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[Display omitted] Airway obstruction caused by viscous mucus is an important pathophysiologic characteristic of persistent inflammation, which can result in organ damage. We investigated the hypothesis that the biophysical characteristics of accumulating granulocytes affect the clinical properties of mucus. Surgically acquired nasal mucus samples from patients with eosinophilic chronic rhinosinusitis and neutrophil-dominant, noneosinophilic chronic rhinosinusitis were evaluated in terms of computed tomography density, viscosity, water content, wettability, and protein composition. Isolated human eosinophils and neutrophils were stimulated to induce the formation of extracellular traps, followed by the formation of aggregates. The biophysical properties of the aggregated cells were also examined. Mucus from patients with eosinophilic chronic rhinosinusitis had significantly higher computed tomography density, viscosity, dry weight, and hydrophobicity compared to mucus from patients with noneosinophilic chronic rhinosinusitis. The levels of eosinophil-specific proteins in mucus correlated with its physical properties. Eosinophil and neutrophil aggregates showed physical and pathologic characteristics resembling those of mucus. Cotreatment with deoxyribonuclease and heparin, which slenderizes the structure of eosinophil extracellular traps, efficiently induced reductions in the viscosity and hydrophobicity of both eosinophil aggregates and eosinophilic mucus. The present study elucidated the pathogenesis of mucus stasis in infiltrated granulocyte aggregates from a novel perspective. These findings may contribute to the development of treatment strategies for eosinophilic airway diseases. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. Age dependent discrepancy between SARS-CoV-2 anti-N and anti-S antibody in children reflected differences in vaccine coverage. [ABSTRACT FROM AUTHOR]

• Active screening of children who had been hospitalized abroad was conducted. • Multidrug-resistant organisms were detected in 19 of 34 cases (56%). • Enterobacteriaceae harboring carbapenemase genes still rare in Japan were isolated. • Hospitalization abroad may be a risk factor for multidrug-resistant organisms. Our infection control team initiated active screening for multidrug-resistant organisms (MDROs) among children who had been hospitalized abroad before their admission to our hospital. MDROs were detected in 19 of 34 cases (56%), including 3 isolates of Enterobacteriaceae harboring carbapenemase genes still rare in Japan. Early recognition of MDROs by screening this population may be required to avoid the introduction of new modes of resistance into the hospital environment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Vaccine-preventable diseases are a significant cause of morbidity and mortality in solid organ transplant recipients who undergo immunosuppression after transplantation. The primary strategy for immunizing transplant recipients is to deliver all potential vaccines prior to transplantation. However, time constraints limit the number of vaccines that may be delivered. In such cases, the administration of live attenuated vaccines that are contraindicated after transplantation should be prioritized. Simultaneous vaccination is also encouraged to maximize the number of vaccines delivered. Immunity induced by both inactivated and live vaccines wane after transplantation. The limited but available evidence suggests that immunization using inactivated vaccines in transplant recipients is both effective and safe. An increasing number of studies also suggest that once patients are under minimal immunosuppression, live attenuated vaccines may be given effectively and safely. The need for serologic monitoring and booster immunizations remain issues for future research. [ABSTRACT FROM AUTHOR]

Abstract: Immunizations using live-attenuated vaccines are not recommended for post-liver transplant children due to its theoretical risks. However, they will encounter vaccine-preventable viral diseases upon returning to real-life situations. We performed a total of 70 immunizations with four individual live-attenuated vaccines to 18 pediatric post-living donor liver transplant (LDLT) recipients who fulfilled a clinical criteria including humoral and cell-mediated immunity. The seroconversion rates at the first dose for measles (strain AIK-C), rubella (strain TO-336), varicella (strain Oka), and mumps (strains Hoshino) were 100% (15/15), 100% (15/15), 82% (9/11), and 82% (9/11), respectively. During observed period (−5 years 11 months), a few cases with waning immunity (antibodies were once produced but the levels fell over time) were seen except after rubella immunization. Clinical diseases after seroconversion or definite serious adverse effects due to immunization were not observed. Immunizations using selected live-attenuated vaccines were safe and effective for post-LDLT children who were not severely immunosuppressed. [Copyright &y& Elsevier]

This report presents three cases of neonatal group B streptococcal ventriculitis and assesses seven others identified by a literature review. In contrast to the well described acute manifestations of group B streptococcal meningitis, disease onset tended to be insidious with four of seven cases presenting over a period of 1 to 6 weeks and six cases presenting with nonspecific signs and symptoms without fever. Persistent protein content elevation and low glucose level in the cerebrospinal fluid was observed, indicating chronic inflammation. All patients developed obstructive hydrocephalus requiring ventriculoperitoneal shunt placement. One child died, and six of nine survivors were left with significant neurologic deficits. Physicians should be aware of this indolent but serious manifestation of group B streptococcal infection. [Copyright &y& Elsevier]

Discordant views regarding host cell death induction by Chlamydia are likely owing to the different methods used for evaluation of apoptosis. Apoptotic and non-apoptotic death owing to both caspase-dependent and -independent activation of the Bax protein occur late in the productive growth cycle. Evidence also suggests that Chlamydia inhibits apoptosis during productive growth as part of its intracellular survival strategy. This is in part owing to proteolytic degradation of the BH3-only family of pro-apoptotic proteins in the mitochondrial pathway. Chlamydia also inhibits apoptosis during persistent growth or in phagocytes, but induces apoptosis in T cells, which suggests that apoptosis has an immunomodulatory role in chlamydial infections. The contribution of apoptosis in disease pathogenesis remains a focus for future research. [Copyright &y& Elsevier]

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. 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. 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%). 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. [ABSTRACT FROM AUTHOR]

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). 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. 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. 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. UMIN000041359 https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000047220. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Objective: To conduct a prospective study to evaluate the immunogenicity and safety of live attenuated vaccines in patients with nephrotic syndrome receiving immunosuppressive agents.Study Design: Patients with nephrotic syndrome receiving immunosuppressive agents with negative or borderline antibody titers (virus-specific IgG levels <4.0) against measles, rubella, varicella, and/or mumps fulfilling the criteria of cellular and humoral immunity were enrolled. Virus-specific IgG levels were measured using an enzyme immunoassay. The primary endpoint was the seroconversion rate (ie, achievement of virus-specific IgG levels ≥4.0) at 2 months after vaccination. Virus-specific IgG levels at 1 year, breakthrough infections (wild-type infections), and adverse events were also evaluated.Results: A total of 116 vaccinations were administered to 60 patients. Seroconversion rates were 95.7% for measles, 100% for rubella, 61.9% for varicella, and 40.0% for mumps. More patients with a borderline antibody titer before vaccination achieved seroconversion than those with negative antibody titer, with statistical significance after varicella and mumps vaccination. The rate of patients who maintained seropositivity at 1 year after vaccination was 83.3% for measles, 94.1% for rubella, 76.7% for varicella, and 20.0% for mumps. No patient experienced breakthrough infection. No serious adverse events, including vaccine-associated infection, were observed.Conclusion: Immunization with live attenuated vaccines may be immunogenic and is apparently safe in our cohort of patients with nephrotic syndrome receiving immunosuppressive agents if their cellular and humoral immunologic measures are within clinically acceptable levels.Trial Registration: UMIN-CTR UMIN 000007710. [ABSTRACT FROM AUTHOR]

The objective of this study was to describe the recent epidemiology of Pneumocystis pneumonia (PCP) in Japan using a nationwide database. 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. 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). The underlying disease and mortality were apparently different between adult and pediatric PCP patients. [ABSTRACT FROM AUTHOR]

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]). [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

• We evaluated trends of pediatric varicella and herpes zoster incidence for 18 years. • Varicella was largely reduced after the vaccine introduction and COVID-19 pandemic. • The vaccine and COVID-19 pandemic had a small impact on herpes zoster incidence. • Risk of herpes zoster was low in children born after the routine vaccine. To determine the epidemiological trends in pediatric varicella and herpes zoster incidence and changes in healthcare resource use from 2005 to 2022 using a nationally representative database in Japan. We conducted a retrospective observational study consisting of 3.5 million children with 177 million person-months during 2005–2022 using Japan Medical Data Center (JMDC) claims database in Japan. We investigated trends in incidence rates of varicella and herpes zoster and changes in healthcare resource use (e.g., antiviral use, office visits, and healthcare costs) over 18 years. Interrupted time-series analyses were used to investigate the impact of the routine varicella vaccination program in 2014 and infection prevention measures against COVID-19 on incidence rates of varicella and herpes zoster and related healthcare utilization. After the introduction of the routine immunization program in 2014, we observed level changes in incidence rates (45.6 % reduction [95 %CI, 32.9–56.0] of varicella cases, antiviral use (40.9 % reduction [95 %CI, 25.1–53.3]), and relevant healthcare costs (48.7 % reduction [95 %CI, 38.2–57.3]). Furthermore, infection prevention measures against COVID-19 were associated with additional level changes in varicella rates (57.2 % reduction [95 %CI, 44.5–67.1]), antiviral use (65.7 % reduction [59.7–70.8]), and healthcare costs (49.1 % [95 %CI, 32.7–61.6]). In contrast, the changes in incidence and healthcare costs for herpes zoster were relatively small, which showed 9.4 % elevated level change with a decreasing trend and 8.7 % reduced level change with a decreasing trend after the vaccine program and the COVID-19 pandemic. The cumulative incidence of herpes zoster in children born after 2014 was lower than that before 2014. Varicella incidence and healthcare resource use were largely affected by the routine immunization program and infection prevention measures against COVID-19, while these impacts on herpes zoster were relatively small. Our study indicates that immunization and infection prevention measures largely changed pediatric infectious disease practices. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. 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. 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). Vaccination with BNT162b2 was acceptably safe and immunogenic for adolescents and young adults with underlying disease. [ABSTRACT FROM AUTHOR]

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. 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. 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]). 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. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

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. 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. 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 × 103/μL), low platelet count (<28.1 × 104/μL), low CSF-glucose (<36 mg/dL), and high CSF-protein (≥142 mg/dL). Changes in serotype prevalence warrant continuous monitoring to observe future trends of pneumococcal meningitis, and further developments in multivalent conjugate vaccines are required. [ABSTRACT FROM AUTHOR]

6 Non-chlamydial non-gonococcal urethritis [Executive summary] • Male urethritis in which neither N. gonorrhoeae nor C. trachomatis is detected is called non-chlamydial non-gonococcal urethritis (I, B). Non-gonococcal urethritis in which chlamydia is detected is called chlamydial urethritis, and urethritis in which neither gonococcus nor chlamydia is detected is called non-chlamydial non-gonococcal urethritis (I, B). Urethritis and cervicitis are frequently caused by Neisseria gonorrhoeae and Chlamydia trachomatis, and gonococcal urethritis and cervicitis and chlamydial urethritis and cervicitis have been used as terms to indicate these conditions. 4 Non-gonococcal urethritis • Urethritis in which gonococci are not detected is called non-gonococcal urethritis (I, A). Urethritis is classified into gonococcal and non-gonococcal urethritis depending on detection or no detection of gonococcus. [Extracted from the article]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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). A total of 225 mucoid-type isolates were collected. The serotype, antimicrobial susceptibility, and multilocus sequence type of these isolates were determined. 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). 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Because of the overabundance of vaccination information on the internet, in the media, and on social media, providing clear and correct information on immunization is critical for parental decision-making. In 2018, the Japan Pediatric Society created and distributed a Vaccine Information Statement (VIS) to provide appropriate immunization information to caregivers. The objectives of the present study were to evaluate the effect of the VIS on immunization rates, adherence to schedule, and parental understanding of immunization in Japan. This cross-sectional study was conducted at 18 centers in 2 prefectures in Japan. Caregivers were assigned to an intervention group, which received the VIS and a questionnaire when their child reached the age of 1 month, and a control group, which received only the questionnaire. Using the self-reported questionnaires, we evaluated vaccination rates and schedule adherence at age 2 months, and parental knowledge, attitudes, and beliefs regarding immunization. Three months later, the questionnaires were returned, and the findings were compared between the 2 groups. We contacted 422 and 428 persons in the intervention and control groups, respectively, and 111/422 (26.3%) and 119/428 (27.8%) returned the surveys. Vaccination rates and adherence rates for the first dose of 4 recommended vaccines did not differ significantly (P > 0.25); however, there were some positive effects on items related to vaccine knowledge (P = 0.03), perceived benefits (P = 0.02), perceived barriers (P < 0.001), and perceived behavioral control (P = 0.01). The VIS improved parent comprehension of infant immunization. Future studies should examine if the effects of such an intervention persist and affect vaccine uptake throughout childhood. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Clinics are high prescribers of antimicrobials in Japan, but the present situation and the attitude of clinic doctors toward prescribing them remain unclear. To investigate the present situation at clinics and clinic doctors' attitude toward antimicrobial stewardship. A questionnaire survey of clinic doctors. A questionnaire targeting doctors was sent to 1500 clinics that were randomly selected from across the country. 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. Various measures such as improving doctor–patient communication and improving clinic doctors' knowledge are necessary to promote antimicrobial stewardship in the outpatient setting. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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 χ2 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. [ABSTRACT FROM AUTHOR]

The WU polyomavirus (WUPyV) was detected by real-time PCR in the sputum of a pediatric liver transplant recipient with interstitial pneumonitis. A lower viral load was observed seven months after the initial detection. The case provides circumstantial evidence suggesting a potential role for WUPyV as a respiratory pathogen in immunocompromised children. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Routine anaerobic blood culture is not recommended in children because obligate anaerobic bacteremia is rare in the pediatric population. However, a number of facultative anaerobic bacteria can cause community and hospital acquired infections in children and the utility of anaerobic blood culture for detection of these organisms is still unclear. We conducted a retrospective analysis of all blood culture samples (n = 24,356) at a children’s hospital in Japan from October 2009 to June 2012. Among the samples that had paired aerobic and anaerobic blood cultures, 717 samples were considered clinically significant with 418 (58%) organisms detected from both aerobic and anaerobic cultures, 167 (23%) detected only from aerobic culture and 132 (18%) detected only from anaerobic culture. While most facultative anaerobes were detectable by aerobic culture, over 25% of Enterobacteriaceae and 15% of Staphylococcus sp. were detected from anaerobic cultures bottles only, suggesting its potential role in selected settings. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]