Evolution over a 15-year period of the clinical characteristics and outcomes of critically ill patients with severe community-acquired pneumonia

Vallès, Jordi; Dı́az, Emili; Martín‐Loeches, Ignacio; Bacelar, N.; Saludes, P.; Lema, J.; Gallego, Miguel; Fontanals, Dionísia; Artigas, Antonio

doi:10.1016/j.medin.2015.07.005

Cited by 41 publications

(26 citation statements)

References 27 publications

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“…This potential overestimation could also explain the high rate of P. aeruginosa co-infection observed in that study (14.1%): in another recent study in patients with influenza-related infection, the authors found a 1.3% rate of P. aeruginosa co-infection in patients with CAP and 8.3% in patients with healthcare-associated pneumonia (HCAP) [9]. The high incidence found in the present study cannot be explained by a local (national) feature, since same authors reported lower rates of P. aeruginosa CAP and HCAP in Spain during this same time [10,11]. Either false positives (patients diagnosed as pneumonia whereas only colonized) or a specific, not yet described, influenza-P. aeruginosa co-infection (Shah at al., found similar incidence of P. aeruginosa [12]) could explain such high rates of P. aeruginosa pneumonia, especially if they truly are community acquired.…”

supporting

confidence: 49%

Co-infection in severe influenza: a new epidemiology?

Luyt

Rice

2016

Intensive Care Med

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supporting

confidence: 49%

Co-infection in severe influenza: a new epidemiology?

Luyt

Rice

2016

Intensive Care Med

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“…Coverslips were then washed 3 times with PBS and fixed for 15 min at RT with 4% paraformaldehyde (PFA) in PBS. Coverslips were then washed once with PBS and aldehydes were quenched by addition of 50 mM NH 4 Cl in PBS for 30 min at 4°C. For double immunofluorescence, coverslips were blocked using 1% bovine serum albumin (BSA) in PBS (blocking buffer) for 1 h at RT and incubated for 1 h at RT with rabbit anti-serotype 4 (Statens Serum Institut; 1:1,000 in blocking buffer).…”

Section: Methodsmentioning

confidence: 99%

Cell Invasion and Pyruvate Oxidase-Derived H ₂ O ₂ Are Critical for Streptococcus pneumoniae-Mediated Cardiomyocyte Killing

et al. 2018

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Streptococcus pneumoniae (the pneumococcus) is the leading cause of community-acquired pneumonia and is now recognized to be a direct contributor to adverse acute cardiac events. During invasive pneumococcal disease, S. pneumoniae can gain access to the myocardium, kill cardiomyocytes, and form bacterium-filled "microlesions" causing considerable acute and long-lasting cardiac damage. While the molecular mechanisms responsible for bacterial translocation into the heart have been elucidated, the initial interactions of heart-invaded S. pneumoniae with cardiomyocytes remain unclear. In this study, we used a model of low multiplicity of S. pneumoniae infection with HL-1 mouse cardiomyocytes to investigate these early events. Using adhesion/invasion assays and immunofluorescent and transmission electron microscopy, we showed that S. pneumoniae rapidly adhered to and invaded cardiomyocytes. What is more, pneumococci existed as intravacuolar bacteria or escaped into the cytoplasm. Pulse-chase assays with BrdU confirmed intracellular replication of pneumococci within HL-1 cells. Using endocytosis inhibitors, bacterial isogenic mutants, and neutralizing antibodies against host proteins recognized by S. pneumoniae adhesins, we showed that S. pneumoniae uptake by cardiomyocytes is not through the well-studied canonical interactions identified for vascular endothelial cells. Indeed, S. pneumoniae invasion of HL-1 cells occurred through clathrin-mediated endocytosis (CME) and independently of choline binding protein A (CbpA)/laminin receptor, CbpA/polymeric immunoglobulin receptor, or cell wall phosphorylcholine/platelet-activating factor receptor. Subsequently, we determined that pneumolysin and streptococcal pyruvate oxidasederived H 2 O 2 production were required for cardiomyocyte killing. Finally, we showed that this cytotoxicity could be abrogated using CME inhibitors or antioxidants, attesting to intracellular replication of S. pneumoniae as a key first step in pneumococcal pathogenesis within the heart. KEYWORDS Cardiac acute events, cardiomyocytes, invasive pneumococcal disease, Streptococcus pneumoniae, facultatively intracellular pathogens, oxidative stress S treptococcus pneumoniae (the pneumococcus) is a Gram-positive bacterium which typically colonizes the nasopharynx asymptomatically (1, 2). However, it is also an opportunistic pathogen, capable of causing a wide spectrum of human diseases, including otitis media, community-acquired pneumonia, bacteremia/sepsis, and meningitis (3-5). In 30% of adults with pneumococcal pneumonia, S. pneumoniae escapes the airway and causes bacteremia/invasive pneumococcal disease (IPD). This typically occurs in those who are Ն65 years of age and/or in some fashion immunocompromised (4). Despite development and use of multiple antipneumococcal vaccines for decades, S. pneumoniae remains a major cause of human morbidity and death worldwide (6).Approximately 20% of adults hospitalized for severe pneumococcal disease experience some sort of major adverse cardiac events (MA...

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“…About 20–50% of healthy children and 8–30% of healthy adults are asymptomatically colonized ( McCullers, 2006 ). Pneumococci cause diseases ranging from mild, i.e., sinusitis, conjunctivitis, and otitis media, to more severe and potentially life-threatening infections, including community-acquired pneumonia, bacteraemia, and meningitis ( Bogaert et al, 2004 ; Valles et al, 2016 ). This bacterium is associated with high morbidity and mortality rates in risk groups such as immunocompromised individuals, children, and elderly ( Black et al, 2010 ; Valles et al, 2016 ).…”

Section: Gram-positive Bacteria Associated With Respiratory Infectionmentioning

confidence: 99%

Port d’Entrée for Respiratory Infections – Does the Influenza A Virus Pave the Way for Bacteria?

et al. 2017

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Bacterial and viral co-infections of the respiratory tract are life-threatening and present a global burden to the global community. Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes are frequent colonizers of the upper respiratory tract. Imbalances through acquisition of seasonal viruses, e.g., Influenza A virus, can lead to bacterial dissemination to the lower respiratory tract, which in turn can result in severe pneumonia. In this review, we summarize the current knowledge about bacterial and viral co-infections of the respiratory tract and focus on potential experimental models suitable for mimicking this disease. Transmission of IAV and pneumonia is mainly modeled by mouse infection. Few studies utilizing ferrets, rats, guinea pigs, rabbits, and non-human primates are also available. The knowledge gained from these studies led to important discoveries and advances in understanding these infectious diseases. Nevertheless, mouse and other infection models have limitations, especially in translation of the discoveries to humans. Here, we suggest the use of human engineered lung tissue, human ex vivo lung tissue, and porcine models to study respiratory co-infections, which might contribute to a greater translation of the results to humans and improve both, animal and human health.

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Evolution over a 15-year period of the clinical characteristics and outcomes of critically ill patients with severe community-acquired pneumonia

Cited by 41 publications

References 27 publications

Co-infection in severe influenza: a new epidemiology?

Co-infection in severe influenza: a new epidemiology?

Cell Invasion and Pyruvate Oxidase-Derived H ₂ O ₂ Are Critical for Streptococcus pneumoniae-Mediated Cardiomyocyte Killing

Port d’Entrée for Respiratory Infections – Does the Influenza A Virus Pave the Way for Bacteria?

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Evolution over a 15-year period of the clinical characteristics and outcomes of critically ill patients with severe community-acquired pneumonia

Cited by 41 publications

References 27 publications

Co-infection in severe influenza: a new epidemiology?

Co-infection in severe influenza: a new epidemiology?

Cell Invasion and Pyruvate Oxidase-Derived H 2 O 2 Are Critical for Streptococcus pneumoniae-Mediated Cardiomyocyte Killing

Port d’Entrée for Respiratory Infections – Does the Influenza A Virus Pave the Way for Bacteria?

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Cell Invasion and Pyruvate Oxidase-Derived H ₂ O ₂ Are Critical for Streptococcus pneumoniae-Mediated Cardiomyocyte Killing