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1.
Clin Microbiol Infect ; 28(6): 844-851, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35259529

RESUMO

OBJECTIVES: Severe COVID-19 is associated with an imbalanced immune response. We hypothesized that patients with enhanced inflammation, as demonstrated by increased levels of certain inflammatory biomarkers, would benefit from interleukin-6 blockage. METHODS: Patients hospitalized with COVID-19, hypoxemia, and at least two of four markedly elevated markers of inflammation (interleukin-6, C-reactive protein, ferritin, and/or D-dimer) were randomized for tocilizumab (TCZ) plus standard of care (SoC) or SoC alone. The primary endpoint was clinical status at day 28 assessed using a seven-category ordinal scale, and the secondary endpoints included intensive care unit admission, respiratory support, and duration of hospital admission. RESULTS: Clinical status at day 28 was significantly better in patients who received TCZ in addition to SoC compared with those who received SoC alone (p = 0.037). By then, 93% of patients who received TCZ (n = 53 of 57) and 86% of control patients (n = 25 of 29) had been discharged from the hospital. In addition, 47% of TCZ patients (n = 27 of 57) and 24% of control patients (n = 7 of 29) had resumed normal daily activities. The median length of hospitalization was 9 days (interquartile range, 7-12) in the TCZ group and 12 days (interquartile range, 9-15) in the control group (p = 0.014). DISCUSSION: In patients hospitalized with COVID-19, hypoxemia, and elevated inflammation markers, administration of TCZ in addition to SoC was associated with significantly better clinical recovery by day 28 and a shorter hospitalization compared with SoC alone.


Assuntos
Tratamento Farmacológico da COVID-19 , Anticorpos Monoclonais Humanizados , Biomarcadores , Humanos , Hipóxia , Inflamação/tratamento farmacológico , Interleucina-6 , Estudos Prospectivos , SARS-CoV-2 , Resultado do Tratamento
2.
EBioMedicine ; 74: 103724, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34844193

RESUMO

BACKGROUND: A key factor behind the unnecessary use of antibiotics is the lack of rapid and accurate diagnostic tests. In this study, we developed a novel and fast flow cytometric single-tube method to detect bacterial infections within 30 minutes. METHODS: Quantitative flow cytometric four-colour analysis of host biomarkers CD35, CD64, CD329, and MHC class I expression on neutrophils and lymphocytes was performed on samples taken from 841 febrile patients with suspected infection. Obtained data was incorporated into the four-colour bacterial infection (FCBI)-index, using the developed bacterial infection algorithm. FINDINGS: In distinguishing between microbiologically confirmed bacterial (n = 193) and viral (n = 291) infections, the FCBI-index method was superior to serum C-reactive protein (CRP) and procalcitonin (PCT). In 269 confirmed viral respiratory tract infections, 43% (95% CI: 37-49%) of the patients had an increased FCBI-index, suggesting probable bacterial coinfection. INTERPRETATION: The proposed FCBI-index test might be a potent additional tool when assessing appropriateness of empiric antibiotic treatment. FUNDING: This study has been financially supported by Turku University Hospital (Turku, Finland) and The Finnish Medical Foundation.


Assuntos
Infecções Bacterianas/diagnóstico , Citometria de Fluxo/instrumentação , Pró-Calcitonina/sangue , Receptores Imunológicos/sangue , Infecções Respiratórias/virologia , Viroses/diagnóstico , Algoritmos , Infecções Bacterianas/sangue , Diagnóstico Diferencial , Testes Diagnósticos de Rotina , Diagnóstico Precoce , Feminino , Finlândia , Citometria de Fluxo/métodos , Humanos , Masculino , Infecções Respiratórias/sangue , Sensibilidade e Especificidade , Viroses/sangue
3.
Clin Infect Dis ; 72(8): 1323-1331, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-32133487

RESUMO

BACKGROUND: Lyme neuroborreliosis (LNB) is often treated with intravenous ceftriaxone even if doxycycline is suggested to be noninferior to ceftriaxone. We evaluated the efficacy of oral doxycycline in comparison to ceftriaxone in the treatment of LNB. METHODS: Patients with neurological symptoms suggestive of LNB without other obvious reasons were recruited. The inclusion criteria were (1) production of Borrelia burgdorferi-specific antibodies in cerebrospinal fluid (CSF) or serum; (2) B. burgdorferi DNA in the CSF; or (3) an erythema migrans during the past 3 months. Participants were randomized in a 1:1 ratio to receive either oral doxycycline 100 mg twice daily for 4 weeks, or intravenous ceftriaxone 2 g daily for 3 weeks. The participants described their subjective condition with a visual analogue scale (VAS) from 0 to 10 (0 = normal; 10 = worst) before the treatment, and 4 and 12 months after the treatment. The primary outcome was the change in the VAS score at 12 months. RESULTS: Between 14 September 2012 and 28 December 2017, 210 adults with suspected LNB were assigned to receive doxycycline (n = 104) or ceftriaxone (n = 106). The per-protocol analysis comprised 82 patients with doxycycline and 84 patients with ceftriaxone. The mean change in the VAS score was -3.9 in the doxycycline group and -3.8 in the ceftriaxone group (mean difference, 0.17 [95% confidence interval, -.59 to .92], which is within the prespecified equivalence margins of -1 to 1 units). Participants in both groups improved equally. CONCLUSIONS: Oral doxycycline is equally effective as intravenous ceftriaxone in the treatment of LNB. CLINICAL TRIALS REGISTRATION: NCT01635530 and EudraCT 2012-000313-37.


Assuntos
Eritema Migrans Crônico , Neuroborreliose de Lyme , Adulto , Antibacterianos/uso terapêutico , Ceftriaxona , Doxiciclina , Eritema Migrans Crônico/tratamento farmacológico , Humanos , Neuroborreliose de Lyme/tratamento farmacológico
4.
Case Rep Cardiol ; 2020: 4921380, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33294230

RESUMO

Diagnosis of Candida spp. infective endocarditis (IE) is challenging, and diagnostic delays are common. We describe two patients with Candida spp. prosthetic valve endocarditis (PVE) and 18fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) as a part of diagnostic workup. We also refer to 5 other cases we found from the published literature. These cases highlight that 18F-FDG-PET/CT can improve diagnostic accuracy in prosthetic valve Candida endocarditis.

5.
J Microbiol Methods ; 152: 61-68, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30063957

RESUMO

The aim of this study was to develop a rapid single-tube two-color flow cytometric method to distinguish between febrile bacterial and viral infections. In this prospective comparative study, the quantitative flow cytometric analysis of CD35 and CD64 on isolated human leukocytes was obtained from 286 hospitalized febrile patients, of which 197 patients were found to have either a bacterial (n = 136) or viral (n = 61) infection. The data from infected patients was compared to 49 healthy controls and 23 patients in an inflammatory state. We developed a flow cytometric marker for bacterial infections, defined as the two-color bacterial infection index (TC-BI-index), by incorporating the quantitative analysis of CD35 and CD64 on isolated neutrophils, monocytes, and B-lymphocytes, which displayed 90% sensitivity and specificity in distinguishing between microbiologically confirmed bacterial (n = 77) and viral infections (n = 61) within 45 min. We propose that TC-BI-index test will be useful in assisting physicians to ascertain whether antibiotic treatment is required, thus limiting unnecessary antimicrobial usage.


Assuntos
Infecções Bacterianas/diagnóstico , Testes Diagnósticos de Rotina/métodos , Febre/microbiologia , Febre/virologia , Citometria de Fluxo/métodos , Viroses/diagnóstico , Linfócitos B/imunologia , Biomarcadores , Humanos , Leucócitos/imunologia , Monócitos/imunologia , Neutrófilos/imunologia , Estudos Prospectivos , Receptores de Superfície Celular/análise , Receptores de Complemento 3b , Receptores de IgG , Sensibilidade e Especificidade
6.
APMIS ; 126(5): 453-456, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29696719

RESUMO

We describe a rare case of prosthetic valve endocarditis caused by the canine bacterium Capnocytophaga canimorsus in a male aged 73 years. The diagnosis of infective endocarditis was unequivocal, as it blood cultures were positive for C. canimorsus and vegetations were detected on transesophageal echocardiography; the modified Duke criteria were fulfilled. PET-CT showed intense 18 F-FDG uptake of the prosthetic valve area. The patient was treated with antibiotics alone (no surgery), and is now on life-long suppressive antibiotic therapy. To our knowledge, this is the third reported case of prosthetic valve endocarditis caused by C. canimorsus and the first one to have been treated conservatively.


Assuntos
Capnocytophaga/isolamento & purificação , Endocardite/etiologia , Próteses Valvulares Cardíacas/efeitos adversos , Idoso , Antibacterianos/uso terapêutico , Ecocardiografia Transesofagiana , Endocardite/tratamento farmacológico , Humanos , Masculino
7.
Med Mycol Case Rep ; 11: 28-30, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27134821

RESUMO

We report a case of Scedosporium apiospermum mold causing ear infection, central skull base osteomyelitis and finally, occlusion of carotid artery in a 48-year-old diabetic man. The exact diagnosis was established and the severity of the disease understood several months after the onset of symptoms. Despite of appropriate antifungal therapy, and repeated surgical and otological procedures, the infection progressed to fatal cerebral infarction.

8.
Diagn Microbiol Infect Dis ; 78(2): 116-26, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24315569

RESUMO

The aim of this study was to develop a rapid and simple flow cytometric bacterial infection marker. In this prospective comparative study, quantitative flow cytometric analysis of CD10, CD35, CD66b, CD282, and MHC Class I molecules on human neutrophils, monocytes, and B-lymphocytes from 141 hospitalized febrile patients with suspected infection and from 50 healthy controls was performed. We developed a flow cytometric marker of local and systemic bacterial infections, designated "bacterial infection (BI)-INDEX", incorporating the quantitative analysis of CD10, CD35, MHCI, CD66b, and CD282 on neutrophils, monocytes, and B-lymphocytes, which displayed 90% sensitivity and 96% specificity in distinguishing between microbiologically confirmed bacterial (n = 31) and viral infections (n = 27) within a 1-h time-frame. We propose that our novel rapid BI-INDEX test will be useful in assisting physicians to ascertain whether antibiotic treatment is required, thus limiting unnecessary antimicrobial usage.


Assuntos
Infecções Bacterianas/diagnóstico , Infecções Bacterianas/metabolismo , Citometria de Fluxo , Adulto , Antígenos de Superfície/metabolismo , Linfócitos B/metabolismo , Infecções Bacterianas/microbiologia , Biomarcadores/metabolismo , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Neutrófilos/metabolismo , Curva ROC , Receptores de Superfície Celular/metabolismo , Reprodutibilidade dos Testes , Adulto Jovem
9.
Hum Immunol ; 74(5): 522-30, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23376460

RESUMO

Several complement regulatory proteins exist on self-cells to prevent damage by the serum complement system. In the present study, we aimed to perform quantitative analysis of membrane-bound complement regulators, CR1 (CD35), MCP (CD46), DAF (CD55), and MIRL (CD59), on peripheral blood neutrophils, monocytes, and lymphocytes from healthy controls (n=36) and febrile patients diagnosed with either bacterial (n=21) or viral (n=26) infections. Our results show that: (a) increased CD35 and CD55 levels on neutrophils and monocytes present potent markers of bacterial infection, (b) increased expression of CD46 on monocytes is an indicator of viral infection, and (c) increased CD59 expression on neutrophils and monocytes is a general infection marker. Additionally, CD19-positive B-lymphocytes represent practically the only lymphocyte population capable of expressing CD35. We further developed two novel clinical flow cytometric markers (indices), specifically, clinical mononucleosis (CM)-INDEX (incorporating CD35, CD55, and CD59 expression on lymphocytes) and clinical bacterial infection (CBI)-INDEX (incorporating CD35 and CD55 expression on neutrophils and lymphocytes), for the effective detection of viral mononucleosis and bacterial infection, respectively. In summary, bacterial and viral infections induce different expression patterns of membrane-bound complement regulators in human leukocytes, which may be effectively exploited in clinical differential diagnosis.


Assuntos
Infecções Bacterianas/diagnóstico , Antígenos CD55/sangue , Antígenos CD59/sangue , Mononucleose Infecciosa/diagnóstico , Leucócitos/metabolismo , Proteína Cofatora de Membrana/sangue , Receptores de Complemento 3b/sangue , Adulto , Idoso , Infecções Bacterianas/sangue , Biomarcadores/sangue , Proteínas Inativadoras do Complemento/análise , Diagnóstico Diferencial , Citometria de Fluxo , Humanos , Mononucleose Infecciosa/sangue , Linfócitos/metabolismo , Pessoa de Meia-Idade , Monócitos/metabolismo , Neutrófilos/metabolismo , Sensibilidade e Especificidade , Adulto Jovem
10.
J Microbiol Methods ; 92(1): 64-72, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23154042

RESUMO

Antibiotic resistance due to the inappropriate use of antimicrobials is one of the most critical public health problems worldwide. A major factor underlying the unnecessary use of antibiotics is the lack of rapid and accurate diagnostic tests. Therefore, we aimed to develop a novel rapid flow cytometric method for distinguishing between febrile bacterial and viral infections. In this prospective comparative study, quantitative flow cytometric analysis of FcγRII/CD32, CR1/CD35, MHC Class I receptor (MHCI), and C5aR/CD88 on human phagocytes was performed in 286 hospitalized febrile patients with suspected infection. After using microbiological and serological detection methods, or clinical diagnosis, 205 patients were identified with either bacterial (n=136) or viral (n=69) infection. Receptor data from patients were compared to those of 50 healthy controls. We developed a flow cytometric marker of local and systemic bacterial infections designated "bacterial infection score (BIS)" incorporating the quantitative analysis of FcγRII/CD32, CR1/CD35, C5aR/CD88 and MHCI on neutrophils and/or monocytes, which displays 91% sensitivity and 92% specificity in distinguishing between microbiologically confirmed bacterial (n=77) and serologically confirmed viral infections (n=61) within 1h. The BIS method was effectively applied to distinguish between bacterial and viral (pandemic H1N1 influenza) pneumonia cases with 96% sensitivity and 92% specificity. We propose that the rapid BIS test can assist physicians in deciding whether antibiotic treatment is necessary, thus reducing unnecessary antimicrobial use.


Assuntos
Infecções Bacterianas/diagnóstico , Biomarcadores/sangue , Técnicas de Laboratório Clínico/métodos , Febre/etiologia , Citometria de Fluxo/métodos , Viroses/diagnóstico , Adulto , Antígenos de Superfície/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fagócitos/química , Estudos Prospectivos , Sensibilidade e Especificidade , Adulto Jovem
11.
J Clin Rheumatol ; 16(1): 19-21, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20051750

RESUMO

This report describes a 72-year-old female patient with a previous history of cured breast cancer who presented with acute monocular visual disturbances, intense unilateral headache, painful temporal artery palpation, high erythrocyte sedimentation rate, and pain and weakness of the femoral muscles. These symptoms and signs were suggestive of temporal arteritis, but the finding of the temporal artery biopsy was negative, and the patient did not respond to corticosteroid treatment. Later, whole body bone scintigraphy revealed dissemination of malignancy throughout her skeleton including the skull. To our knowledge, this is the first report to show that a metastasis in the temporal bone can closely mimic temporal arteritis.


Assuntos
Neoplasias da Mama/patologia , Arterite de Células Gigantes/diagnóstico , Neoplasias Cranianas/diagnóstico por imagem , Neoplasias Cranianas/secundário , Osso Temporal/patologia , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Cintilografia , Medronato de Tecnécio Tc 99m
12.
Clin Immunol ; 133(3): 314-23, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19734101

RESUMO

A flow cytometric quantitative analysis of receptors on neutrophils can be exploited in distinguishing between inflammatory and infectious diseases. In this prospective comparative study, simultaneous quantitative analysis of CD64 and CD35 on peripheral blood neutrophils was performed in febrile patients in order to differentiate between bacterial infections (n=89), viral infections (n=46), and inflammatory diseases (n=21). The patient data was compared to 60 healthy controls. We could divide patients into three groups depending on how they express CD35 and CD64 on neutrophils: (1) patients with a high probability of viral infection (low CD35/low CD64 and low CD35/high CD64), (2) patients with a high probability of inflammatory disease (high CD35/low CD64), and (3) patients with a high probability of bacterial infection (high CD35/high CD64). In summary, simultaneous quantitative analysis of CD64 and CD35 on neutrophils could potentially assist physicians to distinguish between inflammatory and infectious diseases.


Assuntos
Infecções Bacterianas/imunologia , Doenças do Sistema Imunitário/imunologia , Neutrófilos/imunologia , Receptores de Complemento 3b/sangue , Receptores de IgG/sangue , Viroses/imunologia , Adulto , Infecções Bacterianas/sangue , Infecções Bacterianas/diagnóstico , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Feminino , Febre/imunologia , Febre/microbiologia , Febre/virologia , Citometria de Fluxo , Humanos , Doenças do Sistema Imunitário/sangue , Doenças do Sistema Imunitário/diagnóstico , Contagem de Leucócitos , Masculino , Estudos Prospectivos , Receptores de Complemento 3b/imunologia , Receptores de IgG/imunologia , Estatísticas não Paramétricas , Viroses/sangue , Viroses/diagnóstico
13.
Hum Immunol ; 70(4): 237-43, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19480860

RESUMO

To commence proper antibiotic treatment in sepsis, timely knowledge of whether the cause of systemic infection is gram-negative (gram(-)) or gram-positive (gram(+)) bacteria in origin would be beneficial for clinicians. In this clinical prospective study, our objective was to develop a method for distinguishing between gram(+) and gram(-) bacterial infection. In gram(-) bacterial infection (n = 21), the average amount of CD11b on neutrophils was significantly higher than in gram(+) bacterial infection (n = 22). On the contrary, serum C-reactive protein (CRP) level was significantly higher in gram(+) than in gram(-) bacterial infection. By dividing the serum CRP value by the amount of CD11b on neutrophils, we derived a novel marker of gram(+) sepsis, CRP/CD11b ratio, which displayed 76% sensitivity and 80% specificity for the detection of gram(+) sepsis (n = 17) among febrile patients with microbiologically confirmed or clinically diagnosed bacterial infection. The detection of gram(+) sepsis is possible after the combination of neutrophil CD11b data and serum CRP level. In conclusion, our findings indicate that the proposed CRP/CD11b ratio test could potentially assist physicians in determining an appropriate antibiotic treatment in patients with severe bacterial infection.


Assuntos
Proteína C-Reativa/análise , Antígeno CD11b/sangue , Infecções por Bactérias Gram-Positivas/diagnóstico , Sepse/diagnóstico , Análise de Variância , Sedimentação Sanguínea , Diagnóstico Diferencial , Citometria de Fluxo , Infecções por Bactérias Gram-Negativas/sangue , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Positivas/sangue , Humanos , Neutrófilos/metabolismo , Receptores de Complemento 3b/sangue , Sensibilidade e Especificidade , Sepse/sangue
14.
Hum Immunol ; 70(10): 813-9, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19559743

RESUMO

The aim of this study was to compare degranulation of easily mobilizable secretory vesicles (SVs) or secretory vesicle-like granules (SVLGs) in neutrophils, monocytes, and eosinophils of healthy controls (n = 60) and febrile patients with microbiologically confirmed or clinically diagnosed bacterial (n = 89) and viral (n = 46) infections. For this purpose, flow cytometric immunophenotyping of isolated phagocytes was performed using monoclonal antibodies against the phagocytosis receptors CR1 (CD35) and CR3 (CD11b) that are predominantly stored in the SVs of resting neutrophils. Similar to neutrophils, monocytes contain easily mobilizable SVLGs that constitute the main intracellular reservoir of CD35 and CD11b. In both neutrophils and monocytes, activation mechanisms leading to degranulation of SV and SVLG appeared dependent on both intra- and extracellular calcium levels. The kinetics of degranulation of SVLGs in control monocytes was significantly faster than that of SVs of control neutrophils. We conclude that phagocytes in patients with bacterial infections can be arranged in order of decreasing magnitude of SV or SVLG degranulation as follows (from left to right): neutrophils > monocytes " eosinophils. However, in viral infections, the corresponding degranulation order is monocytes > neutrophils approximately eosinophils.


Assuntos
Degranulação Celular/fisiologia , Eosinófilos/imunologia , Infecções/imunologia , Monócitos/imunologia , Neutrófilos/imunologia , Fagocitose , Adulto , Idoso , Antígeno CD11b/imunologia , Grânulos Citoplasmáticos/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Complemento 3b/imunologia , Vesículas Secretórias/imunologia , Regulação para Cima/imunologia
15.
APMIS ; 116(3): 219-22, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18377589

RESUMO

Tungiasis is a parasitic infection widely spread in tropical Africa and in South and Central America. Only a few cases involving travellers have been reported from Europe, and none from the Nordic countries. We report a case of tungiasis in a Finnish journalist returning from Uganda. In this era of increasing intercontinental travel it is important that all physicians are aware of tungiasis.


Assuntos
Ectoparasitoses/etiologia , Sifonápteros , Viagem , Adulto , Animais , Humanos , Masculino
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