Explore the vast range of titles available.

is a pathogen responsible for bacterial vaginosis, which is commonly found in female vaginas and rarely causes infections outside the female genitalia. Here, we report the use of metagenomic next-generation sequencing (mNGS) to detect and confirm pulmonary infection and pleural effusion caused by in a 47-year-old man. The patient's symptoms and imaging improved after 2 weeks of oral ornidazole, and he was cured after 3 months. Overall, the findings of this case demonstrate that mNGS is a useful tool for diagnosis of unexplained lung infections and pleural effusions. Its effectiveness in rapid and accurate etiological diagnosis and monitoring of diseases can allow detection of the etiology of difficult cases that return negative results after traditional cultures.

Pseudomonas aeruginosa is an important opportunistic pathogen responsible for the cause of acute lung injury and acute respiratory distress syndrome. P. aeruginosa isthe leading species isolated from patients with nosocomial infection and is detected in almost all the patients with long term ventilation in critical care units. P. aeruginosa infection is also the leading cause of deleterious chronic lung infections in patients suffering from cystic fibrosis as well as the major reason for morbidity in people with chronic obstructive pulmonary disease. P. aeruginosa infections are linked to diseases with high mortality rates and are challenging for treatment, for which no effective remedies have been developed. Massive lung epithelial cell death is a hallmark of severe acute lung injury and acute respiratory distress syndrome caused by P. aeruginosa infection. Lung epithelial cell death poses serious challenges to air barrier and structural integrity that may lead to edema, cytokine secretion, inflammatory infiltration, and hypoxia. Here we review different types of cell death caused by P. aeruginosa serving as a starting point for the diseases it is responsible for causing. We also review the different mechanisms of cell death and potential therapeutics in countering the serious challenges presented by this deadly bacterium.

Background: Empyema is known as a serious infection, and outcomes of empyema cases remain poor. Pleural fluid culture and blood culture have been reported to give unsatisfactory results. We introduce a novel pleural peels tissue culture during surgery and aim to improve the culture results of empyema. Methods: This was a retrospective study and was obtained from our institute. Patients with stage II or III empyema undergoing video-assisted thoracic surgery decortication from January 2019 to June 2021 were included in the study. Results: There were 239 patients that received a pleural peels tissue culture, a pleural fluid culture, and a blood culture concurrently during the perioperative period. Of these, 153 patients had at least one positive culture and 86 patients showed triple negative culture results. The positive culture rates were 46.9% for pleural peels tissue cultures, 46.0% for pleural fluid cultures, and 10% for blood cultures. The combination of pleural peels tissue culture and pleural fluid culture increased the positive rate to 62.7%. Streptococcus species and Staphylococcus species were the most common pathogens. Conclusion: The combination of pleural peels tissue culture and pleural fluid culture is an effective method to improve the positive culture rate in empyema.

Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment. However, immune-related adverse events (irAEs) are a common side effect which can mimic infection. Additionally, treatment of irAEs with corticosteroids and other immunosuppressant agents can lead to opportunistic infection, which we have classed as immunotherapy infections due to immunosuppression. However, emerging reports demonstrate that some infections can be precipitated by ICIs in the absence of immunosuppressive treatment, in contrast to the majority of reported cases. These infections are characterised by a dysregulated inflammatory immune response, and so we propose they are described as immunotherapy infections due to dysregulated immunity. This review summarises the rapidly emerging evidence of these phenomena and proposes a new framework for considering infection in the context of cancer immunotherapy.

The gut microbiota has an important role in health and disease: gut bacteria can generate metabolites that alter the function of immune cells systemically. Understanding the factors that can lead to changes in the gut microbiome may help to inform therapeutic interventions. This is the first study to systematically dissect the pathway of events from viral lung infection to changes in gut microbiota. We show that the cellular immune response to viral lung infection induces inappetence, which in turn alters the gut microbiome and metabolome. Strikingly, there was an increase in lipids that have been associated with the resolution of disease. This opens up new paths of investigation: first, what is the (presumably secreted) factor made by the T cells that can induce inappetence? Second, is inappetence an adaptation that accelerates recovery from infection, and if so, does the microbiome play a role in this? Respiratory viral infections are extremely common, but their impacts on the composition and function of the gut microbiota are poorly understood. We previously observed a significant change in the gut microbiota after viral lung infection. Here, we show that weight loss during respiratory syncytial virus (RSV) or influenza virus infection was due to decreased food consumption, and that the fasting of mice altered gut microbiota composition independently of infection. While the acute phase tumor necrosis factor alpha (TNF-α) response drove early weight loss and inappetence during RSV infection, this was not sufficient to induce changes in the gut microbiota. However, the depletion of CD8 + cells increased food intake and prevented weight loss, resulting in a reversal of the gut microbiota changes normally observed during RSV infection. Viral infection also led to changes in the fecal gut metabolome, with a significant shift in lipid metabolism. Sphingolipids, polyunsaturated fatty acids (PUFAs), and the short-chain fatty acid (SCFA) valerate were all increased in abundance in the fecal metabolome following RSV infection. Whether this and the impact of infection-induced anorexia on the gut microbiota are part of a protective anti-inflammatory response during respiratory viral infections remains to be determined. IMPORTANCE The gut microbiota has an important role in health and disease: gut bacteria can generate metabolites that alter the function of immune cells systemically. Understanding the factors that can lead to changes in the gut microbiome may help to inform therapeutic interventions. This is the first study to systematically dissect the pathway of events from viral lung infection to changes in gut microbiota. We show that the cellular immune response to viral lung infection induces inappetence, which in turn alters the gut microbiome and metabolome. Strikingly, there was an increase in lipids that have been associated with the resolution of disease. This opens up new paths of investigation: first, what is the (presumably secreted) factor made by the T cells that can induce inappetence? Second, is inappetence an adaptation that accelerates recovery from infection, and if so, does the microbiome play a role in this?

Abstract Rationale The prognostic factors of Mycobacterium avium complex lung disease (MAC-LD) are not clearly defined. Objectives To assess the prognostic factors of all-cause and MAC-specific mortality in patients with MAC-LD, especially in accordance with radiographic features, first-line treatment, and host predisposition. Methods Medical records of 634 HIV-negative patients with MAC-LD treated at our institution in Saitama, Japan were retrospectively analyzed. Measurements and Main Results Patients’ mean age was 68.9 years, and median follow-up period was 4.7 years. Radiographic features included nodular/bronchiectatic (NB) disease: 482 patients (76.0%); fibrocavitary (FC) disease: 105 patients (16.6%); FC+NB disease: 30 patients (4.7%); and other types: 17 patients (3.0%). First-line treatments were observation or one drug: 479 patients (75.6%); 2 to 5 drugs: 131 patients (20.7%); and unknown: 24 patients (3.8%). A multivariate Cox proportional hazard model showed male sex, older age, presence of systemic and/or respiratory comorbidity, non-NB radiographic features, body mass index (BMI) less than 18.5 kg/m2, anemia, hypoalbuminemia, and erythrocyte sedimentation rate greater than or equal to 50 mm/h to be negative prognostic factors for all-cause mortality, and FC or FC+NB radiographic features, BMI less than 18.5 kg/m2, anemia, and C-reactive protein greater than or equal to 1.0 mg/dl to be negative prognostic factors for MAC-specific mortality. Conclusions The first-line treatment regimen was not associated with all-cause mortality. FC or FC+NB disease, BMI less than 18.5 kg/m2, and anemia were negative prognostic factors for both all-cause and MAC-specific mortality.

Emergence of multidrug-resistant (MDR) bacterial infections is a major problem in clinical medicine. Development of new strategies such as phage therapy may be a novel approach for treatment of life-threatening infections caused by MDR bacteria. A newly isolated phage, MMI-Ps₁, with strong lytic activity was used for treatment of acute lung infection with Pseudomonas aeruginosa in a mouse model. Intranasal administration of a single dose of MMI-Ps₁ immediately after infection provided a significant level of protection and increased the survival duration. Moreover, treatment of infected mice with phage as late as 12 hours after infection was still protective. Our in vitro results are the first to show the synergistic elimination of serum-resistant Pseudomonas strains by phage and complement. Phage therapy increases the efficacy of complement-mediated lysis of serum-resistant P. aeruginosa strains, indicating the importance of an intact complement system in clearing Pseudomonas infection during phage therapy.

Neutrophil extracellular traps (NETs) arise from the release of granular and nuclear contents of neutrophils in the extracellular space in response to different classes of microorganisms, soluble factors, and host molecules. NETs are composed by decondensed chromatin fibers coated with antimicrobial granular and cytoplasmic proteins, such as myeloperoxidase, neutrophil elastase (NE), and α-defensins. Besides being expressed on NET fibers, NE and MPO also regulate NET formation. Furthermore, histone deimination by peptidylarginine deiminase 4 (PAD4) is a central step to NET formation. NET formation has been widely demonstrated to be an effective mechanism to fight against invading microorganisms, as deficiency in NET release or dismantling NET backbone by bacterial DNases renders the host susceptible to infections. Therefore, the primary role of NETs is to prevent microbial dissemination, avoiding overwhelming infections. However, an excess of NET formation has a dark side. The pathogenic role of NETs has been described for many human diseases, infectious and non-infectious. The detrimental effect of excessive NET release is particularly important to lung diseases, because NETs can expand more easily in the pulmonary alveoli, causing lung injury. Moreover, NETs and its associated molecules are able to directly induce epithelial and endothelial cell death. In this regard, massive NET formation has been reported in several pulmonary diseases, including asthma, chronic obstructive pulmonary disease, cystic fibrosis, respiratory syncytial virus bronchiolitis, influenza, bacterial pneumonia, and tuberculosis, among others. Thus, NET formation must be tightly regulated in order to avoid NET-mediated tissue damage. Recent development of therapies targeting NETs in pulmonary diseases includes DNA disintegration with recombinant human DNase, neutralization of NET proteins, with anti-histone antibodies and protease inhibitors. In this review, we summarize the recent knowledge on the pathophysiological role of NETs in pulmonary diseases as well as some experimental and clinical approaches to modulate their detrimental effects.

Recent work shows that people with cystic fibrosis (CF) and chronic lung infections generally remain persistently infected after treatment with drugs that target the CF physiological defect (called CFTR modulators). However, changes produced by modulators could increase antibiotic efficacy. Drugs called CFTR modulators improve the physiologic defect underlying cystic fibrosis (CF) and alleviate many disease manifestations. However, studies to date indicate that chronic lung infections that are responsible for most disease-related mortality generally persist. Here, we investigated whether combining the CFTR modulator ivacaftor with an intensive 3.5-month antibiotic course could clear chronic Pseudomonas aeruginosa or Staphylococcus aureus lung infections in subjects with R117H-CFTR , who are highly ivacaftor-responsive. Ivacaftor alone improved CFTR activity, and lung function and inflammation within 48 h, and reduced P. aeruginosa and S. aureus pathogen density by ∼10-fold within a week. Antibiotics produced an additional ∼10-fold reduction in pathogen density, but this reduction was transient in subjects who remained infected. Only 1/5 P. aeruginosa -infected and 1/7 S. aureus -infected subjects became persistently culture-negative after the combined treatment. Subjects appearing to clear infection did not have particularly favorable baseline lung function or inflammation, pathogen density or antibiotic susceptibility, or bronchiectasis scores on CT scans, but they did have remarkably low sweat chloride values before and after ivacaftor. All persistently P. aeruginosa -positive subjects remained infected by their pretreatment strain, whereas subjects persistently S. aureus -positive frequently lost and gained strains. This work suggests chronic CF infections may resist eradication despite marked and rapid modulator-induced improvements in lung infection and inflammation parameters and aggressive antibiotic treatment. IMPORTANCE Recent work shows that people with CF and chronic lung infections generally remain persistently infected after treatment with drugs that target the CF physiological defect (called CFTR modulators). However, changes produced by modulators could increase antibiotic efficacy. We tested the approach of combining modulators and intensive antibiotics in rapid succession and found that while few subjects cleared their infections, combined treatment appeared most effective in subjects with the highest CFTR activity. These findings highlight challenges that remain to improve the health of people with CF.

Background Unsaturated fatty acids targeting quorum sensing (QS) system have shown potential application in reducing bacterial virulence. We aim to investigate the effect of palmitoleic acid (PMA) on P. aeruginosa QS activation, and its impact on infection-induced lung injury. Methods The influence of PMA on QS signaling molecule (3OC12-HSL and C4-HSL) concentrations, pyocyanin production, and QS gene transcription levels were examined in wildtype PAO1 culture. The roles of PMA in reducing infection-induced injury were assessed in human bronchial epithelial BEAS-2B cells and mouse lung infection models, respectively. PMA levels and QS signaling molecule concentrations were tested in the bronchoalveolar lavage fluid (BALF) of bronchiectasis patients with first-time detection of P. aeruginosa infection. Results PMA administration dose-dependently suppressed the expression of QS signaling molecules, pyocyanin, and QS genes during the logarithmic stage of bacterial growth. In BEAS-2B cells, PMA-treated PAO1 filtrates significantly reduced cell apoptosis and expression of IL-8 and IL-6. In mouse lung infection models, prophylactically oral administration of PMA significantly downregulated the expression of P. aeruginosa QS signals and QS genes ( lasR , rhlR , rhlI , lasB , rhlA , phzA1 , phnA ) in lungs, and relieved neutrophilic airway inflammation. Finally, PMA levels were negatively correlated with the concentrations of both 3OC12-HSL and C4-HSL in BALF of bronchiectasis patients, and positively correlated with their forced vital capacity (FVC) and forced expiratory volume in the first second (FEV 1.0 ) . Conclusion Our findings show that PMA inhibits P. aeruginosa QS activation and protects lungs from injury caused by bacterial virulence. Hence, PMA may serve as a potential anti-QS agent against P. aeruginosa infection and would help to alleviate lung injury in bronchiectasis patients.