Systemic treatment with linezolid limits endotracheal tube biofilm development and methicillin-resistant Staphylococcus aureus burden. The potential clinical usefulness of linezolid in decreasing the risk of biofilm-related respiratory infections during prolonged tracheal intubation requires further investigation.
In this animal model of MRSA pneumonia, linezolid showed a better efficacy than vancomycin showed because of a better pharmacokinetics/pharmacodynamics index.
Confocal laser scanning microscopy (CLSM) helps to observe the biofilms formed in the endotracheal tube (ETT) of ventilated subjects and to determine its structure and bacterial viability using specific dyes. We compared the effect of three different treatments (placebo, linezolid, and vancomycin) on the bacterial biofilm viability captured by CLSM. Eight pigs with pneumonia induced by methicillin‐resistant Staphylococcus aureus (MRSA) were ventilated up to 96 h and treated with linezolid, vancomycin, or placebo (controls). ETT images were microscopically examined after staining with the live/dead® BacLight™ Kit (Invitrogen, Barcelona, Spain) with a confocal laser scanning microscope. We analyzed 127 images obtained by CLSM. The median ratio of live/dead bacteria was 0.51, 0.74, and 1 for the linezolid, vancomycin, and control groups, respectively (P = 0.002 for the three groups); this ratio was significantly lower for the linezolid group, compared with the control group (P = 0.001). Images showed bacterial biofilm attached and non‐attached to the ETT surface but growing within secretions accumulated inside ETT. Systemic treatment with linezolid is associated with a higher proportion of dead bacteria in the ETT biofilm of animals with MRSA pneumonia. Biofilm clusters not necessarily attach to the ETT surface.
We assessed whether prolongation of nocturnal noninvasive ventilation (NIV) after recovery from acute hypercapnic respiratory failure (AHRF) in chronic obstructive pulmonary disease (COPD) patients with NIV could prevent subsequent relapse of AHRF.A randomised controlled trial was performed in 120 COPD patients without previous domiciliary ventilation, admitted for AHRF and treated with NIV. When the episode was resolved and patients tolerated unassisted breathing for 4 h, they were randomly allocated to receive three additional nights of NIV (n=61) or direct NIV discontinuation (n=59). The primary outcome was relapse of AHRF within 8 days after NIV discontinuation.Except for a shorter median (interquartile range) intermediate respiratory care unit (IRCU) stay in the direct discontinuation group (4 (2-6) 5 (4-7) days, p=0.036), no differences were observed in relapse of AHRF after NIV discontinuation (10 (17%) 8 (13%) for the direct discontinuation and nocturnal NIV groups, respectively, p=0.56), long-term ventilator dependence, hospital stay, and 6-month hospital readmission or survival.Prolongation of nocturnal NIV after recovery from an AHRF episode does not prevent subsequent relapse of AHRF in COPD patients without previous domiciliary ventilation, and results in longer IRCU stay. Consequently, NIV can be directly discontinued when the episode is resolved and patients tolerate unassisted breathing.
Staphylococcus aureus is one of the most common causes of nosocomial pneumonia contributing to significant morbidity and mortality. Therapeutic options for patients with methicillin-resistant S. aureus (MRSA) infection are limited. In addition, little is known about the S. aureus virulence factors that may influence the presentation and prognosis of severe lower respiratory tract infections. Animal models of severe pneumonia allow investigators to control and exclude potential confounders and to examine the influence of comorbid conditions. Therefore, these models may improve our knowledge of the intimate pathophysiological mechanisms affecting pharmacodynamics, pharmacokinetics and efficacy of therapy. So far, animal research studies on MRSA and vancomycin-resistant S. aureus, performed both in small and large animal models, have improved knowledge of the mechanisms of disease, which may lead to a better treatment for this severe and complex infection in humans.
The objectives of the study were to validate a model of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in ventilated piglets and to study the time-course of biological markers and histopathological changes.12 piglets were intubated and inoculated with 15 mL of a suspension of 10 6 colony forming units of MRSA in every lobe through the bronchoscope channel. The piglets were ventilated for 12 h (n56) and 24 h (n56). Clinical parameters were assessed every 6 h and pro-inflammatory cytokines were measured in serum and in bronchoalveolar lavage (BAL) at baseline and sacrifice. Histopathology of each lobe and cultures from blood, lungs and BAL were performed. Animals developed histopathological evidence of pneumonia at necropsy. At 12 h, pneumonia was present in all animals and was severe pneumonia at 24 h. Microbiological studies confirmed the presence of MRSA. A significant increase in interleukin (IL)-6, IL-8 and tumour necrosis factor-a values was seen in BAL at 24 h and IL-6 at 12 h. In serum, only IL-6 levels had increased significantly at 24 h.In ventilated piglets, bronchoscopic inoculation of MRSA induces pneumonia at 12 h and severe pneumonia at 24 h. This severity was associated with a corresponding increase in systemic and local inflammatory response.
Resultados: Se realizaron 107 (23%) FBS a 69 de los 297 pacientes admitidos en la UVIR. El 68% de las FBS se practicaron a pacientes con ventilación mecánica. La FBS se realizó con fines diagnósticos en 88 ocasiones (82%) y terapéuticos en 19 (18%). La indicación más frecuente para la FBS diagnóstica fue el estudio de infiltrados pulmonares (44 casos; 50%), particularmente en pacientes inmunodeprimidos (24 casos; 27%). Para esta indicación, la rentabilidad diagnóstica de la FBS fue significativamente mejor en los pacientes inmunodeprimidos, respecto a los inmunocompetentes (48% vs 30%; p < 0,01). La FBS no causó complicaciones mayores; únicamente se observó un descenso significativo en la PaO 2 /FiO 2 (182 ± 74 vs 163 ± 79; p < 0,005) cuando se realizó un lavado broncoalveolar. La mortalidad global en la UVIR fue del 14%; del 25% en los pacientes que precisaron FBS y del 45% en aquellos que precisaron FBS adicionales. Conclusiones: La FBS es un procedimiento seguro y rápido que se utiliza con frecuencia en la UVIR y que contribuye significativamente al manejo clínico. Los pacientes de la UVIR que requieren FBS adicionales tienen una elevada mortalidad.
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