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Rello J.,Hospital Universitari Vall dHebron | Rello J.,Research Center Biomedica en Red Enfermedades Respiratorias | Rello J.,Autonomous University of Barcelona | Lisboa T.,Federal University of Rio Grande do Sul | And 2 more authors.
The Lancet Respiratory Medicine | Year: 2014

Lower respiratory tract infections in mechanically ventilated patients are a frequent cause of antibiotic treatment in intensive-care units. These infections present as severe sepsis or septic shock with respiratory dysfunction in intubated patients. Purulent respiratory secretions are needed for diagnosis, but distinguishing between pneumonia and tracheobronchitis is not easy. Both presentations are associated with longlasting mechanical ventilation and extended intensive-care unit stay, providing a rationale for antibiotic treatment initiation. Differentiation of colonisers from true pathogens is difficult, and microbiological data show Staphylococcus aureus and Pseudomonas aeruginosa to be of great concern because of clinical outcomes and therapeutic challenges. Key management issues include identification of the pathogen, choice of initial empirical antibiotic, and decisions with regard to the resolution pattern. © 2014 Elsevier Ltd. Source

Hoiby N.,Rigshospitalet | Hoiby N.,Copenhagen University | Bjarnsholt T.,Rigshospitalet | Bjarnsholt T.,Copenhagen University | And 19 more authors.
Clinical Microbiology and Infection | Year: 2015

Biofilms cause chronic infections in tissues or by developing on the surfaces of medical devices. Biofilm infections persist despite both antibiotic therapy and the innate and adaptive defence mechanisms of the patient. Biofilm infections are characterized by persisting and progressive pathology due primarily to the inflammatory response surrounding the biofilm. For this reason, many biofilm infections may be difficult to diagnose and treat efficiently. It is the purpose of the guideline to bring the current knowledge of biofilm diagnosis and therapy to the attention of clinical microbiologists and infectious disease specialists. Selected hallmark biofilm infections in tissues (e.g. cystic fibrosis with chronic lung infection, patients with chronic wound infections) or associated with devices (e.g. orthopaedic alloplastic devices, endotracheal tubes, intravenous catheters, indwelling urinary catheters, tissue fillers) are the main focus of the guideline, but experience gained from the biofilm infections included in the guideline may inspire similar work in other biofilm infections. The clinical and laboratory parameters for diagnosing biofilm infections are outlined based on the patient's history, signs and symptoms, microscopic findings, culture-based or culture-independent diagnostic techniques and specific immune responses to identify microorganisms known to cause biofilm infections. First, recommendations are given for the collection of appropriate clinical samples, for reliable methods to specifically detect biofilms, for the evaluation of antibody responses to biofilms, for antibiotic susceptibility testing and for improvement of laboratory reports of biofilm findings in the clinical microbiology laboratory. Second, recommendations are given for the prevention and treatment of biofilm infections and for monitoring treatment effectiveness. Finally, suggestions for future research are given to improve diagnosis and treatment of biofilm infections. © 2014 European Society of Clinical Microbiology and Infectious Diseases. Source

Torres A.,Institute Clinic del Torax | Torres A.,Institute dInvestigacions Biomediques August Pi i Sunyer | Torres A.,Research Center Biomedica en Red Enfermedades Respiratorias | Torres A.,University of Barcelona | And 23 more authors.
JAMA - Journal of the American Medical Association | Year: 2015

Importance: In patients with severe community-acquired pneumonia, treatment failure is associated with excessive inflammatory response and worse outcomes. Corticosteroids may modulate cytokine release in these patients, but the benefit of this adjunctive therapy remains controversial. Objective: To assess the effect of corticosteroids in patients with severe communityacquired pneumonia and high associated inflammatory response. Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled trial conducted in 3 Spanish teaching hospitals involving patients with both severe community-acquired pneumonia and a high inflammatory response, which was defined as a level of C-reactive protein greater than 150mg/L at admission. Patients were recruited and followed up from June 2004 through February 2012. Interventions: Patients were randomized to receive either an intravenous bolus of 0.5mg/kg per 12 hours of methylprednisolone (n = 61) or placebo (n = 59) for 5 days started within 36 hours of hospital admission. Main Outcomes and Measures: The primary outcomewas treatment failure (composite outcome of early treatment failure defined as [1] clinical deterioration indicated by development of shock, [2] need for invasive mechanical ventilation not present at baseline, or [3] death within 72 hours of treatment; or composite outcome of late treatment failure defined as [1] radiographic progression, [2] persistence of severe respiratory failure, [3] development of shock, [4] need for invasive mechanical ventilation not present at baseline, or [5] death between 72 hours and 120 hours after treatment initiation; or both early and late treatment failure). In-hospital mortalitywas a secondary outcome and adverse eventswere assessed. Results: There was less treatment failure among patients from the methylprednisolone group (8 patients [13%]) compared with the placebo group (18 patients [31%]) (P = .02), with a difference between groups of 18% (95% CI, 3% to 32%). Corticosteroid treatment reduced the risk of treatment failure (odds ratio, 0.34 [95% CI, 0.14 to 0.87]; P = .02). In-hospital mortality did not differ between the 2 groups (6 patients [10%] in the methylprednisolone group vs 9 patients [15%] in the placebo group; P = .37); the difference between groups was 5% (95% CI, -6% to 17%). Hyperglycemia occurred in 11 patients (18%) in the methylprednisolone group and in 7 patients (12%) in the placebo group (P = .34). Conclusions and Relevance: Among patients with severe community-acquired pneumonia and high initial inflammatory response, the acute use of methylprednisolone compared with placebo decreased treatment failure. If replicated, these findings would support the use of corticosteroids as adjunctive treatment in this clinical population. Trial Registration: clinicaltrials.gov Identifier: NCT00908713. Copyright © 2015 American Medical Association. All rights reserved. Source

Faner R.,Research Center Biomedica en Red Enfermedades Respiratorias | Faner R.,Institute dinvestigacions Biomediques August Pi i Sunyer IDIBAPS | Rojas M.,McGowan Institute for Regenerative Medicine | MacNee W.,Queens Medical Research Institute | And 3 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2012

Aging is a natural process characterized by progressive functional impairment and reduced capacity to respond appropriately to environmental stimuli and injury. The incidence of two common chronic respiratory diseases (chronic obstructive pulmonary disease [COPD] and idiopathic pulmonary fibrosis [IPF]) increaseswith advanced age. It is plausible, therefore, that abnormal regulation of themechanisms of normal aging may contribute to the pathobiology of both COPD and IPF. This review discusses the available evidence supporting a number of aging mechanisms, including oxidative stress, telomere length regulation, cellular and immunosenescence, aswell as changes inanumberofantiagingmoleculesandtheextracellularmatrix,which are abnormal in COPD and/or IPF. A better understanding of these abnormalitiesmay help in the design of novel and better therapeutic interventions for these patients. Copyright © 2012 by the American Thoracic Society. Source

Padilla E.,University of the Balearic Islands | Llobet E.,Research Center Biomedica en Red Enfermedades Respiratorias | Domenech-Sanchez A.,University of the Balearic Islands | Martinez-Martinez L.,Hospital Universitario Marques Of Valdecilla | And 4 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2010

Respiratory infections caused by Klebsiella pneumoniae are characterized by high rates of mortality and morbidity. Management of these infections is often difficult, due to the high frequency of strains that are resistant to multiple antimicrobial agents. Multidrug efflux pumps play a major role as a mechanism of antimicrobial resistance in Gram-negative pathogens. In the present study, we investigated the role of the K. pneumoniae AcrRAB operon in antimicrobial resistance and virulence by using isogenic knockouts deficient in the AcrB component and the AcrR repressor, both derived from the virulent strain 52145R. We demonstrated that the AcrB knockout was more susceptible, not only to quinolones, but also to other antimicrobial agents, including β-lactams, than the wild-type strain and the AcrR knockout. We further showed that the AcrB knockout was more susceptible to antimicrobial agents present in human bronchoalveolar lavage fluid and to human antimicrobial peptides than the wild-type strain and the AcrR knockout. Finally, the AcrB knockout exhibited a reduced capacity to cause pneumonia in a murine model, in contrast to the wild-type strain. The results of this study suggest that, in addition to contributing to the multidrug resistance phenotype, the AcrAB efflux pump may represent a novel virulence factor required for K. pneumoniae to resist innate immune defense mechanisms of the lung, thus facilitating the onset of pneumonia. Copyright © 2010, American Society for Microbiology. All Rights Reserved. Source

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