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1.
J Infect Chemother ; 30(10): 1054-1060, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38636933

RESUMO

INTRODUCTION: Obesity is a risk factor for aggravation of and mortality from coronavirus disease 2019 (COVID-19). We aimed to investigate the relationship between COVID-19 and Body Mass Index (BMI) in the Japanese population. METHODS: We used administrative claims data from an advanced treatment hospital in Japan and extracted data from patients hospitalized for COVID-19. The exposure variable was BMI measured at the time of admission, and the study outcomes were progression to critical illness and death. Analyses were performed for each age group. RESULTS: Overall, 58,944 patients met the inclusion criteria. The risk of critical illness increased monotonically with higher BMI. In contrast, the relationship between BMI and mortality follows a J-shaped curve; being underweight and obese are risk factors for mortality. When stratified by age, similar trends were observed for both critical illness and mortality. CONCLUSION: A higher BMI is a risk factor for the progression of COVID-19 severity, whereas both lower and higher BMIs are risk factors for mortality in the Japanese population.


Assuntos
Índice de Massa Corporal , COVID-19 , Obesidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , COVID-19/mortalidade , COVID-19/epidemiologia , Estado Terminal/mortalidade , População do Leste Asiático , Hospitalização/estatística & dados numéricos , Japão/epidemiologia , Obesidade/epidemiologia , Obesidade/complicações , Obesidade/mortalidade , Fatores de Risco , Índice de Gravidade de Doença
2.
J Infect Chemother ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38944381

RESUMO

BACKGROUND: Human cytomegalovirus (HCMV) infection occurs in immunosuppressed individuals and is known to increase mortality. Patients with coronavirus disease 2019 (COVID-19) are often treated with steroids, require intensive care unit (ICU) treatment, and may therefore be at risk for HCMV infection. However, which factors predispose severely ill patients with COVID-19 to HCMV infection and the prognostic value of such infections remain largely unexplored. This study aimed to examine the incidence and potential risk factors of HCMV infection in patients with severe or critical COVID-19 and evaluate the relationship between HCMV infection and mortality. METHODS AND FINDINGS: We used administrative claims data from advanced treatment hospitals in Japan to identify and analyze patients with severe or critical COVID-19. We explored potential risk factors for HCMV infection using multivariable regression models and its contribution to mortality in patients with COVID-19. Overall, 33,151 patients who progressed to severe or critical COVID-19 illness were identified. The incidence of HCMV infection was 0.3-1.7 % depending on the definition of HCMV infection. Steroids, immunosuppressants, ICU admission, and blood transfusion were strongly associated with HCMV infection. Furthermore, HCMV infection was associated with patient mortality independent of the observed risk factors for death. CONCLUSIONS: HCMV infection is a notable complication in patients with severe or critical COVID-19 who are admitted to the ICU or receive steroids, immunosuppressants, and blood transfusion and can significantly increase mortality risk.

3.
Mycoses ; 67(8): e13773, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39090076

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is one of the noticeable complications of COVID-19 and its incidence varies widely. In Japan, research on the incidence, risk factors and mortality associated with CAPA is limited. OBJECTIVES: This study aimed to explore the incidence and potential risk factors for CAPA in patients with severe or critical COVID-19 and evaluate the relationship between CAPA and mortality of patients with severe or critical COVID-19. METHODS: We investigated the incidence of CAPA in patients with severe and critical COVID-19 using administrative claims data from acute care hospitals in Japan. We employed multivariable regression models to explore potential risk factors for CAPA and their contribution to mortality in patients with severe and critical COVID-19. RESULTS: The incidence of CAPA was 0.4%-2.7% in 33,136 patients with severe to critical COVID-19. Age, male sex, chronic lung disease, steroids, immunosuppressants, intensive care unit admission, blood transfusion and dialysis were potential risk factors for CAPA in patients with severe to critical COVID-19. CAPA was an independent factor associated with mortality. CONCLUSIONS: CAPA is a serious complication in patients with severe and critical COVID-19 and may increase mortality.


Assuntos
COVID-19 , Aspergilose Pulmonar , Humanos , Masculino , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/mortalidade , Feminino , Fatores de Risco , Pessoa de Meia-Idade , Idoso , Japão/epidemiologia , Incidência , Adulto , Aspergilose Pulmonar/epidemiologia , Aspergilose Pulmonar/complicações , SARS-CoV-2 , Idoso de 80 Anos ou mais , Adulto Jovem
4.
Nat Immunol ; 12(10): 966-74, 2011 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-21892173

RESUMO

Natural killer T cells (NKT cells) recognize glycolipid antigens presented by CD1d. These cells express an evolutionarily conserved, invariant T cell antigen receptor (TCR), but the forces that drive TCR conservation have remained uncertain. Here we show that NKT cells recognized diacylglycerol-containing glycolipids from Streptococcus pneumoniae, the leading cause of community-acquired pneumonia, and group B Streptococcus, which causes neonatal sepsis and meningitis. Furthermore, CD1d-dependent responses by NKT cells were required for activation and host protection. The glycolipid response was dependent on vaccenic acid, which is present in low concentrations in mammalian cells. Our results show how microbial lipids position the sugar for recognition by the invariant TCR and, most notably, extend the range of microbes recognized by this conserved TCR to several clinically important bacteria.


Assuntos
Glicolipídeos/imunologia , Bactérias Gram-Positivas/imunologia , Células T Matadoras Naturais/imunologia , Animais , Antígenos CD1d/química , Antígenos CD1d/fisiologia , Linhagem Celular , Glicolipídeos/química , Humanos , Interferon gama/biossíntese , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Antígenos de Linfócitos T/metabolismo
5.
J Infect Chemother ; 29(3): 322-328, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36565806

RESUMO

OBJECTIVE: Most non-tuberculous mycobacteria exhibit intrinsic resistance against the anti-tuberculosis drug isoniazid (INH). We previously found that a pyrazinamidase/nicotinamidase of Mycobacterium smegmatis, named PzaA, has an enzymatic activity to hydrolyze INH, which may contribute to intrinsic resistance. Furthermore, PzaA expression is strongly induced by INH under nitrogen-depleted conditions, although the precise mechanism of this phenomenon remains unclear. Here, we aimed to reveal the mechanism underlying the INH-dependent induction of PzaA using a transcriptomic approach. METHODS: RNA sequencing was performed to identify INH-inducible genes other than pzaA. 5' rapid amplification of cDNA ends analysis was employed to identify the transcription start sites of INH-induced transcription units. The function of a LuxR-like regulator gene (MSMEI_1050) found within the gene cluster containing pzaA was confirmed by gene deletion and complementation experiments involving INH hydrolysis assay and quantitative reverse transcription PCR. RESULTS: RNA sequencing revealed 23 genes that INH strongly induced under conditions of nitrogen depletion, 17 of which were in a gene cluster containing pzaA. This cluster comprised at least three transcription units, including a non-INH-inducible monocistronic unit containing MSMEI_1050. Deletion of this gene deprived M. smegmatis of the ability to respond to INH, and complementation restored this ability. CONCLUSIONS: MSMEI_1050 plays a key role in INH-dependent gene regulation. The precise mechanism of action is to be determined in future studies.


Assuntos
Antituberculosos , Isoniazida , Mycobacterium tuberculosis , Antituberculosos/farmacologia , Proteínas de Bactérias/genética , Sequência de Bases , Isoniazida/farmacologia , Mycobacterium smegmatis/genética , Mycobacterium tuberculosis/genética , Transativadores/genética
6.
J Infect Chemother ; 29(7): 693-699, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37028799

RESUMO

INTRODUCTION: Genetic testing is gaining increasing importance as a part of antimicrobial stewardship (AS). Rapid identification and determination of methicillin susceptibility using the Xpert MRSA/SA BC assay can improve the management of Staphylococcus aureus bacteremia (SAB) and reduce inappropriate antibiotic use. However, few reports have described the effectiveness of this approach. METHODS: The present study aimed to assess the influence of AS using the Xpert MRSA/SA BC assay. Cases were classified into the pre-intervention group (n = 98 patients), in which SAB was identified by traditional culture (November 2017 to November 2019), and the post-intervention group (n = 97 patients), in which the Xpert MRSA/SA BC assay was performed when necessary (December 2019 to December 2021). RESULTS: Patient characteristics, prognosis, duration of antimicrobial use, and length of hospital stay were compared between the groups. The Xpert assay was performed in 66 patients in the post-intervention group (68.0%). The two groups showed no significant differences in severity and mortality. The rate of cases treated with anti-MRSA agents reduced following the intervention (65.3% vs. 40.4%, p = 0.008). The number of cases involving definitive therapy within 24 h was higher in the post-intervention group (9.2% vs. 24.7%, p = 0.007). The hospitalization rate at >60 days was lower in Xpert implementation cases among MRSA bacteremia cases (28.6% vs. 0%, p = 0.01). CONCLUSIONS: Thus, the Xpert MRSA/SA BC assay has potential as an AS tool, especially for early definitive treatment to SAB and reduction of long-term hospitalization in MRSA bacteremia cases.


Assuntos
Gestão de Antimicrobianos , Bacteriemia , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Centros de Atenção Terciária , Japão , Staphylococcus aureus Resistente à Meticilina/genética , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico
7.
Anaerobe ; 80: 102695, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36640992

RESUMO

Clostridium ramosum is one of the obligate anaerobes that constitute the intestinal microbiota, and one of the rare Clostridia. With Clostridium ramosum, very few data have been reported to investigate antimicrobial susceptibility for clinical isolates that have caused bacteremia. Here, we report two cases of Clostridium ramosum bacteremia. The first case was a 54-year-old Japanese man with taking 20mg hydrocortisone for hypopituitarism. He presented to the emergency department for an unknown cause cardiopulmonary arrest. At the hospital day 36, he had fever and a drop in blood pressure. Abdomen computed tomography (CT) revealed free air around the ascending colon, we diagnosed with intestinal perforation, and peritonitis. Blood culture revealed Clostridium ramosum. We administered conservative management by 6-week of antibiotic treatment. The second case was a 78-year-old Japanese man with no significant medical history. He was referred to our hospital with fever and abdominal pain. Abdomen CT revealed perforated appendicitis, and blood cultures revealed Clostridium ramosum. We performed emergency surgery, and administered one-week course of antibiotic treatment. This report demonstrates two cases of Clostridium ramosum bacteremia with intestinal perforation, and the antimicrobial susceptibility of each clinical strain. For the future, it is necessary to accumulate data on the susceptibility of clinical isolates in order to find an appropriate treatment.


Assuntos
Anti-Infecciosos , Bacteriemia , Perfuração Intestinal , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Perfuração Intestinal/diagnóstico , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
8.
J Formos Med Assoc ; 121(4): 848-855, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34272150

RESUMO

BACKGROUND/PURPOSE: Klebsiella pneumoniae bacteremia-induced sepsis is a clinically important condition with a high mortality rate and various known virulence factors. However, studies on the association of these virulence factors with the occurrence of K. pneumoniae bacteremia-induced sepsis are scarce. We aimed to investigate clinical variables and virulence factors in patients with K. pneumoniae bacteremia-induced sepsis. METHODS: We retrospectively reviewed the medical records of 76 patients with K. pneumoniae bacteremia between January 2012 and July 2017. Patients were divided into sepsis (n = 25) and non-sepsis (n = 51) groups. Patient background characteristics, antimicrobial regimens, and prognosis were evaluated. We assessed the distribution of virulence factors related to K. pneumoniae, such as mucoviscosity, capsular polysaccharide, and siderophores. Siderophore production levels were determined by measuring the orange halo zone on chrome azurol S agar plate assay. RESULTS: There were no intergroup differences in male-to-female ratio and age. Multivariable analysis revealed that siderophore production level (p < 0.01) was an independent predictor of K. pneumoniae bacteremia-induced sepsis. Furthermore, the optimal cut-off point of siderophore production to predict sepsis was 9.6 mm (sensitivity, 86%; specificity, 76%; AUC, 0.81). CONCLUSION: Siderophore production was an independent predictor of sepsis caused by K. pneumoniae bacteremia. The optimal cut-off point for siderophore production for sepsis occurrence prediction was 9.6 mm. To improve outcomes, patients with K. pneumoniae bacteremia-induced sepsis with high siderophore production levels should be managed prudently.


Assuntos
Bacteriemia , Infecções por Klebsiella , Sepse , Biomarcadores , Feminino , Humanos , Klebsiella pneumoniae , Masculino , Projetos Piloto , Estudos Retrospectivos , Sideróforos
9.
Pediatr Transplant ; 25(7): e13948, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33326681

RESUMO

Surgical intervention for HB with tumor thrombi extending into the IVC and the RA might requires careful planning of the surgical procedures, including vascular reconstruction and extracorporeal circulation. We herein report a successful case of LDLT for HB with atrial extension of a tumor thrombus by extracorporeal circulation with a transdiaphragmatic approach. The patient was a 5-year-old boy with PRETEXT IV HB with a tumor thrombus that extended into the IVC and the RA. After 4 cycles of chemotherapy and resection of bilateral lung metastases, the size of the primary HB tumor decreased. As the tumor extension from the LHV to the RA had decreased but was still present, we performed LDLT with tumor thrombectomy. The central part of the diaphragm was sagittally incised to expose the suprahepatic IVC and the RA. Venovenous bypass was achieved from the right femoral vein and IMV to the RA En bloc resection of the native liver with the tumor thrombus was then performed. HV anastomosis was made between the newly created orifice on the IVC and the graft LHV. The duration of LDLT was 10 hours and 44 minutes (extracorporeal circulation time: 78 minutes). Pediatric LT for HB with the extension of tumor thrombi into the RA under extracorporeal circulation is a feasible option and allows for the expansion of the indications for transplantation for children with unresectable liver tumors.


Assuntos
Circulação Extracorpórea , Átrios do Coração/cirurgia , Hepatoblastoma/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Pré-Escolar , Humanos , Doadores Vivos , Masculino , Veia Cava Inferior/cirurgia
10.
J Infect Chemother ; 27(3): 521-525, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33067106

RESUMO

Syphilis has recently increased in prevalence in Japan. Neurosyphilis is a special pathological condition of syphilis well known to cause cerebral vasculitis and ischemic stroke. Neurosyphilis in the meningovascular stage rarely causes caliber irregularity of the cerebral blood vessels or cerebral hemorrhage. We describe the case of a 49-year-old Japanese man with neurosyphilis. Cerebral hemorrhage, multiple cerebral infarctions, and caliber irregularity of the cerebral blood vessels were observed, the patient underwent surgery for cerebral hemorrhage on the day of admission, all of which were suspected to be caused by syphilis. He was started on an antibacterial treatment of penicillin on the day of admission and was diagnosed with neurosyphilis the following week based on his serum and spinal fluid test results. His condition improved, and he was transferred to another hospital after 4 weeks of treatment consisting of 3 weeks of infusion treatment with benzylpenicillin followed by oral treatment with amoxicillin. To the best of our knowledge, this is a rare case of neurosyphilis in conjunction with cerebral hemorrhage and cerebral infarction. Clinicians should consider syphilis in the differential diagnosis of cerebral hemorrhage and cerebral infarction and test patients for sexually transmitted diseases, in addition to cerebrospinal fluid testing, when cerebral hemorrhage occurs with an unknown cause. This is especially pertinent when patients present with cerebral infarction or caliber irregularity of the cerebral blood vessels.


Assuntos
Achados Incidentais , Neurossífilis , Infarto Cerebral/diagnóstico por imagem , Humanos , Hemorragias Intracranianas , Japão , Masculino , Pessoa de Meia-Idade , Neurossífilis/complicações , Neurossífilis/diagnóstico , Neurossífilis/tratamento farmacológico
11.
J Infect Chemother ; 27(2): 179-184, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32950394

RESUMO

INTRODUCTION: Clostridioides difficile is an important causative pathogen in antibiotic-associated colitis and nosocomial infections. This study aimed to assess immunochromatographic test results for C. difficile infection and the utility of PCR-based open-reading frame typing (POT) for potentially controlling the intra-ward transmission of C. difficile. METHODS: We conducted a molecular epidemiological analysis using POT to investigate 102 inpatients who tested positive for the C. difficile toxin using immunochromatography in a tertiary-care teaching hospital in Japan between 2016 and 2018; isolates from the patients were obtained and cultured. RESULTS: The number of POT numbers detected in 2016, 2017, and 2018 were 27 (among 34 patients), 20 (among 31 patients), and 28 (among 37 patients), respectively. During this three-year period, there were seven cases whose bacterial strains with the same POT number was identified in the same ward within 6 months. The intra-ward transmission rate was the highest in 2017 (16.1%). Intra-ward transmission was identified at a higher rate in patients whose sample cultures tested toxin-positive than in patients whose sample cultures tested toxin- and glutamate-dehydrogenase-positive via immunochromatography (16% vs. 3%, p < 0.05). CONCLUSIONS: We conclude that the use of immunochromatographic tests for C. difficile diagnosis and epidemiological analyses via POT may be helpful for evaluating intra-ward transmission of C. difficile.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Clostridioides , Clostridioides difficile/genética , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/epidemiologia , Hospitais de Ensino , Humanos , Controle de Infecções , Japão/epidemiologia , Fases de Leitura Aberta , Reação em Cadeia da Polimerase
12.
J Infect Chemother ; 27(6): 906-910, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33549416

RESUMO

INTRODUCTION: Corynebacterium jeikeium normally presents on human skin, and it is often judged as contamination when it is cultured from blood. C. jeikeium can cause infective endocarditis, especially, that associated with cardiac surgery and prosthetic valvular endocarditis. CASE REPORT: A 66-year-old Japanese male patient was diagnosed with C. jeikeium-induced infective endocarditis (IE) and perivalvular abscess after a coronary artery bypass grafting and aortic valve replacement with bioprosthesis; pyogenic spondylodiscitis was also observed. Patch repair for aortic valve annulus and re-Bentall procedure with bioprosthesis was performed for IE and perivalvular abscess. The causative bacterium was confirmed as C. jeikeium on 16S ribosomal RNA sequencing of surgical sample and positive blood culture. The patient underwent six weeks of intravenous antibacterial treatment with vancomycin and an additional two weeks of oral treatment with linezolid, following which, his condition improved. Corynebacterium jeikeium can cause infective endocarditis and perivalvular abscess, which is a more severe condition than IE. CONCLUSION: 16S ribosomal RNA sequencing is useful in diagnosing bacterial species that can cause contamination, such as Corynebacterium spp.


Assuntos
Endocardite Bacteriana , Endocardite , Abscesso/diagnóstico , Idoso , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Corynebacterium/genética , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/tratamento farmacológico , Humanos , Masculino , RNA Ribossômico 16S/genética
13.
Pediatr Cardiol ; 42(3): 654-661, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33403434

RESUMO

We assessed the histological accuracy of X-ray phase-contrast tomography (XPCT) and investigated three-dimensional (3D) ductal tissue distribution in coarctation of the aorta (CoA) specimens. We used nine CoA samples, including the aortic isthmus, ductus arteriosus (DA), and their confluences. 3D images were obtained using XPCT. After scanning, the samples were histologically evaluated using elastica van Gieson (EVG) staining and transcription factor AP-2 beta (TFAP2B) immunostaining. XPCT sectional images clearly depicted ductal tissue distribution as low-density areas. In comparison with EVG staining, the mass density of the aortic wall positively correlated with elastic fiber formation (R = 0.69, P < 0.001). TFAP2B expression was consistent with low-density area including intimal thickness on XPCT images. On 3D imaging, the distances from the DA insertion to the distal terminal of the ductal media and to the intima on the ductal side were 1.63 ± 0.22 mm and 2.70 ± 0.55 mm, respectively. In the short-axis view, the posterior extension of the ductal tissue into the aortic lumen was 79 ± 18% of the diameter of the descending aorta. In three specimens, the aortic wall was entirely occupied by ductal tissue. The ductal intima spread more distally and laterally than the ductal media. The contrast resolution of XPCT images was comparable to that of histological assessment. Based on the 3D images, we conclude that complete resection of intimal thickness, including the opposite side of the DA insertion, is required to eliminate residual ductal tissue and to prevent postoperative re-coarctation.


Assuntos
Aorta Torácica/diagnóstico por imagem , Coartação Aórtica/diagnóstico por imagem , Canal Arterial/diagnóstico por imagem , Aorta Torácica/patologia , Coartação Aórtica/cirurgia , Espessura Intima-Media Carotídea , Canal Arterial/patologia , Humanos , Imageamento Tridimensional/normas , Tomografia Computadorizada por Raios X/normas , Fator de Transcrição AP-2/metabolismo , Raios X
14.
Kyobu Geka ; 74(7): 539-542, 2021 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-34193790

RESUMO

A right-sided classical Blalock-Taussig shunt was created in a 3-year-old male infant with hypoplastic left ventricle, common atrioventricular valve, transposition of the great arteries, and pulmonary stenosis. He was diagnosed with near Eisenmenger pulmonary hypertension at the age of 6 years. Surgery to achieve right heart bypass circulation was not conducted. At 33 years of age, he experienced hemoptysis. Pulmonary artery dissection, a life-threatening condition, was detected upon computed tomography performed when the patient was 35 years of age. After three weeks, surgery with cardiopulmonary bypass requiring pulmonary artery replacement using composite prosthetic conduits, closure of the pulmonary valve, and banding of the previously created Blalock-Taussig shunt was performed. Six years after the surgery, the patient's physical activity is maintained. Although intracardiac repair or definitive palliation with cardiopulmonary bypass is contraindicated in such patients, life-saving surgery with cardiopulmonary bypass that does not worsen pulmonary hypertension can be performed.


Assuntos
Hipertensão Pulmonar , Transposição dos Grandes Vasos , Criança , Pré-Escolar , Dissecação , Ventrículos do Coração , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/cirurgia , Lactente , Masculino , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/cirurgia , Resultado do Tratamento
15.
Med Mycol ; 58(7): 958-964, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32060526

RESUMO

Mucormycosis is a deep-seated fungal infection that mainly develops in patients with severe immunodeficiencies such as those with malignant hematological diseases. Despite poor prognosis, there is no reliable and minimally invasive diagnostic method-such as serodiagnosis-for making a clinical decision regarding the condition. As early diagnosis and early treatment improve the prognosis of mucormycosis, the development of a sensitive early diagnostic method is important. We had previously identified a Rhizopus-specific antigen (RSA) by signal sequence trapping and retrovirus-mediated expression (SST-REX), and evaluated its utility as a diagnostic antigen by constructing a sandwich enzyme-linked immunosorbent assay (ELISA) system to detect serum RSA levels in inoculated mice. In this study, we used the RSA-specific rabbit monoclonal antibodies generated by novel hybridoma technology to improve the sensitivity of the ELISA system. We observed an increase in serum and bronchoalveolar lavage fluid (BALF) levels of RSA in mouse model 1 day after inoculation, suggesting that this newly developed monoclonal antibody-based ELISA system may be useful for the diagnosis of mucormycosis in the early stages of infection. In addition, we measured RSA levels in human serum and BALF, and found that serum RSA level was higher in mucormycosis patients (15.1 ng/ml) than that in invasive pulmonary aspergillosis patients (0.53 ng/ml) and the negative control (0.49 ng/ml). Our results suggest that RSA may be a powerful tool for the diagnosis of pulmonary mucormycosis, and its differentiation from other deep-seated mycoses such as aspergillosis.


Assuntos
Antígenos de Fungos/sangue , Líquido da Lavagem Broncoalveolar/microbiologia , Técnicas e Procedimentos Diagnósticos , Diagnóstico Precoce , Mucormicose/sangue , Mucormicose/diagnóstico , Rhizopus/isolamento & purificação , Animais , Humanos , Camundongos
16.
BMC Infect Dis ; 20(1): 431, 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32563248

RESUMO

BACKGROUND: Good's syndrome (GS) is characterized by immunodeficiency, and can lead to severe infection, which is the most significant complication. Although Mycobacterium rarely causes infection in patients with GS, disseminated nontuberculous mycobacterial (NTM) infection frequently occurs in GS patients that are also positive for the human immunodeficiency virus (HIV) or anti-interferon (IFN)-γ autoantibodies. Here, we report a rare case of GS with NTM without HIV or IFN-γ autoantibodies. CASE PRESENTATION: A 57-year-old Japanese male with GS and myasthenia gravis (treated with prednisolone and tacrolimus) was diagnosed with disseminated NTM infection caused by Mycobacterium abscessus subsp. massiliense. He presented with fever and back pain. Blood, lumbar tissue, urine, stool, and sputum cultures tested positive for M. abscessus. Bacteremia, spondylitis, intestinal lumber abscess, and lung infection were confirmed by bacteriological examination and diagnostic imaging; urinary and intestinal tract infections were suspected by bacteriological examination but not confirmed by imaging. Despite multidrug combination therapy, including azithromycin, imipenem/cilastatin, levofloxacin, minocycline, linezolid, and sitafloxacin, the patient ultimately died of the infection. The patient tested negative for HIV and anti-IFN-γ autoantibodies. CONCLUSIONS: Since myasthenia gravis symptoms interfere with therapy, patients with GS and their physicians should carefully consider the antibacterial treatment options against disseminated NTM.


Assuntos
Pneumopatias/microbiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium abscessus , Doenças da Imunodeficiência Primária/complicações , Antibacterianos/uso terapêutico , Autoanticorpos/sangue , Quimioterapia Combinada , Evolução Fatal , Fluoroquinolonas/uso terapêutico , Soronegatividade para HIV , Humanos , Interferon gama/imunologia , Pneumopatias/complicações , Pneumopatias/imunologia , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/complicações , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/imunologia , Síndrome
17.
Mycoses ; 63(8): 794-801, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32391919

RESUMO

BACKGROUND: Fungal infections are a major complication of neutropaenia following chemotherapy. Their early diagnosis is difficult, and empirical antifungal treatment is widely used, and uses of less toxic drugs that reduce breakthrough infection are required. OBJECTIVE: We conducted a multicentre, open-label, randomised, non-inferiority trial to compare the safety and efficacy of intravenous itraconazole (ivITCZ) and liposomal amphotericin B (LAmB) as empirical antifungal therapy in patients with haematological malignancies with neutropaenia and persistent fever. METHODS: Patients with haematological malignancies who developed fever refractory to broad-spectrum antibacterial agents under neutropaenia conditions were enrolled. Patients were randomised for treatment with LAmB (3.0 mg/kg/d) or ivITCZ (induction: 400 mg/d, maintenance: 200 mg/d). RESULTS: Observed overall favourable response rates of 17/52 (32.7%) and 18/50 (36.0%) in the LAmB and ivITCZ groups, with a model-based estimate of a 4% difference (90% CI, -12% to 20%), did not fulfil the statistical non-inferiority criterion. In the LAmB group, there were two cases of breakthrough infection and five cases of probable invasive fungal disease, whereas in the itraconazole group, neither breakthrough infection nor probable invasive fungal disease occurred. Patients in the ivITCZ group had significantly fewer grade 3-4 hypokalaemia-related events than LAmB group patients (P < .01). The overall incidence of adverse events tended to be lower in the ivITCZ group (P = .07). CONCLUSION: ivITCZ showed similar efficacy and safety as LAmB as empirical antifungal therapy in haematological malignancy patients with febrile neutropaenia, although the small sample size and various limitations prevented demonstration of its non-inferiority.


Assuntos
Anfotericina B , Neutropenia Febril Induzida por Quimioterapia/complicações , Itraconazol , Micoses , Administração Intravenosa , Adulto , Idoso , Anfotericina B/administração & dosagem , Anfotericina B/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Neutropenia Febril Induzida por Quimioterapia/patologia , Feminino , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/patologia , Humanos , Itraconazol/administração & dosagem , Itraconazol/uso terapêutico , Masculino , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , Micoses/etiologia , Adulto Jovem
18.
Pediatr Cardiol ; 41(8): 1689-1696, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32710283

RESUMO

In patients with pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries (PA/VSD/MAPCAs), segmental pulmonary hypertension is common; however, its pathophysiology remains to be elucidated. This study aimed to identify preoperative hemodynamic factors associated with segmental pulmonary hypertension after intracardiac repair in patients with PA/VSD/MAPCAs. This study included 12 patients with PA/VSD/MAPCAs who underwent unifocalization and intracardiac repair from 2009 at our institution. Hemodynamic measurements of preoperative and postoperative cardiac catheterization were collected. Patients were considered to have pulmonary hypertension if the mean pulmonary pressure measured postoperatively at any peripheral pulmonary artery was ≥ 20 mmHg. The data were compared between patients with and without postoperative segmental pulmonary hypertension; p value < 0.05 was considered statistically significant. Intracardiac repair was performed at the age of 2.1 years (range 0.5-28.2 years). Unifocalization was performed separately prior to intracardiac repair in two patients and concomitantly in 10 patients. Postoperative cardiac catheterization, performed 1.2 years (range 0.2-8.7 years) after intracardiac repair, revealed that five patients had segmental pulmonary hypertension. Patients with postoperative pulmonary hypertension had significantly lower preoperative mixed venous oxygen saturation than those without pulmonary hypertension (57% [55-63%] vs. 65% [53-75%], p < 0.05). No significant differences were found between the groups in terms of age at intracardiac repair, preoperative arterial oxygen saturation, and preoperative peripheral pulmonary arterial mean pressure. Lower preoperative mixed venous oxygen saturation was associated with segmental pulmonary hypertension after intracardiac repair in patients with PA/VSD/MAPCAs.


Assuntos
Defeitos dos Septos Cardíacos/cirurgia , Hipertensão Pulmonar/epidemiologia , Oxigênio/metabolismo , Complicações Pós-Operatórias/epidemiologia , Artéria Pulmonar/anormalidades , Atresia Pulmonar/cirurgia , Adolescente , Adulto , Aorta/anormalidades , Aorta/cirurgia , Cateterismo Cardíaco/métodos , Procedimentos Cirúrgicos Cardíacos/métodos , Criança , Pré-Escolar , Circulação Colateral , Feminino , Comunicação Interventricular/cirurgia , Hemodinâmica , Humanos , Hipertensão Pulmonar/fisiopatologia , Lactente , Masculino , Oximetria/métodos , Complicações Pós-Operatórias/fisiopatologia , Período Pré-Operatório , Artéria Pulmonar/cirurgia , Adulto Jovem
19.
Anaerobe ; 64: 102214, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32446953

RESUMO

The effect of antimicrobial stewardship (AS) on anaerobic bacteremia is uncertain. This study aimed to assess the effect of interventions by the AS team (AST) on clinical and microbiological outcomes and antimicrobial use. An AS program was introduced at Osaka City University Hospital in January 2014; an interdisciplinary AST was established. We enrolled patients with anaerobic bacteremia between January 2009 and December 2018. Patients were classified into the pre-intervention group (from January 2009 to December 2013) and the post-intervention group (from January 2014 to December 2018). A significant decrease in definitive carbapenem use (P = 0.0242) and an increase in empiric tazobactam/piperacillin use (P = 0.0262) were observed in the post-intervention group. The de-escalation rate increased significantly from 9.38% to 32.7% (P = 0.0316) in the post-intervention group. The susceptibility of Bacteroides species and 30-day mortality did not worsen in the post-intervention group. These results showed that interventions by an AST can reduce carbapenem use and increase the de-escalation rate without worsening patient outcomes.


Assuntos
Antibacterianos/uso terapêutico , Gestão de Antimicrobianos , Bacteriemia/microbiologia , Bactérias Anaeróbias/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/mortalidade , Carbapenêmicos/uso terapêutico , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Combinação Piperacilina e Tazobactam/uso terapêutico , Prognóstico , Resultado do Tratamento
20.
Eur J Clin Microbiol Infect Dis ; 38(12): 2291-2297, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31605255

RESUMO

Klebsiella pneumoniae bacteremia is a critical clinical presentation that is associated with high mortality. However, extremely few studies have investigated the virulence factors related to mortality of K. pneumoniae bacteremia in patients. The present study elucidated clinical and virulence factors associated with the 30-day mortality of K. pneumoniae bacteremia at a tertiary hospital. The medical records of 129 patients with K. pneumoniae bacteremia admitted to Osaka City University Hospital between January 2012 and December 2018 were retrospectively reviewed. Patient background characteristics, antimicrobial regimens, and prognosis were evaluated. Additionally, virulence factors were assessed using multiplex polymerase chain reaction to elucidate their association with K. pneumoniae. The 30-day mortality was 10.9% in patients with K. pneumoniae bacteremia. The male-to-female ratio, age, and underlying disease did not differ between the non-survivor and survivor groups. Multivariate analysis showed that sepsis (odds ratio (OR), 7.46; p = 0.005) and iutA (OR, 4.47; p = 0.046) were independent predictors associated with the 30-day mortality of K. pneumoniae bacteremia. Despite the relatively low 30-day mortality of patients with K. pneumoniae bacteremia, the treatment of those with sepsis and those infected with K. pneumoniae harboring iutA may require careful management for improving their outcomes.


Assuntos
Bacteriemia/mortalidade , Infecções por Klebsiella/mortalidade , Klebsiella pneumoniae/patogenicidade , Fatores de Virulência/genética , Idoso , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Proteínas de Bactérias/genética , Estudos de Casos e Controles , Feminino , Hospitais Universitários , Humanos , Japão/epidemiologia , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Sepse/tratamento farmacológico , Sepse/microbiologia , Sepse/mortalidade , Centros de Atenção Terciária
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