Guidelines for the Management of Respiratory Infectious Diseases in Children in Japan 2022.

The members of the Japanese Society for Pediatric Infectious Diseases and the Japanese Society of Pediatric Pulmonology have developed Guidelines for the Management of Respiratory Infectious Diseases in Children with the objective of facilitating appropriate diagnosis, treatment and prevention of respiratory infections in children. The first edition was published in 2004 and the fifth edition was published in 2022. The Guideline 2022 consists of 2 parts, clinical questions and commentary, and includes general respiratory infections and specific infections in children with underlying diseases and severe infections. This executive summary outlines the clinical questions in the Guidelines 2022, with reference to the Japanese Medical Information Distribution Service Manual. All recommendations are supported by a systematic search for relevant evidence and are followed by the strength of the recommendation and the quality of the evidence statements.

The efficacy of neutralizing monoclonal antibodies in transplant recipients with mild-to-moderate COVID-19.

INTRODUCTION: Transplant recipients (TRs) are at high risk for severe coronavirus disease 2019 (COVID-19). Neutralizing monoclonal antibodies (mAbs) are used for treating mild-to-moderate COVID-19. However, reports comparing the efficacy of COVID-19 treatment without/with mAbs in TRs are limited. We assessed the efficacy of casirivimab/imdevimab against mild-to-moderate COVID-19 in TRs. METHODS: Forty-one patients were retrospectively evaluated. The duration until defervescence, oxygen (O2) requirement ≥5 L, and neutralizing antibody levels were compared in TRs with COVID-19 without/with casirivimab/imdevimab. RESULTS: Casirivimab/imdevimab was correlated with shorter duration until defervescence and non-requirement of O2 ≥ 5 L in TRs with COVID-19 [mean: without/with: 6 vs. 2; P = 0.0002, hazard ratio (HR) = 0.3333, 95% confidence interval (CI) = 0.1763-0.6301; 15 vs. 8; P < 0.0001, HR = 0.5333, 95% CI = 0.2878-0.9883; P = 0.0377, HR = 0.1502, 95% CI = 0.02511-0.8980]. Casirivimab/imdevimab was associated with early defervescence after adjusting for sex and age (P = 0.013, HR = 0.412, 95% CI = 0.205-0.826). The antibody levels between patients without/with casirivimab/imdevimab on the day of hospitalization were not significantly different (P = 0.1055), including 13 TRs with vaccination. Antibody levels were higher in patients with casirivimab/imdevimab at 3-5 days after hospitalization than in those without, at 7-9 days after hospitalization (P < 0.0001, mean, without/with: 414.9/40000 AU/mL). CONCLUSION: Casirivimab/imdevimab was effective and increased the neutralizing antibody in TRs with mild-to-moderate COVID-19, it may contribute toward preventing the progression.

Polymerase-chain reaction testing to prevent hospital-acquired severe acute respiratory syndrome coronavirus 2 infection in Shinjuku, an epicenter in Tokyo: The Tokyo Women's Medical University model.

Hospital-acquired severe acute respiratory virus coronavirus 2 (SARS-CoV-2) infection is a healthcare challenge. We hypothesized that polymerase chain reaction testing of symptomatic triaged outpatients and all inpatients before hospitalization in Shinjuku, a coronavirus disease 2019 (COVID-19) epicenter in Tokyo, using the Tokyo Women's Medical University (TMWU) model would be feasible and efficient at preventing COVID-19. This retrospective study enrolled 2981 patients from March to May 2020. The prevalence of SARS-CoV-2 infection was 1.81% (95% credible interval [CI]: 0.95-3.47%) in triaged symptomatic outpatients, 0.04% (95% CI: 0.0002-0.2%) in scheduled asymptomatic inpatients, 3.78% (95% CI: 1.82-7.26%) in emergency inpatients, and 2.4% (95% CI: 1.49-3.82%) in symptomatic patients. There were no cases of hospital-acquired SARS-CoV-2 infection. This shows that the TWMU model could prevent hospital-acquired SARS-CoV-2 infection and is feasible and effective in reducing the impact of SARS-CoV-2 infection in the hospitals.

Sharp injuries in Japanese operating theaters of HIV/AIDS referral hospitals 2009-2011.

The aim of this study was to identify how doctors and nurses experienced sharps injuries in operating rooms and the risks for these injuries by analyzing data from 78 Japanese hospitals participating in the nationwide EPINet surveillance system. The years of professional experience of the cases were classified into tertiles separately for doctors and nurses. Suture needles accounted for 54.9% of injuries in doctors and 48.3% of injuries in nurses. Among doctors, injuries occurred most frequently during the use of an item (range: 58.1-64.3%), while among nurses, injuries occurred most frequently (range: 24.7-29.0%) between steps of a multi-step procedure. The frequency of injury by a suture needle held by someone else was 41.1-47.3% (range) among doctors, and 27.0-48.1% (range) among nurses. In conclusion, sharps injuries in the operating room need to address the circumstances of injury and holder of devices based on the specific risk for doctors and nurses to decrease the number of injuries.

[Introducing International State-of-the-Art Clinical Microbiologic Technologies to Japanese Clinical Laboratories--Opening Remarks].

Internationally, recent progress in clinical microbiology has involved adapting for multi-drug-resistant organisms (MDROs) such as carbapenemase-producing Enterobacteriaceae (CRE) using selective culture media and the active surveillance test using real-time PCR, matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) technology for bacterial identification, and molecular epidemiological tools such as multi-locus sequence typing (MLST). In this symposium, we discussed updating to state-of-the-art clinical microbiologic technologies in Japanese clinical laboratories.

[Overview of History and New Demands Regarding Clinical Microbiological Tests in Healthcare Facilities].

Since the 1960s, healthcare-associated infections caused by multi-drug-resistant organisms (MDROs) have been a critical part of hospital quality management. To fight MDROs, diverse antimicrobial agents are developed and used for patients. Recently, super-MDROs such as carbapenemase-producing Enterobacteriaceae (CPE) are spreading throughout the world. There is a chance that such super-MDROs will appear in Japan. For active surveillance (i.e., screening) tests to detect CPE, state-of-the-art methodologies are needed. For example, selective culture media and active surveillance test by real-time PCR, matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) technology for bacterial identification, and molecular epidemiological tools such as multi-locus sequence typing (MLST). In this symposium, we discussed updating to state-of-the-art clinical microbiologic technologies in Japanese clinical microbiologic laboratories.

Incidence rate of needlestick and sharps injuries in 67 Japanese hospitals: a national surveillance study.

BACKGROUND: Determining incidence rates of needlestick and sharps injuries (NSIs) using data from multiple hospitals may help hospitals to compare their in-house data with national averages and thereby institute relevant measures to minimize NSIs. We aimed to determine the incidence rate of NSIs using the nationwide EPINet surveillance system. METHODOLOGY/PRINCIPAL FINDINGS: Data were analyzed from 5,463 cases collected between April 2009 and March 2011 from 67 Japanese HIV/AIDS referral hospitals that participated in EPINet-Japan. The NSI incidence rate was calculated as the annual number of cases with NSIs per 100 occupied beds, according to the demographic characteristics of the injured person, place, timing, device, and the patients' infectious status. The NSI incidence rates according to hospital size were analyzed by a non-parametric test of trend. The mean number of cases with NSIs per 100 occupied beds per year was 4.8 (95% confidence interval, 4.1-5.6) for 25 hospitals with 399 or fewer beds, 6.7 (5.9-7.4) for 24 hospitals with 400-799 beds, and 7.6 (6.7-8.5) for 18 hospitals with 800 or more beds (p-trend<0.01). NSIs frequently occurred in health care workers in their 20 s; the NSI incidence rate for this age group was 2.1 (1.6-2.5) for hospitals having 399 or fewer beds, 3.5 (3.0-4.1) for hospitals with 400-799 beds, and 4.5 (3.9-5.0) for hospitals with 800 or more beds (p-trend<0.01). CONCLUSIONS/SIGNIFICANCE: The incidence rate of NSIs tended to be higher for larger hospitals and in workers aged less than 40 years; injury occurrence was more likely to occur in places such as patient rooms and operating rooms. Application of the NSI incidence rates by hospital size, as a benchmark, could allow individual hospitals to compare their NSI incidence rates with those of other institutions, which could facilitate the development of adequate control strategies.

Complications of adenotonsillectomy: a case report of meningitis due to dual infection with nontypeable Haemophilus influenzae and Streptococcus pneumoniae, and a prospective study of the rate of postoperative bacteremia.

CASE REPORT: Bacterial meningitis is a rare complication of adenotonsillectomy. We present a case of meningitis due to nontypeable Haemophilus influenzae and Streptococcus pneumoniae after adenotonsillectomy. Pulsed-field gel electrophoresis patterns indicated that the oral cavity was the source of H. influenzae and S. pneumoniae isolated from the cerebrospinal fluid. BLOOD CULTURE STUDY: As bacteremia is thought to be one of the etiologies of meningitis, we prospectively investigated the rate of bacteremia as a complication of adenotonsillectomy. Of the 46 patients included in the study, mean age of five years old, 11 (24%) had positive blood cultures during the operation. H. influenzae was the commonest organism grown (seven cultures), three of seven produced beta-lactamase, followed by S. pneumoniae (one culture), H. parainfluenzae (one culture), Peptostreptococcus micros (one culture), and Veillonella spp. (one culture). The bacteria were composed of tonsil or adenoid surface cultures in eight of 11 patients (73%). CONCLUSIONS: We present a rare case of meningitis complicating a adenotonsillectomy procedure, in a three years old boy. Meningitis is a rare complication of adenotonsillectomy, but bacteremia which may lead to meningitis occurs frequently, as the results.

Analysis of the influence of drug resistance factors on the efficacy of combinations of antibiotics for multidrug-resistant Pseudomonas aeruginosa isolated from hospitals located in the suburbs of Kanto area, Japan.

Infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa are very difficult to treat. The aim of this study was to develop more effective treatments by investigating in vitro the effects of combinations of antibiotics against 47 MDR P. aeruginosa isolates harbouring various resistance factors. The isolates included 41 (87%) metallo-ß-lactamase (MBL)-positive strains, 37 (79%) strains with mutations in OprD and 46 (98%) strains carrying the genes encoding aminoglycoside-modifying enzymes (AMEs). The quinolone resistance-determining region was mutated in all of the strains. These strains were classified into 16 groups according to amplified fragment length polymorphism and resistance factors. The effects of combinations of antibiotics on 16 representative strains were determined using a 'Break-point Checkerboard Plate' assay. Combinations of amikacin+aztreonam (coverage rate, 81.3%) and arbekacin+aztreonam (93.8%) inhibited growth. In contrast, combinations of ciprofloxacin+meropenem (6.3%) and ciprofloxacin+ceftazidime (12.5%) were much less effective. Aztreonam and arbekacin (or amikacin) are not substrates for MBLs and AMEs, respectively. We conclude that the combined effects of these drugs were possibly because of resistance factors.

[Infection prevention and control for foodborne infections].

Patients' care for foodborne infections is sometimes very critical, since these patients exerting high copy numbers of contagious pathogens. Recently, Norovirus infection became the most frequent pathogen for large outbreaks in the community and the hospital around the world. Norovirus is alcohol-resistant and highly contagious. For preventing outbreaks of foodborne infections, standard precaution(and contact precaution for diaper changing patients) is required by the CDC's isolation precaution guideline revised at 2007. We need to provide for infection prevention and control in the epidemic winter period not only in healthcare facilities but also for communities.

[Molecular epidemiology of multidrug-resistant organisms].

Recent advance in molecular epidemiology of multidrug-resistant organisms (MDROs) was described. Most of MDROs are spreading over the world in a short period, monitoring of certain epidemic strains of MDROs is very important. Since Cantor et al. developed pulsed-field gel electrophoresis (PFGE) in 1984, genotyping tools became major tools for laboratory based-epidemiologic analysis. Recent advance was developed by two major technologies. One is multilocus sequence typing (MLST) and the other one is matrix assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS). MALDI-TOF-MS technology is still under developing, but near future it will become major tools for MDROs molecular epidemiology.

In vitro combination effects of aztreonam and aminoglycoside against multidrug-resistant Pseudomonas aeruginosa in Japan.

The aim of this study was to evaluate the in vitro combination effects of aztreonam (AZT) and aminoglycosides against multidrug-resistant (MDR) Pseudomonas aeruginosa strains in Japan. We investigated 47 MDR P. aeruginosa strains collected from 8 facilities. We selected the aminoglycosides amikacin (AMK), gentamicin (GM), and arbekacin (ABK) to examine their effects when combined with AZT using the checkerboard method. Of the 47 MDR P. aeruginosa strains, 41 tested positive for metallo-ß-lactamase (MBL). In all combinations, aminoglycosides decreased the minimum inhibitory concentrations of AZT in a dose-dependent manner, and there was no apparent antagonism. The combination effects were scored on a scale of 0 to 4, and statistical analysis was performed using the Wilcoxon signed-rank test. In all 47 strains, AZT + ABK (mean score, 2.02) had the highest score, followed by AZT + AMK (1.68) and AZT + GM (1.38) (ABK versus GM, P < 0.0001). In 41 MBL-positive strains, AZT + ABK (mean score, 2.05) had the highest score, followed by AZT + AMK (1.56) and AZT + GM (1.37) (ABK versus AMK, P = 0.02, and ABK versus GM, P < 0.0001). AZT + ABK was the most promising combination regimen against MDR P. aeruginosa strains; the other promising combinations were AZT + AMK and AZT + GM.

Japanese Guidelines for the Management of Respiratory Infectious Diseases in Children 2007 with focus on pneumonia.

Members of the Japanese Society of Pediatric Pulmonology and the Japanese Society for Pediatric Infectious Diseases developed the Guidelines for the Management of Respiratory Infectious Diseases in Children with the objective of facilitating the appropriate diagnosis and treatment of childhood respiratory infections. To date, a first edition (2004) and a revised edition (2007) have been issued. Many problems complicate the diagnosis of the pathogens responsible for bronchopulmonary infections in children. The Guidelines were the first pediatric guidelines in the world to recommend treatment with antimicrobials suited to causative pathogens as identified from cultures of sputum and other clinical specimens collected from infection sites and satisfying assessment criteria. The major causative microorganisms for pneumonia in infants and children were revealed to be Streptococcus pneumoniae, Haemophilus influenzae and Mycoplasma pneumoniae. This manuscript describes the Guidelines for the Management of Respiratory Infectious Diseases in Children in Japan 2007, with a focus on pneumonia.

Whole blood interferon-gamma assay for tuberculosis in children in Japan.

BACKGROUND: Whole blood interferon-gamma assay QuantiFERON-TB2G (QFT-2G), which is a new specific method for diagnosing tuberculosis (TB), has been developed and used in the clinical field. The aim of the present study was to assess the usefulness of QFT-2G as an indicator, both for diagnosing childhood TB and for assessing therapeutic effectiveness. METHODS: The subjects were 61 children introduced to the TB outpatient department for the first time between June 2004 and March 2006. QFT-2G, the tuberculin test and chest computed tomography (CT) were performed for all patients. RESULTS: Ten patients having typical characteristics of primary tuberculosis (PTB) on chest CT, and diagnosed as having tubercle bacillus infections, all had positive reaction on QFT-2G. Of seven patients who had no abnormalities on diagnostic imaging but who reacted positively on QFT-2G, one developed TB later, and no TB was detected over the period of observation in 44 patients with negative QFT-2G at their first consultation. Moreover, four patients with non-tuberculous acid-fast bacilli in which Mycobacterium avium or Mycobacterium gordonae was detected had negative reaction on QFT-2G. In addition, all 10 patients with positive reactions on QFT-2G in whom the subsequent course of the disease was observed had decrease on QFT after treatment. CONCLUSIONS: QFT-2G is a powerful tool with a wide application both in diagnosis and in assessment of treatment effectiveness in PTB.

[A case of aortitis syndrome diagnosed with 18F-fluorodeoxyglucose-positron tomography (18F-FDG-PET) in the early pre-pulseless phase].

A 14-year-old girl with aortitis syndrome in the early pre-pulseless phase was admitted to our hospital because of slight fever, neck bruit, asymmetrical blood pressure, stenosis or dilatation of the main branch arteries in aorta on chest computed tomography. Laboratory examination revealed a high level of C-reactive protein and an elevated erythrocyte sedimentation rate, as well as hypergammaglobulinemia, and 18F-FDG-PET revealed an accumulation of 18 fluorodeoxyglucose in the great vessels. She was first given pulse therapy with a combination of methylprednisolone and intravenous cyclophosphamide, and then maintenance therapy with oral prednisolone and azathioprine. All the abnormal laboratory parameters improved to normal levels within a month. We suggest that early diagnosis of aortitis syndrome may permit early treatment in the early pre-pulseless phase and could possibly prevent progression to the occlusive phase.

[Usefulness of interferon-gamma-based diagnosis of Mycobacterium tuberculosis infection in childhood tuberculosis].

We studied the usefulness of interferon-gamma measurement reagent QuantiFERON-TB 2 G (QFT-2G), used to diagnose tubercle bacilli infections, as an indicator both for diagnosing primary tuberculosis (PTB) and for assessing therapeutic amorg pediatric Tuberculosis Outpatent cases effectiveness. Five cases showing typical PTB findings, such as cavitation, swollen lymph nodes, and nodular shadows at the pulmonary hilum, and diagnosed as tubercle bacillus infections, all showed positive reactions to QFT-2G, and in 3 asymptomatic cases without abnormalities detected in diagnostic imaging but QFT-2G-positive, one developed tuberculosis (TB) later. Among 12 patients who gave negative reactions to QFT-2G at their first visit and during observation from 6 months to 1 year, no TB occurrences was seen. Patients who were vaccinated for BCG and were tuberculin-positive showed negative reactions to QFT-2G, confirming that QFT-2G is not affected by BCG. One case of nontuberculous acid-fast bacilli in which Mycobacterium avium was detected was QFT-2G-negative. In 1 case, QFT-2G decreased as the patient's conditiorl improved. Without being influenced by BCG vaccination, QFT-2G demonstrated its usefulness in primary TB cases both for diagnosis and for assessing treatment effectiveness. Our results strougly suggested that QFT-2G is a potentially powerful tool with wide applications in diagnosis and assessment of treatment effectiveness in primary TB, even when bacterial elimination is low and diagnosis is difficult.

HLA-DRB1*15021 is the predominant allele in Japanese patients with juvenile dermatomyositis.

OBJECTIVE: To investigate HLA molecules and genes in Japanese patients with juvenile dermatomyositis (JDM). METHODS: Twelve patients (8 girls and 4 boys) with ages of onset between 3 and 15 years were included. HLA class I antigen phenotypes were serologically typed by the Terasaki-NIH standard method. DNA was extracted from peripheral blood leukocytes using the phenol-chloroform extraction procedure, and stored at -70 degrees C until use. Genomic DNA for HLA-DRB1, HLA-DQA1, and HLA-DQB1 alleles in JDM patients and controls was determined by the direct sequence method. RESULTS: HLA-A24 and B52 were each detected in 7 cases (OR = 0.86, 5.02, p = 0.930, 0.006, respectively). HLA-DRB1*15021 was observed in 7 patients. This was significantly more frequent than occurred in the controls (OR = 5.72, p = 0.002). Seven patients out of 12 (58%) had the combination HLA-B52, DRB1*15021, DQA1*0103, and DQB1*0601. CONCLUSION: Our results suggest that the susceptibility gene for JDM either is HLA-DRB1*15021 or is present near the HLA-DRB1 locus. This differs from previous reports that describe the association with HLA-DQA1*0501 in Caucasian patients with JDM. The combination HLA-B52, DRB1*15021, DQA1*0103, and DQB1*0601 may contribute to the pathogenesis of JDM in Japanese patients.