Staphylococcus aureus is a microorganism frequently associated with implant-related infections, owing to its ability to produce biofilms. These infections are difficult to treat because antimicrobials must cross the biofilm to effectively inhibit bacterial growth. Although some antibiotics can penetrate the biofilm and reduce the bacterial load, it is important to understand that the results of routine sensitivity tests are not always valid for interpreting the activity of different drugs. In this review, a broad discussion on the genes involved in biofilm formation, quorum sensing, and antimicrobial activity in monotherapy and combination therapy is presented that should benefit researchers engaged in optimizing the treatment of infections associated with S. aureus biofilms.
1 October 2020 in Arteriosclerosis, Thrombosis, and Vascular Biology
Objective: Alveolar-capillary endothelial cells can be activated by severe acute respiratory syndrome coronavirus 2 infection leading to cytokine release. This could trigger endothelial dysfunction, pyroptosis, and thrombosis, which are the vascular changes, commonly referred to as coronavirus disease 2019 (COVID-19) endotheliopathy. Thus, this study aimed to identify tissue biomarkers associated with endothelial activation/dysfunction and the pyroptosis pathway in the lung samples of patients with COVID-19 and to compare them to pandemic influenza A virus H1N1 subtype 2009 and control cases. Approach and Results: Postmortem lung samples (COVID-19 group =6 cases; H1N1 group =10 cases, and control group =11 cases) were analyzed using immunohistochemistry and the following monoclonal primary antibodies: anti-IL (interleukin)-6, anti-TNF (tumor necrosis factor)-α, anti-ICAM-1 (intercellular adhesion molecule 1), and anticaspase-1. From the result, IL-6, TNF-α, ICAM-1, and caspase-1 showed higher tissue expression in the COVID-19 group than in the H1N1 and control groups. Conclusions: Our results demonstrated endothelial dysfunction and suggested the participation of the pyroptosis pathway in the pulmonary samples. These conditions might lead to systemic thrombotic events that could impair the clinical staff’s efforts to avoid fatal outcomes. One of the health professionals’ goals should be to identify the high risk of thrombosis patients early to block endotheliopathy and its consequences.
Nicolas Henrique Borges, Thiago Mateus Godoy, Bárbara Stadler Kahlow; Onset of dermatomyositis in close association with COVID-19 - a first case reported, Rheum
Staphylococcus aureus are frequently associated with biofilm formation on intravascular devices. Biofilms limit antimicrobial penetration and promote phenotypic resistance, challenging conventional treatment strategies. Vancomycin (VAN) and gentamicin (GEN) have been used clinically, but their combined antibiofilm activity remains underexplored. This study evaluates the efficacy of VAN and GEN, alone and in combination, against biofilms formed by methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) on polyurethane. MICs were determined for VAN and GEN. Biofilm biomass and metabolic activity were quantified using crystal violet and MTT assays, respectively. Biofilm viability was assessed through fluorescence microscopy and a modified Calgary Biofilm Device. A continuous-flow peristaltic model was developed to test treatment under simulated catheter conditions. While monotherapy with VAN or GEN had modest effects, their combination significantly reduced biomass and metabolic activity. VAN 20 mg/L + GEN 8 mg/L and VAN 40 mg/L + GEN 8 mg/L achieved over 70% reduction in MRSA biofilm viability and complete eradication in MBEC assays. Dynamic model assays confirmed biofilm reduction with combination therapy. The combination of VAN/GEN exhibits synergistic antibiofilm activity against S. aureus, particularly MRSA. These findings support its potential application in catheter salvage strategies, including antibiotic lock therapy.
14 December 2020 in Arquivos Brasileiros de Cardiologia
Apresentação de Caso Paciente do sexo masculino, 22 anos, sem comorbidades prévias e uso de medicamentos, foi encaminhado ao nosso hospital em 24/06/2020. Sem sintomas, em 12/06/2020 foi diagnosticado com COVID-19 após um teste de triagem por PCR exigido em sua empresa, e permaneceu em repouso no leito durante a maior parte de seu isolamento. Permaneceu assintomático por 11 dias, porém, em 24/06/2020, deu entrada no pronto-socorro com dor ventilatório-dependente em hemitórax direito. Os sinais vitais revelaram hipertensão (132/78 mmHg), [...] Apresentação de Caso Paciente do sexo masculino, 22 anos, sem comorbidades prévias e uso de medicamentos, foi encaminhado ao nosso hospital em 24/06/2020. Sem sintomas, em 12/06/2020 foi diagnosticado com COVID-19 após um teste de triagem por PCR exigido em sua empresa, e permaneceu em repouso no leito durante a maior parte de seu isolamento. Permaneceu assintomático por 11 dias, porém, em 24/06/2020, deu entrada no pronto-socorro com dor ventilatório-dependente em hemitórax direito. Os sinais vitais revelaram hipertensão (132/78 mmHg),
Objective: Endothelial cells that are close to the alveolar-capillary exchange membranes can be activated by SARS-CoV-2 infection leading to cytokine release and macrophage activation syndrome. This could trigger endothelial dysfunction, pyroptosis, and immunothrombosis, which are the vascular changes commonly referred to as COVID-19 endotheliopathy. Thus, this study aimed to identify tissue biomarkers associated with endothelial activation/dysfunction and the pyroptosis pathway in the lung and myocardial samples of COVID-19 patients and to compare them to pandemic Influenza A virus H1N1 subtype – 2009 and Control cases. Approach and Results: Post-mortem lung (COVID-19 group=6 cases; H1N1 group=10 cases, and Control group=11 cases) and myocardial samples (COVID-19=2 cases and control=1 case) were analyzed using immunohistochemistry and the following monoclonal primary antibodies: anti-CD163, anti-interleukin-6 (IL-6), anti-tumor necrosis factor-alpha (TNF-alpha), anti-intercellular adhesion molecule-1 (ICAM-1), and anti-caspase-1. From the result, IL-6, TNF-alpha, ICAM-1, and caspase-1 showed higher tissue expression in the COVID-19 group than in the H1N1 and control groups. Conclusion: Our results demonstrated the presence of endotheliopathy and suggest the participation of the pyroptosis pathway in both the pulmonary and myocardial samples. These conditions might lead to systemic immunothrombotic events that could impair the efforts of clinical staff to avoid fatal outcomes. One of the goals of health professionals should be to identify the high-risk of immunothrombosis patients early to block endotheliopathy and its consequences.