Publications by authors named "Yuho Horikoshi"

43 Publications

Impact of methicillin-resistant Staphylococcus aureus colonization in a neonatal intensive care unit after discharge.

Pediatr Int 2021 Jan 28;63(1):117-119. Epub 2020 Dec 28.

Division of Infectious Diseases, Department of Pediatrics, Tokyo Metropolitan Children's Medical Center, Fuchu, Tokyo, Japan.

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http://dx.doi.org/10.1111/ped.14374DOI Listing
January 2021

Kawasaki disease following coronavirus disease 2019 with prolonged fecal viral shedding.

Pediatr Int 2021 05 5;63(5):597-599. Epub 2020 Dec 5.

Division of Infectious Diseases, Department of Pediatrics, Tokyo Metropolitan Children's Medical Center, Fuchu, Tokyo, Japan.

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http://dx.doi.org/10.1111/ped.14452DOI Listing
May 2021

Nationwide surveillance of bacterial pathogens isolated from children conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2017: General overview of pathogenic antimicrobial susceptibility.

J Infect Chemother 2021 Feb 1;27(2):139-150. Epub 2020 Dec 1.

Pediatric Sub-committee and the Surveillance Committee of Japanese Society of Chemotherapy (JSC), The Japanese Association for Infectious Diseases (JAID), The Japanese Society for Clinical Microbiology (JSCM), Tokyo, Japan; Department of Pediatrics, Kurume University Hospital, Fukuoka, Japan.

A nationwide surveillance of the antimicrobial susceptibility of pediatric patients to bacterial pathogens was conducted by Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in Japan in 2017. The isolates were collected from 18 medical facilities between March 2017 and May 2018 by the three societies. Antimicrobial susceptibility testing was conducted at the central laboratory (Infection Control Research Center, Kitasato University, Tokyo) according to the methods recommended by the Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 926 strains (331 Streptococcus pneumoniae, 360 Haemophilus influenzae, 216 Moraxella catarrhalis, 5 Streptococcus agalactiae, and 14 Escherichia coli). The ratio of penicillin-resistant S. pneumoniae was 0% based on CLSI M100-ED29 criteria. However, three meropenem or tosufloxacin resistant S. pneumoniae isolates were obtained. Among H. influenzae, 13.1% of them were found to be β-lactamase-producing ampicillin resistant strains, while 20.8% were β-lactamase non-producing ampicillin-resistant strains. No capsular type b strains were detected. In M. catarrhalis, 99.5% of the isolates were β-lactamase-producing strains. All S. agalactiae and E. coli strains were isolated from sterile body sites (blood or cerebrospinal fluid). The ratio of penicillin-resistant S. agalactiae was 0%, while that of extended spectrum β-lactamase-producing E. coli was 14.3%.
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http://dx.doi.org/10.1016/j.jiac.2020.11.020DOI Listing
February 2021

School-based approach for parasitic disease control in Japan and Africa.

Pediatr Int 2021 Mar 16;63(3):264-269. Epub 2021 Feb 16.

Division of Infectious Diseases and the Centre for Global Child Health, The Hospital for Sick Children, Toronto, Ontario, Canada.

Japan has achieved significant improvements in the control and prevention of parasitic infections through a school-based approach since the 1930s. The use of chemical fertilizers in agriculture, safe water and food, and improved sanitation and hygiene also contributed to the near eradication of endemic parasites. However, parasite infections continued to affect children mostly in resource-limited countries. The African continent has one of the highest burdens of such infections. The application of school-based approaches has several advantages where the structure of health-care systems is not optimal. In Africa, soil-transmitted helminths and schistosomiasis are frequently targets for school-based public health intervention. Mass drug administration by teachers at school can reach targeted children effectively and safely. The limitations of this approach include missing unattended children and absentee of teachers. Initially, mass drug administration at school for parasitic infections was thought to improve health and even socioeconomic status of children in the community. However, more recently the socioeconomic impact has been questioned although the reduction of parasitic diseases is still apparent. Moreover, other basic public health measurements such as increased toilet use, assuring safe water access and avoiding the use of human excrement as an agricultural fertilizer, are equally important for control and prevention of parasitic diseases. Further global efforts should be continued to achieve equal health for every child in a sustainable way.
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http://dx.doi.org/10.1111/ped.14535DOI Listing
March 2021

First case of Legionella pneumonia in a female patient with anorexia nervosa.

J Paediatr Child Health 2021 06 14;57(6):950-952. Epub 2020 Aug 14.

Division of Infectious Diseases, Department of Pediatrics, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.

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http://dx.doi.org/10.1111/jpc.15108DOI Listing
June 2021

National trends in appropriate antibiotics use among pediatric inpatients with uncomplicated lower respiratory tract infections in Japan.

J Infect Chemother 2020 Nov 11;26(11):1122-1128. Epub 2020 Aug 11.

Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Japan.

Background: Japan was ranked as the worst country of 36 high-income countries in terms of oral antibiotic consumptions for children. Knowing the patterns and variations of antibiotic use for pediatric inpatients with uncomplicated respiratory infections is an important step to promote judicious antibiotic use.

Methods: Discharge records were extracted for children aged between 3 months and 15 years with acute lower respiratory tract infections for the fiscal years 2010-2014 using a national inpatient database in Japan. We investigated the trends in antibiotic use using mixed effect regression models and ascertained variations and clustering of the practice patterns across different hospitals using unsupervised machine learning methodology.

Results: A total of 280,298 children were included in the study. Total and broad-spectrum antibiotic use, except for fluoroquinolone, showed decreasing trends from 2010 to 2014. Additionally, the proportions of patients who received no antibiotics or only penicillin increased from 17.1% to 9.9% in 2010 to 24.5% and 13.7% in 2014, respectively. Cluster analysis showed that only one-quarter of hospitals used no antibiotics for 28.8% of children and only penicillin for 53.7% of children. In the remaining clusters of hospitals, the piperacillin, 3rd generation cephalosporins, and penicillin beta-lactamase inhibitors were used for 68.5%, 68.5%, and 69.6% of the patients who received antibiotics.

Conclusions: Slightly increasing trends in narrow-spectrum antibiotics were observed. However, the treatment strategy in only one-quarter of hospitals was consistent with the current recommendations. Hospital level interventions to promote and monitor antibiotic use could be helpful to improve antibiotic use for pediatric inpatients.
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http://dx.doi.org/10.1016/j.jiac.2020.04.025DOI Listing
November 2020

CTX-M group gene distribution of extended spectrum beta-lactamase-producing Enterobacteriaceae at a Japanese Children's hospital.

J Infect Chemother 2020 Sep 23;26(9):1005-1007. Epub 2020 Jun 23.

Division of Infectious Diseases, Department of Pediatrics, Tokyo Metropolitan Children's Medical Center, Fuchu, Tokyo, Japan.

Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae have spread globally as one of the most common multidrug resistant organisms. Although a wide variety of ESBL genes were known in each geographical region, few reports existed on the distribution of ESBL genes in Japanese children. To clarify the distribution of ESBL genes, we investigated the CTX-M type of the ESBL-producing Enterobacteriaceae and patient characteristics among hospital-acquired and community-acquired cases. Total of 253 isolates of ESBL-producing Enterobacteriaceae were recovered from 238 pediatric patients. ESBL-producing Enterobacteriaceae were mostly recovered from children with underlying diseases (76.5%). Ratio of community-acquired and hospital-acquired cases was 58.8% and 41.2%, respectively. Compared to the hospital-acquired cases, community-acquired cases had younger age, fewer underlying diseases, and the dominant detection of Escherichia coli. The most common ESBL-producing Enterobacteriaceae was E. coli (79.8%), followed by Klebsiella pneumoniae (9.1%). CTX-M9 group was the most prevalent CTX-M group gene (63.2%), which was dominantly detected in E. coli (72.7%). This was the largest descriptive study to find CTX-M9 group as the most prevalent ESBL genotype among Enterobacteriaceae isolated from Japanese children in line with adult's epidemiology.
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http://dx.doi.org/10.1016/j.jiac.2020.05.017DOI Listing
September 2020

Impacts of Primary Care Physician System on Healthcare Utilization and Antibiotic Prescription: Difference-in-Differences and Causal Mediation Analyses.

Pediatr Infect Dis J 2020 10;39(10):937-942

Office for Infection Control, National Center for Child Health and Development, Tokyo, Japan.

Background: The overutilization of healthcare and overuse/misuse of antibiotics in Japan are responsible for the increase in healthcare expenditure and the development of antimicrobial resistance. The Japanese government started paying incentives to medical facilities for primary care physician registrations, but the impact of this new policy is still unclear.

Methods: We conducted a retrospective cohort study for all pediatric outpatients from April 2015 to December 2016 in Japan, targeting 1.4 million children under 2 years of age. We investigated the effects of primary care physician registration on physician visits, total antibiotic use and admission rates using difference-in-differences (DID) and causal mediation analyses.

Results: DID analyses showed that primary care registration policy contributed to increases in total physician visits, total and broad-spectrum antibiotic use and radiologic study utilization, but reduced out-of-hour visits and did not affect hospitalization rates. Similar results were obtained when we adjusted for and matched on potential confounders. Causal mediation analyses found that the greatest pathway was controlled by direct effects of 53.2 DOTs per 1000 person-months (95% CI: 29.1-77.2), indicating that the effect of new health policy that did not mediate increased outpatient visits mostly contributed to the excess use of antibiotics.

Conclusions: The health policy further increased antibiotic use. On April 2018, a new health policy of paying incentives for not prescribing antibiotics to children with respiratory infection or gastroenteritis was initiated. Further studies are needed whether this new health policy can mitigate the overutilization of healthcare and antibiotic use.
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http://dx.doi.org/10.1097/INF.0000000000002762DOI Listing
October 2020

Prospective monitoring of carbapenem use and pseudomonal resistance across pediatric institutions.

Infect Control Hosp Epidemiol 2020 09 2;41(9):1042-1047. Epub 2020 Jun 2.

National Center for Child Health and Development, Tokyo, Japan.

Objective: To determine whether carbapenem consumption and Pseudomonas aeruginosa resistance rates can be used as benchmarks to compare and improve antimicrobial stewardship programs across multiple pediatric hospitals.

Design: A prospective study.

Setting And Participants: Healthcare institutions in Japan with >100 pediatric beds.

Methods: An annual survey of the total days of therapy (DOT) per 1,000 patient days for carbapenem antibiotics (meropenem, imipenem-cilastatin, panipenem-betamipron, doripenem) and susceptibility rates of Pseudomonas aeruginosa to meropenem and imipenem-cilastatin from each institution was conducted over a 7-year period. Data were reported to the administration, as well as to the infection control team, of each institution annually.

Results: Data were obtained from 32 facilities. The median total carbapenem DOT per 1,000 patient days was 16.6 and varied widely, with a range of 2.7 to 59.0. The median susceptibility to meropenem was 86.6%, ranging from 78.6% to 96.6%. We detected an inverse correlation between total carbapenem DOT versus susceptibility (r = - 0.36; P < .01). Over the 7-year period, the DOT per 1,000 patient days of carbapenem decreased by 27% from a median of 16.0 to 11.7 (P < .01). We also observed an improvement in susceptibility to meropenem from a median of 87% to 89.7% (P = .01) and to imipenem-cilastatin from 79% to 85% (P < .01). The decreases in the use of carbapenem were greater in institutions with antimicrobial stewardship programs led by pediatric infectious disease specialists.

Conclusions: Antimicrobial use and resistance, targeting carbapenems and P. aeruginosa, respectively, can serve as benchmarks that can be utilized to promote antimicrobial stewardship across pediatric healthcare institutions.
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http://dx.doi.org/10.1017/ice.2020.234DOI Listing
September 2020

Pediatric acute dacryocystitis due to Eikenella corrodens: A case report.

J Infect Chemother 2020 May 23;26(5):510-512. Epub 2020 Jan 23.

Department of General Pediatrics, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.

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.
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http://dx.doi.org/10.1016/j.jiac.2019.12.014DOI Listing
May 2020

Incidence and aetiology of serious viral infections in young febrile infants.

J Paediatr Child Health 2020 Apr 15;56(4):586-589. Epub 2019 Nov 15.

Division of Infectious Diseases, Department of Pediatrics, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.

Aim: While the incidence and aetiology of serious bacterial infections among febrile infants younger than 90 days old are well studied, those concerning viral infection are not. There are severe life-threatening viral infections requiring immediate intense therapy. The objective of the study is to describe the incidence and aetiology of serious viral infections (SVI) among young febrile infants.

Methods: A retrospective audit was performed covering all the febrile infants younger than 90 days old admitted to a paediatric emergency department in Japan from 2011 to 2013. SVI was defined as a viral illness that may result in permanent organ dysfunctions or life-threatening complications. Diagnostic investigation consisted of urine and blood culture for all infants, cerebrospinal fluid cultures for infants who do not fulfil the low-risk criteria, rapid antigen tests for several viruses in infants with specific symptoms and blood and/or cerebrospinal fluid polymerase chain reaction of possible viruses for infants with fever without a localising source.

Results: Of 275 cases, 32 and 45 cases were diagnosed as serious viral and bacterial infections, respectively. Intensive care unit admission occurred for three viral and four bacterial infections. Viral aetiology consisted of respiratory syncytial virus (11 cases), aseptic meningitis (9 cases), enterovirus (6 cases), influenza virus (3 cases), rotavirus (2 cases) and herpes simplex virus-1 (1 case). Respiratory (14 cases), central nervous (12 cases) and circulatory (6 cases) systems were affected.

Conclusion: SVI was observed in 11.6% of febrile young infants in a paediatric emergency department.
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http://dx.doi.org/10.1111/jpc.14692DOI Listing
April 2020

Ototoxicity and Nephrotoxicity With Elevated Serum Concentrations Following Vancomycin Overdose: A Retrospective Case Series.

J Pediatr Pharmacol Ther 2019 Sep-Oct;24(5):450-455

Although a high vancomycin serum concentration is known to be associated with nephrotoxicity, its association with ototoxicity is not well known. The purpose of our study was to examine the latter association in pediatric patients, especially in cases of accidental overdose. Pediatric patients who received vancomycin at our facility between March 2010 and December 2015 with a serum trough concentration > 30 mg/L were enrolled. Age, sex, neonatal hearing screening results, estimated peak vancomycin serum concentration, duration of drug exposure, renal function, and hearing test results were collected. The estimated duration of concentrations above 30 or 80 mg/L were simulated with the Sawchuk-Zaske method. We defined a "high concentration" and "toxic concentration" of vancomycin as 30 to 80 mg/L and > 80 mg/L, respectively. Ototoxicity was assessed based on the auditory brain stem response. We identified 4 females and 2 males with normal hearing at birth. Four of the 6 patients were ≤ 3 months old. All the patients reached an estimated peak serum concentration of > 80 mg/L, and 5 exceeded 150 mg/L. The estimated duration of exposure to a high concentration and toxic concentration of vancomycin was 15 to 62 hours and 8 to 43 hours, respectively. All the patients experienced transient renal dysfunction. Although transient ototoxicity was found in 1 patient, prolonged ototoxicity was not observed in any of the patients. All the patients had received an accidental overdose of vancomycin. Prolonged hearing loss due to a high vancomycin serum concentration was not found in any of the subjects in the present report.
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http://dx.doi.org/10.5863/1551-6776-24.5.450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6782114PMC
October 2019

Diagnostic errors in pediatric bacterial osteomyelitis.

Pediatr Int 2019 Oct;61(10):988-993

Division of Infectious Diseases, Department of Pediatrics, Tokyo Metropolitan Children's Medical Center, Fuchu, Tokyo, Japan.

Background: Clinical evidence for improving diagnostic accuracy in pediatric medicine is still scarce. Septic osteomyelitis is sometimes challenging for physicians to diagnose. The aim of this study was to improve patient care through identifying the incidence and reasons for errors in the diagnosis of bacterial osteomyelitis in pediatric patients.

Methods: We retrospectively identified patients younger than 16 years with acute or chronic osteomyelitis at Tokyo Metropolitan Children's Medical Center between April 2010 and September 2017. We extracted data on patient demographics, clinical course, symptoms, locus of the lesions, and diagnosis at presentation and discharge. The patients were categorized into the misdiagnosis and non-misdiagnosis groups following a review by two pediatricians. Misdiagnosis was defined as a difference between the initial and discharge diagnosis. The factors in the two groups were compared, and the types of error in the misdiagnosis group were examined.

Results: In total 71 patients were enrolled. The median age and proportion of boys was 7.6 years (IQR, 1.4-11.2 years) and 66%, respectively. Misdiagnosis occurred in 27 patients (38.0%). Precedent antibiotic use was independently associated with misdiagnosis (P = 0.044). A cognitive error was observed in 88.3% of the misdiagnosis group. The median number of types of error per case was 2.0 (IQR, 2.0-3.0).

Conclusions: The misdiagnosis of septic osteomyelitis in pediatric patients was common and chiefly caused by cognitive errors. Eliminating cognitive errors in diagnosis is highly likely to improve the care of patients with osteomyelitis.
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http://dx.doi.org/10.1111/ped.13979DOI Listing
October 2019

Nationwide survey of indications for oral antimicrobial prescription for pediatric patients from 2013 to 2016 in Japan.

J Infect Chemother 2019 Oct 22;25(10):758-763. Epub 2019 Jun 22.

Division of Infectious Diseases, Department of Medical Subspecialties, National Center for Child Health and Development, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan; Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. Electronic address:

Background: Antimicrobial resistance is a major public health concern. In 2016, the Japanese government launched a national action plan aimed at achieving a 33% and 50% reduction in the number of total and oral antimicrobial prescriptions (cephalosporins, macrolides, and quinolones) from the 2013 figures by 2020, respectively. The purpose of this study was to investigate the indications for recent antimicrobial prescriptions and to identify the primary targets for intervention to achieve the aims of the government's action plan.

Methods: Using the national health claims database, we retrospectively analyzed oral antibiotic prescriptions for Japanese children aged ≦ 15 years from 2013 to 2016. The trends were analyzed based on days of therapy (DOT) per infectious disease-related visit for each antibiotic. For patients whose chief diagnosis was an infectious disease, the number of antimicrobial prescriptions per diagnosis, their proportion, and the details of the type of antimicrobial were investigated.

Results: In total, 297,197,328 infectious disease-related visits were identified during 2013-2016. Total antimicrobial prescriptions showed a 3.7% reduction from 1.519 DOT/visitor in 2013 to 1.463 DOT/visitor in 2016 (P < 0.001). Antimicrobials were prescribed for 31.7% and 36.9% of children with upper and lower respiratory tract infection, accounting for 54.6% and 26.2% of all antimicrobial prescriptions, respectively. Third generation cephalosporins and macrolides comprised the majority of these prescriptions.

Conclusions: Antimicrobials were commonly prescribed for children with respiratory infections. Therefore, promoting appropriate antimicrobial use in this population is required to achieve the 2020 goals set by the action plan.
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http://dx.doi.org/10.1016/j.jiac.2019.03.004DOI Listing
October 2019

Trends in varicella and mumps vaccination rates in children under 3 years of age in a tertiary children's hospital in Japan.

Pediatr Int 2019 Sep;61(9):882-888

Division of Infectious Diseases, Department of Pediatrics, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.

Background: In Japan, the voluntary vaccination rate is not known accurately. Although two doses of the measles and rubella vaccines have been part of the universal vaccine program since 2006, the varicella vaccine was added in October 2014 while the mumps vaccine still remains voluntary. The aim of this study was to evaluate trends in the live measles, rubella, varicella and mumps vaccination rates in Japan.

Methods: This retrospective cohort study was conducted at Tokyo Metropolitan Children's Medical Center between October 2012 and December 2016. Patients aged 1-2 years who were admitted to the Department of General Pediatrics were enrolled. The trend in the vaccination rate against measles, rubella, varicella, and mumps was examined.

Results: The measles and rubella vaccination rate was 80-90%. The varicella vaccination rate in the second quarter of 2012, the third quarter of 2014, and the fourth quarter of 2016 was 34.6%, 67.1%, and 80.7%, respectively. The mumps vaccination rate in the second quarter of 2012, the third quarter of 2014, and the fourth quarter of 2016 was 27.6%, 59.5%, and 61.8%, respectively.

Conclusions: The varicella and mumps vaccination rate improved until 2014 despite the fact that they were voluntary vaccinations. After varicella vaccination was added to the universal vaccination program, the varicella vaccination rate continued to improve. The mumps vaccination, which was not included, failed to improve, suggesting that the universal vaccination program contributed to increasing the uptake of the vaccines it includes.
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http://dx.doi.org/10.1111/ped.13916DOI Listing
September 2019

Enterovirus D68 respiratory infection in a children's hospital in Japan in 2015.

Pediatr Int 2019 Aug 22;61(8):768-776. Epub 2019 Aug 22.

Division of Infectious Diseases, Department of Pediatrics, Tokyo Metropolitan Children's Medical Center, Fuchu, Tokyo, Japan.

Background: Outbreaks of enterovirus D68 (EV-D68) respiratory infections in children were reported globally in 2014. In Japan, there was an EV-D68 outbreak in the autumn of 2015 (September-October). The aim of this study was to compare EV-D68-specific polymerase chain reaction (PCR)-positive and EV-D68-specific PCR-negative patients.

Methods: Pediatric patients admitted for any respiratory symptoms between September and October 2015 were enrolled. Nasopharyngeal swabs were tested for multiplex respiratory virus PCR and EV-D68-specific reverse transcription-PCR. EV-D68-specific PCR-positive and -negative patients were compared regarding demographic data and clinical information.

Results: A nasopharyngeal swab was obtained from 76 of 165 patients admitted with respiratory symptoms during the study period. EV-D68 was detected in 40 samples (52.6%). Median age in the EV-D68-specific PCR-positive and -negative groups was 3.0 years (IQR, 5.5 years) and 3.0 years (IQR, 4.0 years), respectively. The rates of coinfection in the two groups were 32.5% and 47.2%, respectively. There was no significant difference in the history of asthma or recurrent wheezing, length of hospitalization, or pediatric intensive care unit admission rate between the groups. The median days between symptom onset and admission was significantly lower for the EV-D68-positive group (3.0 days vs 5.0 days, P = 0.001). EV-D68 was identified as clade B on phylogenetic analysis. No cases of acute flaccid myelitis were encountered.

Conclusions: More than half of the samples from the children admitted with respiratory symptoms were positive for EV-D68-specific PCR during the outbreak. Asthma history was not associated with the risk of developing severe respiratory infection.
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http://dx.doi.org/10.1111/ped.13903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167638PMC
August 2019

Cefmetazole for extended-spectrum β-lactamase-producing Enterobacteriaceae in pediatric pyelonephritis.

Pediatr Int 2019 Jun 11;61(6):572-577. Epub 2019 Jun 11.

Division of Infectious Diseases, Department of Pediatrics, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.

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.
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http://dx.doi.org/10.1111/ped.13847DOI Listing
June 2019

White chalky dermatitis in a very preterm neonate with fungal skin infection.

Arch Dis Child Fetal Neonatal Ed 2019 Jul 22;104(4):F383. Epub 2019 Feb 22.

Division of Neonatology, Tokyo Metroplitan Children's Medical Center, Fuchu, Tokyo, Japan.

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http://dx.doi.org/10.1136/archdischild-2018-316451DOI Listing
July 2019

Caterpillar Sign in an Infant with Hypertrophic Pyloric Stenosis.

J Pediatr 2019 May 2;208:292. Epub 2019 Feb 2.

Department of General Pediatrics, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.

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http://dx.doi.org/10.1016/j.jpeds.2018.12.058DOI Listing
May 2019

Multidrug-resistant Gram-negative Bacterial Bloodstream Infections in Children's Hospitals in Japan, 2010-2017.

Pediatr Infect Dis J 2019 07;38(7):653-659

From the Division of Infectious Diseases, Department of Pediatrics, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.

Background: The risk factors of multidrug-resistant (MDR) Gram-negative bacilli (GNB) bloodstream infection (BSI) are not yet known in children. Our aim was to evaluate risk factors and outcomes associated with MDR GNB BSI in children.

Methods: Patients with GNB BSI were enrolled between April 2010 and March 2017 at 8 children's hospitals in Japan. Clinical and microbiologic data were collected retrospectively. The risk factors and outcomes of MDR and non-MDR GNB BSI were compared.

Results: In total, 629 GNB BSI episodes met the case definition. The median age and proportion of males were 2 years (interquartile range, 0.3-8.7) and 50.7%, respectively. An underlying disease was found in 94% of patients. The proportion of BSI cases that developed >48 hours after admission was 76.2%. MDR comprised 24.5% of BSI cases. The MDR rate did not change over time (P = 0.540). The effective coverage rate of the initial empiric therapy for the MDR and non-MDR BSI cases was 60.4% and 83.4%, respectively (P < 0.001). The all-cause mortality rate at 28 days for all BSI, MDR-BSI and non-MDR BSI cases was 10.7%, 13.6% and 9.7%, respectively (P = 0.167). MDR BSI was independently associated with cancer chemotherapy within 30 days (odds ratio [OR] 43.90), older age (OR 1.05) and admission to the neonatal ward (OR 0.019).

Conclusions: One-fourth of GNB BSI cases were MDR. Cancer chemotherapy and older age were risk factors for MDR GNB BSI in children's hospitals. MDR did not increase the all-cause mortality rate.
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http://dx.doi.org/10.1097/INF.0000000000002273DOI Listing
July 2019

First report on USA300 outbreak in a neonatal intensive care unit detected by polymerase chain reaction-based open reading frame typing in Japan.

J Infect Chemother 2019 May 28;25(5):400-403. Epub 2018 Dec 28.

Department of Infection Control Science, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; Infection Control Science Research Center, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.

Outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) in the neonatal intensive care unit (NICU) have been reported worldwide. Some outbreaks were caused by USA300, which is a community-associated MRSA clone. In 2011, polymerase chain reaction-based open reading frame typing (POT) for the initial MRSA isolates from all inpatients was started at the Tokyo Metropolitan Children's Medical Center. From March 2014 to April 2015, a total of 131 MRSA strains were isolated, 104 of which were analyzed as healthcare-associated MRSA. Thirteen stains (12.5%) had a POT number of 106-9-93, which strongly suggested USA300; these included 6 from nasal swabs, 6 from blood cultures and 1 from subcutaneous pus. All the MRSA strains were isolated from patients in the NICU; were typed as sequence type 8, spa type t008, and staphylococcal cassette chromosome type mec IVa; and possessed the lukS-lukF and arginine catabolic mobile element-arcA gene. Pulsed-field gel electrophoresis of all the strains, with USA300-0114 as a reference, showed indistinguishable banding pattern. Based on these results, POT was useful in recognizing this first MRSA outbreak of USA300 in a Japanese NICU and was advantageous in terms of swiftness, less cost and monitoring change of the epidemic MRSA lineage.
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http://dx.doi.org/10.1016/j.jiac.2018.12.002DOI Listing
May 2019

A metallo-beta-lactamase producing Enterobacteriaceae outbreak from a contaminated tea dispenser at a children's hospital in Japan.

Infect Control Hosp Epidemiol 2018 Dec 27:1-4. Epub 2018 Dec 27.

1Division of Infectious Diseases,Department of Pediatrics,Tokyo Metropolitan Children's Medical Center,Fuchu,Tokyo,Japan.

An outbreak of metallo-β-lactamase (MBL) producing Klebsiella pneumoniae occurred at a children's hospital in Japan. MBL-producing K. pneumoniae was detected in tea dispenser in the hospital, the use of which was associated with the acquisition of the MBL-producing Enterobacteriaceae. The outbreak ceased after use of the tea dispenser was banned.
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http://dx.doi.org/10.1017/ice.2018.331DOI Listing
December 2018

Targets for Optimizing Oral Antibiotic Prescriptions for Pediatric Outpatients in Japan.

Jpn J Infect Dis 2019 May 25;72(3):149-159. Epub 2018 Dec 25.

Division of Infectious Diseases, Department of Medical Subspecialties, Research Institute, National Center for Child Health and Development.

In Japan, 92.6% of antibiotics consumed are oral agents; most of these are for outpatients. A significant proportion is known to be dispensed for children; however, the specific pattern of antibiotic prescription in accordance with clinical specialty is still unclear. The aim of our study was to identify the key targets for the optimization of oral antibiotic use in children. We analyzed data on oral antimicrobial prescription patterns for children < 16 years old of age in 3 urban districts by using a national database in Japan. Oral prescriptions were categorized according to their class, spectrum, clinical specialty, and type of clinical setting. The antibiotic spectrum was categorized as narrow, broad, or ultra-broad. In total, 132,869,332 antibiotic prescriptions were collected for analysis. The proportions of narrow-spectrum, broad-spectrum, and ultra-broad-spectrum antibiotics were 10.9%, 73.7%, and 15.4% in primary care clinics and 23.4%, 71.1%, and 5.4% in hospitals, respectively. Prescriptions from pediatricians and otolaryngologists in primary care clinics were predominant in the 3 studied areas. Third-generation cephalosporins, quinolones, penems, and carbapenems were prescribed mostly by pediatricians and otolaryngologists. Ultra-broad spectrum antibiotics used in primary care clinics and antibiotics particular to each specialty were identified as key targets for the optimization of oral antibiotic use for pediatric outpatients.
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http://dx.doi.org/10.7883/yoken.JJID.2018.374DOI Listing
May 2019

Comparison of USA300 with non-USA300 methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit.

Int J Infect Dis 2019 Feb 29;79:134-138. Epub 2018 Nov 29.

Division of Infectious Diseases, Department of Pediatrics, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.

Objectives: Reports of USA300 methicillin-resistant Staphylococcus aureus (MRSA) strain were still scarce in neonatal intensive care units (NICUs) and the relationship of USA300 MRSA to clinical infections is still controversial. The primary outcome was the incidence of MRSA infections caused by the USA300 and non-USA300 strains at a NICU in Japan.

Methods: This retrospective cohort study was conducted between November 2011 and October 2016 at Tokyo Metropolitan Children's Medical Center in Japan. All MRSA isolated after 48h of hospitalization were included for analysis by pulsed-field gel electrophoresis (PFGE) using the standard USA300 strain. Genes were tested for Panton-Valentine leukocidin (PVL) and arginine catabolic mobile element (ACME). A whole genome sequence was performed for representative isolates of USA300.

Results: In total, 109 MRSA isolates were included for analysis. PFGE classified 34 and 75 isolates of USA300 and non-USA300 MRSA, respectively. Both PVL and ACME genes were detected in USA300 and non-USA300 strains at rate of 100% (34/34) and 5.3% (4/75), respectively (P<0.05). There was no statistically significant difference in the proportion of clinical diseases between USA- 300 and non-USA 300 strains.

Conclusions: Infants with USA300 MRSA infection did not differ significantly from those with non-USA300 MRSA infection.
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http://dx.doi.org/10.1016/j.ijid.2018.11.020DOI Listing
February 2019

Nationwide study of outpatient oral antimicrobial utilization patterns for children in Japan (2013-2016).

J Infect Chemother 2019 Jan 2;25(1):22-27. Epub 2018 Nov 2.

Division of Infectious Diseases, Department of Medical Subspecialties, National Center for Child Health and Development, Tokyo, Japan; Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, USA. Electronic address:

Background: Antimicrobial resistance (AMR) is a major multinational public health concern. The Japanese government set goals in its AMR action plan to reduce use of oral cephalosporins, macrolides, and quinolones by half between 2013 and 2020. We aimed to evaluate antimicrobial use in children in Japan by observing prescription patterns as an interim assessment of the national AMR action plan.

Methods: Using the national health claims database, we retrospectively analyzed all oral antimicrobials dispensed from outpatient pharmacies in Japan to children under 15 years old from 2013 to 2016 by age, prefecture, type of antimicrobial, and year. Data were presented as days of therapy (DOTs) per 1000 pediatric inhabitants per day (DOTs/PID). The χ test for trends was performed to evaluate annual changes in DOTs/PID overall as well as within each stratum.

Results: A total of 721,627,553 oral antimicrobial DOTs were identified during 2013-2016. No statistically significant changes were observed in total antimicrobial use in children (2013: 28.54 DOTs/PID; 2016: 28.70 DOTs/PID; P = 0.25) and amount of cephalosporins, macrolides, and quinolones prescribed. Prescription rates of all antimicrobials were highest among children 1-5 years old, peaking at 1 year old. Targeted antimicrobials for the AMR action plan showed similar distribution by age.

Conclusion: The amount of antimicrobials prescribed to children in Japan is not decreasing. Overall antimicrobial prescriptions, as well as prescriptions of cephalosporins, macrolides, and quinolones, were most prevalent in children ≤5 years old. Rigorous antimicrobial stewardship interventions targeting infants and younger children are necessary.
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http://dx.doi.org/10.1016/j.jiac.2018.10.002DOI Listing
January 2019

Nuchal Rigidity in Infantile Bacterial Meningitis.

J Pediatr 2019 Apr 30;207:255. Epub 2018 Oct 30.

Department of General Pediatrics Tokyo Metropolitan Children's Medical Center Tokyo, Japan.

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http://dx.doi.org/10.1016/j.jpeds.2018.10.008DOI Listing
April 2019

Hamman's Sign in a Patient with Spontaneous Pneumomediastinum.

J Pediatr 2018 11 14;202:324. Epub 2018 Jul 14.

Department of General Pediatrics Tokyo Metropolitan Children's Medical Center Tokyo, Japan.

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http://dx.doi.org/10.1016/j.jpeds.2018.06.030DOI Listing
November 2018

Chronic otitis media caused by Mycobacterium abscessus spp. massiliense treated with tigecycline in a 10-year-old child.

Int J Infect Dis 2018 Sep 30;74:10-12. Epub 2018 Jun 30.

Division of Infectious Diseases, Department of Pediatrics, Tokyo Metropolitan Children's Medical Center, 2-8-29, Musashidai, Fuchu, Tokyo, 183-8561, Japan. Electronic address:

Mycobacterium abscessus is one of the most pathogenic and chemotherapy-resistant rapidly growing mycobacteria. This Mycobacterium should always be considered as a possible cause of chronic otitis media in children, and treatment might be challenging because of its resistance to multiple antibiotics. There are no reports describing the therapeutic use of tigecycline for the treatment of chronic otitis media caused by M. abscessus. A 10-year-old boy was referred to Tokyo Metropolitan Children's Medical Center with a 7-year history of recurrent otitis media despite treatment with antibiotics and ventilation tubes. Cultures of the otorrhea yielded Mycobacterium abscessus spp. massiliense, and it showed multiple and high-level resistance. The boy required surgery and underwent initial treatment with clarithromycin, amikacin, and tigecycline for 4 weeks. He experienced emesis as a side-effect of tigecycline, which was well controlled with ondansetron. He was treated successfully with 3 months of subsequent oral clarithromycin and linezolid. This is the first pediatric case of chronic otitis media caused by M. abscessus treated with a tigecycline-containing regimen. Although the therapeutic use of tigecycline remains controversial, especially in the pediatric population, it can be an acceptable option in the treatment of chronic otitis media caused by M. abscessus.
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http://dx.doi.org/10.1016/j.ijid.2018.06.019DOI Listing
September 2018

Longer Duration of Urinary Catheterization Increases Catheter-Associated Urinary Tract Infection in PICU.

Pediatr Crit Care Med 2018 10;19(10):e547-e550

Division of Infectious Diseases, Department of Pediatrics, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.

Objectives: Catheter-associated urinary tract infections account for 30% of healthcare-associated infections. To date, few studies have addressed pediatric catheter-associated urinary tract infection in PICUs. The aim of our study was to assess the risk of catheter-associated urinary tract infection in relation to the duration of catheterization in the PICU.

Design: Retrospective cohort study.

Setting: PICU at a tertiary children's hospital.

Patients: Our study was conducted between April 2012 and June 2015 at Tokyo Metropolitan Children's Medical Center in Japan. Children in the PICU with an urethral catheter were included. Catheter-associated urinary tract infection cases were defined according to the National Healthcare Safety Network criteria. The patients' demographic data and isolated organisms were reviewed. Duration of catheterization and the catheter-associated urinary tract infection occurrence rate were analyzed.

Interventions: None.

Measurements And Main Results: Among 1,890 catheterizations, 23 catheter-associated urinary tract infection cases were identified. The overall occurrence rate was 2.35/1,000 catheter-days. Among the patients with catheter-associated urinary tract infection, 13 were boys. The median age was 11 months (interquartile range, 7-35 mo), and the median duration of catheterization was 7 days (interquartile range, 5-12 d). The isolated bacteria were Escherichia coli (26.5%), Enterococcus faecalis (17.6%), and Klebsiella pneumoniae (11.8%). Two species were isolated in each of 11 cases (47.8%). Each additional day of catheterization increased the risk of catheter-associated urinary tract infection (odds ratio, 1.06; 95% CI, 1.02-1.10, and odds ratio adjusted for contact precaution status and surgical procedures was 1.05; 95% CI, 1.01-1.09).

Conclusions: Longer duration of catheterization increased the risk of catheter-associated urinary tract infection by 5% each day at the PICU. Prompt removal of the urethral catheter is strongly recommended whenever feasible.
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http://dx.doi.org/10.1097/PCC.0000000000001628DOI Listing
October 2018

Antimicrobial Stewardship Program in a Pediatric Intensive Care Unit.

J Pediatric Infect Dis Soc 2018 Aug;7(3):e156-e159

Division of Infectious Diseases, Department of Pediatrics, Tokyo Metropolitan Children's Medical Center, Japan.

We conducted an antimicrobial stewardship program in a pediatric intensive care unit. An interrupted time-series analysis revealed a significant reduction in level and trend of days of therapy per 1000 patient-days for antipseudomonal agents. No increase in adverse patient outcomes was found.
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http://dx.doi.org/10.1093/jpids/piy031DOI Listing
August 2018