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Several carbapenemases have been identified globally in Enterobacteriaceae. In Japan, IMP-type carbapenemase is the most prevalent, although cases of carbapenemase-producing Enterobacteriaceae (CPE) bacteremia are still scarce. The present case series and literature review aimed to elucidate the clinical characteristics and treatment strategies for IMP-type CPE bacteremia.Clinical data on pediatric cases of IMP-type CPE bacteremia at the Tokyo Metropolitan Children's Medical Center between 2010 and 2020 were collected, and a review of past studies of IMP-type CPE bacteremia has been provided.Five pediatric episodes of IMP-type CPE bacteremia were identified. Our review of previous literature on IMP-type CPE bacteremia revealed 24 adult patients, but no pediatric patients. All 29 cases had underlying diseases, and 23 (79%) received combination therapy. The median duration of antibiotic therapy was 14 days (interquartile range: 9-14 days). The overall mortality rate was 38% (11/29). The mortality rates associated with monotherapy and combination therapy were 67% (4/6) and 30% (7/23), respectively.We report the first case series of IMP-type CPE bacteremia in children. Our review of past studies suggests that combination therapy might lead to better survival outcomes in patients with IMP-type CPE bacteremia. Further research is needed to establish an optimal treatment strategy for IMP-type CPE bacteremia.

Background Hypermagnesemia can be a fatal condition and should be diagnosed early on. Most reports of hypermagnesemia have been of adults with impaired renal function. We describe the case of a pediatric patient without renal dysfunction who developed severe hypermagnesemia. Case presentation A healthy 20-month-old Asian girl presented to our emergency department with episodes of vomiting and a reduced level of consciousness. The neurological examination showed a symmetric decrease in muscle tone, and the deep tendon reflexes were decreased. On admission, her magnesium (Mg) level was 11.0 mg/dL after receiving magnesium oxide for 4 days because of constipation. She was immediately administered calcium gluconate infusion (3.9 mEq), and then was continuously infused with it (0.23 mEq/h) as a Mg antagonist to cardiac side effects. She was kept hydrated with 0.9% sodium chloride to maintain good urine output to excrete the Mg. The level of the serum Mg decreased to 2.4 mg/dL, enabling her to regain consciousness. During 5 years of follow-up, she was neurologically well, without the recurrence of hypermagnesemia. Conclusions Even in the absence of significant renal dysfunction, the prescription of a laxative containing Mg for constipation can result in severe hypermagnesemia. In addition, the symptoms of hypermagnesemia are nonspecific, and early diagnosis is difficult unless it is actively suspected.

This paper describes a case of papulonecrotic tuberculid after Bacille Calmette-Guerin (BCG) vaccination. A 6-month-old boy was seen in our emergency room with a fever and erythematous papular. He received BCG vaccination at the age of 5 months and there were no systemic problems after the vaccination. There were no abnormal physical findings except for skin lesions and fever. Histopathologically, the lesion was associated with pyogenic granulomatous inflammation and fibrosis, with multiple instances of vascularization and infiltration of various inflammatory cells. Acid-fast stain, culture,and polymerase chain reaction for tuberculous bacillus DNA of the papulonecrotic skin lesions were negative. He was diagnosed papulonecrotic tuberculid caused by BCG vaccination. The fever lasted 10 days, and all lesions healed spontaneously in 2 months. Papulonecrotic tuberculid is a vasculitis caused by an allergic reaction to an internal focus of Mycobacterium tuberculosis or its metabolites. The appearance of an unexplained skin rash may cause parental anxiety, nevertheless the disease may require no treatment unless the patient is immunocompromised. It is necessary to improve awareness regarding the disease as a side effect of BCG vaccination.

Eikenella corrodens is a facultatively anaerobic gram-negative rod bacterium in the oropharynx and respiratory tract. It is a member of HACEK (Haemophilus spp., Aggregatibacter spp., Cardiobacterium hominis, E. corrodens, and Kingella kingae) group commonly associated with endocarditis and craniofacial infections. It is usually susceptible to penicillin, second and third-generation cephalosporins, and carbapenem, but has variable susceptibility to first-generation cephalosporin. We herein provide a description of the first case of pediatric acute dacryocystitis caused by E. corrodens. The patient did not respond to oral cephalexin and required surgical drainage followed by intravenous cefotaxime. Also provided is a brief review of the current literature.

Background Pyelonephritis caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae is an urgent problem in pediatrics. Although carbapenem is the standard therapy for infections caused by ESBL-producing Enterobacteriaceae, some cephamycins, including cefmetazole, are stable against hydrolysis by ESBL. There are few reports, however, on the use of cefmetazole in children. The aim of this study was to evaluate the therapeutic effect of cefmetazole in pediatric pyelonephritis caused by ESBL-producing Enterobacteriaceae. Methods Children with pyelonephritis caused by ESBL-producing Enterobacteriaceae were enrolled between April 2010 and November 2016 at Tokyo Metropolitan Children's Medical Center. Presence of ESBL was tested for using the disk diffusion method. Medical records were reviewed for a past history of bacterial infection. The outcomes were clinical cure rate at 4 weeks and the duration of therapy in the cefmetazole and non-cefmetazole groups. Results Fifty-five patients met the criteria for pyelonephritis caused by ESBL-producing Enterobacteriaceae. The most common causative organisms were Escherichia coli (n = 51; 92.7%), Klebsiella pneumoniae (n = 3; 5.5%), and K. oxytoca (n = 1; 1.8%). Thirty-six and 19 patients were treated with cefmetazole and with other antibiotics as definitive therapy, respectively. There was no difference in the clinical cure rate (86.1% vs 89.5%; P = 0.72) or duration of therapy (median, 7.0 vs 7.0 days; P = 0.73) between the cefmetazole and non-cefmetazole groups. Conclusions Cefmetazole was not inferior to the other antibiotics in the treatment of pyelonephritis caused by ESBL-producing Enterobacteriaceae in children. Cefmetazole is a valuable therapeutic alternative to carbapenems for treating pyelonephritis caused by ESBL-producing Enterobacteriaceae.

Using terahertz-pump and terahertz-probe spectroscopy, we investigated terahertz-induced carrier generation processes in Bi1-xSbx thin films. The field dependence of the terahertz-induced transmittance change indicates distinct nonlinearity related to the Zener tunneling in narrow band-gap materials.

Background Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia causes morbidity and mortality in children. The standard treatment for MRSA bacteremia is vancomycin, which should achieve a 24 hour area under the curve over the minimum inhibitory concentration ratio (AUC/ MIC) of >400. Whether or not attaining AUC/ MIC >400 early in the disease course improves outcomes in children is controversial. The aim of our study was to determine whether early achievement of AUC/ MIC >400 improved outcomes in children with MRSA bacteremia. Methods Children whose blood culture grew MRSA between March 2010 and April 2017 at Tokyo Metropolitan Children’s Medical Center were enrolled. The exclusion criteria were no vancomycin administration, use of extracorporeal membrane oxygenation, no data on dosage and vancomycin MIC, and cases of contamination. Susceptibility testing was performed by a microdilution method. The outcomes of patients who achieved an AUC/MIC >400 at the first assessment prior to the Fourth or Fifth vancomycin dose were compared with those of patients who did not. The clinical outcomes were persistent bacteremia on Days 3 and 7, mortality at 30 days, and the recurrence of MRSA bacteremia. Results In total 175 MRSA isolates from 50 children were identified. Of these 56 episodes were eligible for enrollment. Forty-one subjects (73.2%) were boys. The median age was 9 months (interquartile range: 1.8–120.5 months). The median initial dose of vancomycin was 40 mg/kg (interquartile range: 30–44.3 mg/kg). Among MRSA isolates, vancomycin MIC of < 0.5 mcg/mL, 1 mcg/mL and 2 mcg/mL were 1 (1.8%), 53 (94.6%) and 2 (3.6%), respectively. Fifteen patients (26.8%) achieved AUC/MIC >400 early. The two groups did not differ significantly in terms of persistent bacteremia on Days 3 (P = 0.96) or 7 (P = 0.82), mortality at 30 days (P = 0.47), or the recurrence of MRSA bacteremia (P = 1.0). Conclusion Children with bacteremia who achieved AUC/ MIC>400 early did not differ significantly from children who did not in terms of their clinical outcomes. Disclosures All authors: No reported disclosures.

Background Oral third-generation cephalosporins are often inappropriately prescribed at outpatient clinics in Japan for mild infections by viruses and bacteria susceptible to agents with a narrower spectrum despite the absence of any recommendations for the use of these drugs as a first-line treatment in the existing guidelines. Our aim was to evaluate an antimicrobial stewardship program (ASP) targeting outpatient use of oral third-cephalosporins at an emergency department. Methods Patients visiting the emergency department (ED) at Tokyo Metropolitan Children’s Medical Center in Japan between March 2010 and May 2016 were included. The first period (pre-intervention) between March 2010 and September 2010 had no ASP; the second period (intervention 1) between October 2010 and March 2013 had an ASP with consultations with an infectious diseases’ physician and a no-antibiotic policy for the common cold; and the third period (intervention 2) between April 2013 and May 2016 included an ASP with the requirement for permission to prescribe oral third-generation cephalosporins. We compared the number of prescriptions for third-generation cephalosporin’s prescriptions among the three periods. Antibiotic use was calculated by the number of prescriptions per 1,000 ED visits. Results In total 232,548 patients were included. Oral antibiotics were prescribed for 13,227 cases (5.7 %). Boys numbered 7,440 (66 %), and the median age was 54 months (IQR: 27-98 months). After interventions 1 and 2, the use of oral third-generation cephalosporins declined from 19 per 1,000 ED visits in the pre-intervention period to 6.6 per 1,000 ED visits during intervention 1 (−4.0; 95% CI −6.3 to −1.7, P = 0.001) and 0.10 per 1,000 ED visits during intervention 2 (−0.31; 95% CI −1.8 to 1.2, P = 0.675). Conclusion The ASP at our ED was effective in decreasing the prescription of oral third-generation cephalosporins. Disclosures All authors: No reported disclosures.

Background Antibiotic resistance is a serious and growing concern worldwide. Although Enterobacteriaceae bloodstream infections (BSI) are severe, little is known regarding the impact of multidrug resistance (MDR) on children. This study aimed to describe the clinical and microbiological features of MDR Enterobacteriaceae BSI in a children’s hospital in Japan. Methods Children (48 hours after admission. The most common isolate was Escherichia coli (47.0%) followed by Klebsiella pneumoniae (23.1%). MDR was detected in 35.8% (48/134) of culture, with Escherichia coli occurring with the highest frequency (23.1%) followed by Klebsiella pneumoniae (7.5%). The MDR strains producing ESBL, AmpC, and carbapenemases comprised 17.9%, 7.5%, and 1.5% of the cases, respectively. Multivariate logistic regression analysis showed that the history of corticosteroid use within 30 days was independently associated with the development of MDR Enterobacteriaceae BSI (OR: 3.63; 95% CI: 1.35–9.73). Initial empiric therapy was less effective against MDR, than non-MDR, strains (51.1% vs. 83.8%, P < 0.001). MDR was not significantly associated with an increased rate of all-cause mortality (MDR 10.4% vs. non-MDR 3.5%, P = 0.134) or sepsis-related mortality (MDR 6.3% vs. non-MDR 2.3%, P = 0.349). Conclusion A history of corticosteroid use within 30 days was an independent risk factor for the development of MDR Enterobacteriaceae BSI in children. MDR did not increase the mortality rate significantly. Disclosures All authors: No reported disclosures.

We investigated nonlinear carrier response of semi-metal bismuth under intense terahertz pulse illumination. By applying the intense terahertz field, the transmittance increases more than 10 %, indicating an increase of the effective mass.

An ambiguous query in sequence databases returns a set of similar subsequences, called a mismatch cluster, to the user. The inherent problem is that it is difficult for users to identify the characteristics of very large similar subsequences in a mismatch cluster. In order to support user comprehension of mismatch clusters, it is important to extract a set of ambiguous sequence patterns with the least minimum generalization in the mismatch cluster. The extraction of the ambiguous sequential pattern set requires an enormous amount of computational time, since we have to discover generalized patterns with minimum covers for the mismatch cluster from candidate generalized patterns. The present paper is a proposal for an iterative refinement method to extract ambiguous sequence patterns with minimum cover for mismatch clusters selected from a sequence database. It includes a proposal to use the method with a domain segmentation method to achieve an efficient pattern extraction. Moreover, a prototype implementing the two proposed methods has been applied to three datasets included in PROSITE in order to evaluate their usefulness. The proposed methods resulted in a high capability to extract ambiguous sequential patterns from mismatch clusters that are provided by an ambiguous query in the sequence database.

Dirac-like electrons in solid state have been of great interest since they exhibit many peculiar physical behaviors analogous to relativistic mechanics. Among them, carriers in graphene and surface states of topological insulators are known to behave as massless Dirac fermions with a conical band structure in the two-dimensional momentum space, whereas electrons in semimetal bismuth (Bi) are expected to behave as massive Dirac-like fermions in the three-dimensional momentum space, whose dynamics is of particular interest in comparison with that of the massless Dirac fermions. Here, we demonstrate that an intense terahertz electric field transient accelerates the massive Dirac-like fermions in Bi from classical Newtonian to the relativistic regime; the electrons are accelerated approaching the effective “speed of light” with the “relativistic” beta β = 0.89 along the asymptotic linear band structure. As a result, the effective electron mass is enhanced by a factor of 2.4.

THz pump-THz probe spectroscopy is performed to study carrier dynamics in Bi film. Transmittance of Bi film increases since effective masses of carriers increases by acceleration. After the illumination, transmittance decreases due to carrier increases.

Interactions between conjugated polyenes and light play important role in photosynthesis and vision. To understand and to manipulate the conversion of light energy to chemical energy in conjugated polyenes, we investigated the relaxation processes in the simplest conjugated diene, 1, 3-butadiene (BD) shown in Fig. 1, by time-resolved photoelectron spectroscopy using high harmonics (TRPES) [1]. In BD, the ultrafast relaxation from the excited states mainly takes place via the conical intersection (CI) between S 1 and S 0 ((S 1 /S 0 ) CI ), where the hydrogen atoms at one end of the molecule stick out of the molecular plane to form the pyramidalized structure shown in Fig. 2a. The molecular structure at (S 1 /S 0 ) CI motivated us to control the relaxation pathways by substituting the end hydrogen atoms with methyl groups, preventing the pyramidalization by steric hinderance. To compare with the dynamics of BD, the relaxation processes of 1, 3-pentadiene(PD) and 2, 5-dimethyI-2, 4-hexadine (HD) were investigated by TRPES. The relaxation pathway in HD is expected to be different from the others.