Mechanical ventilation alters the development of staphylococcus aureus pneumonia in rabbit
Ventilator-associated pneumonia (VAP) is common during mechanical ventilation (MV). Beside obvious deleterious effects on muco-ciliary clearance, MV could adversely shift the host immune response towards a pro-inflammatory pattern through toll-like receptor (TLRs) up-regulation. We tested this hypothesis in a rabbit model of Staphylococcus aureus VAP. Pneumonia was caused by airway challenge with S. aureus, in either spontaneously breathing (SB) or MV rabbits (n = 13 and 17, respectively). Pneumonia assessment regarding pulmonary and systemic bacterial burden, as well as inflammatory response was done 8 and 24 hours after S. aureus challenge. In addition, ex vivo stimulations of whole blood…
Mechanical ventilation and Streptococcus pneumoniae pneumonia alter mitochondrial homeostasis.
Abstract Required mechanical ventilation (MV) may contribute to bacterial dissemination in patients with Streptococcus pneumoniae pneumonia. Significant variations in plasma mitochondrial DNA (mtDNA) have been reported in sepsis according to the outcome. The impact of lung stretch during MV was addressed in a model of pneumonia. Healthy or S. pneumoniae infected rabbits were submitted to MV or kept spontaneously breathing (SB). Bacterial burden, cytokines release, mitochondrial DNA levels, integrity and transcription were assessed along with 48-hour mortality. Compared with infected SB rabbits, MV rabbits developed more severe pneumonia with greater concentrations of bacteria in the lungs, …
In vivo efficacy of humanised intermittent versus continuous ceftazidime in combination with tobramycin in an experimental model of pseudomonal pneumonia.
In this study, we compared the efficacy of ceftazidime (CAZ) intermittent versus continuous infusion with or without tobramycin (TOB) for the treatment of pneumonia caused by Pseudomonas aeruginosa in rabbits. Treatments were humanised and mimicked intermittent CAZ (iCAZ) (2g three times daily), continuous CAZ (cCAZ) (4g once daily (qd)) and TOB (10mg/kg qd). Minimum inhibitory concentrations (MICs) were 1mg/L and 4mg/L for TOB and CAZ, respectively. Bacterial efficacy in lungs was as follows: control, 9+/-0.6 colony-forming units (CFU)/g; TOB monotherapy, 8+/-0.5CFU/g; iCAZ monotherapy, 7.8+/-1.4CFU/g; cCAZ monotherapy, 8+/-0.4CFU/g (P = 0.005); and iCAZ+TOB, 8+/-0.5CFU/g; cCAZ+TOB, 7.2+/-…
Mild-stretch mechanical ventilation upregulates toll-like receptor 2 and sensitizes the lung to bacterial lipopeptide.
Introduction Mechanical ventilation (MV) could prime the lung toward an inflammatory response if exposed to another insult such as bacterial invasion. The underlying mechanisms are not so far clear. Toll-like receptors (TLRs) allow the host to recognize selectively bacterial pathogens and in turn to trigger an immune response. We therefore hypothesized that MV modulates TLR2 expression and in turn modifies responsiveness to agonists such as bacterial lipopeptide (BLP). Method Both in vitro and in vivo experiments were conducted. First, TLR2 expression and protein were measured in the A549 pulmonary epithelial cell line submitted to 8-hour cyclic stretch (20% elongation; 20/minute rate). Aft…
Adaptation de Candida albicans dans les tissus humains: du commensalisme à la pathogénicité
National audience; Candida albicans (C. albicans) est un micro-organisme eucaryote appartenant à la flore commensale des muqueuses de l’homme sain. Ce commensalisme résulte d’un équilibre entre la levure et les systèmes de défense de l’hôte. La rupture de cet équilibre chez un patient fragilisé (sujet infecté par le VIH, neutropénique, cancéreux, transplanté ou séjournant en service de réanimation) favorisera une colonisation intense des muqueuses, un envahissement de la barrière digestive et enfin la possibilité de dissémination hématogène. Les candidémies restent des infections graves puisque la mortalité directement attribuable à l’infection est estimée à 38%. Nos travaux ont d’abord por…
Linezolid and atorvastatin impact on pneumonia caused by Staphyloccocus aureus in rabbits with or without mechanical ventilation
International audience; Pneumonia may involve methicillin-resistant Staphylococcus aureus (MRSA), with elevated rates of antibiotics failure. The present study aimed to assess the effect of statins given prior to pneumonia development. Spontaneously breathing (SB) or mechanically ventilated (MV) rabbits with pneumonia received atorvastatin alone, linezolid (LNZ) alone, or a combination of both (n = 5 in each group). Spontaneously breathing and MV untreated infected animals (n = 11 in each group), as well as uninfected animals (n = 5 in each group) were used as controls. Microbiological features and inflammation were evaluated. Data are presented as medians (interquartile range). Linezolid a…
Severe hypovitaminosis D correlates with increased inflammatory markers in HIV infected patients
Abstract Background Even though it has been suggested that antiretroviral therapy has an impact on severe hypovitaminosis D (SHD) in HIV infected patients, it could be speculated that the different levels of residual inflammation on HAART (Highly Active Anti Retroviral Therapy) could contribute to SHD and aggravate bone catabolism in these patients. Methods A cross-sectional study was carried out in an unselected cohort of 263 HIV infected outpatients consulting during Spring 2010. Clinical examinations were performed and medical history, food habits, sun exposure and addictions were collected. Fasting blood samples were taken for immunological, virological, inflammation, endocrine and bone…