Hospitalization of the elderly for invasive pneumococcal disease is frequently accompanied by the occurrence of an adverse cardiac event; these are primarily new or worsened heart failure and cardiac arrhythmia. Herein, we describe previously unrecognized microscopic lesions (microlesions) formed within the myocardium of mice, rhesus macaques, and humans during bacteremic Streptococcus pneumoniae infection. In mice, invasive pneumococcal disease (IPD) severity correlated with levels of serum troponin, a marker for cardiac damage, the development of aberrant cardiac electrophysiology, and the number and size of cardiac microlesions. Microlesions were prominent in the ventricles, vacuolar in appearance with extracellular pneumococci, and remarkable due to the absence of infiltrating immune cells. The pore-forming toxin pneumolysin was required for microlesion formation but Interleukin-1β was not detected at the microlesion site ruling out pneumolysin-mediated pyroptosis as a cause of cell death. Antibiotic treatment resulted in maturing of the lesions over one week with robust immune cell infiltration and collagen deposition suggestive of long-term cardiac scarring. Bacterial translocation into the heart tissue required the pneumococcal adhesin CbpA and the host ligands Laminin receptor (LR) and Platelet-activating factor receptor. Immunization of mice with a fusion construct of CbpA or the LR binding domain of CbpA with the pneumolysin toxoid L460D protected against microlesion formation. We conclude that microlesion formation may contribute to the acute and long-term adverse cardiac events seen in humans with IPD. Hospitalization for community-acquired pneumonia carries a documented risk for adverse cardiac events. These occur during infection and contribute to elevated mortality rates in convalescent individuals up to 1 year thereafter. We describe a previously unrecognized pathogenic mechanism by which Streptococcus pneumoniae, the leading cause of community-acquired pneumonia, causes direct cardiotoxicity and forms microscopic bacteria-filled lesions within the heart. Microlesions were detected in experimentally infected mice and rhesus macaques, as well as in heart sections from humans who succumbed to invasive pneumococcal disease (IPD). Cardiac microlesion formation required interaction of the bacterial adhesin CbpA with host Laminin receptor and bacterial cell wall with Platelet-activating factor receptor. Microlesion formation also required the pore-forming toxin pneumolysin. When infected mice were rescued with antibiotics, we observed robust signs of collagen deposition at former lesion sites. Thus, microlesions and the scarring that occurs thereafter may explain why adverse cardiac events occur during and following IPD.

Pseudomonas aeruginosais a challenging bacterium to treat due to its intrinsic resistance to the antibiotics used most frequently in patients with community-acquired pneumonia (CAP). Data about the global burden and risk factors associated withP. aeruginosa-CAP are limited. We assessed the multinational burden and specific risk factors associated withP. aeruginosa-CAP.We enrolled 3193 patients in 54 countries with confirmed diagnosis of CAP who underwent microbiological testing at admission. Prevalence was calculated according to the identification ofP. aeruginosa. Logistic regression analysis was used to identify risk factors for antibiotic-susceptible and antibiotic-resistantP. aeruginosa-CAP.The prevalence ofP. aeruginosaand antibiotic-resistantP. aeruginosa-CAP was 4.2% and 2.0%, respectively. The rate ofP. aeruginosaCAP in patients with prior infection/colonisation due toP. aeruginosaand at least one of the three independently associated chronic lung diseases (i.e.tracheostomy, bronchiectasis and/or very severe chronic obstructive pulmonary disease) was 67%. In contrast, the rate ofP. aeruginosa-CAP was 2% in patients without priorP. aeruginosainfection/colonisation and none of the selected chronic lung diseases.The multinational prevalence ofP. aeruginosa-CAP is low. The risk factors identified in this study may guide healthcare professionals in deciding empirical antibiotic coverage for CAP patients.

Purpose of review Pneumonia is considered the leading infectious diseases cause of death and the seventh leading cause of death overall in the US. There is significant interest in understanding the relationship between community-acquired pneumonia (CAP) and mortality. Recent findings Most clinical studies examining patients with CAP have used an arbitrary in-hospital or 30-day mortality as a short-term mortality clinical end point. However, long-term mortality (arbitrary >3 months) factors, incidence, prediction, and implications on patient care are important issues that require further evaluation in patients with CAP. This review focuses on the most recent literature assessing the importance and the frequency of long-term associated outcomes in patients with CAP, the risk factors, and possible implications for future strategies. Multiple risk factors that include age, sex, comorbid conditions, type of pneumonia, and severity of illness are associated with higher long-term mortality. In addition, several biomarkers were demonstrated to be independently associated with long-term mortality. Summary Despite advances in the understanding of long-term mortality among CAP patients, there is still a high unacceptable long-term mortality. Public health programs should address this important gap, considering the high level of complexity factors in patients with CAP.

Idiopathic pulmonary fibrosis (IPF), the most lethal form of interstitial pneumonia of unknown cause, is associated with a specific radiological and histopathological pattern (the so-called “usual interstitial pneumonia” pattern) and has a median survival estimated to be between 3 and 5 years after diagnosis. However, evidence shows that IPF has different clinical phenotypes, which are characterized by a variable disease course over time. At present, the natural history of IPF is unpredictable for individual patients, although some genetic factors and circulating biomarkers have been associated with different prognoses. Since in its early stages, IPF may be asymptomatic, leading to a delayed diagnosis. Two drugs, pirfenidone and nintedanib, have been shown to modify the disease course by slowing down the decline in lung function. It is also known that 5–10% of the IPF patients may be affected by episodes of acute and often fatal decline. The acute worsening of disease is sometimes attributed to identifiable conditions, such as pneumonia or heart failure; but many of these events occur without an identifiable cause. These idiopathic acute worsenings are termed acute exacerbations of IPF. To date, clinical biomarkers, diagnostic, prognostic, and theranostic, are not well characterized. However, they could become useful tools helping facilitate diagnoses, monitoring disease progression and treatment efficacy. The aim of this review is to cover molecular mechanisms underlying IPF and research into new clinical biomarkers, to be utilized in diagnosis and prognosis, even in patients treated with antifibrotic drugs.