Clinical features and treatment strategies of febrile urinary tract infection caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae in children: a multicenter retrospective observational study in Japan.

OBJECTIVES: The incidence of infections caused by extended-spectrum beta-lactamase (ESBL)-producing bacteria has increased. This study aimed to clarify the risk factors and treatment strategies for febrile urinary tract infection (fUTI) caused by ESBL-producing bacteria in Japanese children. METHODS: A retrospective observational study was conducted in 21 hospitals among children aged <16 years diagnosed with an fUTI between 2008 and 2017. Clinical data of children with fUTI caused by ESBL-producing and non-ESBL-producing bacteria were compared. RESULTS: Of the 2049 cases of fUTI, 147 (7.2%) were caused by ESBL-producing bacteria. Children in the ESBL group were more likely to have a history of recent antibiotic use or prophylactic antibiotic use, and experience recurrent UTIs (P <0.001) compared with those in the non-ESBL group. Of the 124 cases of fUTI due to ESBL-producing bacteria that were reviewed, 20 and 100 had concordant and discordant antibiotic use, respectively, and four had unknown antibiotic susceptibility. The median time from the start of treatment to fever resolution was 24 hours and did not differ significantly by therapy group (P = 0.39). CONCLUSION: ESBL-producing bacteria should be considered in children with recurrent UTIs and recent antibiotic use. Most children with fUTI experience clinical improvement regardless of the choice of antibiotic.

Obturator pyomyositis and labium majus cellulitis: A case report and literature review.

Pyomyositis is a rare, subacute, deep bacterial infection of the skeletal muscle. When treatment is delayed, pyomyositis causes abscess formation and progresses to sepsis; therefore, its early diagnosis is important. However, the clinical presentation and laboratory findings of pyomyositis are not specific; hence, diagnosis often takes time. We encountered the case of a girl with obturator pyomyositis and redness and swelling of the labium majus, which we considered as potentially important symptoms for distinguishing obturator pyomyositis from septic hip arthritis. An 8-year-old Japanese girl presented to our hospital with fever and right hip pain. On physical examination, she had redness and swelling of the right labium majus and a right limp. She was diagnosed with obturator pyomyositis and labium majus cellulitis with magnetic resonance imaging. Her clinical presentation markedly improved after starting antibiotic therapy with intravenous cefazolin for 2 weeks and oral cefaclor for 1 week. Improvement in the inflammation of the obturator muscle and labium majus was confirmed with follow-up magnetic resonance imaging. She recovered fully with no long-term sequelae. In conclusion, obturator pyomyositis rather than septic hip arthritis should be considered in children with a limp and hip and perineal pain, particularly girls with redness and swelling of the labium majus. In addition, imaging studies, including magnetic resonance imaging, should be performed for early diagnosis.

Clinical characteristics of pediatric febrile urinary tract infection in Japan.

BACKGROUND: Febrile urinary tract infection (fUTI) is the most common serious bacterial infection in children. Despite this, there have been no studies examining the clinical features of pediatric fUTI in Japan. The purpose of this study was to describe the clinical characteristics of fUTI in Japanese children. METHODS: A multicenter, retrospective, observational study was conducted at 21 hospitals in Japan. Children under the age of 15 years who were diagnosed with fUTI between 2008 and 2017 were included. The diagnostic criteria were a temperature over 38 °C and the presence of a single bacterial pathogen in urine culture. Patient characteristics were obtained from medical records. RESULTS: In total, 2,049 children were included in the study. The median age was 5 months, and 59.3% were male. It was found that 87.0% of the males and 53.2% of the females were under 1 year of age. The main causative pathogens identified were Escherichia coli and Enterococcus spp., accounting for 76.6% and 9.8% of infections, respectively. CONCLUSIONS: There was a male predominance of fUTI in Japanese children, particularly in infants. Enterococcus spp. were the second most frequent causative pathogen; therefore, Gram staining of urine samples is strongly recommended before initiating antibiotic therapy.

Age-Specific Differences in Foreign Bodies Ingested by Children: A Cohort Study of 252 Japanese Cases.

Background and Objectives: When children accidentally ingest foreign bodies, they may be unable to communicate adequately; it is often difficult to identify the causative foreign body unless someone is watching over them. In such instances, to identify the causative foreign body during clinical practice, we aimed to determine if it varies according to age. Materials and Methods: From April 2013 to June 2018, 252 records of pediatric patients with a confirmed diagnosis of foreign-body ingestion were retrospectively examined in a Japanese university hospital. Comparisons among multiple age groups, according to type of ingested foreign body, were analyzed using Kruskal‒Wallis tests. The differences between the individual data were tested using the Steel‒Dwass test. Results: The median age of the patients was 15 months, and of the total patients, 140 were boys (55.5%). The types of foreign bodies ingested were as follows, in order of frequency: cigarettes (n = 44, 17%, median age: 12 months), plastics (n = 43, 17%, median age: 11 months), chemicals (n = 27, 11%, median age: 13 months), internal medicines (n = 26, 10%, median age: 33 months), and metals (n = 26, 10%, median age: 35 months). The median age was significantly different among the types of causative foreign bodies (p < 0.01). The patient age for the ingestion of cigarettes was significantly younger than that for ingesting metals or coins. The age for ingesting internal medicines was significantly older than that for ingesting plastics, cigarettes, paper, or chemicals (p < 0.01). Conclusions: The causative foreign body ingested differed according to age. This will be valuable information for physicians that encounter pediatric patients who may have ingested an unknown foreign body in Japanese pediatric emergency or general practice settings.

A Combination Therapy for Kawasaki Disease with Severe Complications: a Case Report.

Kawasaki disease (KD) is a form of acute multisystem vasculitis that presents with various complications, including coronary artery aneurysm. Heart failure and brain damage are rare, but life-threatening complications are associated with KD. Here, we describe a 4-year-old girl who developed intravenous immunoglobulin-resistant KD with both left ventricular failure and acute encephalopathy. On day 8 of the illness, the low left ventricular ejection fraction, mitral regurgitation, and low blood pressure, which required continuous administration of dobutamine, were observed during the treatments for KD, including intravenous immunoglobulin. She also appeared unconscious, where the electroencephalogram showed slow waves of activity in all regions of the brain. The cardiac performance improved after she received plasma exchange for three days. However, her unconsciousness with slow waves of activity on electroencephalogram and fever continued after the plasma exchange. Therefore, she was treated with methylprednisolone pulse, followed by prednisolone, as well as intravenous immunoglobulin. Finally, she recovered without any cardiac or neurological sequelae not only at the time she was discharged, but also throughout the follow-up period. The combination therapy using plasma exchange and methylprednisolone pulse may be a treatment option for severe KD with left ventricular failure and acute encephalopathy complications.

Non-high-density Lipoprotein Cholesterol Levels in Japanese Obese Boys with Metabolic Syndrome.

AIM: To investigate the relationship between the clustering of metabolic syndrome (MetS) components and non-high-density lipoprotein cholesterol (non-HDL-C) levels in Japanese obese boys. METHODS: Subjects were 58 obese boys aged 12.0±2.6 years, which were categorized into three subgroups: abdominal obesity, pre-MetS (abdominal obesity＋1 component), and MetS (abdominal obesity＋2 or more components). RESULTS: Sixteen (27.6%) and 32 (55.2%) of the obese boys were diagnosed as pre-MetS and MetS, respectively. The mean non-HDL-C level in total subjects was 139.0±36.4 mg/dl and that in boys with abdominal obesity, pre-MetS, and MetS were 112.9±34.4, 135.4±37.9, and 149.0±32.6 mg/dl, respectively (p=0.0183, ANOVA). CONCLUSIONS: Japanese obese boys with MetS exhibited elevated non-HDL-C levels, suggesting that they may have a higher risk for the development of atherosclerotic diseases.

Invasive Community-Acquired Methicillin-Resistant Staphylococcus aureus in a Japanese Girl with Disseminating Multiple Organ Infection: A Case Report and Review of Japanese Pediatric Cases.

Pediatric invasive community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection is very serious and occasionally fatal. This infectious disease is still a relatively rare and unfamiliar infectious disease in Japan. We report a positive outcome in a 23-month-old Japanese girl with meningitis, osteomyelitis, fasciitis, necrotizing pneumonia, urinary tract infection, and bacteremia due to CA-MRSA treated with linezolid. PCR testing of the CA-MRSA strain was positive for PVL and staphylococcal enterotoxin b and negative for ACME. SCC mec was type IVa. This case underscores the selection of effective combinations of antimicrobial agents for its treatment. We need to be aware of invasive CA-MRSA infection, which rapidly progresses with a serious clinical course, because the incidence of the disease may be increasing in Japan.

Apolipoprotein A-V level may contribute to the development of obesity-associated dyslipidemia.

AIM: In a mice study, insulin suppressed apolipoprotein A-V (apoA-V) gene expression in a dose dependent manner. Thus, we investigated the association between apoA-V levels and dyslipidemias in obese children with hyperinsulinemia. METHODS: The subjects were 17 obese children (15 male, 2 female) aged 11.8 ± 2.4 years. Total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), triglyceride (TG), apoA-V and insulin levels were determined. RESULTS: Obese children with hyperinsulinemia had greater percent overweight, higher TG level, lower HDLC level and lower apoA-V level than those without hyperinsulinemia. In simple regression analysis, apoA-V level correlated negatively with TG (r = -0.613, p = 0.0152) and insulin levels (r = -0.566, p = 0.0279), and positively correlated with HDLC (r = 0.811, p = 0.0002). In stepwise regression analysis, insulin level emerged as the independent determinant of TG level after apoA-V level was taken into account, whereas apoA-V emerged as the independent determinant of HDLC level after adjusting for insulin level. CONCLUSIONS: Insulin may be a potent regulator of serum apoA-V level in obesity, and apoA-V level may partly contribute to the development of obesity-associated dyslipidemia.

Treatment responses for disseminated intravascular coagulation in 25 children treated with recombinant thrombomodulin: a single institution experience.

INTRODUCTION: Recombinant thrombomodulin (rTM), which degrades factors Va and VIIIa by activating protein C, has been developed as a new drug for treating disseminated intravascular coagulation (DIC). MATERIALS AND METHODS: Since July 2009, we have treated 25 children with DIC using rTM (380 U/kg/day, or 130 U/kg/day for newborns) as a first-line therapy. Median duration of rTM administration was 5 consecutive days (range, 2-13 days). We employed DIC criteria of the Japan Welfare and Health Ministry. The first day on which rTM treatment was given was defined as day 1. RESULTS: Median patients age was 3 years. Underlying diseases were hematological disorders (n=13) and severe infection (n=12). Overall, 20 of the 25 patients had recovered from DIC by day 7 and 22 of the 25 patients remained alive at day 28. Median Pediatric Logistic Organ Dysfunction score improved from 11 on day 1 to 2 on day 7 (p=0.009). Laboratory data (median) on day 7 (prothrombin time (PT) ratio, 1.15; fibrin and fibrinogen degradation products (FDP), 9.6 mg/l; D-dimer, 1.6 mg/l FEU; antithrombin, 112%; protein C, 105%) were significantly improved compared to results on day 1 (PT ratio, 1.39; FDP, 21.6 mg/l; D-dimer, 6.4 mg/l FEU; antithrombin, 86%; protein C, 54%). Whereas, 5 patients failed to respond and serious bleeding events were observed in 2 newborns. CONCLUSION: The efficacy of rTM cannot be assessed from the present dataset, due to several limitations such as the small heterogenous patient cohort, and the lack of age- and disease-matched controls. Nevertheless, this case-series remains important in terms of enabling further prospective control studies to evaluate the efficacy of rTM in children.

Early postnatal changes of lipoprotein subclass profile in late preterm infants.

BACKGROUND: Late preterm infants (LPIs; 34-37 gestational weeks at birth) have higher risk for several morbidities than do term infants (TIs). It has been suggested that a cholesterol and fatty acid supply may improve their outcomes. We investigated the lipoprotein subclass profile in LPIs to evaluate their early postnatal lipid metabolism. METHODS: Eighty-one infants (25 LPIs, 56 TIs) were included. Cholesterol and triglyceride (TG) concentrations in 12 lipoprotein subclasses were measured at birth and at 1 month using HPLC. RESULTS: In LPIs, the cord blood exhibited higher cholesterol concentrations in medium and large subclasses of very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) compared to the values in TIs. During the first month of life, LPIs had greater increases in cholesterol concentrations of medium and large subclasses of VLDL than TIs, whereas postnatal increases in cholesterol concentrations of medium and large subclasses of LDL and HDL were smaller. TG concentrations were not different in each VLDL subclass at birth and at 1 month. CONCLUSIONS: In LPIs, cord blood lipoprotein subclass profiles and the early postnatal change exhibited different, especially in cholesterol concentrations.

Very low-density lipoprotein in the cord blood of preterm neonates.

Human fetuses have markedly low levels of serum lipids and a unique lipoprotein profile with respect to quality, with low-density lipoprotein (LDL)-like particle as the dominant cholesterol carrier. However, little is known about triglyceride (TG) distribution. In addition, lipid metabolism is important in lung development, with indications that TG from very low-density lipoprotein (VLDL) is essential for surfactant synthesis. We investigated TG distribution in preterm neonate cord blood and the relationship of VLDL-TG levels with respiratory distress syndrome (RDS). The study included 103 appropriate-for-gestational-age neonates (61 males). We performed serum lipoprotein analyses in cord blood by high-performance liquid chromatography with gel permeation columns. Term neonates had low cord blood TG concentrations distributed equally to the LDL and VLDL fractions. However, preterm neonates had even lower TG concentrations, with VLDL as the dominant carrier. The LDL-TG and high-density lipoprotein-TG concentrations in cord blood increased gradually with gestational age, but cord blood VLDL-TG concentrations increased dramatically from 32 to 34 weeks of gestational age. Neonates with RDS exhibited no RDS-specific lipoprotein profile; however, most were born before the timing of the dramatic VLDL-TG increase. Our results suggest that 34 weeks of gestation is a critical period for TG metabolism, indicating the need for evaluation of the lipid nutritional state in preterm neonates.