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1.
Gerodontology ; 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37847782

RESUMO

OBJECTIVES: To survey oral status in detail and clarify the factors associated with nutritional status as evaluated by the Mini Nutritional Assessment. BACKGROUND: Malnutrition is common in older adults and increases the risk of frailty, sarcopenia, and mortality. However, few longitudinal studies have been performed to investigate the causal effect of oral status on malnutrition in detail, and the information reported in those longitudinal studies has been limited to dentition status and swallowing ability. MATERIALS AND METHODS: The participants in this prospective cohort study were patients who visited the Preventive Dentistry Clinic at Okayama University Hospital from November 2017 to January 2021. The number of teeth, periodontal condition, oral function (oral diadochokinesis, masticatory ability, number of bacteria in tongue coating, occlusal force, oral moisture, tongue pressure, swallowing function), nutritional status, the number of comorbidities, and mental health status were examined. These variables were analysed using structural equation modelling (SEM). RESULTS: The final analysis included 141 participants (40 males and 101 females; mean age, 73.5 ± 6.3 years; follow-up rate: 79.7%). The results of the SEM revealed that oral status (number of teeth present and swallowing function) was positively associated with nutritional status 2 years later. In addition, age was negatively associated with oral status. CONCLUSION: In community-dwelling older adult dental patients (age ≥60 years), oral function at baseline was associated with nutritional status two years later.

2.
Cancer Sci ; 113(9): 3110-3119, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35611470

RESUMO

This post-marketing surveillance (PMS) was initiated in Japan to identify factors affecting the safety and effectiveness of pembrolizumab monotherapy in patients with advanced non-small cell lung cancer (NSCLC) with programmed cell death ligand-1 (PD-L1) expression. This PMS was conducted from December 2016 to June 2019 at 717 centers across Japan. Patients with unresectable advanced/recurrent NSCLC who received pembrolizumab monotherapy as first-line (1L) treatment for PD-L1-expressing tumors (Tumor Proportion Score [TPS] ≥ 50%) or second-line or later (2L+) treatment for tumors with PD-L1 TPS ≥ 1% were enrolled and followed up for 1 year. Of 2805 registered patients, 2740 and 2400 comprised the safety and effectiveness analysis sets, respectively. The median age (range) was 69 (27-92) years; 55.7% and 29.2% of patients experienced treatment-related adverse events and adverse events of special interest (AEOSIs), respectively. More common AEOSIs included interstitial lung disease, endocrine disorders, liver dysfunction, colitis/severe diarrhea, infusion reactions, and severe skin disorders. The frequency of experiencing ≥2 AEOSIs was low (1L, 6.5%; 2L+, 2.8%). Most AEOSIs occurred within 150 days after initiation of pembrolizumab monotherapy. At 1-year follow-up, the objective response rate was 39.2% (1L, 51.5%; 2L+, 30.0%). In conclusion, the 1-year safety and effectiveness of pembrolizumab monotherapy in patients with unresectable advanced/recurrent NSCLC as 1L treatment for tumors with PD-L1 TPS ≥ 50% and 2L+ treatment for tumors with PD-L1 TPS ≥ 1% were similar to those reported in phase 2/3 trials.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Japão , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Vigilância de Produtos Comercializados
3.
Cytokine ; 149: 155723, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34662822

RESUMO

PURPOSE: The anticoagulant agent recombinant thrombomodulin (rTM) activates protein C to prevent excessive coagulation and also possibly regulates hyper-inflammation via neutralization of high-mobility-group B1 (HMG-B1). The glycocalyx layer in endothelial cells also plays a pivotal role in preventing septic shock-associated hyperpermeability. The present study examined the effect of rTM in a murine model of Streptococcus pneumoniae-induced sepsis. METHODS: Male C57BL/6N mice were injected intratracheally via midline cervical incision with 2 × 107 CFU of S. pneumoniae (capsular subtype 19A). Control mice were sham-treated identically but injected with saline. rTM (10 mg/kg) was injected intraperitoneally 3 h after septic insult. Blood concentrations of soluble inflammatory mediators (interleukin [IL]-1ß, IL-6, IL-10, and tumor necrosis factor [TNF]-α) were determined using a microarray immunoassay. Serum concentrations of HMG-B1 and syndecan-1, as a parameter of glycocalyx damage, were determined by enzyme-linked immunosorbent assay. The glycocalyx was also evaluated with electron microscopy. The lungs were removed, and digested to cells, which were then stained with a mixture of fluorophore-conjugated antibodies. Anti-mouse primary antibodies included PE-Cy7-conjugated anti-CD31, AlexaFluor 700-conjugated anti-CD45, PerCP-Cy5.5-conjugated anti-CD326, APC-conjugated anti-TNF-α, PE-conjugated anti-IL-6, and PE-conjugated anti-IL-10. A total of 1 × 106 cells per sample were analyzed, and 2 × 105 events were recorded by flow cytometry, and parameters were compared with/without rTM treatment. RESULTS: The blood concentration of TNF-α was significantly reduced 24 h after intratracheal injection in S. pneumoniae-challenged mice treated with rTM (P = 0.016). Levels of IL-10 in the lung endothelium of rTM-treated S. pneumoniae-challenged mice increased significantly 12 h after intratracheal injection (P = 0.03). Intriguingly, serum HMGB-1 and syndecan-1 levels decreased significantly (P = 0.010 and 0.015, respectively) in rTM-treated mice 24 h after intratracheal injection of S. pneumoniae. Electron microscopy indicated that rTM treatment preserved the morphology of the glycocalyx layer in septic mice. CONCLUSIONS: These data suggest that rTM modulates local inflammation in the lung endothelium, thus diminishing systemic inflammation, i.e., hypercytokinemia. Furthermore, rTM treatment reduced serum syndecan-1 levels, thus preventing glycocalyx damage. The use of rTM to treat sepsis caused by bacterial pneumonia could therefore help prevent both excessive inflammation and glycocalyx injury in the lung endothelium.


Assuntos
Glicocálix/metabolismo , Inflamação/metabolismo , Infecções Pneumocócicas/metabolismo , Proteínas Recombinantes/metabolismo , Choque Séptico/metabolismo , Streptococcus pneumoniae/patogenicidade , Trombomodulina/metabolismo , Animais , Modelos Animais de Doenças , Células Endoteliais , Proteína HMGB1/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-10 , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/metabolismo
4.
Epidemiol Infect ; 150: e66, 2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-35311634

RESUMO

After the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13), serotype replacement has occurred in Japan, and serotype 24 has become the most common serotype in paediatric invasive pneumococcal disease (IPD). To understand the characteristics of serotype 24-IPD in Japanese children in the post-PCV13 era, we conducted a retrospective study in children aged ≤15 years from 2010 to 2020 using a database of paediatric IPD surveillance in Chiba prefecture, Japan. We identified a total of 357 IPD cases and collected clinical information on 225 cases (24: 32 cases, non-24: 193 cases). Compared with the non-serotype 24-IPD, serotype 24-IPD was independently related to be <2 years of age [odds ratio (OR) 3.91, 95% confidence interval (CI) 1.47-10.44; P = 0.0064] and bacteremia (OR 2.28, 95% CI 1.01-5.13; P = 0.0475), as a result of the multivariate regression analysis. We also conducted a bacterial analysis, and the isolates of serotype 24-IPD had tendencies of PCG-susceptible (24: 100.0%, non-24: 61.3%; P < 0.0001) and macrolide-resistance (24: 100.0%, non-24: 87.3%; P = 0.0490). Their multilocus sequence typing was mostly ST2572 and the variants, which were unique to Japan. This tendency might have been a result of the progress made in the Japanese PCV13 immunisation programme.


Assuntos
Infecções Pneumocócicas , Streptococcus pneumoniae , Criança , Pré-Escolar , Humanos , Incidência , Lactente , Japão/epidemiologia , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas , Estudos Retrospectivos , Sorogrupo
5.
Epidemiol Infect ; 150: e184, 2022 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-36408537

RESUMO

This is the first report on a population-based prospective study of invasive group B streptococcus (GBS) disease among children aged <15 years conducted over a period of 11 years in Japan. This study investigated the incidence and clinical manifestations of invasive GBS disease in children in Chiba Prefecture, Japan, and analysed the serotypes and drug susceptibility of GBS strains isolated during the study period. Overall, 127 episodes of invasive GBS disease were reported in 123 patients. Of these, 124 were observed in 120 patients aged <1 year, and the remaining three episodes were reported in a 9-year-old child and two 14-year-old children with underlying disease. For patients aged <1 year, the incidence rate per 1000 live births was 0.24 (0.15-0.36). The incidences of early-onset disease and late-onset disease were 0.04 (0.0-0.09) and 0.17 (0.08-0.25), respectively. The rate of meningitis was 45.2%, and the incidence of GBS meningitis was higher than that of other invasive diseases among children in Japan. Of the 109 patients for whom prognosis was available, 7 (6.4%) died and 21 (19.3%) had sequelae. In total, 68 strains were analysed. The most common were serotype III strains (n = 42, 61.8%), especially serotype III/ST17 strains (n = 22, 32.4%). This study showed that the incidence of invasive GBS disease among Japanese children was constant during the study period. Because of the high incidence of meningitis and disease burden, new preventive strategies, such as GBS vaccine, are essential.


Assuntos
Infecções Estreptocócicas , Streptococcus agalactiae , Humanos , Criança , Japão/epidemiologia , Estudos Prospectivos , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Sorogrupo
6.
Gerodontology ; 39(4): 359-365, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34599786

RESUMO

OBJECTIVES: To clarify the associations among oral status, nutritional status and physical status in Japanese independent older adults. BACKGROUND: It is important to focus on factors affecting physical status associated with life dysfunction, long-term care and mortality. However, there are very few reports of the associations among oral status, nutritional status and physical status. MATERIALS AND METHODS: Patients who visited the Preventive Dentistry Clinic at Okayama University Hospital from November 2017 to January 2019 participated in this cross-sectional study. Number of teeth, periodontal condition and oral function were recorded. Bacteria counts in tongue dorsum, oral wettability, tongue pressure, tongue and lip movement function [oral diadochokinesis (ODK)], masticatory ability, bite force and swallowing function were measured. Nutritional status was assessed by the Mini Nutritional Assessment. Physical frailty status and Elderly Status Assessment Set were also evaluated. These variables were analysed by structural equation modelling (SEM). RESULTS: Data from 203 patients were analysed (63 males and 140 females). Patients ranged in age from 60 to 93 years. The final model of the path diagram was completed by SEM. ODK was positively associated with nutritional status, and nutritional status was negatively associated with frailty. Age was associated with ODK, nutritional status and frailty. CONCLUSION: Based on the associations among age, ODK, nutritional status and frailty, maintaining tongue movement function may contribute to good nutritional status and physical status in Japanese independent older adults.


Assuntos
Fragilidade , Estado Nutricional , Masculino , Feminino , Humanos , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Língua , Pressão , Japão/epidemiologia , Vida Independente
7.
J Infect Chemother ; 27(7): 1020-1026, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33658143

RESUMO

INTRODUCTION: In 2010, oral fluoroquinolone tosufloxacin (TFX) granules were released as the first oral respiratory quinolone for children in Japan. METHODS: To investigate the recent trend of H. influenzae strains with low susceptibility to quinolones in children, we analyzed the gene sequences of quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, parC, and parE of 23 clinical isolates from 15 patients aged <15 years with an MIC of ≥0.5 µg/mL for TFX from 2010 to 2018. RESULTS: Amino acid substitutions were observed in both GyrA and ParC in 13 strains (81%, 13/16), except two strains with a TFX MIC of 0.5 µg/mL with amino acid substitution in only GyrA and one strain with a TFX MIC of 1 µg/mL with no amino acid substitution. Four ST422 strains were observed in 2018, the detection age range was wide (0-7 years), and the residential city was varied. A total of 3/15 patients had a clear history of TFX treatment. CONCLUSIONS: Even for the strain with an MIC of 0.5 µg/mL for TFX, it is highly possible that it harbors a mutation in gyrA, which is the first step toward quinolone resistance, and it may also harbor mutations in both gyrA and parC. Furthermore, several specific sequence type quinolone-resistant H. influenzae strains, particularly ST422, may be widespread among children in Japan. It is necessary to investigate changes in resistance both at the MIC and gene levels. The continuous monitoring of strains and the use of antimicrobial drugs in treatment should be carefully observed.


Assuntos
Haemophilus influenzae , Quinolonas , Substituição de Aminoácidos , Criança , Pré-Escolar , DNA Girase/genética , DNA Topoisomerase IV/genética , Fluoroquinolonas/farmacologia , Haemophilus influenzae/genética , Humanos , Lactente , Recém-Nascido , Japão , Testes de Sensibilidade Microbiana , Mutação
8.
J Infect Chemother ; 27(1): 65-69, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32873462

RESUMO

INTRODUCTION: Neisseria lactamica is a commensal bacterium of the upper respiratory tract in humans and is closely related to Neisseria meningitidis. N. lactamica colonization may contribute to preventing N. meningitidis colonization and invasive meningococcal disease. However, the transference of antimicrobial resistance genes from N. lactamica to N. meningitidis has been reported. METHODS: In this study, we aimed to identify N. lactamica using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and performed multilocus sequence typing of seven N. lactamica strains isolated from Japanese children. We also analyzed the antimicrobial susceptibility of these strains and the mutations in their antimicrobial resistance genes (penA, gyrA, and parC). RESULTS: All the N. lactamica strains could be identified using MALDI-TOF MS. All strains were of different sequence types (STs), including five new STs. Five strains had intermediate susceptibility, two were resistant to ampicillin, and all had five out of the five known PBP2 mutations. Six strains were resistant to levofloxacin. Among the quinolone-resistant strains, three had GyrA mutations, and three had both ParC and GyrA mutations. CONCLUSIONS: N. lactamica STs may vary in Japanese children, and penicillin- and quinolone-resistant strains may be prevalent. We should pay attention not only to the drug resistance of N. meningitidis but also to the drug susceptibility of N. lactamica whose drug-resistance genes may transfer to N. meningitidis.


Assuntos
Infecções Meningocócicas , Neisseria lactamica , Neisseria meningitidis , Criança , Humanos , Japão/epidemiologia , Neisseria lactamica/genética , Neisseria meningitidis/genética , Sistema Respiratório
9.
J Infect Chemother ; 27(12): 1756-1759, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34376350

RESUMO

We describe a patient with invasive Haemophilus influenzae type b (Hib) infection despite being completely immunized by a conjugate Hib vaccine. Although Hib vaccination has contributed to significant reduction in invasive Hib infection, there are some case reports of invasive Hib infections despite immunization. Immunoglobulin (Ig) deficiency is the main cause of primary vaccine failure, and IgG2 subclass deficiency is known to be the leading cause. A previously healthy 13-month-old boy visited the outpatient clinic with a 5-day history of fever (40.0 °C), cough, and vomiting, and was diagnosed with bacterial meningitis, purulent pericarditis, and arthritis. Hib was recovered from blood, cerebrospinal fluid, and pericardial fluid. Immunological examination revealed subnormal IgG and IgA titers at 13 and 17 months of age. Serum IgG2 titer was recovered at 17 months of age despite being low at 13 months. Comprehensive gene analysis for primary immunodeficiency syndromes (primary antibody deficiency, common variable immunodeficiency, and toll-like receptor abnormalities) were negative. The antibody titer against Hib [anti-polyribosylribitol phosphate (PRP) antibody] was lower than the long-term protective titer (1.0 µg/ml) at 13 months of age, but was reactively increased to 2.38 µg/mL two months after booster immunization. Transient hypogammaglobulinemia of infancy (THI) is described as an accentuation and prolongation of the physiologic Ig nadir that is normally observed during infancy and defined as low IgG and IgA levels in the first three years of life. We speculate that he developed an invasive Hib infection as a result of primary Hib vaccine failure caused by THI.


Assuntos
Agamaglobulinemia , Infecções por Haemophilus , Vacinas Anti-Haemophilus , Haemophilus influenzae tipo b , Anticorpos Antibacterianos , Infecções por Haemophilus/tratamento farmacológico , Humanos , Lactente , Masculino , Vacinas Conjugadas
10.
Aging Clin Exp Res ; 33(2): 399-405, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32306370

RESUMO

BACKGROUND: Since oral organs function in the first stage of the swallowing process, it is possible that decline in swallowing function can be partly related to oral frailty. AIMS: The purpose of this study was to investigate the association between swallowing function and oral function among community-dwelling elderly Japanese and to propose cut-off values for screening of decline in swallowing function. METHODS: A total of 188 participants were included in the analysis. The number of present teeth and functioning teeth were counted. Bacteria counts in tongue coat, oral wettability, tongue pressure, oral diadochokinesis (ODK), masticatory ability and bite force were examined. Swallowing function was assessed using the 10-item Eating Assessment Tool (EAT-10). Receiver operating characteristic curves were used to determine the cut-off points of each oral function parameter. A logistic regression model was performed to determine the combination of parameters with the highest accuracy for differentiating decline in swallowing function from normal. RESULTS: Subjects with ODK /pa/ sound < 6.2 times/second had higher prevalence of swallowing problems than those with 6.2 times/second or more. EAT-10 scores of one or more were significantly related to older age (≥ 71 years old; odds ratio [OR] 4.321) and reduced ODK /pa/ sound (< 6.2 times/second; OR 2.914). CONCLUSIONS: Among community-dwelling elderly Japanese, those who were suspected of having decline in swallowing function had lower oral function than those who did not, and the cut-off values were 71 years of age and ODK /pa/ sound 6.2 times/s.


Assuntos
Deglutição , Vida Independente , Idoso , Estudos Transversais , Deglutição/fisiologia , Humanos , Japão , Pressão , Língua
11.
Acta Odontol Scand ; 79(2): 118-123, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32692586

RESUMO

OBJECTIVE: The purpose of this study was to investigate the association between the incidence of early childhood caries (ECC) and factors of the daytime childcare environment among toddlers in a rural area of Japan. MATERIAL AND METHODS: This was a prospective cohort study. Data collected from 2011 to 2015 were obtained for initially caries-free, 18-month-old toddlers (N = 640). Dentists recorded the numbers of decayed, missing and filled teeth (caries incidence) of toddlers at baseline (age 18 months) and follow-up (age 3 years). In addition, a questionnaire survey was conducted on guardians at baseline to record data on lifestyle. RESULTS: In total, 159 (24.8%) toddlers had newly identified ECC at follow-up. Logistic regression analyses indicated that the incidence of ECC was significantly associated with receiving daytime care at a nursery school (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.05-2.30; p = .029), prolonged breastfeeding (OR, 1.71; 95%CI, 1.15-2.55; p = .008), and snacking ≥3 times a day (OR, 2.39; 95%CI, 1.53-3.74; p < .001). CONCLUSION: These findings suggest that receiving daytime care at a nursery school, prolonged breastfeeding, and frequent snacking are associated with an increased risk of ECC among Japanese toddlers in rural areas.


Assuntos
Suscetibilidade à Cárie Dentária , Cárie Dentária , Criança , Pré-Escolar , Cárie Dentária/epidemiologia , Feminino , Humanos , Incidência , Lactente , Japão/epidemiologia , Prevalência , Estudos Prospectivos , Fatores de Risco
12.
J Infect Chemother ; 26(7): 749-751, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32409019

RESUMO

The non-encapsulated Streptococcus pneumoniae (NESp) has emerged and increased in the clinical setting. The majority of NESp strains have been isolated from the nasopharynxes of healthy carriers and from respiratory specimens of patients with otitis media. NESp strains were shown to be more effective than encapsulated counterparts at forming biofilms. Therefore, NESp should become one of the leading causes of emerging refractory respiratory disease after the introduction of pneumococcal conjugate vaccines. We report the first case of multidrug-resistant - including fluoroquinolone-resistant - NESp isolated from the intrabronchial aspirate of a patient with pneumonia. Drug-resistant NESp infections can possibly emerge as a clinical problem and thus the continuous monitoring of NESp infections is of utmost importance.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Pneumonia Pneumocócica/tratamento farmacológico , Streptococcus pneumoniae/efeitos dos fármacos , Adolescente , Ampicilina/farmacologia , Ampicilina/uso terapêutico , Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Testes de Sensibilidade Microbiana , Miopatias Congênitas Estruturais , Oftalmoplegia , Pneumonia Pneumocócica/diagnóstico , Pneumonia Pneumocócica/microbiologia , Canal de Liberação de Cálcio do Receptor de Rianodina/deficiência , Escarro/microbiologia , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificação , Sulbactam/farmacologia , Sulbactam/uso terapêutico , Cefozopran
13.
J Infect Chemother ; 26(9): 959-962, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32402734

RESUMO

Individuals with immunosuppressive condition have a high risk of invasive Haemophilus influenzae type b (Hib) infection. In Japan, routine Hib vaccination program for children under 5 years old was introduced in December 2008. However, the national policy does not make provision for individuals aged ≥5 years who have medical conditions associated with a high risk of invasive Hib disease to receive Hib vaccine. We measured serum anti-polyribosylribitol phosphate specific (anti-PRP) antibodies to Hib in patients aged ≥5 years with hematological malignancies and asplenia and evaluated their levels of anti-PRP antibodies in post administration of Hib vaccine era. A total of 65 patients (48 with hematological malignancies, and 17 with asplenia) were included in this study, of which 84% had not received Hib vaccine. In addition, 95.4% had short-term protective levels of anti-PRP antibodies (defined as ≥0.15 µg/mL) and 41.5% had long-term protective levels of anti-PRP antibodies (defined as ≥1.0 µg/mL). Five patients had low anti-PRP antibody levels despite a history of Hib vaccination. Our results suggest that young patients with underlying diseases such as hematological malignancies and asplenia may be at risk of invasive Hib disease. Hence, we recommend they should receive Hib vaccines even if they are over the age limit for routine Hib vaccination program.


Assuntos
Infecções por Haemophilus , Vacinas Anti-Haemophilus , Haemophilus influenzae tipo b , Neoplasias Hematológicas , Anticorpos Antibacterianos , Criança , Pré-Escolar , Infecções por Haemophilus/epidemiologia , Infecções por Haemophilus/prevenção & controle , Haemophilus influenzae , Humanos , Lactente , Japão/epidemiologia , Polissacarídeos , Vacinas Conjugadas
14.
J Infect Chemother ; 26(7): 745-748, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32171658

RESUMO

Although the pneumococcal conjugate vaccine (PCV) has decreased the incidence of invasive pneumococcal disease (IPD) in children, cases of IPD caused by non-PCV serotypes have been increasing. Here, we report two cases of bacterial meningitis caused by meropenem-resistant Streptococcus pneumoniae; in both the cases, 13-valent PCV (PCV13) had been administered. The isolated S. pneumoniae strains were non-PCV13 serotype 35B and resistant to penicillin G, cefotaxime, and meropenem. In addition, multilocus sequence typing (MLST) revealed the sequence type (ST) to be 558. In case 1, a 6-month-old girl recovered without sequelae after antibiotic therapy comprising cefotaxime and vancomycin, whereas in case 2, a 9-month-old boy was treated with an empirical treatment comprising ceftriaxone and vancomycin administration. However, maintaining the blood concentration of vancomycin within the effective range was difficult, due to which the antibiotics were changed to panipenem/betamipron. During the treatment, he presented with seizures, which were effectively controlled with antiepileptic drugs. The rate of incidence of penicillin-susceptible IPD has been substantially increasing after the introduction of PCV. However, an upsurge in IPD cases due to multidrug-resistant (MDR) serotype 35B has been reported in countries where PCV13 was introduced before introducing in Japan. Moreover, an increase in the proportion of MDR serotype 35B and decrease in the susceptibility to broad-spectrum antimicrobials, including meropenem, have been reported. Hence, the number of meningitis cases caused by MDR serotype 35B/ST558 may increase in the future.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Meningite Pneumocócica/tratamento farmacológico , Meropeném/farmacologia , Streptococcus pneumoniae/genética , Antibacterianos/uso terapêutico , Cefotaxima/farmacologia , Cefotaxima/uso terapêutico , Feminino , Humanos , Lactente , Masculino , Meningite Pneumocócica/sangue , Meningite Pneumocócica/diagnóstico , Meningite Pneumocócica/microbiologia , Meropeném/uso terapêutico , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Vacinas Pneumocócicas/administração & dosagem , Sorotipagem , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/isolamento & purificação , Tienamicinas/farmacologia , Tienamicinas/uso terapêutico , Resultado do Tratamento , beta-Alanina/análogos & derivados , beta-Alanina/farmacologia , beta-Alanina/uso terapêutico
15.
J Infect Chemother ; 25(10): 750-757, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31235348

RESUMO

The prevalence of nonencapsulated Streptococcus pneumoniae (NESp) has increased with the introduction of pneumococcal conjugate vaccines in children; however, the bacteriological characteristics of NESp have not been sufficiently clarified. In this study, NESp strains isolated from the nasopharyngeal carriage of children from four nursery schools in Japan were analyzed for molecular type, antibiotic susceptibility, and biofilm productivity. A total of 152 putative S. pneumoniae strains were identified by optochin-susceptibility analysis, of which 21 were not serotypeable by slide agglutination, quellung reaction, or multiplex PCR. Among these 21 strains, three were lytA-negative and, therefore, not S. pneumoniae. The remaining 18 strains were positive for lytA, ply, pspK, and bile solubility and were confirmed as NESp. Therefore, the isolation rate of NESp in the S. pneumoniae strains in this study was 12.0% (18/149). Molecular-typing analyses classified five strains as two existing sequence types (STs; ST7502 and ST7786), and 13 strains formed four novel STs. Horizontal spread was suspected, because strains with the same ST were often isolated from the same nursery school. The NESp isolates were generally susceptible to most antimicrobials, with the exception of macrolides; however, all isolates possessed more than one abnormal penicillin-binding protein gene. Furthermore, NESp strains were more effective than encapsulated counterparts at forming biofilms, which showed obvious differences in morphology. These data indicated that NESp strains should be continuously monitored as emerging respiratory pathogens.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Infecções Pneumocócicas/terapia , Vacinas Pneumocócicas/uso terapêutico , Streptococcus pneumoniae/isolamento & purificação , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/genética , Humanos , Lactente , Recém-Nascido , Japão/epidemiologia , Testes de Sensibilidade Microbiana , Tipagem Molecular/métodos , Mutação , Mucosa Nasal/microbiologia , Proteínas de Ligação às Penicilinas/genética , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Prevalência , Sorotipagem , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/imunologia , Fatores de Virulência/genética
16.
J Infect Chemother ; 25(8): 630-634, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30902556

RESUMO

Panton Valentine Leukocidin (PVL) is one of the many toxins produced by Staphylococcus aureus. In Japan, PVL-positive S. aureus strains are mainly methicillin-resistant S. aureus (MRSA). Data regarding PVL-positive methicillin-sensitive S. aureus (MSSA) are scarce. In this report, we describe a case of severe infection by PVL-positive MSSA. A 12-year-old healthy girl was admitted with high fever and pain in the lower back. Computed tomography revealed a diagnosis of psoitis and multiple venous thromboses. Blood cultures obtained after admission revealed infection with MSSA. Her fever continued despite adequate antibiotic therapy. On the fifth hospitalization day, she developed bladder dysfunction, and an abscess was noted near the third lumbar vertebra. She underwent an emergency operation and recovered. Bacterial analyses revealed that the causative MSSA was a PVL-producing single variant of ST8 (related to USA300clone), of sequence type 2149. PVL is known to cause platelet activation. This case demonstrates the need for detailed analyses of the causative strain of bacteria in cases of S. aureus infection with deep vein thrombosis, even in cases of known MSSA infection.


Assuntos
Toxinas Bacterianas/efeitos adversos , Exotoxinas/efeitos adversos , Leucocidinas/efeitos adversos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Infecções Estafilocócicas/complicações , Trombose Venosa/etiologia , Trombose Venosa/microbiologia , Antibacterianos/uso terapêutico , Criança , Feminino , Humanos , Japão , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Trombose Venosa/tratamento farmacológico
17.
J Clin Microbiol ; 56(7)2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29720429

RESUMO

Haemophilus influenzae type b (Hib) conjugate vaccines have led to dramatic reductions in Hib disease among young children worldwide. Nontypeable H. influenzae (NTHi) is now the major cause of invasive H. influenzae infections. We investigated the clinical characteristics of invasive NTHi diseases among children in Japan, to clarify the pathogenicity of isolated NTHi strains. The mortality rate was 10.7%, with deaths occurring mainly among children with underlying comorbidities. Biotypes II and III were the most common, and most strains (64.3%) had multiple amino acid substitutions at the Asp-350, Ser-357, Ser-385, and/or Met-377 sites of penicillin-binding protein 3. Two strains were ß-lactamase positive and ampicillin-clavulanate resistant. Biofilm indices varied widely, and IS1016 was detected in 10.7% of the strains tested. Moreover, there was wide variation in the characteristics of invasive NTHi strains. NTHi strains, showing great genetic diversity, are responsible for most invasive H. influenzae infections in children in the postvaccine era. Continuous monitoring of NTHi strains responsible for invasive diseases in children is important to detect changes in the epidemiology of invasive H. influenzae infections in the postvaccine era.


Assuntos
Infecções por Haemophilus/microbiologia , Haemophilus influenzae/classificação , Haemophilus influenzae/fisiologia , Antibacterianos/farmacologia , Aderência Bacteriana/genética , Técnicas de Tipagem Bacteriana , Biofilmes/crescimento & desenvolvimento , Criança , Pré-Escolar , Elementos de DNA Transponíveis , Farmacorresistência Bacteriana/genética , Variação Genética , Genoma Bacteriano/genética , Infecções por Haemophilus/epidemiologia , Infecções por Haemophilus/mortalidade , Infecções por Haemophilus/fisiopatologia , Haemophilus influenzae/efeitos dos fármacos , Haemophilus influenzae/genética , Humanos , Lactente , Recém-Nascido , Japão/epidemiologia , Testes de Sensibilidade Microbiana , Análise de Sequência de DNA
18.
Med Mycol ; 56(6): 679-686, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29087483

RESUMO

Invasive fungal infection (IFI) is a life-threating infectious disease in high-risk neonates. Strategies for the treatment and prevention of IFI in neonates in Japan remain unclear. We conducted a nationwide retrospective survey to determine IFI incidence between January 2014 and October 2015. Primary survey questionnaires were submitted to 309 medical facilities that regularly treat high-risk neonates. The questionnaire assessed IFI incidence during the study period, methods for preventing fungal infection in early delivery neonates, and methods for preventing mother-to-child fungal transmission. The secondary questionnaire was for facilities that had IFI cases and replied to the primary questionnaire. In total, 128 medical facilities (41.4%) completed the primary questionnaire, 17/128 facilities recorded 23 proven or probable IFI cases. Estimated annual IFI incidence was 0.33/1000 live births of hospitalized neonates. Patient data at IFI onset were available for all 23 patients. Birth weight was < 1000 g in 18 patients. Causative microorganisms were identified in 22 patients. Candida species (n = 21) were the most common pathogens, and one patient had mucormycosis. The mortality rate was 17.4%. Regarding neonatal fungal prophylaxis, 55/128 facilities (43.0%) reported administering therapy. The most frequently used prophylactic drugs were fluconazole, then micafungin. Fungal prophylaxis for mothers who showed fungal colonization was performed in 30/128 facilities (23.4%). Oxiconazole vaginal tablets were most commonly used as prophylaxis for high-risk mothers. In Japan, the diagnosis, treatment, and prevention of neonatal IFI varied. Continuous surveillance and treatment regimen for neonatal IFI are required to improve outcomes in high-risk neonates.


Assuntos
Candida/isolamento & purificação , Candidíase Invasiva/epidemiologia , Candidíase Invasiva/mortalidade , Doenças do Prematuro/epidemiologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida/classificação , Candida/efeitos dos fármacos , Candidíase Invasiva/tratamento farmacológico , Causas de Morte , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/tratamento farmacológico , Doenças do Prematuro/mortalidade , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Japão/epidemiologia , Masculino , Mães , Estudos Retrospectivos , Fatores de Risco , Inquéritos e Questionários
19.
J Infect Chemother ; 24(5): 401-403, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29373267

RESUMO

We report a case of mediastinal subcutaneous and multiple muscular abscesses caused by group B streptococcus serotype VIII in a type 2 diabetes mellitus patient. The patient arrived at the hospital with the chief complaint of immobility, and blood examination results suggested an acute infection and poorly controlled diabetes mellitus. Group B streptococcal bacteria were cultured from the patient's blood, and identified as serotype VIII upon further analysis. The patient recovered without any sequelae after percutaneous drainage, antibiotic therapy, and intensive glycemic control. Although the incidence of group B streptococcal infection in non-pregnant adults has recently increased in many developed countries, information on serotype VIII infection is quite limited. The reason is that serotype VIII group B streptococci are a Japan-specific serotype, and rarely cause invasive infections, even in Japan. Therefore, further surveillance and case reports should be documented in the future.


Assuntos
Abscesso/microbiologia , Diabetes Mellitus Tipo 2/complicações , Doenças do Mediastino/microbiologia , Infecções Estreptocócicas/complicações , Streptococcus/classificação , Abscesso/diagnóstico por imagem , Drenagem , Feminino , Humanos , Incidência , Japão , Doenças do Mediastino/diagnóstico por imagem , Pessoa de Meia-Idade , Sorogrupo , Infecções Estreptocócicas/sangue , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/microbiologia , Streptococcus/isolamento & purificação
20.
J Infect Chemother ; 24(7): 510-514, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29534849

RESUMO

Haemophilus influenzae is a major pathogenic bacteria causing invasive disease, which is classified into six capsular serotypes (a-f) and non-typeable (NT) strains. Capsular serotyping of H. influenzae is traditionally determined by serological methods and more recently by PCR methods. However, these methods are time-consuming and expensive. In the present study, matrix-associated laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) was evaluated as an alternative method for capsular serotyping of H. influenzae clinical strains. We created an in-house database of all six serotypes and NT H. influenzae strains using the main spectrum creation standard method set to the default parameters in MADI-TOF MS. We evaluated the performance of the in-house database using 79 clinical strains already identified by PCR and 58 prospectively collected clinical strains. Measurements were performed using the Bruker MALDI BioTyper system. The peak list was matched against the reference library using the integrated pattern algorithm of the software. The best-matched spectrum was considered the serotyping result. All 137 test strains were correctly identified as H. influenzae using MALDI-TOF MS. The sensitivity and specificity for identification for type b, type e, and type f capsular serotypes and NT H. influenzae using MALDI-TOF MS were 100%/94.3%, 94.7%/97.9%, 97.4%/97.9%, and 85.5%/99.2%, respectively. Our findings indicate that MALDI-TOF MS is a useful alternative method for capsular serotyping of H. influenzae strains. This method is faster and more cost-effective than traditional methods and will therefore be useful for routine applications in clinical laboratories.


Assuntos
Cápsulas Bacterianas/imunologia , Infecções por Haemophilus/microbiologia , Haemophilus influenzae/classificação , Sorotipagem/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , DNA Bacteriano/genética , Infecções por Haemophilus/diagnóstico , Haemophilus influenzae/genética , Haemophilus influenzae/imunologia , Humanos , Sensibilidade e Especificidade , Software
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