The rate of medication persistence was examined in patients with schizophrenia or schizoaffective disorder during switching from previously administered antipsychotics to brexpiprazole, a new ...dopamine D2 receptor partial agonist. A multicenter, single‐arm, open‐label 24‐week interventional study was conducted, consisting of two 12‐week consecutive periods: an initial switch (by plateau cross‐titration) with the subsequent period, followed by a second maintenance period. Prior antipsychotics were olanzapine or risperidone/paliperidone. The primary and secondary outcome measures were medication persistence rates after the first 12 weeks and changes from baseline in the Specific Levels of Functioning Scale (SLOF), Subjective Well‐being under Neuroleptic drug treatment Short form (SWNS), and Positive and Negative Syndrome Scale (PANSS) scores, respectively. In total, 79 patients were administered brexpiprazole and the medication persistence rate at 12 weeks was 78.5%, which was significantly higher than the predefined threshold of 65%. Regarding the prior medication, the persistence rate at 12 weeks was 84.6% for olanzapine and 72.5% for risperidone/paliperidone. Significant improvements from baseline were observed in the SLOF, SWNS, and PANSS scores. There were no adverse events of concern. Thus, brexpiprazole appeared to be a suitable antipsychotic on switching from olanzapine, risperidone, or paliperidone.
The medication persistent rate after switching from olanzapine or risperidone/paliperidone to brexpiprazole in patients with schizophrenia or schizoaffective patients was 78.5%, exceeding the predefined threshold of 65% using a longer tapering period than in the previous trial. In addition, significant improvements in functioning, well‐being, and symptoms were observed with no adverse events of concern. Brexpiprazole appeared to be a suitable antipsychotic to switch to.
BACKGROUND:Nontypeable Haemophilus influenzae is a particularly important cause of acute otitis media (AOM). There is a high prevalence of β-lactamase–nonproducing ampicillin-resistant (BLNAR) ...strains in Japanese children, which is associated with recurrent AOM and prolonged treatment. The aim of this study was to investigate the antimicrobial susceptibility profile, mechanisms of ampicillin resistance and molecular epidemiology of ampicillin resistance in H. influenzae strains causing AOM in Japanese children.
METHODS:One hundred fifty-seven strains of H. influenzae isolated from the middle ear fluid of pediatric patients (aged 0–3 years) with AOM from various areas of Japan were studied. The antimicrobial susceptibility profile, genes encoding β-lactamase and alterations of penicillin-binding protein 3 were investigated. Genetic relatedness among ampicillin-resistant isolates was examined by multilocus sequence typing and pulsed-field gel electrophoresis.
RESULTS:Of 157 isolates, 108 (68.8%) demonstrated reduced susceptibility to ampicillin, including 95 (60.5%) of β-lactamase–nonproducing isolates and 13 (8.3%) of β-lactamase–producing isolates. All BLNAR (minimum inhibitory concentration of ampicillin ≥ 4 mg/L) isolates had amino acid substitutions related to ampicillin resistance. Multilocus sequence typing and pulsed-field gel electrophoresis demonstrated genetic diversity although there were 2 clusters of highly resistant isolates with identical STs (sequence types; ST161 and 549).
CONCLUSIONS:Alterations of penicillin-binding protein 3 represented the most prevalent mechanism of ampicillin resistance among H. influenzae isolates causing AOM in Japanese children. BLNAR isolates from children with AOM demonstrated genetic diversity. This study identified for the first time ST clones associated with BLNAR H. influenzae causing AOM in Japanese children.
The prevalence of ESBL has been increasing worldwide. In this study, we investigated the molecular characteristics of ESBL among clinical isolates of Escherichia coli from a Japanese tertiary ...hospital. A total of 71 consecutive and nonduplicate clinical isolates of ESBL-positive E. coli collected at Tohoku University Hospital between January 2008 and March 2011 were studied. The antimicrobial susceptibility profile of these strains was determined. PCR and sequencing were performed to identify genes for β-lactamase (bla(TEM), bla(SHV), bla(OXA-1-like), and bla(CTX-M)) and plasmid-mediated quinolone resistance determinants (PMQR). The isolates were also analyzed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Of the 71 strains, 68 were positive for CTX-M, 28 were positive for TEM, four were positive for OXA-1, and one was positive for SHV. Sequencing revealed that CTX-M-14 was the most prevalent (31/71), followed by CTX-M-27 (21/71) and then CTX-M-15 (9/71). Of the 28 TEM-positive strains, one was TEM-10 and the rest were TEM-1. One SHV-positive strain was SHV-12. The 21 CTX-M-27-producing isolates were divided into 14 unique PFGE types, while the 9 CTX-M-15 producers were divided into 8 types. Based on MLST, 9 CTX-M-14 procedures, 19 CTX-M-27 procedures, and 8 CTX-M-15 producers belonged to ST131. Thirty-five (94.6%) of the 37 ST131 E. coli strains showed resistance to levofloxacin, which was a higher rate than among non-ST131 strains (63.6%). Among ESBL-producing isolates, one, two, and six possessed qnrB, qnrS, qepA, and aac(6')-Ib-cr, respectively. Of the 6 isolates with aac(6')-Ib-cr, 4 carried the CTX-M-15 gene. Our data suggest that CTX-M-15-producing E. coli ST131 has emerged as a worldwide pandemic clone, while CTX-M-27 (a variant of CTX-M-14) is also spreading among E. coli ST131 in Japan.
The third-generation cephalosporin (3GC)-resistant E. coli strains have been detected worldwide in humans and animals. Hence, in this study, we evaluated the prevalence and genetic characteristics of ...3GC-resistant E. coli in livestock, farmers, and patients to further analyse if livestock serves as a potential reservoir of antimicrobial-resistant bacteria.
Faecal samples were collected from 330 healthy livestock (216 cattle and 114 swine), 61 healthy livestock farmers (52 cattle farmers and 9 swine farmers), and 68 non-duplicate 3GC-resistant E. coli isolates were also obtained from the clinical specimens of patients in Japan between 2013 and 2015. Genes associated with resistance in 3GC-resistant E. coli were identified using polymerase chain reaction (PCR) and DNA sequencing. Genotypic diversity was determined by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE).
We obtained 39 and 17 non-duplicated 3GC-resistant E. coli strains from healthy livestock (33 cattle and six swine) and livestock farmers, respectively. All isolates carried either CTX-M-type extended-spectrum β-lactamase or plasmid-mediated AmpC β-lactamase genes, with CTX-M-14 being the most frequent. CTX-M producers from livestock and patients belonged to 22 and 19 different sequence types (STs), respectively, and only three STs were the same. Among the 3GC-resistant E. coli from livestock and farmers, three types of CTX-M producers have shown similar characteristics (CTX-M genotype, ST, PFGE patterns, and antimicrobial susceptibilities) and were identified as clonal isolates shared among their farms.
Our study findings indicate that CTX-M-14 is predominant in Japan. No distinct relationship was observed between the 3GC-resistant E. coli isolated from livestock and patients; however, some clonal relatedness was observed between the isolates from livestock and farmers due to their close contact.
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•CTX-M-14 is predominantly detected in livestock, farmers, and patients.•No distinct relationship in 3GC-resistant E. coli isolates of livestock and patients.•Clonal relatedness between livestock and farmers was due to their close contact.
Dear Editor, Carbapenem-resistant Enterobacteriaceae have acquired carbapenemase genes 1, which differ substantially across countries 2. Transferable carbapenemase IMP-type metallo-β-lactamases, ...particularly IMP-1 and IMP-6, are commonly identified in the clinical setting in Japan 3, 4 and exhibit different substrate specificity despite having a difference of only one amino acid (IMP-6: Ser214Gly). IMP-1 producers are more resistant to imipenem than to meropenem, whereas IMP-6 producers are more resistant to meropenem 5. We previously found that the susceptibility rate of IMP-6-positive Escherichia coli was higher for imipenem than for meropenem 3. Thus, IMP-6-producing isolates may be erroneously categorized as imipenem-susceptible, which could lead to treatment failure in patients. KCI Citation Count: 2
Although outbreaks of parainfluenza virus type 3 (PIV-3) have been reported in children, to our knowledge none have been reported in a nursery school. As the symptoms of PIV-3 infection are similar ...to those of COVID-19 infection, accurate diagnosis of PIV-3 and other respiratory viruses is important during the COVID-19 pandemic.
We experienced an outbreak of upper respiratory symptoms at a nursery school in Miyagi Prefecture, Japan, from 29/5/2021 to 13/6/2021 and aimed to determine the causative organism(s).
A multiplex polymerase chain reaction (PCR) assay which enabled rapid detection of a variety of causative microorganisms of respiratory tract infections was used to analyse 13 nasopharyngeal swabs collected during the outbreak. Infection Prevention and control measures were implemented to prevent further spread of infection.
All 13 samples were positive for PIV-3 infection. 2 of the 13 samples were also positive for rhinovirus/enterovirus and 1 sample was also positive rhinovirus/enterovirus and coronavirus NL 63. No samples were positive for SARS-CoV-2.
Children in school settings are especially vulnerable to respiratory viral infections, including COVID-19. Children under two years are unable to wear masks reliably, and the COVID-19 vaccine was approved only for older children. Multiplex PCR assays can be used for the rapid diagnosis of respiratory infections.
We identified an outbreak of PIV-3 in a nursery school during the COVID-19 pandemic. The investigation of the outbreak highlighted that it was important not to overlook other respiratory infections including PIV-3 during the COVID-19 pandemic. The multiplex PCR assay provided rapid and accurate diagnosis of the causative organisms in the outbreak and helped to direct appropriate interventions to control the outbreak.
Mutations in the quinolone resistance-determining regions (QRDRs) of
DNA gyrase (
) and topoisomerase IV (
) are linked to fluoroquinolone (FQ) resistance. We developed a mismatched PCR-restriction ...fragment length polymorphism (RFLP) assay to detect mutations in the
and
QRDRs associated with FQ resistance in
.
Based on the conserved sequences of
and
, two primer sets were designed for mismatched PCR-RFLP to detect mutations in
(codons 83 and 87) and
(codons 80 and 84) by introducing an artificial restriction enzyme cleavage site into the PCR products. This assay was evaluated using 58
strains and 37 other Acinetobacter strains that have been identified by RNA polymerase β-subunit gene sequence analysis.
PCR amplification of
and
was successful for all
strains. In 11 FQ -susceptible strains, the
and
PCR products were digested by the selected restriction enzymes at the site containing
(codons 83 and 87) and
(codons 80 and 84). PCR products from 47 FQ-resistant strains containing mutations in
and
were not digested by the restriction enzymes at the site containing the mutation. As for the non-
strains, although amplification products for
were obtained for 28 strains, no
amplification product was obtained for any strain.
This assay specifically amplified
and
from
and detected
and
mutations with FQ resistance.
Abstract Introduction Streptococcus pneumoniae is one of the most common bacteria causing otorhinolaryngological infections, such as acute otitis media and upper respiratory tract infection. Our ...group surveyed the drug susceptibility profile of S. pneumoniae isolates from otorhinolaryngology patients. Materials and methods A total of 41,069 S. pneumoniae isolates were detected at Miyagi Medical Association Health Center between May 2001 and December 2012. Specimens were obtained from patients at 40 otorhinolaryngology outpatient clinics in Miyagi Prefecture, Japan. The minimum inhibitory concentrations (MICs) of 8 antimicrobial agents were measured using the broth microdilution method according to Clinical and Laboratory Standards Institute guidelines. Results In children aged 0–2 years old, the MIC50 values of penicillins decreased after 2010 (PCG: 1 μg/ml (2010) to 0.06 μg/ml (2012); ABPC: 1 μg/ml (2010) to 0.25 μg/ml (2012)). The prevalence of penicillin-resistant S. pneumoniae (PRSP) decreased from 35.2% (2010) to 14.6% (2012) in rhinorrhea specimens and from 43.4% (2010) to 14.3% (2012) in otorrhea specimens. Susceptibility to cephems (ceftriaxone and cefditoren) and carbapenems (panipenem) also showed improvement after 2010. For macrolides (clarithromycin) and lincosamides (clindamycin), MIC50 values increased in all age groups during the study period, and a high level of resistance was seen until 2012. There were no marked changes of susceptibility to fluoroquinolones (LVFX) during the study period. Conclusion Improvement of susceptibility of S. pneumoniae to β-lactams occurred after 2010 in Miyagi Prefecture, Japan.