Factors affecting the antimicrobial changes during treatment for acute otitis media in Japan: A retrospective cohort study using classification and regression trees (CART) analysis.

OBJECTIVES: Factors that affect the change of first-line antimicrobial agents were investigated to further promote their appropriate use. METHODS: This descriptive study used an electronic medical records database. Total 16,353 of the 199,896 patients enrolled between 1996 and 2019 met the inclusion criteria and formed the overall pediatric acute otitis media (AOM) cohort. The factors leading to the change in first-line antimicrobial agents within 14 days were analyzed using classification and regression trees (CART) analysis. RESULTS: This antimicrobial treatment cohort, involved 4860 cases of AOM alone and 9567 cases of AOM with other diseases. The size of the medical facility based on number of beds and historical duration of patient registration impacted on antimicrobial changes. CONCLUSIONS: The current results show that hospital-wide or nation-wide antimicrobial stewardship promotion could be the most influencing factor for antimicrobial changes. Particularly in cases of AOM where other diseases coexist, a more accurate diagnosis and definition of treatment failure of first-line drug are suggested to be important while establishing future treatment strategies. The current study is important to promote appropriate antimicrobial use for AOM treatment.

Inferring the true number of SARS-CoV-2 infections in Japan.

INTRODUCTION: In Japan, as of December 31, 2021, more than 1.73 million laboratory-confirmed cases have been reported. However, the actual number of infections is likely to be under-ascertained due to the epidemiological characteristics such as mild and subclinical infections and limited testing availability in the early days of the pandemic. In this study, we infer the true number of infections in Japan between January 16, 2020, and December 31, 2021, using a statistical modelling framework that combines data on reported cases and fatalities. METHODS: We used reported COVID-19 deaths and age-specific infection fatality ratios (IFR) to impute the true number of infections. Estimates of IFR were informed from published studies and were adjusted to reflect the effects of pharmaceutical interventions, mass vaccination, and evolving variants. To account for the uncertainty in IFR, we sampled values from relevant distributions. RESULTS: We estimated that as of December 31, 2021, 3.07 million (CrI: 2.05-4.24 million) people had been infected in Japan, which is 1.77 times higher than the 1.73 million reported cases. Our meta-analysis confirmed that these findings were consistent with the intermittent seroprevalence studies conducted in Japan. CONCLUSIONS: We have estimated that a substantial number of COVID-19 infections in Japan were unreported, particularly in adults. Our approach provides a more realistic assessment of the true underlying burden of COVID-19. The results of this study can be used as fundamental components to strengthen population health control and surveillance measures.

Improvement in the appropriate antimicrobial usage for treating pediatric acute otitis media in Japan: A descriptive study using nation-wide electronic medical record data.

OBJECTIVES: We investigated changes in prescriptions for antimicrobial agents to treat children with acute otitis media (AOM). METHODS: A descriptive study using an electronic medical record database. Of 199,896 patients enrolled between 2001 and 2019, a total of 10,797 were aged <16 years and had AOM as their first and primary disease (overall pediatric AOM cohort). In addition, 4786 patients with AOM without other comorbidities (pediatric AOM cohort) were included. RESULTS: In the overall pediatric AOM cohort, the age distribution ranged from 11% to 23% for those younger than 2 years and from 66% to 77% for those younger than 6 years, with no change over time. In the pediatric AOM cohort, the antimicrobial prescription rate was 91% in 2001 but declined to 40% by 2019. Antimicrobial use increased from 0% to 75% for penicillins, whereas use of cephalosporins decreased from 84% to 10%. The prescription rate for acetaminophen alone increased from 33% to 58%. There were no differences in the incidence of adverse reactions among the prescribed antimicrobials. CONCLUSIONS: Due to education efforts and promotion of the proper use of antimicrobials through means such as the Clinical practice guidelines for the diagnosis and management of acute otitis media in children (2006) and the Manual of Antimicrobial Stewardship (2016), a change in the use of antimicrobials occurred, leading to a trend to more proper use of these agents.

Antihistamines for Allergic Rhinitis Treatment from the Viewpoint of Nonsedative Properties.

Antihistamines targeting the histamine H1 receptor play an important role in improving and maintaining the quality of life of patients with allergic rhinitis. For more effective and safer use of second-generation drugs, which are recommended by various guidelines, a classification based on their detailed characteristics is necessary. Antihistamines for first-line therapy should not have central depressant/sedative activities. Sedative properties (drowsiness and impaired performance) are associated with the inhibition of central histamine neurons. Brain H1 receptor occupancy (H1RO) is a useful index shown to be correlated with indices based on clinical findings. Antihistamines are classified into non-sedating (<20%), less-sedating (20⁻50%), and sedating (≥50%) groups based on H1RO. Among the non-sedating group, fexofenadine and bilastine are classified into "non-brain-penetrating antihistamines" based on the H1RO. These two drugs have many common chemical properties. However, bilastine has more potent binding affinity to the H1 receptor, and its action tends to last longer. In well-controlled studies using objective indices, bilastine does not affect psychomotor or driving performance even at twice the usual dose (20 mg). Upon selecting antihistamines for allergic rhinitis, various situations should be taken into our consideration. This review summarizes that the non-brain-penetrating antihistamines should be chosen for the first-line therapy of mild allergic rhinitis.

Changes in epidemiologic characteristics and antimicrobial resistance of Streptococcus pyogenes isolated over 10 years from Japanese children with pharyngotonsillitis.

Introduction. Pharyngotonsillitis caused by Streptococcus pyogenes (group A streptococci, or GAS) is among the most common infections treated with antibiotics in pediatric patients.Aim. This study aimed to analyse changes in molecular epidemiology and antibiotic susceptibility among GAS isolates in three study periods spanning 10 years.Methodology. GAS isolated from paediatric patients with pharyngotonsillitis during Period I (mid-2007 to 2008, n=235), Period II (2012, n=210), and Period III (2018, n=189) were analysed for emm type, multilocus sequence type (MLST), antibiotic susceptibility, and macrolide (ML)- and quinolone (QL)-resistance genes.Results. Over 20 % of isolates represented emm1 and emm12 types, remaining common in all three periods. Among other emm types, emm4 was common in Period I, emm28 and emm89 in Period II, and emm3 and emm89 in Period III. All isolates remained highly susceptible to penicillins and cephalosporins. Isolates possessing mefA, ermA, or ermB genes mediating ML resistance increased from 34.9 % in Period I to 60.9 % in Period II, but fell to 27.5 % in Period III. QL-resistant isolates with amino acid substitutions affecting ParC and/or GyrA gradually increased from 11.5 to 14.3 %. Specific sequence types identified by MLST and emm typing were associated closely with ML or QL resistance.Conclusion. Our findings indicate that even in ambulatory care, antibiotic choice for these infections should be based on rapid identification and characterization of causative pathogens.

Efficacy of a novel oral carbapenem, tebipenem pivoxil (TBM-PI), against experimental otitis media caused by penicillin resistant Streptococcus pneumoniae in chinchilla.

An animal model of otitis media using chinchillas was developed to evaluate the efficacy of tebipenem pivoxil (TBM-PI) against experimental otitis media. Chinchillas inoculated via the transbullar approach with Streptococcus pneumoniae serogroup 6 were included in the efficacy study with TBM-PI, amoxicillin (AMX) or untreated as controls. TBM-PI resulted in survival rate of 83%, compared with 25% survival for AMX and 0% survival for controls (p<0.01). Quantitative cultures in the middle ear effusions at day 5 of the TBM-PI group yielded 3.5+/-2.4log(10)CFUs/ml. TBM-PI is a promising antibiotic for the treatment of acute otitis media.

Structural studies on IgG oligosaccharides of patients with primary Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune disease, and some patients have been found to have SS complicated with rheumatoid arthritis (RA), in which IgG is known to carry abnormal N-linked oligosaccharides. In order to investigate the relationship between SS and RA, the structures of N-linked oligosaccharides of IgG from 12 primary SS patients without RA, 9 RA patients, and 8 healthy individuals were analyzed using reversed-phase high-performance liquid chromatography, in combination with sequential exoglycosidase treatment and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. All of the IgG samples obtained from primary SS patients, RA patients, and healthy individuals contained the same series of biantennary complex-type oligosaccharides, but the ratio of each oligosaccharide differed among these 3 groups. The incidence of galactose-lacking N-linked oligosaccharides obtained from the IgG of RA patients was significantly higher than that from healthy individuals, but that from the serum IgG of primary SS patients varied among individuals. The patients with primary SS were classified into two groups based on the galactosylation levels of IgG oligosaccharides; one group exhibits galactosylation levels as low as those of RA patients and another exhibits levels similar to those of healthy individuals. Measurement of levels of rheumatoid factor (RF) revealed that primary SS patients with a high incidence of RF belonged to the low galactosylation group, as did RA patients. These results suggest that appearance of IgG carrying abnormal N-linked oligosaccharides in primary SS may be related to future complication with RA.