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1.
Artículo en Inglés | MEDLINE | ID: mdl-31182539

RESUMEN

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.


Asunto(s)
Amidinas/farmacología , Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Saccharomyces cerevisiae/efectos de los fármacos , Adenosina Trifosfato/metabolismo , Animales , Candida albicans/metabolismo , Bovinos , Complejo I de Transporte de Electrón/metabolismo , Complejo II de Transporte de Electrones/metabolismo , Pruebas de Sensibilidad Microbiana , Mitocondrias/metabolismo , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/metabolismo , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/metabolismo , NADH Deshidrogenasa/metabolismo , Ratas , Saccharomyces cerevisiae/metabolismo
2.
Sci Rep ; 9(1): 9331, 2019 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-31249356

RESUMEN

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.


Asunto(s)
Antifúngicos/farmacología , Candida/efectos de los fármacos , Micafungina/farmacología , Fibrosis Peritoneal/complicaciones , Peritonitis/complicaciones , Peritonitis/microbiología , Animales , Biomarcadores , Citocinas , Modelos Animales de Enfermedad , Histocitoquímica , Humanos , Ratones , Fibrosis Peritoneal/patología , Peritonitis/tratamiento farmacológico , Peritonitis/patología , Pronóstico , Resultado del Tratamiento
3.
J Infect Chemother ; 25(9): 702-707, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30982729

RESUMEN

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.


Asunto(s)
Antibacterianos/uso terapéutico , Cefalosporinas/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Antibacterianos/administración & dosificación , Programas de Optimización del Uso de los Antimicrobianos , Cefalosporinas/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto Joven
4.
Intern Med ; 57(23): 3485-3490, 2018 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-30101932

RESUMEN

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.


Asunto(s)
Enfermedades Pulmonares Fúngicas/complicaciones , Enfermedades Pulmonares Fúngicas/microbiología , Nódulos Pulmonares Múltiples/complicaciones , Nódulos Pulmonares Múltiples/microbiología , Scedosporium/aislamiento & purificación , Anciano , Femenino , Humanos , Inmunocompetencia , Enfermedades Pulmonares Fúngicas/cirugía , Nódulos Pulmonares Múltiples/cirugía
5.
J Infect Chemother ; 24(6): 434-442, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29530544

RESUMEN

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.


Asunto(s)
Antibacterianos/farmacocinética , Linezolid/farmacocinética , Organofosfatos/farmacocinética , Oxazoles/farmacocinética , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Anciano , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Femenino , Humanos , Japón , Linezolid/administración & dosificación , Linezolid/uso terapéutico , Masculino , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Organofosfatos/administración & dosificación , Organofosfatos/uso terapéutico , Oxazoles/administración & dosificación , Oxazoles/uso terapéutico , Estudios Prospectivos , Resultado del Tratamiento
6.
PLoS One ; 12(3): e0174547, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28355256

RESUMEN

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.


Asunto(s)
Biomarcadores/sangre , Moléculas de Adhesión Celular/sangre , Fibrosis Pulmonar Idiopática/sangre , Fibrosis Pulmonar Idiopática/diagnóstico , Adulto , Anciano , Animales , Biomarcadores/química , Moléculas de Adhesión Celular/química , Línea Celular , Estudios de Cohortes , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Curva ROC
8.
Intern Med ; 55(21): 3211-3214, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27803422

RESUMEN

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.


Asunto(s)
Fármacos Dermatológicos/efectos adversos , Infliximab/efectos adversos , Choque Séptico/diagnóstico , Infecciones Estreptocócicas/diagnóstico , Streptococcus agalactiae/aislamiento & purificación , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad , Psoriasis/tratamiento farmacológico , Recurrencia , Choque Séptico/etiología , Choque Séptico/microbiología , Infecciones Estreptocócicas/etiología , Infecciones Estreptocócicas/microbiología
9.
Intern Med ; 55(19): 2849-2853, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27725547

RESUMEN

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.


Asunto(s)
Adenocarcinoma/secundario , Neoplasias de los Conductos Biliares/patología , Colangiocarcinoma/patología , Neoplasias Pulmonares/secundario , Adenocarcinoma del Pulmón , Anciano , Autopsia , Neoplasias de los Conductos Biliares/diagnóstico , Conductos Biliares Intrahepáticos/patología , Colangiocarcinoma/diagnóstico , Humanos , Masculino , Tomografía Computarizada por Rayos X
10.
Intern Med ; 55(19): 2877-2880, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27725552

RESUMEN

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.


Asunto(s)
Criptococosis/inmunología , Infliximab/inmunología , Infliximab/uso terapéutico , Enfermedades Pulmonares Fúngicas/inmunología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Antifúngicos/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Criptococosis/tratamiento farmacológico , Fluconazol/uso terapéutico , Humanos , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Masculino
11.
FEMS Yeast Res ; 16(5)2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27370212

RESUMEN

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.


Asunto(s)
Candida glabrata/enzimología , Candida glabrata/fisiología , Cobre/metabolismo , Estrés Oxidativo , ATPasas de Translocación de Protón/metabolismo , Vacuolas/enzimología , Vacuolas/metabolismo , Álcalis/toxicidad , Candida glabrata/genética , Candida glabrata/metabolismo , Catalasa/metabolismo , Citosol/química , Eliminación de Gen , Peróxido de Hidrógeno/toxicidad , Chaperonas Moleculares/genética , Especies Reactivas de Oxígeno/análisis , Superóxido Dismutasa/metabolismo
12.
Respir Res ; 17(1): 79, 2016 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-27401332

RESUMEN

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.


Asunto(s)
Fibrosis Pulmonar Idiopática/epidemiología , Anciano , Biomarcadores/sangre , Líquido del Lavado Bronquioalveolar/citología , Enfermedades Cardiovasculares/epidemiología , Comorbilidad , Progresión de la Enfermedad , Eosinófilos , Femenino , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/mortalidad , Inmunosupresores/uso terapéutico , Incidencia , Japón/epidemiología , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Eosinofilia Pulmonar/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo
13.
Intern Med ; 55(13): 1775-8, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27374682

RESUMEN

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.


Asunto(s)
Adenocarcinoma/inmunología , Adenocarcinoma/terapia , Quimioradioterapia , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/terapia , Proteínas Tirosina Quinasas Receptoras/inmunología , Adenocarcinoma del Pulmón , Adulto , Quinasa de Linfoma Anaplásico , Femenino , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ
14.
Kekkaku ; 91(2): 27-32, 2016 Feb.
Artículo en Japonés | MEDLINE | ID: mdl-27263221

RESUMEN

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.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Antígenos/inmunología , Ensayo de Inmunoadsorción Enzimática/métodos , Glucolípidos/inmunología , Glicopéptidos/inmunología , Inmunoglobulina A/sangre , Complejo Mycobacterium avium/inmunología , Infección por Mycobacterium avium-intracellulare/diagnóstico , Juego de Reactivos para Diagnóstico , Pruebas Serológicas/métodos , Tuberculosis Pulmonar/diagnóstico , Anciano , Bronquiectasia , Reacciones Falso Positivas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad
15.
Intern Med ; 55(9): 1213-7, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27150883

RESUMEN

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.


Asunto(s)
Huésped Inmunocomprometido , Nocardiosis/diagnóstico , Anciano , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Humanos , Inmunosupresores/uso terapéutico , Pulmón/patología , Masculino , Prednisolona , ARN Ribosómico 16S , Esputo , Tomografía Computarizada por Rayos X/efectos adversos
16.
BMC Pulm Med ; 16: 39, 2016 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-26956147

RESUMEN

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.


Asunto(s)
Infecciones Comunitarias Adquiridas/mortalidad , Confusión/epidemiología , Técnicas de Apoyo para la Decisión , Mortalidad Hospitalaria , Hipotensión/epidemiología , Neoplasias/epidemiología , Neumonía/mortalidad , Actividades Cotidianas , Adolescente , Adulto , Factores de Edad , Infecciones Comunitarias Adquiridas/epidemiología , Comorbilidad , Conducta Alimentaria , Femenino , Hospitalización , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Neumonía/epidemiología , Análisis de Regresión , Factores de Riesgo , Adulto Joven
17.
Chemotherapy ; 61(2): 93-8, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26606381

RESUMEN

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.


Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Ácido Oxónico/uso terapéutico , Tegafur/uso terapéutico , Anciano , Anciano de 80 o más Años , Anemia/inducido químicamente , Antimetabolitos Antineoplásicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Esquema de Medicación , Combinación de Medicamentos , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Náusea/inducido químicamente , Neutropenia/inducido químicamente , Ácido Oxónico/efectos adversos , Tegafur/efectos adversos , Resultado del Tratamiento , Vómitos/inducido químicamente
18.
Jpn J Infect Dis ; 69(2): 91-6, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26073727

RESUMEN

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).


Asunto(s)
Antibacterianos/uso terapéutico , Bacteriemia/epidemiología , Bacteriemia/mortalidad , Infecciones por Pseudomonas/epidemiología , Infecciones por Pseudomonas/mortalidad , Pseudomonas aeruginosa/efectos de los fármacos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Hospitales Universitarios , Humanos , Huésped Inmunocomprometido , Japón/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia , Adulto Joven
19.
Support Care Cancer ; 24(2): 615-619, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26108172

RESUMEN

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.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Fiebre/inducido químicamente , Neoplasias/tratamiento farmacológico , Neutropenia/etiología , Adulto , Anciano , Anciano de 80 o más Años , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
20.
BMC Infect Dis ; 15: 426, 2015 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-26471715

RESUMEN

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.


Asunto(s)
Infecciones por Bacterias Grampositivas/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Enterococcus faecalis/efectos de los fármacos , Enterococcus faecalis/aislamiento & purificación , Enterococcus faecium/efectos de los fármacos , Enterococcus faecium/aislamiento & purificación , Femenino , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Inmunosupresores/uso terapéutico , Japón/epidemiología , Modelos Logísticos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Vancomicina/farmacología , Vancomicina/uso terapéutico
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