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1.
Artigo em Inglês | MEDLINE | ID: mdl-31182539

RESUMO

The novel arylamidine T-2307 exhibits broad-spectrum in vitro and in vivo antifungal activities against clinically significant pathogens. Previous studies have shown that T-2307 accumulates in yeast cells via a specific polyamine transporter and disrupts yeast mitochondrial membrane potential. Further, it has little effect on rat liver mitochondrial function. The mechanism by which T-2307 disrupts yeast mitochondrial function is poorly understood, and its elucidation may provide important information for developing novel antifungal agents. This study aimed to determine how T-2307 promotes yeast mitochondrial dysfunction and to investigate the selectivity of this mechanism between fungi and mammals. T-2307 inhibited the respiration of yeast whole cells and isolated yeast mitochondria in a dose-dependent manner. The similarity of the effects of T-2307 and respiratory chain inhibitors on mitochondrial respiration prompted us to investigate the effect of T-2307 on mitochondrial respiratory chain complexes. T-2307 particularly inhibited respiratory chain complexes III and IV not only in Saccharomyces cerevisiae but also in Candida albicans, indicating that T-2307 acts against pathogenic fungi in a manner similar to that of yeast. Conversely, T-2307 showed little effect on bovine respiratory chain complexes. Additionally, we demonstrated that the inhibition of respiratory chain complexes by T-2307 resulted in a decrease in the intracellular ATP levels in yeast cells. These results indicate that inhibition of respiratory chain complexes III and IV is a key factor for selective disruption of yeast mitochondrial function and antifungal activity.


Assuntos
Amidinas/farmacologia , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Saccharomyces cerevisiae/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Animais , Candida albicans/metabolismo , Bovinos , Complexo I de Transporte de Elétrons/metabolismo , Complexo II de Transporte de Elétrons/metabolismo , Testes de Sensibilidade Microbiana , Mitocôndrias/metabolismo , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , NADH Desidrogenase/metabolismo , Ratos , Saccharomyces cerevisiae/metabolismo
2.
Sci Rep ; 9(1): 9331, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31249356

RESUMO

Candida peritonitis is a crucial disease, however the optimal antifungal therapy regimen has not been clearly defined. Peritoneal fibrosis (PF) can be caused by abdominal surgery, intra-abdominal infection, and malignant diseases, and is also widely recognized as a crucial complication of long-term peritoneal dialysis. However, the influence of PF on Candida peritonitis prognosis remains unknown. Here, we evaluated the severity of Candida peritonitis within the context of PF and the efficacy of micafungin using mice. A PF mouse model was generated by intraperitoneally administering chlorhexidine gluconate. Candida peritonitis, induced by intraperitoneal inoculation of Candida albicans, was treated with a 7-day consecutive subcutaneous administration of micafungin. Candida infection caused a higher mortality rate in the PF mice compared with the control mice on day 7. Proliferative Candida invasion into the peritoneum and intra-abdominal organs was confirmed pathologically only in the PF mice. However, all mice in both groups treated with micafungin survived until day 20. Micafungin treatment tends to suppress inflammatory cytokines in the plasma 12 h after infection in both groups. Our results suggest that PF enhances early mortality in Candida peritonitis. Prompt initiation and sufficient doses of micafungin had good efficacy for Candida peritonitis, irrespective of the underlying PF.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Micafungina/farmacologia , Fibrose Peritoneal/complicações , Peritonite/complicações , Peritonite/microbiologia , Animais , Biomarcadores , Citocinas , Modelos Animais de Doenças , Histocitoquímica , Humanos , Camundongos , Fibrose Peritoneal/patologia , Peritonite/tratamento farmacológico , Peritonite/patologia , Prognóstico , Resultado do Tratamento
3.
J Infect Chemother ; 25(9): 702-707, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30982729

RESUMO

Oral antibiotic therapy for patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) usually involves an aminopenicillin with clavulanic acid, a macrolide, or a quinolone. To date, however, the clinical efficacy and safety of the oral cephalosporin cefditoren pivoxil has not been evaluated in Japanese patients with acute exacerbations of COPD. We conducted a prospective, multicenter, single arm, interventional study from January 2013 to March 2017 to determine the efficacy and safety of oral administration of 200 mg cefditoren pivoxil three times daily for 7 days in a cohort of 29 eligible patients from 15 hospitals. The mean age (SD) of participants was 73.1 (8.1) years and 28 had a smoking history (the mean [SD] of smoking index, 1426.7 [931.7]). The primary efficacy endpoint was clinical response (cure rate) at test of cure, which was set at 5-10 days after treatment ceased. Of the 23 patients finally analyzed, cure was achieved in 15 (65.2%), while 8 (34.8%) remained uncured. Previous experience of acute exacerbations significantly affected the cure rate: none of the three patients who had at least two prior exacerbations were cured, while 15 of the 20 patients with one or fewer prior exacerbations were cured (p = 0.032). The microbiological eradication rate was 88.9% at test of cure. During treatment, mild pneumonia was reported as an adverse event in one patient (3.4%) but resolved within 10 days of onset. We conclude that cefditoren pivoxil represents a viable alternative for antibiotic therapy in patients with few prior exacerbations.


Assuntos
Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração Oral , Adulto , Idoso , Antibacterianos/administração & dosagem , Gestão de Antimicrobianos , Cefalosporinas/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
4.
Intern Med ; 57(23): 3485-3490, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30101932

RESUMO

Scedosporium apiospermum is an opportunistic fungus that can cause various types of infections, including localized infections and life-threatening disseminated infections, particularly in immunocompromised patients. Treatment is especially challenging due to its multidrug resistance. We herein report the case of a 73-year-old woman who was non-immunocompromised but developed S. apiospermum lung infection and a pulmonary tumorlet. To our knowledge, this is the first report of the coexistence of pulmonary S. apiospermum infection and tumorlet. The lung lesion was successfully treated by surgical excision without any antifungal agents, and no recurrence of the tumorlet or S. apiospermum infection has occurred.


Assuntos
Pneumopatias Fúngicas/complicações , Pneumopatias Fúngicas/microbiologia , Nódulos Pulmonares Múltiplos/complicações , Nódulos Pulmonares Múltiplos/microbiologia , Scedosporium/isolamento & purificação , Idoso , Feminino , Humanos , Imunocompetência , Pneumopatias Fúngicas/cirurgia , Nódulos Pulmonares Múltiplos/cirurgia
5.
J Infect Chemother ; 24(6): 434-442, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29530544

RESUMO

The objective of this open-label, randomised (i.e. 2:1 ratio), Phase 3 study was to compare the efficacy and safety of tedizolid phosphate 200 mg, once-daily treatment with that of linezolid 600 mg, twice-daily treatment for 7-14 days in Japanese adult patients (N = 125) with skin and soft tissue infections (SSTIs) and/or for 7-21 days for those with SSTI-related bacteraemia, caused by confirmed or highly suspected methicillin-resistant Staphylococcus aureus (MRSA). Primary outcome was clinical cure rate at test-of-cure (TOC, in SSTI: 7-14 days, in bacteraemia: 4-6 weeks after end-of-therapy [EOT]) time point in the microbiologically evaluable MRSA (ME-MRSA) population (N = 39). Secondary endpoints were clinical and microbiological response rates at EOT. Safety parameters were evaluated in the safety analysis population up to follow up. Data analysis was descriptive in nature. Baseline characteristics of patients were similar between treatment groups. At TOC in the ME-MRSA population, clinical cure rate was similar in tedizolid phosphate (92.6%) and linezolid (88.9%) groups. At EOT, clinical cure (tedizolid phosphate: 93.1%, linezolid: 90.0%) and microbiological success (tedizolid phosphate: 93.1%, linezolid: 100.0%) rates were similar in the ME-MRSA population. Both treatments were well tolerated; overall treatment-emergent adverse events (TEAEs) in tedizolid phosphate (79.5%) and linezolid (75.6%) treatment groups were similar. Drug-related TEAEs were numerically lower with tedizolid phosphate versus linezolid (30.1%; 39.0%, respectively), as well as gastrointestinal (21.7%; 26.8%) and myelosuppression-related (2.4%; 22.0%) TEAEs. One death occurred in the linezolid group. Tedizolid phosphate may be an appropriate antibiotic for the treatment of SSTIs in Japanese adult patients. International clinical trial registration number: NCT01967225. Japanese clinical trial registration number: JapicCTI-132308.


Assuntos
Antibacterianos/farmacocinética , Linezolida/farmacocinética , Organofosfatos/farmacocinética , Oxazóis/farmacocinética , Dermatopatias Bacterianas/tratamento farmacológico , Infecções dos Tecidos Moles/tratamento farmacológico , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Feminino , Humanos , Japão , Linezolida/administração & dosagem , Linezolida/uso terapêutico , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Organofosfatos/administração & dosagem , Organofosfatos/uso terapêutico , Oxazóis/administração & dosagem , Oxazóis/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento
6.
PLoS One ; 12(3): e0174547, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28355256

RESUMO

The natural course of idiopathic pulmonary fibrosis (IPF) is variable. Predicting disease progression and survival in IPF is important for treatment. We previously demonstrated that serum periostin has the potential to be a prognostic biomarker for IPF. Our aim was to use monomeric periostin in a multicenter study to evaluate its efficacy in diagnosing IPF and predicting its progression. To do so, we developed a new periostin kit to detect only monomeric periostin. The subjects consisted of 60 IPF patients in a multicenter cohort study. We applied monomeric periostin, total periostin detected by a conventional kit, and the conventional biomarkers-KL-6, SP-D, and LDH-to diagnose IPF and to predict its short-term progression as estimated by short-term changes of %VC and % DL, CO. Moreover, we compared the fraction ratios of monomeric periostin to total periostin in IPF with those in other periostin-high diseases: atopic dermatitis, systemic scleroderma, and asthma. Monomeric periostin showed the greatest ability to identify IPF comparable with KL-6 and SP-D. Both monomeric and total periostin were well correlated with the decline of %VC and % DL, CO. Clustering of IPF patients into high and low periostin groups proved useful for predicting the short-term progression of IPF. Moreover, the relative ratio of monomeric periostin was higher in IPF than in other periostin-high diseases. Measuring monomeric periostin is useful for diagnosing IPF and predicting its short-term progression. Moreover, the ratio of monomeric periostin to total periostin is elevated in IPF compared to other periostin-high diseases.


Assuntos
Biomarcadores/sangue , Moléculas de Adesão Celular/sangue , Fibrose Pulmonar Idiopática/sangue , Fibrose Pulmonar Idiopática/diagnóstico , Adulto , Idoso , Animais , Biomarcadores/química , Moléculas de Adesão Celular/química , Linhagem Celular , Estudos de Coortes , Progressão da Doença , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Curva ROC
8.
Intern Med ; 55(21): 3211-3214, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27803422

RESUMO

Streptococcal toxic shock syndrome caused by group B streptococcus (GBS) is a rare, but lethal disease. We experienced a 45-year-old woman with pustular psoriasis who developed toxic shock-like syndrome during infliximab treatment. Surprisingly, similar episodes recurred three times in one year with restarting of infliximab treatments. In the third episode, GBS were detected in blood, urine, and vaginal secretion cultures. These episodes of shock syndrome were possibly due to GBS. To the best of our knowledge, this is the first case report of recurrent streptococcal toxic shock syndrome possibly caused by GBS which was induced by anti-TNF-α inhibitor therapy. The restarting of biological agents in patients with a history of toxic shock syndrome should therefore be avoided as much as possible.


Assuntos
Fármacos Dermatológicos/efeitos adversos , Infliximab/efeitos adversos , Choque Séptico/diagnóstico , Infecções Estreptocócicas/diagnóstico , Streptococcus agalactiae/isolamento & purificação , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Psoríase/tratamento farmacológico , Recidiva , Choque Séptico/etiologia , Choque Séptico/microbiologia , Infecções Estreptocócicas/etiologia , Infecções Estreptocócicas/microbiologia
9.
Intern Med ; 55(19): 2849-2853, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27725547

RESUMO

We herein report the first case of pulmonary metastasis with lepidic growth that originated from cholangiocarcinoma. A 77-year-old man was admitted to our hospital due to exertional dyspnea and liver dysfunction. Computed tomography showed widespread infiltration and a ground-glass opacity in the lung and dilation of the intrahepatic bile duct. The pulmonary lesion progressed rapidly, and the patient died of respiratory failure. Cholangiocarcinoma and lepidic pulmonary metastasis were pathologically diagnosed by an autopsy. Lepidic pulmonary growth is an atypical pattern of metastasis, and immunopathological staining is useful to distinguish pulmonary metastasis from extrapulmonary cancer and primary pulmonary adenocarcinoma.


Assuntos
Adenocarcinoma/secundário , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Neoplasias Pulmonares/secundário , Adenocarcinoma de Pulmão , Idoso , Autopsia , Neoplasias dos Ductos Biliares/diagnóstico , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/diagnóstico , Humanos , Masculino , Tomografia Computadorizada por Raios X
10.
Intern Med ; 55(19): 2877-2880, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27725552

RESUMO

A 35-year-old non-HIV patient developed pulmonary cryptococcosis after the initiation of infliximab. He recovered by fluconazole treatment and completed the therapy for a total of 6 months. However, he experienced a relapse 16 months later during retreatment with infliximab, revealing an interesting clinical course contradicting retreatment. This case also represents the first case of relapsed pulmonary cryptococcosis suspected during treatment with a biologic agent. Both of these aspects generated important clinical questions about the length of pulmonary cryptococcosis treatment and the necessity of introducing a second prophylaxis for such patients.


Assuntos
Criptococose/imunologia , Infliximab/imunologia , Infliximab/uso terapêutico , Pneumopatias Fúngicas/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Antifúngicos/uso terapêutico , Doença de Crohn/tratamento farmacológico , Criptococose/tratamento farmacológico , Fluconazol/uso terapêutico , Humanos , Pneumopatias Fúngicas/tratamento farmacológico , Masculino
11.
FEMS Yeast Res ; 16(5)2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27370212

RESUMO

Vacuolar H(+)-ATPase (V-ATPase) is responsible for the acidification of eukaryotic intracellular compartments and plays an important role in oxidative stress response (OSR), but its molecular bases are largely unknown. Here, we investigated how V-ATPase is involved in the OSR by using a strain lacking VPH2, which encodes an assembly factor of V-ATPase, in the pathogenic fungus Candida glabrata The loss of Vph2 resulted in increased H2O2 sensitivity and intracellular reactive oxygen species (ROS) level independently of mitochondrial functions. The Δvph2 mutant also displayed growth defects under alkaline conditions accompanied by the accumulation of intracellular ROS and these phenotypes were recovered in the presence of the ROS scavenger N-acetyl-l-cysteine. Both expression and activity levels of mitochondrial manganese superoxide dismutase (Sod2) and catalase (Cta1) were decreased in the Δvph2 mutant. Phenotypic analyses of strains lacking and overexpressing these genes revealed that Sod2 and Cta1 play a predominant role in endogenous and exogenous OSR, respectively. Furthermore, supplementation of copper and iron restored the expression of SOD2 specifically in the Δvph2 mutant, suggesting that the homeostasis of intracellular cupper and iron levels maintained by V-ATPase was important for the Sod2-mediated OSR. This report demonstrates novel roles of V-ATPase in the OSR in C. glabrata.


Assuntos
Candida glabrata/enzimologia , Candida glabrata/fisiologia , Cobre/metabolismo , Estresse Oxidativo , ATPases Translocadoras de Prótons/metabolismo , Vacúolos/enzimologia , Vacúolos/metabolismo , Álcalis/toxicidade , Candida glabrata/genética , Candida glabrata/metabolismo , Catalase/metabolismo , Citosol/química , Deleção de Genes , Peróxido de Hidrogênio/toxicidade , Chaperonas Moleculares/genética , Espécies Reativas de Oxigênio/análise , Superóxido Dismutase/metabolismo
12.
Respir Res ; 17(1): 79, 2016 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-27401332

RESUMO

BACKGROUND: Acute exacerbations of idiopathic pulmonary fibrosis are major causes of morbidity and mortality among patients with idiopathic pulmonary fibrosis. However, acute exacerbations remain unpredictable. The aim of this study was to investigate risk factors for acute exacerbations of idiopathic pulmonary fibrosis. METHODS: We performed a retrospective cohort study of patients with idiopathic pulmonary fibrosis who visited our institutions from January 1999 to September 2014. We investigated risk factors for acute exacerbations in patients with idiopathic pulmonary fibrosis diagnosed retrospectively based on the official 2011 idiopathic pulmonary fibrosis ATS/ERS/JRS/ALAT Update Statement. RESULTS: The idiopathic pulmonary fibrosis study cohort included 65 subjects. The median follow-up period was 2.6 years. During follow-up, 24 patients (36.9 %) experienced acute exacerbations. A Kaplan-Meier curve demonstrated that the 1-year, 2-year, and 3-year incidences of acute exacerbation were 9.6, 19.2 and 31.0 %, respectively. Acute exacerbation exerted a significant impact on overall survival among those with the disease. A log-rank test showed that baseline cardiovascular diseases, higher GAP (gender, age, physiology) stage (≥II), higher serum lactate dehydrogenase level (≥180 U/L), higher serum surfactant protein-D level (≥194.7 ng/mL), higher neutrophil (≥1.77 %) and eosinophil (≥3.21 %) percentages in bronchoalveolar lavage fluid samples, and treatment with an immunosuppressive agent after diagnosis were associated with poor acute exacerbation-free probability. In the Cox analysis adjusted for treatment with an immunosuppressive agent, baseline cardiovascular diseases, higher GAP stage (≥II), and higher eosinophil percentage (≥3.21 %) in bronchoalveolar lavage fluid samples were predictors of an acute exacerbation of idiopathic pulmonary fibrosis. CONCLUSIONS: This study demonstrated that baseline cardiovascular diseases, higher GAP stage (≥II), and higher eosinophil percentage (≥3.21 %) in bronchoalveolar lavage fluid samples were associated with the onset of an acute exacerbation of idiopathic pulmonary fibrosis.


Assuntos
Fibrose Pulmonar Idiopática/epidemiologia , Idoso , Biomarcadores/sangue , Líquido da Lavagem Broncoalveolar/citologia , Doenças Cardiovasculares/epidemiologia , Comorbidade , Progressão da Doença , Eosinófilos , Feminino , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/mortalidade , Imunossupressores/uso terapêutico , Incidência , Japão/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Eosinofilia Pulmonar/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo
13.
Intern Med ; 55(13): 1775-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27374682

RESUMO

To detect the anaplastic lymphoma kinase (ALK) fusion gene in non-small cell lung cancer, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are the standard methods. However, there are discrepancies between them. We herein report a 40-year-old woman with ALK fusion-positive adenocarcinoma that changed from positive to negative in IHC due to chemo-radiotherapy. Recurrence of the disease restored the IHC expression, whereas FISH was positive throughout the entire clinical course. Our experience suggests that we should therefore carefully evaluate samples after chemotherapy and radiotherapy.


Assuntos
Adenocarcinoma/imunologia , Adenocarcinoma/terapia , Quimiorradioterapia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Receptores Proteína Tirosina Quinases/imunologia , Adenocarcinoma de Pulmão , Adulto , Quinase do Linfoma Anaplásico , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente
14.
Kekkaku ; 91(2): 27-32, 2016 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-27263221

RESUMO

PURPOSE: The diagnosis of Mycobacterium avium complex pulmonary disease (MAC-PD) can be challenging. A serodiagnosis enzyme immunoassay (EIA) kit, which detects the serum anti-glycopeptidolipid (GPL) core IgA antibody, has been commercialized recently; however, its clinical usefulness in the diagnosis of MAC-PD is still unclear. This study aimed to evaluate the availability of this kit and identify factors affecting testing accuracy. METHODS: We performed a retrospective study of 195 patients who were evaluated with an EIA kit at Nagasaki University Hospital between November 2012 and March 2014. RESULTS: 12 of 16 (75.0%) MAC patients have underlying diseases ; 8 of 16 (50%) had complications associated with respiratory diseases. There were no significant differences between the seropositive and seronegative background of patients with confirmed MAC-PD. Regarding the accuracy of serodiagnosis EIA kit, its sensitivity and specificity were 81.3% and 88.3% (with a cut-off value of 0.7 U/ml), respectively. Of false-positive patients with bronchiectasis, 28.6 % demonstrated a good response to anti-MAC treatment, indicating that the sensitivity of the EIA kit might be higher than that of culture-based diagnosis because patients with clinically diagnosed MAC-PD were included in the false-positive population. CONCLUSIONS: In the current study, the serodiagnosis EIA kit demonstrated good sensitivity and specificity for the diagnosis of MAC-PD. Further clinical investigations are necessary to clarify the role of this kit in definitively diagnosing MAC infections.


Assuntos
Anticorpos Antibacterianos/sangue , Antígenos/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Glicolipídeos/imunologia , Glicopeptídeos/imunologia , Imunoglobulina A/sangue , Complexo Mycobacterium avium/imunologia , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Kit de Reagentes para Diagnóstico , Testes Sorológicos/métodos , Tuberculose Pulmonar/diagnóstico , Idoso , Bronquiectasia , Reações Falso-Positivas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade
15.
Intern Med ; 55(9): 1213-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27150883

RESUMO

A 68-year-old man was admitted to our hospital with anorexia and leg pain. He was diagnosed with ANCA-associated vasculitis through a renal biopsy. Immunosuppression with two courses of steroid pulse therapies and intravenous cyclophosphamide followed by oral prednisolone at 40 mg/day were administered. About one month after starting the immunosuppression therapy, he complained of hemosputum. Chest computed tomography showed a cavitary lesion in the lung. Cultures from his sputum showed Nocardia species, and we were able to identify the species as N. concava using a 16S rRNA gene sequence analysis. Only three detailed reports of N. concava infection have so far been published worldwide.


Assuntos
Hospedeiro Imunocomprometido , Nocardiose/diagnóstico , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Pulmão/patologia , Masculino , Prednisolona , RNA Ribossômico 16S , Escarro , Tomografia Computadorizada por Raios X/efeitos adversos
16.
BMC Pulm Med ; 16: 39, 2016 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-26956147

RESUMO

BACKGROUND: No mortality prediction rule is suited for non-elderly patients with community-acquired pneumonia. Therefore, we tried to create a mortality prediction rule that is simple and suitable for non-elderly patients with community-acquired pneumonia. METHODS: Because of low mortality at young age, we used information from an administrative database that included A-DROP data. We analysed the rate and risk factors for in-hospital community-acquired pneumonia-associated death among non-elderly patients and created a mortality prediction rule based on those risk factors. RESULTS: We examined 49,370 hospitalisations for patients aged 18-64 years with community-acquired pneumonia. The 30-day fatality rate was 1.5%. Using regression analysis, five risk factors were selected: patient requires help for feeding, the existence of malignancy, confusion, low blood pressure, and age 40-64 years. Each risk factor of our proposed mortality risk scoring system received one point. A total point score for each patient was obtained by summing the points. The negative likelihood ratio for the score 0 group was 0.01, and the positive likelihood ratio for the score ≥4 group was 19.9. The area under the curve of the risk score for non-elderly (0.86, 95% confidence interval: 0.84-0.87) was higher than that of the A-DROP score (0.72, 95% confidence interval: 0.70-0.74) (P < 0.0001). CONCLUSIONS: Our newly proposed mortality risk scoring system may be appropriate for predicting mortality in non-elderly patients with community-acquired pneumonia. It showed a possibility of a better prediction value than the A-DROP and is easy to use in various clinical settings.


Assuntos
Infecções Comunitárias Adquiridas/mortalidade , Confusão/epidemiologia , Técnicas de Apoio para a Decisão , Mortalidade Hospitalar , Hipotensão/epidemiologia , Neoplasias/epidemiologia , Pneumonia/mortalidade , Atividades Cotidianas , Adolescente , Adulto , Fatores Etários , Infecções Comunitárias Adquiridas/epidemiologia , Comorbidade , Comportamento Alimentar , Feminino , Hospitalização , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Pneumonia/epidemiologia , Análise de Regressão , Fatores de Risco , Adulto Jovem
17.
Chemotherapy ; 61(2): 93-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26606381

RESUMO

BACKGROUND: S-1, a novel oral fluoropyrimidine, is active in the treatment of non-small cell lung cancer (NSCLC). However, data on S-1 for elderly patients with NSCLC are insufficient. METHODS: Eligibility criteria were no prior chemotherapy, stage IIIB or IV NSCLC, performance status 0-1, age >70 years, and adequate hematological, hepatic, and renal functions. Patients received S-1 (40 mg/m(2) twice a day) for 28 consecutive days. This schedule was repeated every 6 weeks. The primary end point was the tumor response rate. RESULTS: Thirty-two patients were enrolled and 31 patients were evaluable for response. The patients' median age was 80 years (range: 71-88). The response rate was 22.6% (95% CI: 11-38). Neutropenia, anemia, thrombocytopenia, febrile neutropenia, and diarrhea of grade ≥ 3 occurred in 6, 6, 10, 3, and 3%, respectively. CONCLUSIONS: In elderly patients with previously untreated advanced NSCLC, S-1 appears to be well tolerated and demonstrates encouraging activity.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Ácido Oxônico/uso terapêutico , Tegafur/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anemia/induzido quimicamente , Antimetabólitos Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Esquema de Medicação , Combinação de Medicamentos , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Náusea/induzido quimicamente , Neutropenia/induzido quimicamente , Ácido Oxônico/efeitos adversos , Tegafur/efeitos adversos , Resultado do Tratamento , Vômito/induzido quimicamente
18.
Jpn J Infect Dis ; 69(2): 91-6, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26073727

RESUMO

Pseudomonas aeruginosa bacteremia occurs mainly in immunocompromised patients. However, P. aeruginosa bacteremia in immunocompetent patients has also been reported. The aim of this study was to evaluate the clinical characteristics of P. aeruginosa bacteremia in relation to the immune status of the patients. The medical records of 126 adult patients with P. aeruginosa bacteremia in Nagasaki University Hospital were retrospectively reviewed between January 2003 and December 2012. Of 126 patients with P. aeruginosa bacteremia, 60 patients (47.6%) were classified as immunocompetent. Mortality in immunocompetent patients tended to be lower than in immunocompromised patients (7-day mortality, 8% vs. 30%, P < 0.01; 30-day mortality, 23% vs. 39%, P = 0.053). Multivariate analysis showed that a higher sequential organ failure assessment score (hazard ratio [HR]: 1.27, P < 0.01) and underlying malignancies (HR: 3.33, P < 0.01) were independently associated with 30-day mortality. Initial antibiotic therapy (HR: 0.21, P < 0.01) and patients' immune status (HR: 0.29, P = 0.02) also had a significant impact on survival. However, there was a significant interaction between these 2 variables (P = 0.03 for interaction). A subgroup analysis showed that in immunocompromised, but not immunocompetent patients, initial appropriate antibiotic therapy was associated with lower mortality (30-day mortality 20.5% vs. 66.7%, P < 0.01 by log-rank test).


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/epidemiologia , Bacteriemia/mortalidade , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/mortalidade , Pseudomonas aeruginosa/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitais Universitários , Humanos , Hospedeiro Imunocomprometido , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
19.
Support Care Cancer ; 24(2): 615-619, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26108172

RESUMO

BACKGROUND: This study was undertaken to analyze the characteristics of fever after cancer chemotherapy in order to reduce unnecessary medical care. METHODS: Retrospectively, 1016 consecutive cycles of cancer chemotherapy were analyzed. Fever was defined as a temperature of ≥ 37.5 °C lasting for 1 h. Age, sex, tumor histology, the treatment regimen, the timing of fever onset, the number of days for which the fever persisted, the cause of the fever, the presence or absence of radiotherapy, and the use of granulocyte colony-stimulating factor (G-CSF) were examined. RESULTS: The patients included 748 males and 268 females (median age = 68, range = 29-88), of whom 949, 52, and 15 were suffering from lung cancer, malignant pleural mesothelioma, and other diseases, respectively. Fever was observed in 367 cycles (36 %), including 280 cycles (37 %) involving males and 87 cycles (32 %) involving females. Fever occurred most commonly in the first cycles and was higher than later cycles (41 vs. 30 %, p < 0.001). Fever occurred most frequently on posttreatment days 4 (8 %), 3 (7 %), and 12 (7 %), and the distribution of fever episodes exhibited two peaks on posttreatment days 3 and 4 and 10-14. Fever on posttreatment days 3 and 4 was most commonly observed in patients treated with gemcitabine (20 %) or docetaxel (18 %). The causes of fever included infection (47 %; including febrile neutropenia [24 %]), adverse drug effects (24 %), unknown causes (19 %), and tumors (7 %). Radiotherapy led to a significant increase in the frequency of fever (46 vs. 34 %, p < 0.001). Thirty-three percent of patients received G-CSF, and the incidence ratios of fever in patients who received G-CSF were higher than those who did not receive G-CSF (44 vs. 31 %, p < 0.001). CONCLUSION: The febrile episodes that occurred on posttreatment days 3 and 4 were considered to represent adverse drug reactions after cancer chemotherapy. Physicians should be aware of this feature of chemotherapy-associated fever and avoid unnecessary examination and treatments including prescribing antibiotics.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Febre/induzido quimicamente , Neoplasias/tratamento farmacológico , Neutropenia/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
BMC Infect Dis ; 15: 426, 2015 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-26471715

RESUMO

BACKGROUND: Enterococcus spp. are particularly important etiological agents of nosocomial infections. However, the clinical characteristics of and risk factors for enterococcal infections in clinical settings are poorly understood. METHODS: The sample included patients with Enterococcus spp. infections detected from clinical samples at Nagasaki University Hospital between 2010 and 2011 and patients with enterococcal colonization (control patients). In this retrospective study, the risk factors for enterococcal infections were analyzed by comparing infected and control patients via multivariate logistic regression. RESULTS: A total of 182 infected (mean age, 64.6 ± 18.2 years; 114 men) and 358 control patients (patients with enterococcal colonization) (mean age, 61.6 ± 22.4 years; 183 men) were included. Enterococcal infections were classified as intraperitoneal (n = 87), urinary tract (n = 28), or bloodstream (n = 20) infections. Cancer and hematological malignancies were the most common comorbidities in enterococcal infections. Carbapenem and vancomycin were administered to 43.8 % and 57.9 % of patients infected with Enterococcus faecalis and Enterococcus faecium, respectively. No vancomycin-resistant enterococci were isolated. Multivariate analysis identified abdominal surgery (odds ratio [OR], 2.233; 95 % confidence interval [CI], 1.529-3.261; p ≤ 0.001), structural abnormalities of the urinary tract (OR, 2.086; 95 % CI, 1.088-4.000; p = 0.027), male sex (OR, 1.504; 95 % CI, 1.032-2.190; p = 0.033), and hypoalbuminemia (OR, 0.731; 95 % CI, 0.555-0.963; p = 0.026) as independent risk factors for enterococcal infections. Multivariate analysis showed abdominal surgery (OR, 2.263; 95 % CI, 1.464-3.498; p ≤ 0.001), structural abnormalities of the urinary tract (OR, 2.634; 95 % CI, 1.194-5.362; p = 0.008), and hypoalbuminemia (OR, 0.668; 95 % CI, 0.490-0.911; p = 0.011) were independent risk factors for E. faecalis infection. Finally, immunosuppressive agent use (OR, 3.837; 95 % CI, 1.397-10.541; p = 0.009) and in situ device use (OR, 3.807; 95 % CI, 1.180-12.276; p = 0.025) were independent risk factors for E. faecium infection. CONCLUSIONS: These findings might inform early initiation of antimicrobial agents to improve clinical success.


Assuntos
Infecções por Bactérias Gram-Positivas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/isolamento & purificação , Enterococcus faecium/efeitos dos fármacos , Enterococcus faecium/isolamento & purificação , Feminino , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Imunossupressores/uso terapêutico , Japão/epidemiologia , Modelos Logísticos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Vancomicina/farmacologia , Vancomicina/uso terapêutico
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