiratory distress syndrome (2.6% vs. 0.02%), respiratory distress of other etiologies (16% vs. 2%), culture-proven sepsis (0.7% vs. 0.2%), hypoglycemia (3% vs. 0.4%), temperature instability (0.4% vs. 0.05%), feeding difficulty (2% vs. 0.4%), and hyperbilirubinemia needing phototherapy (14% vs. 3%). Late-preterm infants also had higher hospital readmission rate (4.4% vs. 2.3%, p<0.001) and neonatal mortality rate (0.3% vs. 0.08%, p=0.03)., Conclusion: Late-preterm infants have increased risk of neonatal morbidities associated with organ immaturity. The results of this study emphasize the importance of judicious obstetrical decision-making when considering late preterm delivery, and the need to set up anticipatory clinical guidelines for the care of late preterm infants., (Copyright © 2012. Published by Elsevier B.V.)

Objectives: Neonatal enterovirus infections have diverse manifestations, from asymptomatic to fatal. An understanding of the risk factors associated with severe cases might help to reduce enterovirus-related morbidity and mortality., Methods: From July 1989 through June 1998, neonates with virus culture-confirmed nonpolio enterovirus infection at Chang Gung Children's Hospital were enrolled in the study and divided into three groups: nonspecific febrile illness; aseptic meningitis; and hepatic necrosis with coagulopathy (HNC). Demographic factors, clinical manifestations, laboratory data and outcome were analyzed to reveal factors associated with clinical severity and fatality., Results: There were 146 cases including 43 neonates with nonspecific febrile illness, 61 with aseptic meningitis and 42 with HNC. By multiple logistic regression analysis, the most significant factors associated with HNC were prematurity, maternal history of illness, earlier age of onset (< or =7 days), higher white blood cell count (WBC > or =15 000/mm3) and lower hemoglobin (< or =10.7 g/dl). In 10 (24%) of 42 cases, HNC was fatal. In comparison with nonfatal cases of HNC, fatal cases had higher WBC, lower hemoglobin, higher bilirubin and higher incidence of concurrent myocarditis. Multivariate analysis showed the most significant factors associated with fatality from HNC to be total bilirubin >14.3 mg/dl (adjusted odds ratio, 29.1; 95% confidence interval, 2.5 to 355.5; P = 0.007) and concurrent myocarditis (adjusted odds ratio, 13.7; 95% confidence interval, 1.1 to 177.2; P = 0.04). Intravenous immunoglobulin did not correlate with clinical outcomes in cases with HNC., Conclusions: Prematurity, maternal history of illness, earlier age of onset, higher WBC and lower hemoglobin are significant factors associated with HNC; higher total bilirubin and concurrent myocarditis were most significantly associated with fatality from HNC.