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Introduction: Information on the clinical utility of daptomycin in patients with persistent bacteremia and daptomycin's pharmacokinetic data in pediatric patients has been sparse. In addition, reports on the experience of using daptomycin in children undergoing solid organ transplantation have been extremely limited. The authors describe a pediatric case of persistent bacteremia after solid organ transplantation successfully treated by daptomycin. Blood daptomycin concentrations were measured by liquid chromatography-mass spectrometry and pharmacokinetic analysis was performed. We also conducted a literature review on the use of daptomycin in children with persistent bacteremia., Case Report: An eight-year-old girl who underwent small bowel and liver transplantation experienced persistent bacteremia due to Staphylococcus epidermidis. The bacteremia persisted despite standard therapy; however, it finally resolved with the addition of daptomycin. The patient had renal dysfunction and the initial dosing resulted in excessive drug exposure. The dosage was adjusted based on the pharmacokinetic analysis. The dosage of administrated teicoplanin was also adjusted according to trough concentration values. In the literature review, we identified 12 cases of neonates and 24 cases of post-neonatal children with the experience of using daptomycin for persistent bacteremia; however, no solid organ transplant recipient was identified. Similar trends in blood concentrations and dose ratios of teicoplanin and daptomycin were observed over time., Discussion: More information is required regarding the clinical utility and pharmacokinetics of daptomycin in pediatric patients with persistent bacteremia. Referring to the exposure to renally excreted drugs that are routinely measured and pharmacokinetic analysis of daptomycin may be useful in optimizing the dose of daptomycin in special patient populations, including those with renal impairment., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Data on the safety and antibody response of the BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in children aged 5-11 years with underlying diseases are limited. Thus, our study aimed to address this gap., Methods: This prospective observational study investigated the antibody titers for SARS-CoV-2 spike protein receptor-binding domain (S-IgG) and nucleocapsid protein (N-IgG) in patients aged 5-11 years with chronic underlying diseases following two doses of BNT162b2. Additionally, a questionnaire was used to assess adverse events (AEs) arising within 7 days after each dose. Data on severe AEs arising within 28 days after each dose were extracted from the patients' electronic medical records., Results: Among 122 patients, 24.6% (30/122) were immunocompromised. Furthermore, 79 patients experienced at least one AE following vaccination, but all recovered without sequelae, including one severe case after the first dose. The seropositivity rate after the second dose was 99.1% (116/117). Excluding 19 N-IgG-positive patients, the geometric mean antibody titer (GMT) was significantly higher in immunocompetent patients than in immunocompromised patients (1496 U/mL [95% confidence interval 1199-1862] vs. 472 U/mL [200-1119], p = 0.035). Additionally, the GMT of S-IgG was higher in N-IgG-positive patients than in N-IgG-negative patients (8203 [5847-11482] U/mL vs. 1127 [855-1486] U/mL, p < 0.001)., Conclusions: BNT162b2 is acceptably safe and immunogenic for children aged 5-11 years with underlying diseases. Although seroconversion was satisfactory in immunocompromised patients, the titers were lower than in immunocompetent patients., Competing Interests: Declaration of competing interest K. Shoji received payment for lectures from bioMérieux Japan, Gilead Sciences, Inc., Viatris, Inc., and Moderna Japan Co., Ltd. C. Ogimi received payment for lectures from Pfizer, AstraZeneca, and bioMérieux Japan. I. Miyairi received payment for lectures from bioMérieux Japan, Gilead Sciences, Inc., Pfizer, AstraZeneca, Sanofi, and Shionogi Pharmaceuticals. All other authors declare that they do not have any potential, perceived, or real conflicts of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: COVID-19 has become widespread in Japanese children. However, the impact of varying immunization coverage on the seroprevalence of SARS-CoV-2 in children is unknown., Methods: We examined the SARS-CoV-2 antibody in children aged 0 to 18 who were hospitalized at a university hospital from June 2020 through May 2023. The SARS-CoV-2 anti-nucleoprotein (N) antibody and anti-RBD spike (S) protein antibody was measured., Results: A total of 586 cases were enrolled. The median age was 4 years old (interquartile range 1-9), and 362 (61.8 %) were male. The seroprevalence of anti-S antibodies gradually increased from October 2021 and reached 60 percent by early 2023. The anti-N antibody increased starting in January 2022 and reached 50 percent in May 2023. There was a discrepancy in the seroprevalence of anti-S and N antibodies in children 0 years of age or 12 years and older until the fall of 2022. This discrepancy was minimal for children 1-4 years of age and relatively small in the 5-11-year-old group., Discussion: The data suggests that approximately half of the children in our cohort had been infected with SARS-CoV-2 by May 2023. The discrepancy in seropositivity between the anti-S and N antibodies corresponded to the reported vaccine uptake of each target age group, which suggested protective effects of immunization. However, this effect appeared to diminish after early 2023., Conclusion: Age dependent discrepancy between SARS-CoV-2 anti-N and anti-S antibody in children reflected differences in vaccine coverage., Competing Interests: Declaration of competing interest IM has received honoraria for lectures from; Pfizer, AstraZeneca, Shionogi, Meiji Seika Pharma, Daiichi-sankyo, Biken, Takeda pharmaceuticals, and Sanofi. The other authors have no conflict of interest to declare., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Introduction: Antimicrobial resistance is a global issue, and implementation of antimicrobial stewardship programs in outpatient settings is crucial. Japan has also focused on outpatient oral antimicrobial stewardship programs and difficulties in standardizing prescriptions have led to overprescription in primary emergency medical centers. There is a lack of research investigating the antibiotic prescription status of pediatric primary emergency medical centers and the benchmark prescription rates in pediatric outpatient settings., Methods: We conducted a multi-center, cross-sectional study of seven pediatric primary emergency medical centers located in five prefectures of Japan. We retrospectively extracted data from health claims or directly obtained them from charts at each institution and evaluated trends in the antibiotic prescription rate based on the AWaRe classification between April 2016 and December 2019., Results: Our study included 383,525 encounters, with the most common infectious disease diagnosis being acute upper respiratory tract infection in 93,449 cases (24.4 %). The antibiotic prescription rate during the study period was 7.4 %, representing a decrease of 46 %, from 10.2 % in 2016 to 5.5 % in 2019. The percentage of prescriptions in the Access group increased at all institutions; however, it exceeded 60 % in only three facilities in 2019. The percentage of third-generation cephalosporins varied among facilities, ranging from 1.7 % to 59.4 %, as of 2019., Conclusions: For pediatric primary emergency medical centers where antimicrobial stewardship programs are implemented, we suggest 5 % as a reasonable benchmark level for the antibiotic prescription rate. Prescribing the antibiotics in the Access groups less frequently remains a domestic challenge in Japan., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest to disclose. Informed Consent and Ethical Approval. We obtained opt-out consent from the patients' parents. This study was approved by the institutional ethics committees of Kobe Children's Hospital (Approval Number 2021–61)., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: The COVID-19 pandemic posed substantial challenges to healthcare systems. Understanding the responses of pediatric health services is crucial for future pandemic planning and preparedness, yet such data remains limited., Methods: In this retrospective cohort study, we analyzed data from administrative databases developed by Japan Medical Data Center and DeSC Healthcare Inc. The dataset comprised records of 2,612,511 children, totaling 60,224,888 person-months, from January 2020 to May 2022. Multivariate generalized estimation equations were used to examine the incidence rates of COVID-19 and associated health resource use., Results: Our analysis revealed that the incidence rates of COVID-19 gradually increased from Wave I (2.2 cases per 100,000 person-months) to Wave V (177.8cases per 100,000 person-months), with a notable elevation during Wave VI (2367.7 cases per 100,000 person-months). While nucleic acid amplification tests were primarily used during Waves I-V, the use of rapid antigen tests markedly increased in Wave VI. The hospitalization rates increased gradually from 0.2 in Wave I to 10.2 events per 100,000 person-months in Wave VI, and the case-hospitalization risk decreased from 14.9% in Wave II to 0.7% in Wave VI. Additionally, we observed decreasing trends in the use of antibiotics (Wave I, 31.8%; Wave VI, 9.0%), whereas antipyretic use rose from Wave I (56.1%) to Wave VI (86.6%)., Conclusions: Our study highlighted essential changes in the nationwide pediatric healthcare system's response to the COVID-19 pandemic. These findings provide valuable insights into the future pandemic planning and preparedness., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Voriconazole pharmacokinetics (PK) are known to be affected by genetic polymorphisms of drug-metabolizing enzymes such as CYP2C19; however, such information is limited for the pediatric population. The primary aim of this study is to establish a voriconazole PK model incorporating CYP2C19 phenotypes in Japanese children with malignancy or inborn errors of immunity., Methods: CYP2C19 genotypes were assessed by whole-genome genotyping and defined as follows: *17/*17: ultrarapid metabolizer (URM), *1/*17: rapid metabolizer (RM), *1/*1:normal metabolizer (NM), *1/*2, *1/*3, *2/*17:intermediate metabolizer (IM), and *2/*2, *2/*3, *3/*3: poor metabolizer (PM). Population PK analysis was performed. The voriconazole serum concentration profile was described by a two-compartment model with first-order absorption, mixed linear and nonlinear (Michaelis-Menten) elimination., Results: Voriconazole concentration data were available from 60 patients with a median age of 5.3 years. The phenotypes predicted from CYP2C19 genotypes were RM in 1 (2 %), NM in 21 (35 %) patients, IM in 27 (45 %) patients, and PM in 11 (18 %) patients. Underlying diseases included 38 (63%) patients with hematological malignancy and 18 (30 %) patients with inborn errors of immunity. Among the CYP2C19 phenotypes, PM was predicted to show complete inhibition (the degree of V max inhibition [V max, inh ] = 100 %; V max  = 0). The estimated parameters of V max,inh were +0.8 higher in patients with gamma-glutamyl transpeptidase (γ-GTP) Grade 2 or higher and +2.7 higher when C-reactive protein (CRP) levels were 2.0 mg/dL or higher., Conclusion: CYP2C19 genetic polymorphisms, γ-GTP, and CRP affect V max,inh of voriconazole in children with malignancy or inborn errors of immunity., Competing Interests: Declaration of competing interest KS received honoraria for lectures from Viatris, Inc. IM and MK received honoraria from Pfizer for lectures. All the other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Introduction: The melting temperature (T m ) mapping method (TM) identifies bacterial species by intrinsic patterns of T m values in the 16S ribosomal RNA gene (16S rDNA) extracted directly from whole blood. We examined potential clinical application of TM in children with bloodstream infection (BSI)., Methods: This was a prospective observational study at a children's hospital in Japan from 2018 to 2021. In patients with diagnosed or suspected BSI, we investigated the match rates of pathogenic bacteria identified by TM and blood culture (BC), the inspection time to identification of TM, and the amount of bacterial DNA in blood samples., Results: The median age of 81 patients (93 samples) was 3.6 years. Of 23 samples identified by TM, 11 samples matched the bacterial species with BC (positive-match rate, 48 %). Of 64 TM-negative samples, 62 samples were negative for BC (negative-match rate, 97 %). Six samples, including one containing two pathogenic bacterial species, were not suitable for TM identification. In total, the matched samples were 73 of 93 samples (match rate, 78 %). There were seven samples identified by TM in BC-negative samples from blood collected after antibiotic therapy. Interestingly, the bacteria were matched with BC before antibiotic administration. These TM samples contained as many 16S rDNA copies as the BC-positive samples. The median inspection time to identification using TM was 4.7 h., Conclusions: In children with BSI, TM had high negative-match rates with BC, the potential to identify the pathogenic bacteria even in patients on antibiotic therapy, and more rapid identification compared to BC., Registering Clinical Trials: UMIN000041359https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr&#95;view.cgi?recptno=R000047220., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: The coronavirus disease-2019 (COVID-19) pandemic presented an unprecedented challenge to societies, necessitating adaptations in infection prevention measures. While there is ample data on infection prevention practices in workplace and healthcare settings, comprehensive data specific to childcare facilities has been lacking., Methods: We conducted a nationwide web-based survey capturing responses from various childcare facilities (N = 549). This aimed to understand the adaptation in infection prevention measures between fiscal years 2022 and 2023, the status of events and activities, and the factors influencing decision-making related to infection prevention., Results: From 2022 to 2023, most childcare facilities reduced infection prevention practices like mandatory mask-wearing (46.9 %-7.5 %) and eating without conversing (56.5 %-7.4 %), whereas they continued high levels of hand sanitization and checking child's health condition before attendance. The frequency of events and activities (e.g., athletic meets, field trips) increased, with many being held without restrictions. Surprisingly, 62.8 % of facilities used items not recommended for infection prevention. The influence of local government guidelines (risk ratio, 0.69; 95%CI, 0.53-0.90) and the input from junior teachers (risk ratio, 0.85; 95%CI, 0.72-0.99) were associated with reduced risk of using inappropriate items. Furthermore, childcare facilities emphasized the need to collaborate with public health and medical professionals for more accurate and efficient decision-making during pandemics., Conclusions: The survey provides insights into the evolving practices of Japanese childcare facilities during the COVID-19 pandemic. It underscores the importance of refining information sources, enhancing decision-making processes, and fostering collaboration with the medical community for future pandemics and natural disasters., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

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])., Competing Interests: Declaration of competing interest KS received honoraria from Viatris Inc. All other coauthors do not have any conflicts of interests to disclose directly related to the study., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

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)., Competing Interests: Declaration of competing interest K. Shoji received payment for lectures from bioMérieux Japan, Nippon Becton Dickinson Company, Ltd., Viatris, Inc., Meiji Seika Pharma Co., Ltd., AstraZeneca K.K., Novartis Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., and Gilead Sciences, Inc. S. Tsuzuki received payment for supervising medical articles from Gilead Sciences, Inc. I. Miyairi received payment for lectures from Astellas Pharma, Sanofi K.K., Pfizer, Inc., Takeda Pharmaceutical Company, Ltd., Biken Group, Shionogi & Company, Ltd., bioMérieux Japan, and Gilead Sciences, Inc. The other authors declare that they do not have any conflicts of interests directly associated with the study., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Introduction: Shiga toxin-producing Escherichia coli (STEC) causes hemorrhagic colitis and hemolytic uremic syndrome (STEC-HUS). Understanding its prognostic factors is essential for immediate interventions. We examined early-phase unfavorable prognostic factors among patients with STEC-HUS using a nationwide database., Material and Methods: This is a retrospective cohort study to analyze practice patterns and identify prognostic factors among patients with STEC-HUS. We used the Diagnosis Procedure Combination Database, which includes approximately half of the acute-care hospitalized patients in Japan. We enrolled patients who were hospitalized for STEC-HUS from July 2010 to March 2020. The composite unfavorable outcome included in-hospital death, mechanical ventilation, dialysis, and rehabilitation at discharge. Unfavorable prognostic factors were assessed using a multivariable logistic regression model., Results: We included 615 patients with STEC-HUS (median age, 7 years). Of them, 30 (4.9%) patients had acute encephalopathy and 24 (3.9%) died within 3 months of admission. Unfavorable composite outcome was observed in 124 (20.2%) patients. Significant unfavorable prognostic factors were age of 18 years or older, methylprednisolone pulse therapy, antiepileptic drug administration, and respiratory support within 2 days of admission., Discussion: Patients requiring early steroid pulse therapy, antiepileptic drugs, and respiratory support were considered to be in poor general condition; such patients should receive aggressive intervention to avoid worse outcomes., Competing Interests: Conflicts of interest All authors declare that they do not have any conflicts of interests directly associated with the study., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Information regarding effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant strains on clinical manifestations and outcomes of coronavirus disease 2019 (COVID-19) in pregnant women is limited., Methods: A retrospective observational study was conducted using the data from the nationwide COVID-19 registry in Japan. We identified pregnant patients with symptomatic COVID-19 hospitalized during the study period. The Delta and Omicron variants of concern (VOC) predominant periods were defined as August 1 to December 31, 2021 and January 1 to May 31, 2022, respectively. Clinical characteristics were compared between the patients in the Delta and Omicron VOC periods. In addition, logistic regression analysis was performed to identify risk factors for developing moderate-to-severe COVID-19., Results: During the study period, 310 symptomatic COVID-19 cases of pregnant women were identified; 111 and 199 patients were hospitalized during the Delta and Omicron VOC periods, respectively. Runny nose and sore throat were more common, and fatigue, dysgeusia, and olfactory dysfunction were less common manifestations observed in the Omicron VOC period. In the multivariable logistic regression analysis, onset during the later stage of pregnancy (OR: 2.08 [1.24-3.71]) and onset during the Delta VOC period (OR: 2.25 [1.08-4.90]) were independently associated with moderate-to-severe COVID-19, whereas two doses of SARS-CoV-2 vaccine were protective against developing moderate-to-severe COVID-19 (OR: 0.34 [0.13-0.84])., Conclusions: Clinical manifestations of COVID-19 in pregnant women differed between the Delta and Omicron VOC periods. SARS-CoV-2 vaccination was still effective in preventing severe COVID-19 throughout the Delta and Omicron VOC periods., Competing Interests: Declaration of competing interest K. Shoji received payment for lectures from Mitsubishi Tanabe Pharma, Astellas, AbbVie GK, Biomerieux Japan, Nippon Becton Dickinson Company, Ltd., VIATRIS and Gilead. S. Tsuzuki received payment for supervising medical articles from Gilead Sciences, Inc. The other authors declare that they do not have any conflicts of interests directly associated with the study., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Data are limited regarding the safety of and antibody response to the BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger ribonucleic acid vaccine in adolescents and young adults with underlying disease., Methods: This prospective observational study enrolled patients age 12-25 years with chronic underlying disease who received 2 doses of BNT162b2. A 18-item questionnaire was used to assess adverse events within 7 days post-vaccination, and data regarding severe adverse events were collected from electronic medical records. An antibody titer for the receptor-binding domain of the spike protein in SARS-CoV-2 was used to assess antibody response after the second vaccine dose., Results: Study participants were 429 patients (241 [56.2%] age 12-15 years; 188 [43.8%] age 16-25 years). The most common underlying diseases were genetic or chromosomal abnormalities and/or congenital anomalies, followed by endocrine or metabolic diseases; 32% of participants were immunocompromised. Severe adverse events were observed after the second dose in 1 (0.4%) patient age 12-15 years and in 2 (1.1%) patients age 16-25 years; all patients recovered. Seropositivity after the second vaccine dose was 99.0%. The geometric mean antibody titer was higher in patients age 12-15 years versus 16-25 years (1603.3 [1321.8-1944.7] U/mL vs. 949.4 [744.2-1211.0] U/mL). Compared with immunocompetent patients, immunocompromised patients had a lower antibody titer (2106.8 [1917.5-2314.7] U/mL vs. 467.9 [324.4-674.8] U/mL)., Conclusions: Vaccination with BNT162b2 was acceptably safe and immunogenic for adolescents and young adults with underlying disease., Competing Interests: Declaration of competing interest K. Shoji received payment for lectures from Biomelieux Japan, Gilead and VIATRIS. All the other authors have indicated they have no conflict of interests directly associated with this work., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Clinical characteristics of bacteremic urinary tract infection due to third-generation cephalosporin-resistant Escherichia coli in children remain unclear. We conducted a case control study comparing the clinical information of the third-generation cephalosporin-susceptible group (S-E. coli group) and the third-generation cephalosporin-resistant group (R-E. coli group). The R-E. coli group included extended-spectrum beta-lactamases (ESBLs) or AmpC-producing E. coli. We identified 52 cases of bacteremic UTI due to E. coli; 42 cases were in the S-E. coli group and 10 cases were in the R-E. coli group. Empiric antibiotics were more likely to be inappropriate for pediatric patients with bacteremic urinary tract infection due to third-generation cephalosporin-resistant E. coli than those infected by susceptible E. coli (60% vs. 0%, P < 0.001). However, duration of fever and rate of relapse were not significantly different. The outcomes of bacteremic UTI due to multidrug-resistant E. coli in children were satisfactory regardless of susceptibility to empiric antibiotics., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: In 2016, the Japanese government set the National Action Plan on antimicrobial resistance to reduce antibiotic prescriptions. However, the trends and variations of antibiotic prescription patterns in a routine healthcare setting during the fiscal year 2013-2018 across different clinics at a national level are unclear., Methods: This retrospective cohort study included all clinics with >100 pediatric outpatients with infectious diseases per month during the fiscal year 2013-2018 using a national database in Japan. We investigated the trends in antibiotic prescription rates and their patterns and variations across different clinics over the six years following the 2019 World Health Organization Access, Watch, Reserve antibiotic groups, and Amoxicillin Index., Results: A total of 2278 clinics with 94,414,170 infectious disease-related visits were eligible for the study. Most clinics showed higher Watch percentages (median 85.4%; IQR, 68.5-95.1) than Access percentages (median, 13.8%; IQR, 4.2-30.7) and Amoxicillin Index (median, 13.3%; IQR, 3.9-30.4). The introduction of the Action Plan changed annual absolute reductions in the antibiotic prescription rates from -16.0 DOTs/1000 visitors (95%CI, -16.4-15.6) to -239.3 per 1000 visitors (95%CI, -240.0-238.6). However, these impacts were heterogeneous across clinics. From 2013 to 2018, 41.4% reduced the antibiotic prescription rates by >33.3% (median, -1035.5 DOTs/1000 visitors; IQR, -1519.4-680.2), 18.7% did not change the rates (median, -40.3 DOTs/1000 visitors; IQR, -168.4-68.6), and 7.3% increased the rates by >10% (499.5 DOTs per 1000 visitors; IQR, 232.6-837.5)., Conclusions: We observed the National Action Plan's impacts and extensive prescription variations across different pediatric clinics. However, one-fourth of clinics did not improve antibiotic prescription patterns even after introducing the Action Plan., (Copyright © 2021. Published by Elsevier Ltd.)

Competing Interests: Declaration of Competing Interest Soichi Arakawa received a lecture fee from Taisho Toyama Pharmaceutical Co., Ltd. Ryoichi Hamasuna received a lecture fee from Daiichi Sankyo Co., Ltd., research funds from EIDIA Co., Ltd. Hiroshi Kiyota received donations from Daiichi Sankyo Co., Ltd., Toyama Pharmaceutical Co., Ltd., Astellas Pharm Inc., Sanofi K.K., Taisho Toyama Pharmaceutical Co. Ltd. and Taiho Pharmaceutical Co. Ltd. Satoshi Takahashi received donations from Shino-Test Co. Ltd and Daiichi Sankyo Co., Ltd.,

Introduction: The characteristics of pneumococcal isolates and their associations with outcomes in pediatric meningitis are unclear. This study aimed to clarify serotypes and resistance genotypes of Streptococcus pneumoniae from children with meningitis and evaluate the patient prognoses and backgrounds., Methods: Large-scale surveillance was conducted from 2002 to 2016 through periods I-V. Serotypes and penicillin (PEN) resistance genotypes were analyzed for pneumococcal isolates (n = 459) and cerebrospinal fluid (CSF) samples (n = 25). Furthermore, underlying diseases (n = 251), prognoses (n = 202), and laboratory data were evaluated., Results: The number of meningitis cases decreased drastically after the introduction of 7-valent pneumococcal conjugate vaccine (PCV7) to -53.6% and after switching to PCV13 to -70.2%. In particular, this reduction was apparent at ≤3 years of age. The proportion of the PCV7 serotype decreased sharply from 70.1% before introduction to 2.6% during period V; however, the non-vaccine type increased from 17.5% to 87.2%. The PEN resistance rate (gPRSP) was decreased from approximately 49% to 12.2% during period V. Among cases revealed prognosis, sequelae and mortality rates were 16.3% and 5.4%, respectively. The rate of the patients with underlying diseases was 26.3% and relatively high in ≥6 years. Laboratory data associated with a poor prognosis were low white blood cell count (<12.7 × 10 3 /μL), low platelet count (<28.1 × 10 4 /μL), low CSF-glucose (<36 mg/dL), and high CSF-protein (≥142 mg/dL)., Conclusions: Changes in serotype prevalence warrant continuous monitoring to observe future trends of pneumococcal meningitis, and further developments in multivalent conjugate vaccines are required., Competing Interests: Declaration of competing interest S. Iwata has received grant support from Sumitomo Dainippon Pharma Co., Ltd., Pfizer Japan Inc., Taisho Toyama Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Astellas Pharma Inc., and MSD K. K. K. Ubukata has received payment for lectures from Meiji Seika Pharma Co., Ltd., Pfizer Japan Inc., and HORIBA, Ltd. I. Miyairi has received payments for lectures from Sumitomo Dainippon Pharma Co., Ltd., bioMelieux Japan Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Japan Vaccine Co., Ltd., Sanofi, Tanabe Mitsubishi Pharma Co., Ltd., Abbvie Inc. and Abbott diagnostics. The other authors declare that they have no conflict of interest., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Streptococcus pneumoniae with a mucoid-type capsule is associated with invasive pneumococcal diseases (IPDs). Despite the introduction of pneumococcal vaccines, IPDs caused by mucoid-type isolates are still prevalent. The present study aimed to characterize mucoid-type S. pneumoniae isolated from IPD patients throughout Japan in 2017 (post-vaccination era)., Methods: A total of 225 mucoid-type isolates were collected. The serotype, antimicrobial susceptibility, and multilocus sequence type of these isolates were determined., Results: The prevalence of IPDs caused by mucoid-type isolates was high in adults, especially in the elderly (≥65 years of age), and prognosis in these patients was significantly poor. Of the mucoid-type isolates, the predominant serotype was serotype 3 (84.4%), and the remaining were serotypes 37 (15.1%) and 8 (0.4%). Antimicrobial susceptibility showed that most mucoid isolates exhibited the penicillin-intermediate resistant S. pneumoniae genotype (gPISP). However, the serotype 3 isolate exhibited the penicillin-resistant S. pneumoniae genotype (gPRSP). This gPRSP isolate was classified into ST166, which is related to serotypes 9 V and 11 strains. Sequence analysis of the capsule-coding regions and its flanking regions indicated that recombination occurred upstream and downstream of the capsule-coding region, suggesting that gPRSP (serotype 9 V/ST166) obtaining the type-3 capsule gene cluster resulted in the emergence of gPRSP (serotype 3/ST166)., Conclusions: Our findings indicated that IPDs caused by mucoid-type S. pneumoniae are still a serious concern and mucoid-type S. pneumoniae with novel phenotype could emerge via capsular switching in response to environmental changes such as introduction of vaccines and improper use of antimicrobial agents., Competing Interests: Declaration of competing interest S. Iwata has received grant support from Sumitomo Dainippon Pharma Co., Ltd., Pfizer Japan Inc., Taisho Toyama Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Astellas Pharma Inc., and MSD K. K. H. Mukae has received grant support from MSD K. K., Astellas Pharma Inc., TAIHO Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co.,Ltd., Daiichi Sankyo Co., Ltd., Eli Lilly Japan K.K., FUJIFILM Pharma Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Toyama Chemical Co.,Ltd., Meiji Seika Pharma Co., Ltd., Novartis Phama Co.,Ltd., Nippon Boehringer Ingelheim Co., Ltd., and Pfizer Japan Inc. T. Ishida has received payment for lectures from MSD K. K. H. Kiyota has received grant support from Taisho Toyama Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Astellas Pharma Inc., Toyama Chemical Co.,Ltd. and Sanofi K.K. K. Ubukata has received payment for lectures from Meiji Seika Pharma Co., Ltd. and Pfizer Japan Inc. The other authors declare that they have no conflict of interest., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: In 2019, the Japanese Society of Chemotherapy and the Japanese Association for Infectious Diseases reported nationwide, cross-sectional questionnaire survey data investigating the clinical status of clinic doctors' attitudes to antimicrobial stewardship. This study aimed to identify factors determining clinic doctors' attitudes concerning antimicrobial prescription for patients with a common cold or bronchitis., Methods: In February 2018, 1500 randomly selected community-based medical clinics in Japan were sent a questionnaire. Primary and secondary endpoints were clinic doctors' attitudes concerning antimicrobial prescription, and antimicrobial medication types prescribed for patients with a common cold or bronchitis, respectively. We used multivariable linear regression analysis to identify factors associated with primary and secondary outcomes., Results: We analyzed 269 of 274 responses (response rate, 18.3%). Linear regression analysis was used to identify determinants of proactive attitudes to antimicrobial prescription, including whether clinic doctors encountering patients with upper respiratory symptoms and no underlying illnesses, and diagnosed with a common cold would prescribe antimicrobial medication (β = 0.283, t = 4.279, p = 0.000); whether clinic doctors frequently experienced requests from patients (or their families) with a common cold to prescribe antimicrobial medication (β = 0.389, t = 6.133, p = 0.000), and; clinic doctors' awareness of antimicrobial stewardship in the past year (β = -0.157, t = -2.456, p = 0.015). Determinants of proactive attitudes to prescribing broader-spectrum antimicrobials for patients with a common cold included clinic doctors' attitudes concerning antimicrobial prescription (β = 0.165, t = 2.622, p = 0.009), whether the respondent was a pediatrician (β = -0.288, t = -4.583, p = 0.000), and clinic doctors' attitudes to antimicrobial prescription (β = 0.262, t = 4.075, p = 0.000) for patients with bronchitis., Conclusion: This study identified factors among clinic doctors that determined their attitudes to antimicrobial prescription concerning patients with a common cold or bronchitis. Identification and targeting of clinic doctors who unnecessarily prescribe antimicrobial medication is urgently required to promote antimicrobial stewardship in an outpatient setting., Competing Interests: Declaration of competing interest Shigefumi Maezaki received lecture fees from Pfizer Japan Inc., Astellas Pharma Inc., Sumitomo Dainippon Pharma Co., Ltd., Shionogi & Co., Ltd., MSD K.K., KYORIN Pharmaceutical Co., Ltd., and Taisho Toyama Pharmaceutical Co., Ltd. Tetsuya Matsumoto received lecture fees from MSD K.K., Pfizer Japan Inc., Taisho Toyama Pharmaceutical Co., Ltd., and Meiji Seika Pharma Co., Ltd., and research funding from Kewpie Corp. The following authors declare no conflicts of interest associated with this manuscript: Norio Ohmagari, Yoshiaki Gu, Shinichiro Morioka, Shinya Tsuzuki, Hiroshi Soeda, Chikara Nakahama, Naoki Hasegawa, Yumiko Fujitomo, Masayuki Maeda, and Isao Miyairi., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: The objective of this study was to describe the recent epidemiology of Pneumocystis pneumonia (PCP) in Japan using a nationwide database., Methods: We extracted data of inpatients with PCP from the Diagnostic Procedure Combination database, a national inpatient database in Japan, from January 2010 to December 2016., Results: During the study period, 4293 PCP patients were identified, including 4073 adults and 220 children. In adults, the most common comorbidity was hematologic malignancy (31%), followed by diabetes mellitus (30%), rheumatic/collagen diseases (26%), and solid organ tumors (18%). In children, there were few patients with rheumatic diseases (5%) or diabetes mellitus (2%), but immunodeficiency (without human immunodeficiency virus) was more common (28%). Few biological products were used for adult and pediatric patients; CD20 inhibitors, TNF-α inhibitors, interleukin receptor inhibitors, and CTLA-4 inhibitor were used for 8.6% and 2.4%, 1.3% and 0%, 1.2% and 4.7%, and 0.2% and 0% of adult and pediatric patients, respectively. Based on data stratified by bed count, the annual numbers of PCP patients in Japan were estimated as 2221 adults and 123 pediatric patients. The mortality was higher in adults (27%) than in pediatric patients (21%) (P = 0.041)., Conclusions: The underlying disease and mortality were apparently different between adult and pediatric PCP patients., Competing Interests: Declaration of Competing Interest All authors do not have any potential, perceived, or real conflict of interest., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Bordetella pertussis (B. pertussis) infection occasionally causes severe respiratory infections in children. Potential association between virulence-associated gene alleles and severe clinical outcomes has been suggested; however, frequencies of these alleles in pediatric patients with severe pertussis have not been clarified. We retrospectively tested stored respiratory samples collected from B. pertussis-positive patients by polymerase chain reaction targeting for major virulence-associated genes; fimbrae (fim) serotype 3 (fim3), pertactin (prn), pertussis toxin A (ptxA), and pertussis toxin promotor (ptxP). Based on the identified sequences, multilocus sequence typing (MLST) was conducted. Association of gene allele frequency and clinical outcomes such as management in pediatric intensive care unit, intubation, and mortality was analyzed. Out of 25 patients with available samples, the most prevalent allele for each virulence-associated gene was fim3A (17/21, 83%), ptxA1 (20/23, 87%), prn2 (13/16, 81%), and ptxP3 (14/17, 82%). In the study, total of 3 MLST types were identified; MLST-1 from 3 patients (19%), MLST-2 from 10 patients (63%), and MLST-4 from 3 patients (19%). Detection rate of the major MLST type; MLST-2 was significantly higher for patients who required intubation compared to those who did not (6/6, 100% vs 4/10, 40%; p = 0.034). In conclusion, MLST-2 was the most common MLST type in B. pertussis isolated from Japanese children with severe pertussis. Further studies investigating its causal association with disease severity is warranted., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Clinics are high prescribers of antimicrobials in Japan, but the present situation and the attitude of clinic doctors toward prescribing them remain unclear., Objective: To investigate the present situation at clinics and clinic doctors' attitude toward antimicrobial stewardship., Study Design: A questionnaire survey of clinic doctors., Methods: A questionnaire targeting doctors was sent to 1500 clinics that were randomly selected from across the country., Results: Among 274 respondents (response rate, 18.3%), 269 provided consent and their responses were analyzed. Awareness of the National Action Plan on Antimicrobial Resistance and the Manual of Antimicrobial Stewardship was low, but awareness of antimicrobial stewardship was high. A certain proportion of doctors prescribed antimicrobials for the common cold and acute bronchitis, and macrolides were the most commonly prescribed group of antimicrobials. Such prescription was not based solely on the doctors' knowledge but was also influenced by complex factors such as the doctor-patient relationship., Conclusion: Various measures such as improving doctor-patient communication and improving clinic doctors' knowledge are necessary to promote antimicrobial stewardship in the outpatient setting., Competing Interests: Declaration of Competing Interest Shigefumi Maezaki received lecture fees from Pfizer Japan Inc., Astellas Pharma Inc., Sumitomo Dainippon Pharma Co., Ltd., Shionogi & Co., Ltd., MSD K.K., KYORIN Pharmaceutical Co., Ltd., and Taisho Toyama Pharmaceutical Co., Ltd. Tetsuya Matsumoto received lecture fees from MSD K.K., Pfizer Japan Inc., Taisho Toyama Pharmaceutical Co., Ltd., and Meiji Seika Pharma Co., Ltd., and research funding from Kewpie Corp. The following authors declare no conflicts of interest associated with this manuscript: Norio Ohmagari, Yoshiaki Gu, Hiroshi Soeda, Chikara Nakahama, Naoki Hasegawa, Yumiko Fujitomo, Masayuki Maeda, and Isao Miyairi., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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 trend  < 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., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The significance of anaerobic bacteria as a pathogen in urinary tract infection (UTI) in children is unclear. A two-month-old infant presenting with poor feeding received a diagnosis of polymicrobial anaerobic UTI by next-generation sequencing and was found to have obstructive uropathy. Anaerobic bacteria may be a cause of UTI in children with urinary tract obstruction., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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 2 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 trend  = 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., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Influenza A(H1N1)pdm09 virus infections often manifest severe respiratory symptoms, particularly in patients with a past history of allergic disease. Most of these findings were reported during the 2009 pandemic. The purpose of this study was to detail the clinical characteristics of influenza virus-induced lower respiratory infection (LRI) during the A(H1N1)pdm09-predominant 2015-2016 season., Methods: We retrospectively reviewed the clinical characteristics of influenza-induced LRI cases in children admitted to a tertiary children's hospital. Molecular diagnostic evaluation was performed on samples obtained from the most severe cases., Results: We identified 66 patients with influenza-associated hospitalization and included 21 patients with influenza virus-induced LRI for analyses. Twelve patients (57%) were admitted to the pediatric intensive care unit, seven (33%) required mechanical ventilation, and three (14%) required extracorporeal membrane oxygenation. Plastic bronchitis (PB) was identified in six patients (29%), among whom a past medical history of asthma or food allergy were noted in all six patients. A past history of allergic disease was more common among patients with, than among those without, PB (p = 0.009). A(H1N1)pdm09 was detected from all the PB cases, and phylogenetic analyses of the hemagglutinin and neuraminidase genes demonstrated that this virus belonged to subclades 6B.1 and 6B.2. In the six PB cases, we found one patient with H275Y mutation in neuraminidase., Conclusion: Allergic disease was a risk factor for developing PB due to influenza A(H1N1)pdm09 infection during the 2015-16 season., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Pertussis is characterized by intense, prolonged coughing in children often followed by a distinctive whooping sound on inspiration. However, the clinical manifestations and natural course of pertussis in disabled children are largely unknown. We experienced a case of pertussis in a disabled girl who had previously undergone a tracheostomy and laryngotracheal separation. She presented with increased tracheal secretions and required hospitalization but did not develop a cough. Pertussis was suspected from the sputum Gram stain, which revealed numerous, short gram-negative rods that did not grow on chocolate agar. A nucleic acid amplification test was positive for Bordetella pertussis and the patient improved on azithromycin. Pertussis may present without its cardinal symptoms in disabled children., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Coagulase-negative Staphylococcus (CoNS) is the predominant cause of catheter-related bloodstream infections (CRBSI). Infants in neonatal intensive care units (NICU) often suffer from CoNS CRBSI, which are often refractory to treatment., Objectives: We sought to evaluate risk factors for developing persistent bacteremia due to CoNS CRBSI in infants, in order to identify those who require early aggressive management., Methods: We conducted a retrospective case-control study of infants in the NICU who developed CRBSI due to CoNS. Patient demographics, condition and management of CRBSI were compared between those with persistent and non-persistent bacteremia. Furthermore, prognosis of infants in the NICU after CoNS CRBSI was evaluated., Results: Seventy six episodes of CRBSI, including 17 persistent bacteremia and 59 non-persistent bacteremia, were analyzed. In univariate analyses, persistent bacteremia was significantly associated with corrected age equivalent to gestational age of 22-28 weeks at onset of CRBSI [Odds ratio (OR) = 4.33; P = 0.04], platelet count <100,000/μL (OR = 11.5; P < 0.001), use of vasopressor (OR = 5.38; P = 0.003), and delayed CVC removal (OR = 6.25; P = 0.003). In multivariate analysis, persistent bacteremia was significantly associated with platelet count <100,000/μL (OR = 7.80; P = 0.007), and delayed CVC removal (OR = 5.07; P = 0.03). Infants with persistent bacteremia tended to have a lower survival rate after CoNS CRBSI, however this was not statistically significant (P = 0.21)., Conclusions: Early CVC removal should be considered for the treatment of CRBSI due to CoNS in infants with platelet counts of less than 100,000/μL., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The resistance of Staphylococcus aureus (S. aureus) to antibiotics is an increasing problem. Clindamycin has been used as empiric therapy for the rising incidence of community-acquired methicillin-resistant S. aureus (MRSA). As such, the local rate of inducible resistance against clindamycin is an important consideration. This multicenter study was conducted to identify the incidence of inducible clindamycin resistance of S. aureus isolates in Tokyo, the most populous city in Japan. A total of 2408 adult and pediatric samples were collected from a university hospital and two pediatric hospitals between January 2011 and December 2011. Among the 2341 samples analyzed, the incidence of inducible clindamycin resistance in erythromycin-resistant and clindamycin-susceptible/intermediate isolates was found to be 91% (n = 585), a figure much higher compared to most reports from other countries. In conclusion, we found a very high rate of inducible clindamycin resistance in macrolide-resistant S. aureus isolates in our geographic area., (Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)