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1.
J Med Virol ; 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34411312

RESUMO

This study aimed to determine the frequency of SARS-CoV-2 RNA in serum and its association with the clinical severity of COVID-19. This retrospective cohort study performed at Toyama University Hospital included consecutive patients with confirmed COVID-19. The prevalence of SARS-CoV-2 RNAemia and the strength of its association with clinical severity variables were examined. Fifty-six patients were included in this study. RNAemia was detected in 19.6% (11/56) patients on admission, and subsequently in 1.0% (1/25), 50.0% (6/12), and 100.0% (4/4) moderate, severe, and critically ill patients, respectively. Patients with RNAemia required more frequent oxygen supplementation (90.0% vs. 13.3%), ICU admission (81.8% vs. 6.7%), and invasive mechanical ventilation (27.3% vs. 0.0%). Among patients with RNAemia, the median viral loads of nasopharyngeal (NP) swabs that were collected around the same time as the serum sample were significantly higher in critically ill (5.4 log10 copies/µl; interquartile range [IQR]: 4.2-6.3) than in moderate-severe cases (2.6 log10 copies/µl; [IQR: 1.1-4.5]; p = 0.030) and were significantly higher in nonsurvivors (6.2 log10 copies/µl [IQR: 6.0-6.5]) than in survivors (3.9 log10 copies/µl [IQR: 1.6-4.6]; p = 0.045). This study demonstrated a relatively high proportion of SARS-CoV-2 RNAemia and an association between RNAemia and clinical severity. Moreover, among the patients with RNAemia, the viral loads of NP swabs were correlated with disease severity and mortality, suggesting the potential utility of combining serum testing with NP tests as a prognostic indicator for COVID-19, with higher quality than each separate test.

2.
Sci Rep ; 11(1): 16535, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34400739

RESUMO

Adaptive immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics remain largely unknown. The neutralizing antibody (NAb) levels in patients with coronavirus disease 2019 (COVID-19) are helpful for understanding the pathology. Using SARS-CoV-2 pseudotyped virus, serum sample neutralization values in symptomatic COVID-19 patients were measured using the chemiluminescence reduction neutralization test (CRNT). At least two sequential serum samples collected during hospitalization were analyzed to assess NAbs neutralizing activity dynamics at different time points. Of the 11 patients, four (36.4%), six (54.5%), and one (9.1%) had moderate, severe, and critical disease, respectively. Fifty percent neutralization (N50%-CRNT) was observed upon admission in 90.9% (10/11); all patients acquired neutralizing activity 2-12 days after onset. In patients with moderate disease, neutralization was observed at earliest within two days after symptom onset. In patients with severe-to-critical disease, neutralization activity increased, plateauing 9-16 days after onset. Neutralization activity on admission was significantly higher in patients with moderate disease than in patients with severe-to-critical disease (relative % of infectivity, 6.4% vs. 41.1%; P = .011). Neutralization activity on admission inversely correlated with disease severity. The rapid NAb response may play a crucial role in preventing the progression of COVID-19.


Assuntos
Imunidade Adaptativa , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/diagnóstico , SARS-CoV-2/imunologia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/imunologia , COVID-19/sangue , COVID-19/imunologia , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19 , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Neutralização/estatística & dados numéricos , Estudos Retrospectivos , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Fatores de Tempo
4.
J Infect Chemother ; 27(7): 1122-1125, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33853730

RESUMO

This study aimed to assess the nasopharyngeal viral load at discharge or time of discontinued isolation in coronavirus 2019 (COVID-19) patients admitted to our hospital and discharged under the current symptom-based criteria in Japan. Patients diagnosed with COVID-19 by reverse transcription polymerase chain reaction and hospitalized at Toyama University Hospital were included in the analysis. Nasopharyngeal viral load was measured when symptom-based criteria for discharge or end of isolation in the accommodations were met, and examined the relationship between viral load and days after onset or age. From the perspective of virus isolation limit, the amount of infectious viral load was defined at 50 copies/µL by nasopharyngeal sample. Thirty-three patients with laboratory-confirmed COVID-19 were included in the analysis, after excluding critical and fatal cases. Mean nasopharyngeal viral load at discharge or end of isolation was 1.90 log-copies/µL, and 64% of patients were discharged with over 50 copies/µL. No correlation was apparent between age and viral load at discharge, and viral load remained relatively high at discharge or end of isolation in all age groups. Although attempts at infectious virus isolation are necessary, infection control precautions even after discharge or discontinued isolation in accommodations may be needed, as the date of onset mostly depended on self-reporting by patients.


Assuntos
COVID-19 , Alta do Paciente , Humanos , Japão , SARS-CoV-2 , Carga Viral
5.
BMC Pharmacol Toxicol ; 22(1): 13, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33663616

RESUMO

BACKGROUND: Linezolid is administered as a fixed dose to all patients despite evidence of overexposure and thrombocytopenia in renal impairment. The aims of this study were to evaluate the risk of thrombocytopenia and the utility of therapeutic drug monitoring (TDM), and to propose alternate dosing regimens in patients with renal impairment. METHODS: We retrospectively reviewed patients ≥13 years old for whom serum linezolid trough concentration (Cmin) was measured during linezolid treatment. Patients with episodes of infection were divided into groups by presence of renal impairment (RI group) or absence of renal impairment (non-RI group), and by use of Cmin-based TDM (TDM group) or not (non-TDM group) during linezolid treatment. RESULTS: In the 108 patients examined by multivariable analyses, renal impairment was independently associated with increased risk of thrombocytopenia (OR 3.17, 95%CI 1.10-9.12) and higher Cmin. Analysis of the utility of TDM in the RI group showed that clinical failure rate was significantly lower in the TDM subgroup than in the non-TDM subgroup. Furthermore, in the RI group, dosage adjustments were needed in 90.5% of the TDM subgroup. All episodes administered a reduced dose of 300 mg every 12 h in the RI group showed Cmin ≥ 2.0 mg/L. Additional analysis of 53 episodes in which Cmin was measured within 48 h after starting administration showed that the initial standard dose for 2 days was sufficient to rapidly reach an effective therapeutic concentration in the RI group. CONCLUSIONS: Empirical dose reduction to 300 mg every 12 h after administration of the initial fixed dose for 2 days and Cmin-based TDM may improve safety outcomes while maintaining appropriate efficacy among patients with renal impairment.

6.
J Infect Chemother ; 27(7): 1119-1121, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33781692

RESUMO

INTRODUCTION: The detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) is the standard method for the diagnosis of coronavirus disease 2019 (COVID-19). This PCR test can be positive even in patients who have recovered from the disease, and the duration for achieving viral clearance has not been clarified yet. METHODS: This study was conducted between April 3, 2020, and June 17, 2020, at the Toyama University Hospital and the Toyama Rehabilitation Home. We collected the data of patients with COVID-19, analyzing the duration until twice-consecutive negative qRT-PCR test. RESULTS: A total of 42 patients were enrolled. The median duration of the twice-consecutive negative qRT-PCR test was 29.0 d (interquartile range: 25.75-35.25). The longest duration of viral shedding was 73 d. The duration of viral clearance was significantly longer in the older (>65 years) group than in the younger group (34.5 d vs. 25.0 d, P < 0.0001). CONCLUSION: This study demonstrated that viral clearance tends to be sustained in the older adults.


Assuntos
COVID-19 , SARS-CoV-2 , Idoso , Humanos , Pessoa de Meia-Idade , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Eliminação de Partículas Virais
7.
Int J Infect Dis ; 106: 33-35, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33746092

RESUMO

As of October 2020, there is still no specific drug to treat COVID-19 as it rages worldwide. Favipiravir, indicated for the treatment of new and re-emerging influenza infections, has been suggested to be effective against SARS-CoV-2, although this is not yet fully validated. We administered favipiravir to a 64-year-old female patient with COVID-19. Her symptoms resolved quickly after the start of treatment, with reduction of SARS-CoV-2 viral load, but she developed a fever again on day 12. Since the fever was relieved by discontinuation of favipiravir, and based on positive results with a drug-induced lymphocyte stimulation test, we diagnosed her with favipiravir-induced drug fever. A decrease in the serum concentration of favipiravir was observed along with resolution of the fever. The present case suggests that drug fever should be considered in the differential diagnosis of relapsing fever episodes in COVID-19 patients receiving favipiravir.


Assuntos
Amidas/efeitos adversos , COVID-19/tratamento farmacológico , COVID-19/imunologia , Febre/induzido quimicamente , Ativação Linfocitária/efeitos dos fármacos , Pirazinas/efeitos adversos , Amidas/farmacologia , Amidas/uso terapêutico , COVID-19/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Pirazinas/farmacologia , Pirazinas/uso terapêutico , Carga Viral/efeitos dos fármacos
8.
Virol J ; 18(1): 16, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33435994

RESUMO

BACKGROUND: SARS-CoV-2 is a novel coronavirus that emerged in 2019 and is now classified in the genus Coronavirus with closely related SARS-CoV. SARS-CoV-2 is highly pathogenic in humans and is classified as a biosafety level (BSL)-3 pathogen, which makes manipulating it relatively difficult due to its infectious nature. METHODS: To circumvent the need for BSL-3 laboratories, an alternative assay was developed that avoids live virus and instead uses a recombinant VSV expressing luciferase and possesses the full length or truncated spike proteins of SARS-CoV-2. Furthermore, to measure SARS-CoV-2 neutralizing antibodies under BSL2 conditions, a chemiluminescence reduction neutralization test (CRNT) for SARS-CoV-2 was developed. The neutralization values of the serum samples collected from hospitalized patients with COVID-19 or SARS-CoV-2 PCR-negative donors against the pseudotyped virus infection evaluated by the CRNT were compared with antibody titers determined from an enzyme-linked immunosorbent assay (ELISA) or an immunofluorescence assay (IFA). RESULTS: The CRNT, which used whole blood collected from hospitalized patients with COVID-19, was also examined. As a result, the inhibition of pseudotyped virus infection was specifically observed in both serum and whole blood and was also correlated with the results of the IFA. CONCLUSIONS: In conclusion, the CRNT for COVID-19 is a convenient assay system that can be performed in a BSL-2 laboratory with high specificity and sensitivity for evaluating the occurrence of neutralizing antibodies against SARS-CoV-2.


Assuntos
Anticorpos Neutralizantes/sangue , Teste Sorológico para COVID-19/métodos , COVID-19/sangue , Testes de Neutralização/métodos , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vírus da Estomatite Vesicular Indiana/genética , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Linhagem Celular , Convalescença , Humanos , Concentração Inibidora 50 , Luminescência , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética
9.
PLoS One ; 15(12): e0243597, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33296437

RESUMO

OBJECTIVE: To investigate the relationship between viral load and secondary transmission in novel coronavirus disease 2019 (COVID-19). METHODS: Epidemiological and clinical data were obtained from immunocompetent laboratory-confirmed patients with COVID-19 who were admitted to and/or from whom viral loads were measured at Toyama University Hospital. Using a case-control approach, index patients who transmitted the disease to at least one other patient were analysed as "cases" (index patients) compared with patients who were not the cause of secondary transmission (non-index patients, analysed as "controls"). The viral load time courses were assessed between the index and non-index symptomatic patients using non-linear regression employing a standard one-phase decay model. RESULTS: In total, 28 patients were included in the analysis. Median viral load at the initial sample collection was significantly higher in symptomatic than in asymptomatic patients and in adults than in children. Among symptomatic patients (n = 18), non-linear regression models showed that the estimated viral load at onset was higher in the index than in the non-index patients (median [95% confidence interval]: 6.6 [5.2-8.2] vs. 3.1 [1.5-4.8] log copies/µL, respectively). In adult (symptomatic and asymptomatic) patients (n = 21), median viral load at the initial sample collection was significantly higher in the index than in the non-index patients (p = 0.015, 3.3 vs. 1.8 log copies/µL, respectively). CONCLUSIONS: High nasopharyngeal viral loads around onset may contribute to secondary transmission of COVID-19. Viral load may help provide a better understanding of why transmission is observed in some instances, but not in others, especially among household contacts.


Assuntos
COVID-19 , Modelos Biológicos , Nasofaringe , SARS-CoV-2/metabolismo , Carga Viral , Adolescente , Adulto , Idoso , COVID-19/metabolismo , COVID-19/transmissão , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Nasofaringe/metabolismo , Nasofaringe/virologia
10.
J Infect Chemother ; 26(12): 1324-1327, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32900659

RESUMO

Most patients with coronavirus disease 2019 (COVID-19) have just only mild symptoms, but about 5% are very severe. Although extracorporeal membranous oxygenation (ECMO) is sometimes used in critically patients with COVID-19, ECMO is only an adjunct, not the main treatment. If the patient's condition deteriorates and it is determined to be irreversible, it is necessary to decide to stop ECMO. A 54-year-old man was admitted on day 6 of onset with a chief complaint of high fever and cough. Computed tomography (CT) showed a ground glass opacity in both lungs, and reverse transcription-polymerase chain reaction (RT-PCR) diagnosed COVID-19. He was admitted to the hospital and started to receive oxygen and favipiravir. After that, his respiratory condition deteriorated, and he was intubated and ventilated on day 9 of onset, and ECMO was introduced on day 12. Two days after the introduction of ECMO, C-reactive protein (CRP) increased, chest X-p showed no improvement in pneumonia, and PaO2/FiO2 decreased again. As D-dimer rose and found a blood clot in the ECMO circuit, we had to decide whether to replace the circuit and continue with ECMO or stop ECMO. At this time, the viral load by RT-PCR was drastically reduced to about 1/1750. We decided to continue ECMO therapy and replaced the circuit. The patient's respiratory status subsequently improved and ECMO was stopped on day 21 of onset. In conclusion, viral load measurement by RT-PCR may be one of the indicators for promoting the treatment of severe COVID-19 patients.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Oxigenação por Membrana Extracorpórea/métodos , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Carga Viral/métodos , Amidas/uso terapêutico , Antivirais/uso terapêutico , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Tomada de Decisões , Hospitalização , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pirazinas/uso terapêutico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2 , Tomografia Computadorizada por Raios X , Resultado do Tratamento
11.
J Infect Chemother ; 26(6): 588-595, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32085966

RESUMO

In most existing studies on the impact of infectious disease (ID) specialty care on bloodstream infections, ID consultations were started upon request or mandatory after notification of positive blood cultures; however, initial antibiotic therapy had already been administrated at that time by attending physicians. This study aimed to assess the impact of early ID consultation at the time of blood culture collection on therapeutic management and outcome of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. This retrospective cohort study investigated all patients with MRSA bacteremia (MRSAB) from 2011 to 2018. Proactive ID consultations were available 24 h per day, 7 days per week and obtained upon request by attending physicians, and patients were classed as having early ID consultation (at the time of blood culture collection) or late ID consultation (after notification of positive blood cultures), or none. A total of 55 first MRSAB episodes were included. In the ID consultation group, a significantly higher proportion of patients were treated for more than 14 days, and significantly more echocardiography and follow-up blood cultures were performed. Moreover, patients in the ID consultation group were hospitalized for a significantly shorter period overall. With respect to cost, we noted a possible association between ID consultation and lower hospital charges. Furthermore, relative to late ID consultation, patients receiving early ID consultation were more likely to receive appropriate empirical therapy and had significantly lower all-cause in-hospital mortality (odds ratio, 0.034; 95% confidence interval [CI], 0.0002-0.51; p = 0.015) and long-term mortality (hazard ratio, 0.17; 95% CI, 0.033-0.83; p = 0.028).


Assuntos
Bacteriemia/microbiologia , Bacteriemia/mortalidade , Intervenção Médica Precoce , Staphylococcus aureus Resistente à Meticilina , Encaminhamento e Consulta , Infecções Estafilocócicas/mortalidade , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Hemocultura , Farmacorresistência Bacteriana , Feminino , Mortalidade Hospitalar , Humanos , Tempo de Internação , Masculino , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Análise de Sobrevida , Resultado do Tratamento
12.
J Infect Chemother ; 26(1): 119-123, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31300378

RESUMO

Slackia exigua is an obligate anaerobic coccobacillus associated with dental infection, but rarely causes extraoral infection. We report two cases of monomicrobial bacteremia caused by S. exigua isolated from two institutions. The first case involved community-acquired bacteremia associated with pleural empyema in a 69-year-old man. The second case involved hospital-acquired bacteremia secondary to postoperative intra-abdominal abscess in a 73-year-old man with primary intestinal diffuse large B-cell lymphoma. S. exigua was finally identified by 16S ribosomal RNA gene sequencing analyses in both cases. In the first case, our attempts to identify the organism using commercial identification kits for anaerobes resulted in inaccurate identification as Gemella morbillorum. However, S. exigua was promptly identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry in the second case. The epidemiology and clinical characteristics of S. exigua extraoral infection remain unclear because of the limitations in accurate identification and because only 19 cases of extraoral S. exigua infection have been reported previously, including four cases of bacteremia. Physicians should focus on this species, which can cause community-acquired infections and spread via various routes even in patients with no comorbidities. Further studies are needed to clarify the clinical characteristics of extraoral S. exigua infections.


Assuntos
Actinobacteria , Bacteriemia , Infecções por Bactérias Gram-Positivas , Abscesso Abdominal , Actinobacteria/genética , Actinobacteria/isolamento & purificação , Idoso , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Masculino , Tipagem Molecular , Derrame Pleural , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
13.
IDCases ; 18: e00640, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692509

RESUMO

Nocardia farcinica usually infects the respiratory tract and can sometimes cause central nervous system infections; however, it rarely infects the prostate. Here we report the first case of N. farcinica detected in the purulence specimen drained from a prostate abscess. A 70-year-old Japanese male receiving steroid and cyclosporine treatment came to our department with chief complaint of turbid urine. Computed tomography revealed a low-density lesion in his prostate. Antibiotic administration and prostatic drainage were effective. N. farcinica was detected in the cultures of urine and prostatic drainage purulence specimens. Nocardiosis should be included in the differential diagnosis in immunosuppressive patients with prostate abscess.

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