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1.
PLoS One ; 16(3): e0247356, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33667247

RESUMO

BACKGROUND: Hydroxychloroquine (HCQ) and azithromycin (AZM) are antimalarial drugs recently reported to be active against severe acute respiratory syndrome coronavirus- 2 (SARS-CoV-2), which is causing the global COVID-19 pandemic. In an emergency response to the pandemic, we aimed to develop a quantitation method for HCQ, its metabolites desethylhydroxychloroquine (DHCQ) and bisdesethylchloroquine (BDCQ), and AZM in human plasma. METHODS: Liquid chromatography tandem mass spectrometry was used to develop the method. Samples (20 µL) are extracted by solid-phase extraction and injected onto the LC-MS/MS system equipped with a PFP column (2.0 × 50 mm, 3 µm). ESI+ and MRM are used for detection. Ion pairs m/z 336.1→247.1 for HCQ, 308.1→179.1 for DHCQ, 264.1→179.1 for BDCQ, and 749.6→591.6 for AZM are selected for quantification. The ion pairs m/z 342.1→253.1, 314.1→181.1, 270.1→181.1, and 754.6→596.6 are selected for the corresponding deuterated internal standards (IS) HCQ-d4, DHCQ-d4, BDCQ-d4, and AZM-d5. The less abundant IS ions from 37Cl were used to overcome the interference from the analytes. RESULTS: Under optimized conditions, retention times are 0.78 min for BDCQ, 0.79 min for DHCQ, 0.92 min for HCQ and 1.87 min for AZM. Total run time is 3.5 min per sample. The calibration ranges are 2-1000 ng/mL for HCQ and AZM, 1-500 ng/mL for DHCQ and 0.5-250 ng/mL for BDCQ; samples above the range are validated for up to 10-fold dilution. Recoveries of the method ranged from 88.9-94.4% for HCQ, 88.6-92.9% for DHCQ, 88.7-90.9% for BDCQ, and 98.6%-102% for AZM. The IS normalized matrix effect were within (100±10) % for all 4 analytes. Blood samples are stable for at least 6 hr at room temperature. Plasma samples are stable for at least 66 hr at room temperature, 38 days at -70°C, and 4 freeze-thaw cycles. CONCLUSIONS: An LC-MS/MS method for simultaneous quantitation of HCQ, DHCQ, BDCQ, and AZM in human plasma was developed and validated for clinical studies requiring fast turnaround time and small samples volume.


Assuntos
Antibacterianos/sangue , Antimaláricos/sangue , Azitromicina/sangue , Cloroquina/análogos & derivados , Hidroxicloroquina/análogos & derivados , Hidroxicloroquina/sangue , Coleta de Amostras Sanguíneas/métodos , Cloroquina/sangue , Cromatografia Líquida de Alta Pressão/métodos , Monitoramento de Medicamentos/métodos , Ácido Edético/sangue , Humanos , Limite de Detecção , Espectrometria de Massas em Tandem/métodos
2.
J Trop Pediatr ; 67(1)2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33787904

RESUMO

LAY SUMMARY: Clinical and laboratory parameters of multisystem inflammatory syndrome in children (MIS-C) mimic Kawasaki disease (KD). KD has been described in association with dengue, scrub typhus and leptospirosis. However, MIS-C with concomitant infection has rarely been reported in literature. A 14-year-old-girl presented with fever and rash with history of redness of eyes, lips and tongue. Investigations showed anemia, lymphopenia, thrombocytosis with elevated erythrocyte sedimentation rate, C-reactive protein, pro-brain natriuretic peptide, Interleukin-6, ferritin and d-dimer. Scrub typhus immunoglobulin M was positive. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) level was also elevated. A diagnosis of MIS-C with concomitant scrub typhus was proffered. Child received azithromycin, intravenous immunoglobulin and methylprednisolone. After an afebrile period of 2.5 days, child developed unremitting fever and rash. Repeat investigations showed anemia, worsening lymphopenia, thrombocytopenia, transaminitis, hypertriglyceridemia, hyperferritinemia and hypofibrinogenemia which were consistent with a diagnosis of macrophage activation syndrome (MAS). KD, MIS-C and MAS represent three distinct phenotypes of hyperinflammation seen in children during coronavirus disease pandemic. Several tropical infections may mimic or coexist with MIS-C which can be a diagnostic challenge for the treating physician. Identification of coexistence or differentiation between the two conditions is important in countries with high incidence of tropical infections to guide appropriate investigations and treatment.


Assuntos
/complicações , Síndrome de Ativação Macrofágica/diagnóstico , Tifo por Ácaros/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica , Adolescente , Azitromicina/uso terapêutico , Biomarcadores/sangue , /diagnóstico , Criança , Feminino , Febre/etiologia , Humanos , Imunoglobulina G/sangue , Imunoglobulinas Intravenosas/uso terapêutico , Síndrome de Ativação Macrofágica/complicações , Síndrome de Ativação Macrofágica/tratamento farmacológico , Síndrome de Ativação Macrofágica/imunologia , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Pandemias , Tifo por Ácaros/complicações , Tifo por Ácaros/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/imunologia
3.
Vopr Virusol ; 66(1): 40-46, 2021 03 07.
Artigo em Russo | MEDLINE | ID: mdl-33683064

RESUMO

INTRODUCTION: Analysis of the pathogenesis of coronavirus infection caused SARS-CoV-2 indicates a significant impact of hemorheological disorders on its course and outcomes. It is known that chronic cardiovascular diseases are associated with the risk of severe course and lethal outcomes both in COVID-19 and other infectious diseases. Therefore, in each case it is necessary to study the interaction and mutual influence of different components of the treatment program prescribed to such patients.The purpose of this work was to evaluate the effect of coagulation activity on the course of a novel coronavirus infection (COVID-19) and to justify the management of comorbid patients having been received novel oral anticoagulants (NOACs) in previously selected doses according to indications in concomitant somatic diseases. MATERIAL AND METHODS: Total 76 cases of confirmed coronavirus infection in patients who had been received initial therapy on an outpatient basis were analyzed. 26 patients who received NOACs (rivaroxaban, apixaban, dabigatran) made up the main group and 50 - the comparison (control) group in which patients had not been administered any drugs that affect blood clotting until the episode of COVID-19. All patients have been prescribed therapy following the Provisional guidelines «Prevention, diagnosis and treatment of coronavirus infection (COVID-19)¼ (https://static-0.minzdrav.gov.ru/system/attachments/attaches/). RESULTS AND DISCUSSION: The number of hospitalizations was significantly fewer in the group of patients who had been received NOACs (19 vs. 66% in the control group). No deaths or cases of severe respiratory and/or renal failure were observed in the main group, while adverse outcomes were noted in 14% of patients who had not been administered these drugs. CONCLUSION: Taking NOACs reduces the probability of severe course and adverse outcomes in the development of coronavirus infection caused by SARS-CoV-2, which indicates a significant contribution of coagulation mechanisms to the pathogenesis in COVID-19. There were no indications for drug replacement and correction of anticoagulant therapy regimens in patients who received adequate therapy with oral anticoagulants for treating a non-severe form of coronavirus infection in ambulatory patient settings.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Doença das Coronárias/tratamento farmacológico , Coagulação Intravascular Disseminada/tratamento farmacológico , Hipertensão/tratamento farmacológico , Arteriosclerose Intracraniana/tratamento farmacológico , Acetilcisteína/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/mortalidade , Fibrilação Atrial/virologia , Azitromicina/uso terapêutico , /patologia , Estudos de Coortes , Comorbidade , Doença das Coronárias/diagnóstico , Doença das Coronárias/mortalidade , Doença das Coronárias/virologia , Dabigatrana/uso terapêutico , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/mortalidade , Coagulação Intravascular Disseminada/virologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/mortalidade , Hipertensão/virologia , Indóis/uso terapêutico , Interferon alfa-2/uso terapêutico , Arteriosclerose Intracraniana/diagnóstico , Arteriosclerose Intracraniana/mortalidade , Arteriosclerose Intracraniana/virologia , Masculino , Pessoa de Meia-Idade , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , /patogenicidade , Índice de Gravidade de Doença , Análise de Sobrevida
4.
Vopr Virusol ; 66(1): 47-54, 2021 03 07.
Artigo em Russo | MEDLINE | ID: mdl-33683065

RESUMO

INTRODUCTION: Interferons are produced in response to the presence of pathogens in cells and are responsible for the proper formation of immune reaction. Preliminary data obtained in studies of properties of recombinant interferon gamma (IFN-γ) that involved patients with community-acquired pneumonia (including bacterial), acute respiratory viral infection (ARVI), influenza and new coronavirus infection have shown promising results.The purpose of the study was to assess the effect of subcutaneous administration of IFN-γ in patients with viral pneumonia on the changes of vital signs and the duration of hospital stay. MATERIAL AND METHODS: An open-label, randomized, low-interventional study included patients with moderate new coronavirus infection COVID-19 over 18 years of age of both sexes. IFN-γ 500,000 IU was administered s/c, daily, once a day, during 5 days. RESULTS: IFN-y in addition to complex therapy of the disease resulted in more favorable changes in the stabilization of vital signs, as well as in reduced length of fever and hospital stay by 2 days what allows suggesting a positive effect of this substance on the recovery processes in patients with moderate COVID-19. Special emphasis should be made to the fact that patients who received recombinant IFN- γ experienced no progression of respiratory failure and required no transfer to intensive care unit. DISCUSSION: This study confirms earlier obtained data on the positive effect of IFN-y on the rate of clinical stabilization and recovery of patients with community-acquired pneumonia and viral infections. Presented results are limited to a small number of patients; further study of drug properties in post-marketing studies is required. CONCLUSION: Progress in the treatment of patients with moderate COVID-19 by adding recombinant IFN-γ to the complex therapy may reasonably expand the range of existing treatment options for this infection.


Assuntos
Anti-Infecciosos/uso terapêutico , Anticoagulantes/uso terapêutico , Fatores Imunológicos/uso terapêutico , Interferon gama/uso terapêutico , Idoso , Ampicilina/uso terapêutico , Azitromicina/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , /patologia , Enoxaparina/uso terapêutico , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória , /patogenicidade , Índice de Gravidade de Doença , Resultado do Tratamento , Vancomicina/uso terapêutico
5.
6.
Front Immunol ; 12: 574425, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33643308

RESUMO

The rapid advancement of the COVID-19 pandemic has prompted an accelerated pursuit to identify effective therapeutics. Stages of the disease course have been defined by viral burden, lung pathology, and progression through phases of the immune response. Immunological factors including inflammatory cell infiltration and cytokine storm have been associated with severe disease and death. Many immunomodulatory therapies for COVID-19 are currently being investigated, and preliminary results support the premise of targeting the immune response. However, because suppressing immune mechanisms could also impact the clearance of the virus in the early stages of infection, therapeutic success is likely to depend on timing with respect to the disease course. Azithromycin is an immunomodulatory drug that has been shown to have antiviral effects and potential benefit in patients with COVID-19. Multiple immunomodulatory effects have been defined for azithromycin which could provide efficacy during the late stages of the disease, including inhibition of pro-inflammatory cytokine production, inhibition of neutrophil influx, induction of regulatory functions of macrophages, and alterations in autophagy. Here we review the published evidence of these mechanisms along with the current clinical use of azithromycin as an immunomodulatory therapeutic. We then discuss the potential impact of azithromycin on the immune response to COVID-19, as well as caution against immunosuppressive and off-target effects including cardiotoxicity in these patients. While azithromycin has the potential to contribute efficacy, its impact on the COVID-19 immune response requires additional characterization so as to better define its role in individualized therapy.


Assuntos
Azitromicina/uso terapêutico , Inflamação/tratamento farmacológico , Neutrófilos/imunologia , Citocinas/metabolismo , Humanos , Imunomodulação , Pandemias
7.
Lancet ; 397(10279): 1063-1074, 2021 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-33676597

RESUMO

BACKGROUND: Azithromycin, an antibiotic with potential antiviral and anti-inflammatory properties, has been used to treat COVID-19, but evidence from community randomised trials is lacking. We aimed to assess the effectiveness of azithromycin to treat suspected COVID-19 among people in the community who had an increased risk of complications. METHODS: In this UK-based, primary care, open-label, multi-arm, adaptive platform randomised trial of interventions against COVID-19 in people at increased risk of an adverse clinical course (PRINCIPLE), we randomly assigned people aged 65 years and older, or 50 years and older with at least one comorbidity, who had been unwell for 14 days or less with suspected COVID-19, to usual care plus azithromycin 500 mg daily for three days, usual care plus other interventions, or usual care alone. The trial had two coprimary endpoints measured within 28 days from randomisation: time to first self-reported recovery, analysed using a Bayesian piecewise exponential, and hospital admission or death related to COVID-19, analysed using a Bayesian logistic regression model. Eligible participants with outcome data were included in the primary analysis, and those who received the allocated treatment were included in the safety analysis. The trial is registered with ISRCTN, ISRCTN86534580. FINDINGS: The first participant was recruited to PRINCIPLE on April 2, 2020. The azithromycin group enrolled participants between May 22 and Nov 30, 2020, by which time 2265 participants had been randomly assigned, 540 to azithromycin plus usual care, 875 to usual care alone, and 850 to other interventions. 2120 (94%) of 2265 participants provided follow-up data and were included in the Bayesian primary analysis, 500 participants in the azithromycin plus usual care group, 823 in the usual care alone group, and 797 in other intervention groups. 402 (80%) of 500 participants in the azithromycin plus usual care group and 631 (77%) of 823 participants in the usual care alone group reported feeling recovered within 28 days. We found little evidence of a meaningful benefit in the azithromycin plus usual care group in time to first reported recovery versus usual care alone (hazard ratio 1·08, 95% Bayesian credibility interval [BCI] 0·95 to 1·23), equating to an estimated benefit in median time to first recovery of 0·94 days (95% BCI -0·56 to 2·43). The probability that there was a clinically meaningful benefit of at least 1·5 days in time to recovery was 0·23. 16 (3%) of 500 participants in the azithromycin plus usual care group and 28 (3%) of 823 participants in the usual care alone group were hospitalised (absolute benefit in percentage 0·3%, 95% BCI -1·7 to 2·2). There were no deaths in either study group. Safety outcomes were similar in both groups. Two (1%) of 455 participants in the azothromycin plus usual care group and four (1%) of 668 participants in the usual care alone group reported admission to hospital during the trial, not related to COVID-19. INTERPRETATION: Our findings do not justify the routine use of azithromycin for reducing time to recovery or risk of hospitalisation for people with suspected COVID-19 in the community. These findings have important antibiotic stewardship implications during this pandemic, as inappropriate use of antibiotics leads to increased antimicrobial resistance, and there is evidence that azithromycin use increased during the pandemic in the UK. FUNDING: UK Research and Innovation and UK Department of Health and Social Care.


Assuntos
Gestão de Antimicrobianos , Azitromicina/uso terapêutico , Síndrome da Liberação de Citocina/prevenção & controle , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Azitromicina/farmacologia , /diagnóstico , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/virologia , Farmacorresistência Bacteriana , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Admissão do Paciente/estatística & dados numéricos , Fatores de Risco , /isolamento & purificação , Fatores de Tempo , Resultado do Tratamento , Reino Unido
8.
J Med Case Rep ; 15(1): 143, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741059

RESUMO

BACKGROUND: There are limited data on cardiovascular complications of coronavirus disease 2019 in pregnancy, and there are only a few case reports on coronavirus disease 2019 related cardiomyopathy in pregnancy. Differentiation between postpartum cardiomyopathy and coronavirus disease 2019 related cardiomyopathy in pregnant women who develop severe acute respiratory syndrome coronavirus-2 infection during peripartum could be challenging. Here, we present a case of possible coronavirus disease 2019 related cardiomyopathy in a pregnant patient, followed by a discussion of potential differential diagnosis. CASE PRESENTATION: In this case report, we present the case of a young pregnant Iranian woman who developed heart failure with pulmonary edema after cesarean section. She was treated because of low left ventricular ejection fraction and impression of postpartum cardiomyopathy, and her severe dyspnea improved by intravenous furosemide. On day 3, she exhibited no orthopnea or leg edema, but she was complaining of severe and dry cough. Further evaluation showed severe acute respiratory syndrome coronavirus-2 infection. CONCLUSIONS: The possibility of severe acute respiratory syndrome coronavirus-2 infection should be considered in any pregnant woman who develops cardiomyopathy and pulmonary edema.


Assuntos
/diagnóstico , Cardiomiopatias/diagnóstico , Insuficiência Cardíaca/diagnóstico , Transtornos Puerperais/diagnóstico , Edema Pulmonar/diagnóstico , Adulto , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Azitromicina/uso terapêutico , /terapia , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/fisiopatologia , Cesárea , Tosse/fisiopatologia , Diagnóstico Diferencial , Diuréticos/uso terapêutico , Dispneia/fisiopatologia , Ecocardiografia , Eletrocardiografia , Feminino , Furosemida/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Interferon beta/uso terapêutico , Pulmão/diagnóstico por imagem , Pré-Eclâmpsia , Gravidez , Transtornos Puerperais/tratamento farmacológico , Transtornos Puerperais/fisiopatologia , Edema Pulmonar/tratamento farmacológico , Edema Pulmonar/fisiopatologia , Volume Sistólico , Tomografia Computadorizada por Raios X
9.
Medicine (Baltimore) ; 100(12): e25135, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761679

RESUMO

BACKGROUND: Mycoplasma pneumonia is a common disease in pediatrics, and macrolides is the first choice for the treatment. However, the increase of antibiotic resistance of macrolides makes it more and more complicated for clinical treatment. Due to the long term treatment of macrolides, it may increase the incidence of nausea, vomiting, abdominal pain, diarrhea, and other gastrointestinal symptoms, vascular phlebitis, liver and kidney function damage. Tanreqing injection, a Chinese herbal extraction injection, has advantages in the treatment of mycoplasma pneumonia in children, and it could improve the curative effect, shortening the course of disease, and reducing the side effects. Yet there is a lack of standard clinical studies to verify it, so this randomized controlled trial (RCT) will evaluate the efficacy and safety of Tanreqing injection combined with azithromycin in the treatment of mycoplasma pneumonia in children. METHODS: This is a prospective RCT to study the efficacy and safety of Tanreqing injection combined with azithromycin in the treatment of mycoplasma pneumonia in children. It is approved by the Clinical Research Society of our hospital. According to the 1:1 ratio, the patients will be randomly divided into Tanreqing injection combined with azithromycin group (observation group) and azithromycin group (control group). Duration of hospitalization, clinical improvement 7 days after admission, changing laboratory tests, pulmonary function, immunoglobulin level, and adverse reactions will be compared between the 2 groups. The data will be analyzed by SPSS 16.0 software. DISCUSSION: This study will evaluate the efficacy and safety of Tanreqing injection combined with azithromycin in the treatment of mycoplasma pneumonia in children. The results of this experiment will provide clinical basis for the treatment of mycoplasma pneumonia in children with Tanreqing injection combined with azithromycin. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/X6VFS.


Assuntos
Antibacterianos/administração & dosagem , Azitromicina/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Mycoplasma pneumoniae , Pneumonia por Mycoplasma/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Humanos , Injeções , Masculino , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
10.
Cardiovasc Ther ; 2021: 6683098, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33688374

RESUMO

Background: Hydroxychloroquine with or without azithromycin was one of the common therapies at the beginning of the COVID-19 pandemic. They can prolong QT interval, cause torsade de pointes, and lead to sudden cardiac death. We aimed to assess QT interval prolongation and its risk factors in patients who received hydroxychloroquine with or without azithromycin. Methods: This study was a retrospective cohort study. One hundred seventy-two confirmed COVID-19 patients were included in this study, hospitalized at Babol University of Medical Sciences hospitals between March 5, 2020, and April 3, 2020. Patients were divided into two groups: hydroxychloroquine alone and hydroxychloroquine with azithromycin. Electrocardiograms were used for outcome assessment. Results: 83.1% of patients received hydroxychloroquine plus azithromycin vs. 16.9% of patients who received only hydroxychloroquine. The mean age of patients was 59.2 ± 15.4.The mean of posttreatment QTc interval in the monotherapy group was shorter than the mean of posttreatment QTc interval in the combination therapy group, but it had no significant statistical difference (462.5 ± 43.1 milliseconds vs. 464.3 ± 59.1 milliseconds; p = 0.488). Generally, 22.1% of patients had a prolonged QTc interval after treatment. Male gender, or baseline QTc ≥ 450 milliseconds, or high-risk Tisdale score increased the likelihood of prolonged QTc interval. Due to QTc prolongation, fourteen patients did not continue therapy after four days. Conclusions: Hospitalized patients treated by hydroxychloroquine with or without azithromycin had no significant difference in prolongation of QT interval and outcome. The numbers of patients with prolonged QT intervals in this study emphasize careful cardiac monitoring during therapy, especially in high-risk patients.


Assuntos
Arritmias Cardíacas/induzido quimicamente , Azitromicina/efeitos adversos , Hidroxicloroquina/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Adulto , Idoso , Azitromicina/administração & dosagem , Eletrocardiografia/efeitos dos fármacos , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
PLoS One ; 16(3): e0248128, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33730088

RESUMO

BACKGROUND: The COVID-19 pandemic remains a significant global threat. However, despite urgent need, there remains uncertainty surrounding best practices for pharmaceutical interventions to treat COVID-19. In particular, conflicting evidence has emerged surrounding the use of hydroxychloroquine and azithromycin, alone or in combination, for COVID-19. The COVID-19 Evidence Accelerator convened by the Reagan-Udall Foundation for the FDA, in collaboration with Friends of Cancer Research, assembled experts from the health systems research, regulatory science, data science, and epidemiology to participate in a large parallel analysis of different data sets to further explore the effectiveness of these treatments. METHODS: Electronic health record (EHR) and claims data were extracted from seven separate databases. Parallel analyses were undertaken on data extracted from each source. Each analysis examined time to mortality in hospitalized patients treated with hydroxychloroquine, azithromycin, and the two in combination as compared to patients not treated with either drug. Cox proportional hazards models were used, and propensity score methods were undertaken to adjust for confounding. Frequencies of adverse events in each treatment group were also examined. RESULTS: Neither hydroxychloroquine nor azithromycin, alone or in combination, were significantly associated with time to mortality among hospitalized COVID-19 patients. No treatment groups appeared to have an elevated risk of adverse events. CONCLUSION: Administration of hydroxychloroquine, azithromycin, and their combination appeared to have no effect on time to mortality in hospitalized COVID-19 patients. Continued research is needed to clarify best practices surrounding treatment of COVID-19.


Assuntos
Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Hidroxicloroquina/uso terapêutico , Pandemias/prevenção & controle , Gerenciamento de Dados/métodos , Quimioterapia Combinada/métodos , Feminino , Hospitalização , Humanos , Masculino , /efeitos dos fármacos
12.
Microb Drug Resist ; 27(3): 281-290, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33729874

RESUMO

The coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2, has recently emerged worldwide. In this context, there is an urgent need to identify safe and effective therapeutic strategies for treatment of such highly contagious disease. We recently reported promising results of combining hydroxychloroquine and azithromycin as an early treatment option. Although ongoing clinical trials are challenging the efficacy of this combination, many clinicians claim the authorization to or have already begun to use it to treat COVID-19 patients worldwide. The aim of this article is to share pharmacology considerations contributing to the rationale of this combination, and to provide safety information to prevent toxicity and drug-drug interactions, based on available evidence.


Assuntos
Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Hidroxicloroquina/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/farmacologia , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Azitromicina/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Quimioterapia Combinada , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/farmacologia
13.
BMC Infect Dis ; 21(1): 273, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33736608

RESUMO

BACKGROUND: The emergence and spread of antimicrobial resistance (AMR) in Neisseria gonorrhoeae, nationally and internationally, is a serious threat to the management and control of gonorrhoea. Limited and conflicting data regarding the epidemiological drivers of gonococcal AMR internationally have been published. We examined the antimicrobial susceptibility/resistance of gonococcal isolates (n = 15,803) collected across 27 European Union/European Economic Area (EU/EEA) countries in 2009-2016, in conjunction to epidemiological and clinical data of the corresponding patients, to elucidate associations between antimicrobial susceptibility/resistance and patients' gender, sexual orientation and anatomical site of infection. METHODS: In total, 15,803 N. gonorrhoeae isolates from the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP), 2009-2016, were examined. Associations between gonococcal susceptibility/resistance and patients' gender, sexual orientation and anatomical site of infection were investigated using univariate and multivariate logistic regression analysis. Statistical significance was determined by Pearson χ2-test or Fisher's exact test with two-tailed p-values of < 0.05 indicating significance. RESULTS: The overall gonococcal resistance from 2009 to 2016 was 51.7% (range during the years: 46.5-63.5%), 7.1% (4.5-13.2%), 4.3% (1.8-8.7%), and 0.2% (0.0-0.5%) to ciprofloxacin, azithromycin, cefixime, and ceftriaxone, respectively. The level of resistance combined with decreased susceptibility to ceftriaxone was 10.2% (5.7-15.5%). Resistance to cefixime and ciprofloxacin, and resistance combined with decreased susceptibility to ceftriaxone were positively associated with urogenital infections and heterosexual males, males with sexual orientation not reported and females (except for ciprofloxacin), i.e. when compared to men-who-have-sex-with-men (MSM). Azithromycin resistance was positively associated with heterosexual males, but no association was significant regarding anatomical site of infection. CONCLUSIONS: Overall, sexual orientation was the main variable associated with gonococcal AMR. Strongest positive associations were identified with heterosexual patients, particularly males, and not MSM. To provide evidence-based understanding and mitigate gonococcal AMR emergence and spread, associations between antimicrobial susceptibility/resistance and patients' gender, sexual orientation and anatomical site of infection need to be further investigated in different geographic settings. In general, these insights will support identification of groups at increased risk and targeted public health actions such as intensified screening, 3-site testing using molecular diagnostics, sexual contact tracing, and surveillance of treatment failures.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Gonorreia/microbiologia , Neisseria gonorrhoeae/efeitos dos fármacos , Fatores Sexuais , Minorias Sexuais e de Gênero , Azitromicina/uso terapêutico , Cefixima/uso terapêutico , Ceftriaxona/uso terapêutico , Ciprofloxacino/uso terapêutico , União Europeia , Feminino , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Heterossexualidade , Homossexualidade Masculina , Humanos , Masculino , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae/isolamento & purificação , Comportamento Sexual
15.
Int J Mol Sci ; 22(4)2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33669352

RESUMO

Cystic fibrosis (CF) is an inherited disorder caused by mutations in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, an ATP-gated chloride channel expressed on the apical surface of airway epithelial cells. CFTR absence/dysfunction results in defective ion transport and subsequent airway surface liquid dehydration that severely compromise the airway microenvironment. Noxious agents and pathogens are entrapped inside the abnormally thick mucus layer and establish a highly inflammatory environment, ultimately leading to lung damage. Since chronic airway inflammation plays a crucial role in CF pathophysiology, several studies have investigated the mechanisms responsible for the altered inflammatory/immune response that, in turn, exacerbates the epithelial dysfunction and infection susceptibility in CF patients. In this review, we address the evidence for a critical role of dysfunctional inflammation in lung damage in CF and discuss current therapeutic approaches targeting this condition, as well as potential new treatments that have been developed recently. Traditional therapeutic strategies have shown several limitations and limited clinical benefits. Therefore, many efforts have been made to develop alternative treatments and novel therapeutic approaches, and recent findings have identified new molecules as potential anti-inflammatory agents that may exert beneficial effects in CF patients. Furthermore, the potential anti-inflammatory properties of CFTR modulators, a class of drugs that directly target the molecular defect of CF, also will be critically reviewed. Finally, we also will discuss the possible impact of SARS-CoV-2 infection on CF patients, with a major focus on the consequences that the viral infection could have on the persistent inflammation in these patients.


Assuntos
Anti-Inflamatórios/uso terapêutico , Fibrose Cística/tratamento farmacológico , Inflamação/tratamento farmacológico , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Inflamatórios/farmacologia , Azitromicina/farmacologia , Azitromicina/uso terapêutico , /tratamento farmacológico , Canabinoides/farmacologia , Canabinoides/uso terapêutico , Fibrose Cística/complicações , Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Eicosanoides/metabolismo , Humanos , Inflamação/complicações , Inflamação/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Roscovitina/farmacologia , Roscovitina/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Timalfasina/farmacologia , Timalfasina/uso terapêutico
16.
Rev Esp Quimioter ; 34(2): 145-150, 2021 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-33522213

RESUMO

OBJECTIVE: Despite the impact of SARS-CoV-2 infection in geriatrics, data on nonagenarian patients is scarce. The aim of this study is to describe the clinical features of COVID19-diagnosed nonagenarians, as well as its clinical evolution and therapeutic response. METHODS: Retrospective observational study of nonagenarians, admitted for COVID-19. Sociodemographic and clinical variables were registered, including previous polypharmacy. Blood analysis data and COVID-19-specific treatment were registered. RESULTS: A total of 79 patients were included, with 50.6% (40 patients) of mortality. None of the comorbidities registered correlated with mortality, which was significantly higher among patients with moderate/complete functional dependence, compared to those mild-dependents/independents (59.5% vs 40.5%; p=0.015). Most prescribed drugs were hydroxychloroquine/chloroquine and azithromycin. Non-survivors presented higher counts of leukocytes and neutrophils, and higher lymphopenia. CONCLUSIONS: Nonagenarians with functional dependence presented higher mortality, irrespective of comorbidities or treatment received. Implementing an integral geriatric evaluation would enhance the implementation of personalized therapeutic strategies for nonagenarians.


Assuntos
Idoso de 80 Anos ou mais , /mortalidade , Hospitalização , Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Cloroquina/uso terapêutico , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Desempenho Físico Funcional , Polimedicação , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
18.
Drug Discov Ther ; 15(1): 39-41, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33612572

RESUMO

An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which began in Wuhan, China in December 2019, has rapidly spread all over the world. The World Health Organization characterized the disease caused by SARS-CoV-2 (COVID-19) as a pandemic in March 2020. In the absence of specific treatments for the virus, treatment options are being examined. Drug repurposing is a process of identifying new therapeutic uses for approved drugs. It is an effective strategy to discover drug molecules with new therapeutic indications. This strategy is time-saving, low-cost, and has a minimal risk of failure. Several existing approved drugs such as chloroquine, hydroxychloroquine, doxycycline, azithromycin, and ivermectin are currently in use because of their efficacy in inhibiting COVID-19. Multidrug therapy, such as a combination of hydroxychloroquine and azithromycin, a combination of doxycycline and ivermectin, or a combination of ivermectin, doxycycline, and azithromycin, has been successfully administered. Multidrug therapy is efficacious because the mechanisms of action of these drugs differ. Moreover, multidrug therapy may prevent the emergence of drug-resistant SARS-CoV-2.


Assuntos
/tratamento farmacológico , Quimioterapia Combinada/métodos , Azitromicina/uso terapêutico , Doxiciclina/uso terapêutico , Reposicionamento de Medicamentos , Humanos , Hidroxicloroquina/uso terapêutico , Ivermectina/uso terapêutico , Resultado do Tratamento
20.
Trials ; 22(1): 126, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33563325

RESUMO

BACKGROUND: The rapid emergence and the high disease burden of the novel coronavirus SARS-CoV-2 have created a medical need for readily available drugs that can decrease viral replication or blunt the hyperinflammatory state leading to severe COVID-19 disease. Azithromycin is a macrolide antibiotic, known for its immunomodulatory properties. It has shown antiviral effect specifically against SARS-CoV-2 in vitro and acts on cytokine signaling pathways that have been implicated in COVID-19. METHODS: DAWn-AZITHRO is a randomized, open-label, phase 2 proof-of-concept, multicenter clinical trial, evaluating the safety and efficacy of azithromycin for treating hospitalized patients with COVID-19. It is part of a series of trials testing promising interventions for COVID-19, running in parallel and grouped under the name DAWn-studies. Patients hospitalized on dedicated COVID wards are eligible for study inclusion when they are symptomatic (i.e., clinical or radiological signs) and have been diagnosed with COVID-19 within the last 72 h through PCR (nasopharyngeal swab or bronchoalveolar lavage) or chest CT scan showing typical features of COVID-19 and without alternate diagnosis. Patients are block-randomized (9 patients) with a 2:1 allocation to receive azithromycin plus standard of care versus standard of care alone. Standard of care is mostly supportive, but may comprise hydroxychloroquine, up to the treating physician's discretion and depending on local policy and national health regulations. The treatment group receives azithromycin qd 500 mg during the first 5 consecutive days after inclusion. The trial will include 284 patients and recruits from 15 centers across Belgium. The primary outcome is time from admission (day 0) to life discharge or to sustained clinical improvement, defined as an improvement of two points on the WHO 7-category ordinal scale sustained for at least 3 days. DISCUSSION: The trial investigates the urgent and still unmet global need for drugs that may impact the disease course of COVID-19. It will either provide support or else justify the discouragement of the current widespread, uncontrolled use of azithromycin in patients with COVID-19. The analogous design of other parallel trials of the DAWN consortium will amplify the chance of identifying successful treatment strategies and allow comparison of treatment effects within an identical clinical context. TRIAL REGISTRATION: EU Clinical trials register EudraCT Nb 2020-001614-38 . Registered on 22 April 2020.


Assuntos
Antivirais/efeitos adversos , Azitromicina/efeitos adversos , /genética , Padrão de Cuidado , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Azitromicina/administração & dosagem , Bélgica/epidemiologia , /virologia , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Reação em Cadeia da Polimerase , Estudo de Prova de Conceito , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto Jovem
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