Characterisation of a refined rat model of respiratory infection with Pseudomonas aeruginosa and the effect of ciprofloxacin

AbstractBackgroundWe sought to characterise a refined rat model of respiratory infection with P. aeruginosa over an acute time course and test the antibiotic ciprofloxacin.MethodsAgar beads were prepared±SPAN®80. Rats were inoculated with sterile agar beads or those containing 105 colony forming units (cfu) P. aeruginosa via intra-tracheal dosing. Bacterial load and inflammatory parameters were measured.ResultsDiffering concentrations of SPAN® 80 modified median agar bead diameter and reduced particle size distribution. Beads prepared with 0.01% v/v SPAN®80 were evaluated in vivo. A stable lung infection up to 7days post infection was achieved and induced BALF neutrophilia 2 and 5days post infection. Ciprofloxacin (50mg/kg) significantly attenuated infection without affecting the inflammatory parameters measured.ConclusionSPAN® 80 can control the particle size and lung distribution of agar beads and P. aeruginosa-embedded beads prepared with 0.01%v/v SPAN®80 can induce infection and inflammation over 7days

The role of phosphodiesterase isoenzymes in eosinophils and lymphocytes

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN013388 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Ivacaftor Therapy in the Context of CFTR Genotype

Cystic fibrosis (CF) is a life-shortening disease arising as a consequence of mutations within the CFTR gene. Novel therapeutics for CF are emerging that target CF transmembrane conductance regulator protein (CFTR) defects resulting from specific CFTR variants. Ivacaftor is a drug that potentiates CFTR gating function and is specifically indicated for CF patients with a particular CFTR variant, G551D-CFTR (rs75527207). Here, we provide therapeutic recommendations for ivacaftor based on preemptive CFTR genotype results

Immunocompromised patients with acute respiratory distress syndrome : Secondary analysis of the LUNG SAFE database

The aim of this study was to describe data on epidemiology, ventilatory management, and outcome of acute respiratory distress syndrome (ARDS) in immunocompromised patients. Methods: We performed a post hoc analysis on the cohort of immunocompromised patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) study. The LUNG SAFE study was an international, prospective study including hypoxemic patients in 459 ICUs from 50 countries across 5 continents. Results: Of 2813 patients with ARDS, 584 (20.8%) were immunocompromised, 38.9% of whom had an unspecified cause. Pneumonia, nonpulmonary sepsis, and noncardiogenic shock were their most common risk factors for ARDS. Hospital mortality was higher in immunocompromised than in immunocompetent patients (52.4% vs 36.2%; p < 0.0001), despite similar severity of ARDS. Decisions regarding limiting life-sustaining measures were significantly more frequent in immunocompromised patients (27.1% vs 18.6%; p < 0.0001). Use of noninvasive ventilation (NIV) as first-line treatment was higher in immunocompromised patients (20.9% vs 15.9%; p = 0.0048), and immunodeficiency remained independently associated with the use of NIV after adjustment for confounders. Forty-eight percent of the patients treated with NIV were intubated, and their mortality was not different from that of the patients invasively ventilated ab initio. Conclusions: Immunosuppression is frequent in patients with ARDS, and infections are the main risk factors for ARDS in these immunocompromised patients. Their management differs from that of immunocompetent patients, particularly the greater use of NIV as first-line ventilation strategy. Compared with immunocompetent subjects, they have higher mortality regardless of ARDS severity as well as a higher frequency of limitation of life-sustaining measures. Nonetheless, nearly half of these patients survive to hospital discharge. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013