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.

A neonatal prolonged QT syndrome due to maternal use of oral tricyclic antidepressants.

UNLABELLED: It is known that tricyclic antidepressants induce long QT intervals associated with forms of life-threatening arrhythmia such as torsades de pointes (TdP), and these adverse effects may also occur in neonates whose mothers take tricyclic antidepressants. We report a neonatal case of prolonged QT interval and TdP caused by clomipramine that was transferred transplacentally from the mother. Administration of magnesium sulfate was effective to abolish TdP. CONCLUSION: When mothers take tricyclic antidepressants during pregnancy, their newborns should be watched carefully for drug-induced long QT syndrome and TdP. WHAT IS KNOWN: •Tricyclic antidepressant can prolong the QT interval. It may be used for depression in pregnancy. What is New: •This is the first neonatal case report of prolonged QT interval and TdP caused by clomipramine transferred transplacentally from the mother.

Yersinia enterocolitica bacteremia and enterocolitis in a previously healthy 20-month-old girl.

Yersinia enterocolitica is a gram-negative bacillus that can cause illness ranging from a self-limiting enterocolitis to life-threatening bacteremia. Y. enterocolitica biotype 1B, serotype O:8 (1B/O:8), is the most pathogenic of the Yersinia species because of the presence of the high-pathogenicity island and the Yersinia virulence plasmid (pYV). Here, we report a pediatric case of Y. enterocolitica 1B/O:8 bacteremia and enterocolitis. A 20-month-old girl was admitted to hospital with fever,pharyngitis, and abdominal pain on day 2. Blood culture on admission was positive for Y. enterocolitica 1B/O:8. Stool culture on day 5 after cefotaxime treatment was also positive for Y. enterocolitica 1B/O:8, but only after cold enrichment at 4°C for 3 weeks. PCR assays identified the pYV only in stool specimens, indicating that strains from routine blood culture at 37°C lacked the pYV. The present case showed the usefulness of stool culture with cold enrichment and agglutination test for the diagnosis of Y. enterocolitica infection. We would therefore like to emphasize the importance of collection and preservation of stool specimens for the identification of pYV. To our knowledge, this is the first reported pediatric case of Y. enterocolitica 1B/O:8 bacteremia.

Phenotypic spectrum of CHARGE syndrome with CHD7 mutations.

CHD7 gene mutations were identified in 17 (71%) of 24 children clinically diagnosed to have CHARGE syndrome (C, coloboma of the iris or retina; H, heart defects; A, atresia of the choanae; R, retardation of growth and/or development; G, genital anomalies; and E, ear abnormalities). Colobomata, hearing loss, laryngomalacia, and vestibulo-cochlear defect were prevalent. Molecular testing for CHD7 enables an accurate diagnosis and provides health anticipatory guidance and genetic counseling to families with CHARGE syndrome.

Adrenocorticotropic hormone and 17-hydroxyprogesterone levels during high-dose glucocorticoid supplement for the management of clitoroplasty of CYP21A2 deficiency.

ACTH and 17-hydroxyprogesterone (17OHP) levels during clitoro- and labinoplasty for CYP21A2 deficiency have not been reported. In this study, we measured these levels during surgery. Intensive glucocorticoid supplement (IGS Tx; intravenous bolus injection of daily dose (14.6 to 22.2 mg/m(2)) of hydrocortisone followed by continuous infusion of three times the daily dose for 24 hours) was done to eight patients for surgery. ACTH and 17OHP levels were generally suppressed during operation by this protocol, but mid-surgical elevations of ACTH and 17OHP levels were observed in four out of the eight. In another three patients than the eight as described, oral dexamethasone pretreatment (1 mg/m(2)) was administered for two days before surgery in addition to IGS Tx. ACTH and 17OHP levels were completely suppressed throughout operation, indicating that this kind of additional pretreatment is more effective approach.

Hydrochlorothiazide effectively reduces urinary calcium excretion in two Japanese patients with gain-of-function mutations of the calcium-sensing receptor gene.

Gain-of-function mutations of the calcium-sensing receptor (CaR) gene cause autosomal dominant and/or sporadic hypocalcemia with hypercalciuria. Because treatment of the hypocalcemia with vitamin D and/or calcium in patients with such mutations results in increased hypercalciuria, nephrocalcinosis, and renal impairment, its use should be limited to alleviating the symptoms of symptomatic patients. Because thiazide diuretics have been successfully used to treat patients with hypercalciuria and hypoparathyroidism, they are theoretically useful in reducing urine calcium excretion and maintaining serum calcium levels in patients with gain-of-function mutations of the CaR gene. In this study, we report on the clinical course, molecular analysis, and effects of hydrochlorothiazide therapy in two Japanese patients with gain-of-function mutations of the CaR gene. Within a few weeks after birth, they developed generalized tonic seizures due to hypocalcemia (serum calcium values: 1.1 mmol/liter and 1.3 mmol/liter, respectively). Despite treatment with the standard dose of 1,25-dihydroxyvitamin D(3) in one patient and 1alpha-hydroxyvitamin D(3) in the other, acceptable serum calcium levels near the lower limit of normal were not established, and their urinary calcium excretion inappropriately increased. Addition of hydrochlorothiazide (1 mg/kg) reduced their urinary calcium excretion and maintained their serum calcium concentrations near the lower limit of normal, allowing the 1,25-dihydroxyvitamin D(3) and 1alpha-hydroxyvitamin D(3) doses to be reduced, and it alleviated their symptoms. A heterozygous missense mutation was identified in both patients. In one patient, the mutation was A843E in the seventh transmembrane domain of the CaR, and in the other it was L125P in the N-terminal extracellular domain. In vitro transient transfection of their mutant CaR cDNAs into HEK293 cells shifted the concentration-response curve of Ca(2+) to the left. In conclusion, two sporadic cases of hypercalciuric hypocalcemia were due to de novo gain-of-function mutations of the CaR gene. Hydrochlorothiazide with vitamin D(3) successfully reduced the patients' urinary calcium excretion and controlled their serum calcium concentrations and symptoms. Thiazide diuretics are effective in patients with gain-of function mutations of the CaR gene.