RESUMO
INTRODUCTION: Macrolide antibiotics have immunomodulatory properties which may be beneficial in viral infections. However, the precise effects of macrolides on T cell responses to COVID, differences between different macrolides, and synergistic effects with other antibiotics have not been explored. METHODS: We investigated the effect of antibiotics (amoxicillin, azithromycin, clarithromycin, and combined amoxicillin with clarithromycin) on lymphocyte intracellular cytokine levels and monocyte phagocytosis in healthy volunteer PBMCs stimulated ex vivo with SARS-CoV-2 S1+2 spike protein. A retrospective cohort study was performed on intensive care COVID-19 patients. RESULTS: Co-incubation of clarithromycin with spike protein-stimulated healthy volunteer PBMCs ex vivo resulted in an increase in CD8+ (p = 0.004) and CD4+ (p = 0.007) IL-2, with a decrease in CD8+ (p = 0.032) and CD4+ (p = 0.007) IL-10. The addition of amoxicillin to clarithromycin resulted in an increase in CD8+ IL-6 (p = 0.010), decrease in CD8+ (p = 0.014) and CD4+ (p = 0.022) TNF-alpha, and decrease in CD8+ IFN-alpha (p = 0.038). Amoxicillin alone had no effect on CD4+ or CD8+ cytokines. Co-incubation of azithromycin resulted in increased CD8+ (p = 0.007) and CD4+ (p = 0.011) IL-2. There were no effects on monocyte phagocytosis. 102 COVID-19 ICU patients received antibiotics on hospital admission; 62 (61%) received clarithromycin. Clarithromycin use was associated with reduction in mortality on univariate analysis (p = 0.023), but not following adjustment for confounders (HR = 0.540; p = 0.076). CONCLUSIONS: Clarithromycin has immunomodulatory properties over and above azithromycin. Amoxicillin in addition to clarithromycin is associated with synergistic ex vivo immunomodulatory properties. The potential benefit of clarithromycin in critically ill patients with COVID-19 and other viral pneumonitis merits further exploration.
Assuntos
Tratamento Farmacológico da COVID-19 , Claritromicina , Amoxicilina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Citocinas , Humanos , Interleucina-2 , Macrolídeos/farmacologia , Estudos Retrospectivos , SARS-CoV-2 , Glicoproteína da Espícula de CoronavírusAssuntos
Pneumonia/terapia , Doença Pulmonar Obstrutiva Crônica/terapia , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/terapia , Lesão Pulmonar Induzida por Ventilação Mecânica/prevenção & controle , Resistência das Vias Respiratórias , Permeabilidade Capilar , Humanos , Hipóxia , Complacência Pulmonar , Pressões Respiratórias Máximas , Pneumonia Associada à Ventilação Mecânica , Respiração com Pressão Positiva/métodos , Pressão , Volume de Ventilação PulmonarAssuntos
Antivirais/uso terapêutico , Hospedeiro Imunocomprometido , Vírus da Influenza A Subtipo H1N1 , Pneumonia Viral/tratamento farmacológico , Zanamivir/uso terapêutico , Administração por Inalação , Adulto , Anti-Inflamatórios/uso terapêutico , Líquido da Lavagem Broncoalveolar/virologia , Cuidados Críticos/métodos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Doença de Hodgkin/tratamento farmacológico , Humanos , Infusões Intravenosas , Metilprednisolona/uso terapêutico , Neutropenia/induzido quimicamente , Neutropenia/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Resultado do Tratamento , Carga ViralRESUMO
This article reviews the current literature and practice of tracheostomy with consideration of timing and the benefits of early tracheostomy, taking account of the results from the recent TracMan study.
