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1.
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
2.
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
3.
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
4.
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.

5.
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
6.
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
7.
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.

8.
Intern Med ; 57(2): 253-258, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29093391

RESUMO

A 53-year-old man was admitted to the hospital with a diagnosis of cellulitis and osteomyelitis. Twenty-four days after the initiation of daptomycin and sulbactam/ampicillin, he developed a fever and pulmonary infiltration. Bronchoalveolar lavage revealed a high number of eosinophils, while an intracutaneous test revealed positivity for daptomycin. The patient improved after discontinuing antimicrobial therapy. The plasma daptomycin minimum concentration (Cmin) was elevated (27.4 µg/mL), but plasma protein binding of daptomycin was low (87.8%). Although the pathophysiology of eosinophilic pneumonia remains unclear, antigenic stimulation due to daptomycin accumulation in the alveoli may have caused continuous immune activation.


Assuntos
Antibacterianos/efeitos adversos , Daptomicina/efeitos adversos , Eosinofilia Pulmonar/induzido quimicamente , Ampicilina/uso terapêutico , Anti-Infecciosos/efeitos adversos , Líquido da Lavagem Broncoalveolar/imunologia , Eosinófilos , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Eosinofilia Pulmonar/diagnóstico , Sulbactam/uso terapêutico
9.
Intern Med ; 57(3): 429-435, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29093394

RESUMO

Mycobacterium bovis infection after intravesical Bacillus Calmette-Guérin (BCG) therapy is rare. A 65-year-old Japanese man with history of bladder cancer and intravesical BCG therapy, presented with low-grade fever. An aneurysm with perianeurysmal fluid was suspected and endovascular aortic repair was performed. After 160 days, he developed blood-streaked sputum and computed tomography images revealed that the perianeurysmal fluid area was increasing in size. A multiplex polymerase chain reaction using sputum identified M. bovis. Treatment with anti-tuberculosis drugs reduced the size of the perianeurysmal fluid area. After intravesical BCG therapy, the possibility of M. bovis infection should be considered, thus further investigations are required.


Assuntos
Antibacterianos/uso terapêutico , Aneurisma da Aorta Abdominal/etiologia , Aneurisma da Aorta Abdominal/cirurgia , Vacina BCG/uso terapêutico , Infecções por Mycobacterium/tratamento farmacológico , Infecções por Mycobacterium/etiologia , Tuberculose Cardiovascular/tratamento farmacológico , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Administração Intravesical , Idoso , Aneurisma da Aorta Abdominal/microbiologia , Grupo com Ancestrais do Continente Asiático , Humanos , Masculino , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Tretoquinol , Tuberculose Cardiovascular/diagnóstico , Tuberculose Cardiovascular/microbiologia , Tuberculose Cardiovascular/cirurgia
10.
BMC Infect Dis ; 17(1): 584, 2017 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-28835212

RESUMO

BACKGROUND: It has been suggested that more than 100 bacterial species can be identified using only seven universal bacterial primer sets in the melting temperature (Tm) mapping method and that these findings can be obtained within 3 h of sterile site collection. CASE PRESENTATION: A 67-year-old Japanese man with type 2 diabetes visited our hospital complaining of progressive lower back pain for 2 months. The patient was suspected to have spondylodiscitis on magnetic resonance imaging of the spine. Blood culture and transcutaneous vertebral biopsy were subsequently performed. Using the Tm mapping method, Parvimonas micra was detected from a transcutaneous vertebral biopsy specimen in 3 h. Gram-positive cocci were also detected by Gram staining and P. micra was identified directly from the anaerobic blood culture by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Four days after admission, the biopsy specimen culture isolate was identified as P. micra. CONCLUSIONS: The Tm mapping method may be useful for the diagnosis of bacterial infections where diagnosis is challenging because of the difficulty of culturing.


Assuntos
Discite/diagnóstico , Infecções por Bactérias Gram-Positivas/diagnóstico , Peptostreptococcus/genética , Idoso , Primers do DNA/química , Diabetes Mellitus Tipo 2/microbiologia , Discite/microbiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Peptostreptococcus/isolamento & purificação , Peptostreptococcus/patogenicidade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Coluna Vertebral/microbiologia , Temperatura
11.
J Infect Chemother ; 22(5): 331-4, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26732509

RESUMO

Linezolid is an effective antibiotic against most gram-positive bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus. Although linezolid therapy is known to result in thrombocytopenia, dosage adjustment or therapeutic drug monitoring of linezolid is not generally necessary. In this report, however, we describe the case of a 79-year-old woman with recurrent methicillin-resistant S. aureus osteomyelitis that was successfully treated via surgery and combination therapy using linezolid and rifampicin under therapeutic drug monitoring for maintaining an appropriate serum linezolid concentration. The patient underwent surgery for the removal of the artificial left knee joint and placement of vancomycin-impregnated bone cement beads against methicillin-resistant S. aureus after total left knee implant arthroplasty for osteoarthritis. We also initiated linezolid administration at a conventional dose of 600 mg/h at 12-h intervals, but reduced it to 300 mg/h at 12-h intervals on day 9 because of a decrease in platelet count and an increase in serum linezolid trough concentration. However, when the infection exacerbated, we again increased the linezolid dose to 600 mg/h at 12-h intervals and performed combination therapy with rifampicin, considering their synergistic effects and the control of serum linezolid trough concentration via drug interaction. Methicillin-resistant S. aureus infection improved without reducing the dose of or discontinuing linezolid. The findings in the present case suggest that therapeutic drug monitoring could be useful for ensuring the therapeutic efficacy and safety of combination therapy even in patients with osteomyelitis who require long-term antibiotic administration.


Assuntos
Antibacterianos/uso terapêutico , Linezolida/uso terapêutico , Staphylococcus aureus Resistente à Meticilina , Osteomielite/tratamento farmacológico , Rifampina/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Monitoramento de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Joelho/microbiologia , Joelho/patologia , Linezolida/administração & dosagem , Linezolida/sangue , Osteomielite/microbiologia , Patela/microbiologia , Patela/patologia , Rifampina/administração & dosagem , Rifampina/sangue , Infecções Estafilocócicas/microbiologia
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