Search

BackgroundPostoperative bloodstream infection (BSI) is the most important determinant of recipient morbidity and mortality after liver transplantation (LT). Children who underwent LT are at the highest risk of developing BSI because of the significant surgical intervention, use of multiple devices, and administration of immunosuppressive agents. However, information regarding the risk factors for BSI in children after LT is limited.MethodsWe retrospectively reviewed 210 children who underwent living-donor LT at the largest pediatric LT center in Japan. Patients' characteristics, blood culture results and clinical outcomes were extracted from electronic medical records. Univariate and multivariate analyses were performed to identify the risk factors for BSI.ResultsAmong the 210 LT recipients, 53 (25%) recipients experienced 86 episodes of BSI during the observational period. The source of the BSI was identified only in 38%: catheter-related BSI (27%) peritonitis (7%), urinary tract infection (2%), pneumonia (1%) and infectious endocarditis (1%). A multivariate analysis demonstrated that body weight (P = 0.03), volume of blood loss during LT (P < 0.001) and cytomegalovirus (CMV) antigenemia positivity (P = 0.04) were independently associated with the development of BSI. The risk factors for BSI differed when we analyzed the subjects according to age (≤24 months and >24 months), blood loss and pediatric end-stage liver disease/model for end-stage liver disease versus positive CMV antigenemia.ConclusionsThe volume of blood loss, postoperative CMV antigenemia positivity and body weight were associated with the development of BSI after LT in pediatric living-donor recipients. To identify the age-specific predictors of BSI in children who underwent LT, age-specific analyses are crucial.

Background: LT is an elective treatment choice for children diagnosed with GSD1b that can improve their quality of life and stabilize their glucose intolerance. However, careful attention should be paid to immunosuppression after LT due to the susceptibility to infection because of neutropenia and neutrophil dysfunction in GSD1b patients. This study revealed the immunological features and complications in the early post‐LT period. Methods: We compared findings between 11 (1.9%) children with GSD1b and 273 children with BA. Analyses using the PSM were performed to overcome selection bias. Results: Despite persistent low tacrolimus trough levels in GSD1b patients, none of these children developed TCMR within 1 month after LDLT (GSD1b: 0/11 [0%] vs. BA: 86/273 [31.5%], p =.038). This result was also confirmed in PSM. The incidence of bloodstream infections was higher in GSD1b patients than in BA patients in the early phase of the post‐transplant period (GSD1b: 4/11 [36.4%] vs. BA: 33/273 [12.1%], p =.041), but not reach statistical significance in PSM. In a phenotypic analysis, the ratio of CD8+ T cells in GSD1b recipients' peripheral blood mononuclear cell samples was lower than in recipients with BA through the first month after LDLT. Conclusions: We found that GSD1b recipients were more likely to develop postoperative bloodstream infection than recipients with BA but did not experience TCMR despite low tacrolimus levels in the early post‐LDLT period. A tailored immunosuppression protocol should be prepared for GSD1b recipients after LDLT. [ABSTRACT FROM AUTHOR]

Recent guidelines suggest that LAVs may be given to LT recipients meeting certain criteria. However, information is still limited. We sought to evaluate the safety of LAVs, including measles, mumps, rubella, and varicella to LT recipients following our clinically based immunization protocol for LT recipients. We conducted a case‐series analysis on safety of LAVs for measles, rubella, varicella, and mumps given to LT recipients at our institution from July 2010 to July 2019. Patients who underwent LT at age <20 years who visited our immunization clinic were included. LT recipients were vaccinated if 2 years had lapsed from LT, had no signs of rejection within 6 months, and were on minimal immunosuppressants. Patient demographics, underlying diseases, type and number of vaccines administered, date of vaccination, and adverse events occurring within 4 weeks after vaccination were extracted from their medical records. During the study period, LAVs were administered 422 times to 209 patients who met criteria and included 225 doses of MR combination vaccine, 224 doses of varicella vaccine, and 215 doses of mumps vaccine. Underlying diseases included cholestatic liver diseases (n = 125), followed by metabolic diseases (n = 33) and acute liver failure (n = 19). Nine non‐critical adverse events (2.1%) possibly associated with LAVs were reported, but there were no serious adverse events, including hospitalizations or deaths. In conclusion, LAVs administered to LT recipients were safe without any serious adverse events following our relatively simple institutional protocol. [ABSTRACT FROM AUTHOR]

Background: The strategy to eradicate polio is based on preventing infection by immunizing all children until the world is polio‐free. However, data regarding efficacy of polio‐containing vaccination in immunocompromised patients such as LT recipients are limited. Methods: We conducted an observational study at the largest pediatric transplant center in Japan from January 2011 to January 2015. LT recipients were enrolled after transplantation, and those who had completed the Japanese polio vaccination program were eligible for the study. Patients' demographics were collected from their medical records. Antibody titers against poliovirus serotypes 1‐3 were measured using the neutralization test at the routine follow‐up visits after enrollment. Factors associated with seropositivity against each type of poliovirus were evaluated. Results: Sixty‐four patients who had received the complete polio vaccination series were enrolled in the study. Of these, 37 patients had received all series of polio‐containing vaccination before LT. Median age of the patients was 75 months. Their underlying diseases included the following: 40 (63%) with cholestatic liver diseases and 11 (17%) with metabolic disorders. After a median interval of 43 months after LT, seropositivity rates against poliovirus 1, 2, and 3 were 93.8% (60/64), 92.2% (59/64), and 54.7% (35/64), respectively. Among 32 patients who had received only oral polio vaccine (OPV), seropositivity against poliovirus 3 was particularly low (25.0%). No factors associated with seropositivity against each type of poliovirus were identified. Conclusions: In the LT recipients, seropositivity for poliovirus 3 was low, suggesting a need for additional inactivated polio‐containing vaccination after LT, especially for patients who had received only OPV. [ABSTRACT FROM AUTHOR]

Background: Herpes zoster (HZ) may cause complications; however, information regarding complications of HZ in children is relatively sparse. We reviewed cases of HZ in children retrospectively and investigated the risk factors contributing to the development of complications. Methods: A retrospective observational study was conducted at a tertiary care children's hospital in Japan. Children receiving a diagnosis of HZ between January 2010 and October 2016 were identified from electronic medical records. In this study, the following diseases were recognized as complications of HZ: bacterial skin infection, facial paralysis, meningitis, uveitis and keratitis, postherpetic neuralgia, acute retinal necrosis, pneumonia, and otitis interna. Details regarding clinical information of HZ patients with complications were described. Results: We found 138 cases with HZ. Among these, 58 (42%) occurred in immunocompetent children and 80 cases (58%) occurred in immunocompromised children. Complications were observed in 10 cases of immunocompromised children and in eight cases of immunocompetent children. Although secondary bacterial skin infection was the most common complication (n = 6, 33.3%), severe complications such as facial paralysis (n = 3, 16.7%), meningitis (n = 2, 11.1%), uveitis and keratitis (n= 2, 11.1%), acute retinal necrosis (n = 1, 5.6%), pneumonia (n = 1, 5.6%), and otitis interna (n = 1, 5.6%) were observed. Patients with complications tended to have a rash on the head or neck, compared with those without complications (n = 9, 50% vs n = 18, 15%; P = 0.001). Conclusions: Severe HZ complications may occur in immunocompetent children. Development of a rash on the head or neck might be a risk factor for complications. [ABSTRACT FROM AUTHOR]

Background: Few studies have characterized the clinical manifestations of delayed antibiotic hypersensitivity (AH) diagnosed using objective methods. The lymphocyte transformation test (LTT) is a reproducible method to diagnose type IV hypersensitivity. The purpose of the study was to evaluate the characteristics of delayed AH diagnosed on LTT in children. Methods: We performed a retrospective analysis of patients who were evaluated for AH using LTT at National Center for Child Health and Development, Tokyo, from 2002 to 2014. We extracted patient demographics, type and duration of antibiotics, and clinical characteristics from the medical records. Clinical manifestations were compared between LTT‐positive and LTT‐negative cases. Results: Seventy‐five cases for which 101 drugs were tested were included in this study. LTT was positive against 34 drugs in 26 cases. Median age was 5 years (IQR, 1–9 years), and 49% of patients had underlying disease. LTT was performed at a median of 18 days (IQR, 4–59 days) after the suspected episode. The median number of days from the initiation of therapy to the onset of symptoms was 4. Rash was the most common manifestation (89%). Fever (>38°C) was observed in 20 cases (27%). Onset of fever preceded the rash in nine cases (45%), appeared simultaneously in five (25%), appeared afterwards in four (20%), and was unknown in two (10%). Fever was an independent factor associated with AH when comparing LTT‐positive and LTT‐negative cases (OR, 3.61; 95%CI: 1.03–12.64). Conclusions: Fever was a common presenting symptom of delayed AH in children aged ≤18 years. [ABSTRACT FROM AUTHOR]

The article focuses on bacterial meningitis due to Streptococcus pneumoniae is a fatal infectious disease during childhood and studies in the 1990s suggested an increasing rate of third-generation cephalosporin resistance. Topics include the recommendation for the addition of carbapenem antibiotics to third-generation cephalosporins as empiric therapy, and the cephalosporin-resistant S. pneumoniae decreased to a point where the necessity of vancomycin as empiric therapy was not even debated.

Background: Febrile children 3–36 months old, who had a body temperature >39°C and white blood cell (WBC) count >15 000/mm3 were known to be at risk for occult pneumococcal bacteremia (OPB) in the pre‐pneumococcal conjugate vaccine (PCV) era. The positive predictive value of these criteria, however, decreased dramatically after the introduction of PCV, indicating a need for alternative criteria. A high rate of febrile seizures has been noted in children with OPB, suggesting that screening may still be practical in this population. We performed a retrospective analysis to evaluate factors that predict OPB in patients visiting the emergency department (ED) with febrile seizures. Methods: Children 3–36 months old who visited the ED for febrile seizures and had blood cultures taken were included. Patients with underlying diseases were excluded from analysis. We performed statistical analyses comparing patient demographics according to the presence or absence of OPB. Results: One thousand and eighty‐two patients visited the ED with febrile seizure, and blood cultures were taken in 397, of whom 87% had received more than three doses of PCV. Of the nine patients with OPB, eight (89%) met the risk criteria. In contrast, only 12% (48/388) of those without OPB met the criteria. In this population, those who fulfilled the risk criteria were more likely to have OPB than those who did not (14.3% vs 0.3%; likelihood ratio, 7.17). Conclusions: High WBC count and fever may effectively predict OPB in pediatric patients with febrile seizure in the post‐PCV era. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to describe the epidemiology of childhood group B streptococcus (GBS) disease including late late-onset disease (LLOD) and to clinically characterize recurrent cases and twin-sibling cases in Japan. Methods: We collected information on infants (<1 year of age) with invasive GBS disease and institutional information about births and transfers through a nationwide questionnaire between 2011 and 2015. Results: We identified 133 infants with early-onset disease (EOD), 274 late-onset disease (LOD), and 38 LLOD from 149 institutes. The case fatality rate (CFR) of EOD, LOD, and LLOD was 4.5, 4.4, and 0%, respectively. CFR in EOD was significantly ( P < 0.001) associated with preterm birth, but not that in LOD and LLOD. Twenty-nine percent of infants with meningitis (49/169) had neurologic sequelae. We showed clinical details of 12 recurrent cases that accounted for 2.8% of the total patients, and 4 sets of both twins affected; 4 of 12 recurrent cases and 3 of 4 twin-sibling sets were also associated with preterm birth. Based on the livebirth number of 581,488, the instituted-based incidence of EOD, LOD, and LLOD was estimated as 0.09 (95% CI 0.06-0.11), 0.12 (95% CI 0.11-0.14), and 0.01 (95% CI 0.01-0.02) per 1000 livebirths, respectively. Conclusions: CFR of EOD and LOD in Japan is comparable with that in high-income European countries or the United States, and their incidence is much lower. Our findings also describe the clinical details of LLOD, recurrent infections, and infections in twin siblings. This study is the largest among Asian childhood GBS studies ever reported. [ABSTRACT FROM AUTHOR]

Background: Invasive diseases due to Moraxella catarrhalis are rare in children, even in immunocompromised hosts. Therefore, data regarding clinical characteristics and risk factors of such patients are limited. The aim of this study is to compare the clinical characteristics of patients with bacteremia due to Moraxella catarrhalis against those with bacteremia due to Streptococcus pneumoniae and Haemophilus influenzae.Methods: We performed a retrospective case-control study to compare patients younger than 18 years of age with positive blood cultures for the three pathogens between June 2008 and May 2014 at our institution. Data regarding patients' demographics and clinical course were collected from their medical records. Three group comparisons, with M. catarrhalis as reference, were made by the Fisher's exact test and Wilcoxon rank sum test for discrete and continuous variables, respectively.Results: There were eight cases of M. catarrhalis, 110 cases of S. pneumoniae (105 patients) and 22 cases of H. influenzae. The M. catarrhalis group consisted of six females (75 %) with a mean age of 16 months. The majority of patients (7/8, 88 %) had underlying diseases; however, only one was immunocompromised. Characteristically, six patients (75 %) had medical devices including trans-nasal devices (5/8, 63 %). Univariate analysis revealed that underlying conditions (P = 0.005), trans-nasal devices (P < 0.001), and lower body weight (P = 0.016) and low white blood cell count (P = 0.011) at the onset of illness were associated with the M. catarrhalis group compared to the S. pneumoniae group. Meanwhile, the higher rates of the patients with underlying conditions and trans-nasal devices were associated with the M. catarrhalis group compared to the H. influenzae group (P = 0.039, P < 0.001, respectively).Conclusions: The presence of underlying conditions, particularly in those with trans-nasal devices, were characteristic features of patients with bacteremia due to M. catarrhalis. [ABSTRACT FROM AUTHOR]

Background Empiric antimicrobial coverage in compromised hosts commonly includes pseudomonal coverage but often lacks coverage against Stenotrophomonas maltophilia. Identification of risk factors specific for S. maltophilia infection may lead to prompt initiation of appropriate antibiotics and improved outcome. Methods We conducted a retrospective analysis of pediatric patients with bacteremia due to S. maltophilia or Pseudomonas aeruginosa from April 2002 to July 2014 at a tertiary children's hospital. Patient demographics, underlying disease, clinical course, and treatment were compared between S. maltophilia and P. aeruginosa cases. Results Nineteen children with S. maltophilia bacteremia and 49 children with P. aeruginosa bacteremia were identified. On multivariate logistic regression analysis, use of carbapenems within 7 days prior to onset (OR, 5.00; 95%CI: 1.25-20.07; P = 0.02) and previous intensive care unit stay (OR, 3.75; 95%CI: 1.13-12.47; P = 0.03) were significantly associated with S. maltophilia bacteremia compared with P. aeruginosa bacteremia. The majority of the S. maltophilia bacteremia patients had central line-associated bloodstream infection (79%), compared with the P. aeruginosa bacteremia patients (37%, P = 0.002). There were nine children (47%) who had polymicrobial infection in the S. maltophilia bacteremia group, in contrast to four (8%) in the P. aeruginosa bacteremia group (OR, 10.13; 95%CI: 2.59-39.56; P = 0.001). Consultation with an infectious diseases physician was associated with a lower rate of persistent S. maltophilia bacteremia ( P = 0.04). Conclusions Stenotrophomonas maltophilia should be considered in breakthrough bacteremia in pediatric patients who receive carbapenems within 7 days prior to onset. [ABSTRACT FROM AUTHOR]

Abstract: Immunizations using live-attenuated vaccines are not recommended for post-liver transplant children due to its theoretical risks. However, they will encounter vaccine-preventable viral diseases upon returning to real-life situations. We performed a total of 70 immunizations with four individual live-attenuated vaccines to 18 pediatric post-living donor liver transplant (LDLT) recipients who fulfilled a clinical criteria including humoral and cell-mediated immunity. The seroconversion rates at the first dose for measles (strain AIK-C), rubella (strain TO-336), varicella (strain Oka), and mumps (strains Hoshino) were 100% (15/15), 100% (15/15), 82% (9/11), and 82% (9/11), respectively. During observed period (−5 years 11 months), a few cases with waning immunity (antibodies were once produced but the levels fell over time) were seen except after rubella immunization. Clinical diseases after seroconversion or definite serious adverse effects due to immunization were not observed. Immunizations using selected live-attenuated vaccines were safe and effective for post-LDLT children who were not severely immunosuppressed. [Copyright &y& Elsevier]

The article presents a case study of a 4-month-old girl presented to the emergency department with fever and rash. Topics include real-time polymerase chain reaction of the vesicular contents has positive for Herpes simplex virus (HSV) type 2 DNA; and the present report describes the appearance of anogenital HSV-2 infection in a female infant.

Maintaining good asthma control minimizes the risk of exacerbations and lung function decline and is a primary goal of asthma management. The Japanese Pediatric Asthma Guidelines (JPGL) employs different classification criteria for control status from other guidelines, stressing a higher level of control. Based on JPGL, we previously developed a caregiver-completed questionnaire for assessing and achieving best asthma control in preschoolers. In this study, we aimed to develop a questionnaire for school-age children and adolescents. A working questionnaire comprising 14 items for patients and 34 items for caregivers was administered to 362 asthma patients aged 6–15 years and their caregivers. Separately, physicians filled out a questionnaire to determine JPGL-defined control. Logistic regression analysis was performed to construct a model to predict control levels using data from a randomly selected set of completed questionnaires from two-thirds of the subjects. Validation was performed using the remaining questionnaires. A set of 7 questions, encompassing self-assessed control status at the time of the visit and in the past month, and nocturnal/early morning asthma symptoms for patients and frequency of asthma symptoms, dyspnea, rescue beta-agonist use, and asthma hospitalization for caregivers, were selected and the 7-item model showed a good statistical fit with AIC of 110.5. The model has been named the Best Asthma Control Test for School Children and Adolescents (Best ACT-S). Best ACT-S scores differed significantly in the hypothetical direction among the groups of different JPGL-defined control levels, step-up/down treatment decisions, and presence/non-presence of exacerbations in the previous year. The Best ACT-S is a valid questionnaire for children/adolescents aiming for best asthma control. [ABSTRACT FROM AUTHOR]

There are few reports on the association between antipyretic use and antibody titers in adolescents and young adults following SARS-CoV-2 vaccination. Multivariable linear regression analyses were performed to examine the association between antipyretic use and antibody titers. The use of antipyretics was not associated with antibody titers (β coefficient [95% CI] = −0.107 [–0.438 to 0.224]). [ABSTRACT FROM AUTHOR]

Clinical efficacy of remdesivir in children with COVID-19 is unclear. This propensity-score-matched retrospective cohort study of children with COVID-19 showed that the rate of patients achieving defervescence on Day 4 was higher in the remdesivir group than in the non-remdesivir group, but was not statistically different (86.7% vs 73.3%, P = 0.333). [ABSTRACT FROM AUTHOR]

Antimicrobial stewardship programs (ASP) for oral antibiotics is still uncommon, despite the fact that oral antibiotics prescription accounts for 90% of total antibiotic consumption in developed countries. We introduced preauthorization and prospective audit and feedback (PAF) system on broad-spectrum oral antimicrobials as a part of ASP intervention from October 2015 in a tertiary children's hospital in Japan. Antimicrobial consumption and cost of targeted oral antimicrobials decreased from 11.1 days of therapy (DOT) per 1000 outpatient visits and 860,040 yen ($ 7167: 1 $ = 120 yen) to 1.9 DOT per 1000 outpatient visits and 142,200 yen ($ 1185) annually, respectively (p < 0.001). Interrupted time-series analysis showed that prescriptions for targeted antimicrobials decreased rapidly after initiation of preauthorization (p < 0.001). Prescriptions for non-targeted oral antimicrobial increased temporarily (p < 0.001), but a decreasing trend was found after the initiation (p < 0.001). In pre-intervention period, the main indications for using targeted antimicrobials were upper and lower respiratory infection, urinary tract infections, prophylaxis for medical procedures and otitis media, but only 21.4% of them were appropriate prescription. The appropriate prescription rate of post -intervention period increased to 58.5%. During the study period, the susceptibility pattern of major bacteria to these antimicrobials did not change. In conclusion, introduction of the preauthorization and PAF for selected oral antimicrobials decreased the antimicrobial use of both targeted and non-targeted antimicrobials. This intervention may be an effective method of ASP for other children's hospitals. [ABSTRACT FROM AUTHOR]

Persistent Gram-negative rod (GNR) bacteremia is uncommon under appropriate antibiotic therapy. A recent study showed that follow-up blood cultures (FUBCs) to confirm clearance 24–48 h after initiation of antibiotics, added little value in the management of GNR bacteremia in adults. However, the utility of FUBC in children is still unknown. We retrospectively reviewed the microbiology database to identify children aged <18 years with GNR bacteremia. Clinical information including gender, age, underlying diseases, presence of central venous line (CVC), source of bacteremia, and organisms was extracted from medical records. FUBCs for 99 episodes of GNR bacteremia in children became positive in 21%, which led to intervention in 57% of the episodes. In multivariate analysis between FUBC positive (n = 21) and negative (n = 78) groups, presence of CVC (n = 18, 86% vs n = 38, 49%, P = 0.001) and resistance to empirical antibiotics (n = 3, 14% vs n = 4, 5%, P = 0.04) were independently associated with positive FUBCs. Interestingly, no positive FUBC was observed in cases due to UTI (n = 13). Contrary to findings in adults, FUBC may still be useful in the management of GNR bacteremia in children. [ABSTRACT FROM AUTHOR]

Highlights • WU polyomavirus (WUPyV) was detected in 14 children with respiratory failure. • Of these children, eight had a perinatal disease and three were immunocompromised. • Multiplex PCR and culture were negative for other pathogens in five patients. • These five patients showed perihilar infiltrates after several days of symptoms. • WUPyV can be a pathogen in children with a history of perinatal disease. Abstract Background WU polyomavirus (WUPyV) is a relatively new virus associated with respiratory infections. However, its role is unclear in children with severe respiratory failure. Objectives We aimed to evaluate the characteristics of severe respiratory failure associated with WUPyV infection in children. Study design We retrospectively reviewed cases of respiratory tract infection at a tertiary children's hospital in Japan and performed real-time polymerase chain reaction (PCR) for WUPyV using residual extracted nucleic acid samples taken from respiratory tract samples of pediatric patients primarily with respiratory failure. We investigated the clinical characteristics of patients positive for WUPyV and assessed samples positive for WUPyV for other respiratory pathogens using multiplex PCR. Results WUPyV was detected in 14 of 318 specimens of respiratory tract infections. The median age was 34 months and males were predominant (n = 11, 64%). An underlying disease was found in 11 (79%) patients including five preterm and three immunocompromised patients. The most common clinical diagnosis was pneumonia (n = 13, 93%). The majority of the samples were endotracheal tube aspirates (n = 11, 79%). Other viruses were co-detected in nine (64%) patients, while WUPyV was the only pathogen detected in five patients with a history of admission to the neonatal intensive care unit. These five patients presented with fever and cough, and perihilar infiltrates were detected on chest radiograph in several days. Conclusions WUPyV was detected in children with severe respiratory failure independently or concurrently with other pathogens. WUPyV can be a pathogen for children with a history of preterm birth or an underlying disease. [ABSTRACT FROM AUTHOR]

Abstract: Routine anaerobic blood culture is not recommended in children because obligate anaerobic bacteremia is rare in the pediatric population. However, a number of facultative anaerobic bacteria can cause community and hospital acquired infections in children and the utility of anaerobic blood culture for detection of these organisms is still unclear. We conducted a retrospective analysis of all blood culture samples (n = 24,356) at a children’s hospital in Japan from October 2009 to June 2012. Among the samples that had paired aerobic and anaerobic blood cultures, 717 samples were considered clinically significant with 418 (58%) organisms detected from both aerobic and anaerobic cultures, 167 (23%) detected only from aerobic culture and 132 (18%) detected only from anaerobic culture. While most facultative anaerobes were detectable by aerobic culture, over 25% of Enterobacteriaceae and 15% of Staphylococcus sp. were detected from anaerobic cultures bottles only, suggesting its potential role in selected settings. [Copyright &y& Elsevier]