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Staphylococcus pseudintermedius is usually a commensal bacterium of microbiota of dogs and cats that can become pathogenic in these animals. In the past two decades, an increasing number of human infections caused by this pathogen was reported; only two pediatric cases were due to methicillin-susceptible isolates. We describe the first case of methicillin-resistant S. pseudintermedius diagnosed in a 12-year-old immunocompromised girl with refractory anaplastic ependymoma, presented with life-threatening pneumonia and bacteremia. The girl had close contact with her two pet dogs. This case emphasizes that immunocompromised children should be advised on proper handling of household pets to minimize the risk of infection, which could be life threatening.

Pleuritic chest pain from bacterial pneumonia is often reported in human medicine. However, studies investigating pain associated with bovine respiratory disease (BRD) are lacking. The objectives of this study were to assess if bacterial pneumonia elicits a pain response in calves with experimentally induced BRD and to determine the analgesic effects of transdermally administered flunixin. A total of 26 calves, 6-7 mo of age, with no history of BRD were enrolled into one of three treatment groups: 1) experimentally induced BRD + transdermal flunixin at 3.3 mg/kg twice, 24 h apart (BRD + FTD); 2) experimentally induced BRD + placebo (BRD + PLBO); and 3) sham induction + placebo (CNTL + PLBO). Calves induced with BRD were inoculated with Mannheimia haemolytica via bronchoalveolar lavage. Outcomes were collected from -48 to 192 h post-treatment and included serum cortisol, infrared thermography, mechanical nociceptive threshold, substance P, kinematic gait analysis, visual analog scale (VAS), clinical illness score, computerized lung score, average activity and rumination level, prostaglandin E2 metabolite, plasma serum amyloid A, and rectal temperature. Outcomes were evaluated using either a generalized logistic mixed model for categorical variables or a generalized linear mixed model for continuous variables. Right front force differed by treatment (P = 0.01). The BRD + PLBO had lower mean force applied to the right front limb (85.5 kg) compared with BRD + FTD (96.5 kg; P < 0.01). Average VAS differed by a treatment by time interaction (P = 0.01). The VAS scores differed for BRD + PLBO at -48 (3.49 mm) compared with 168 and 192 h (13.49 and 13.64 mm, respectively) (P < 0.01). Activity for BRD + PLBO was higher at -48 h (27 min/h) compared with 48, 72, 120, and 168 h (≤ 22.24 min/h; P < 0.01). Activity differed by a treatment by time interaction (P = 0.01). Activity for BRD + FTD was higher at -48 and 0 h (28.2 and 28.2 min/h, respectively) compared to 48, 72, 96, and 168 h (≤23.7 min/h; P < 0.01). Results show a combination of reduced activity levels, decreased force on the right front limb, and increased VAS pain scores all support that bacterial pneumonia in cattle is painful. Differences in right front force indicate that flunixin transdermal may attenuate certain pain biomarkers in cattle with BRD. These findings suggest that BRD is painful and analgesic drugs may improve the humane aspects of care for cattle with BRD., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Although critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate immune dynamics during Coronavirus Disease 2019 (COVID-19) ARDS, compared to ARDS from other respiratory pathogens, is unclear. Moreover, mechanisms underlying the beneficial effects of dexamethasone during severe COVID-19 remain elusive. Using single-cell RNA sequencing and plasma proteomics, we discovered that, compared to bacterial ARDS, COVID-19 was associated with expansion of distinct neutrophil states characterized by interferon (IFN) and prostaglandin signaling. Dexamethasone during severe COVID-19 affected circulating neutrophils, altered IFN active neutrophils, downregulated interferon-stimulated genes and activated IL-1R2 + neutrophils. Dexamethasone also expanded immunosuppressive immature neutrophils and remodeled cellular interactions by changing neutrophils from information receivers into information providers. Male patients had higher proportions of IFN active neutrophils and preferential steroid-induced immature neutrophil expansion, potentially affecting outcomes. Our single-cell atlas (see 'Data availability' section) defines COVID-19-enriched neutrophil states and molecular mechanisms of dexamethasone action to develop targeted immunotherapies for severe COVID-19., (© 2021. The Author(s).)

Backgroud: Pneumonia is one of the leading causes of death in children under 5 years old. Viruses have historically been the most common cause of community-acquired pneumonia in children. Co-infections in severe pneumonia are more concern by clinicians., Method: It was a perspective and descriptive study. Real-time polymerase chain reaction (RT-PCR) is a modern test that was used to detect many new pathogens, including microbiological co-infections. RT-PCR technique was used in this study to investigate the causes of severe pneumonia., Results: Through the analysis of nasopharyngeal aspiration samples from 95 children with severe community-acquired pneumonia, the positive RT-PCR rate was 90.5%. Viral-bacterial co-infection accounted for the highest proportion (43.1%), followed by bacterial co-infection (33.7%), viral infection (7.4%), bacterial infection (6.3%) and the remaining 9.5% was unknown. In the co-infections groups, the five main bacteria species detected by PCR were Streptococcus pneumoniae, Haemophilus influenzae, MRSA, Moraxella catarrhalis and Mycoplasma pneumoniae., Conclusion: Antibiotic treatment should focus on detected microbes in cases of severe pneumonia for having a good result., (© 2021 Japan Pediatric Society.)

Background: Cefazolin is a first-generation cephalosporin commonly used for skin and soft tissue infections, abdominal and orthopedic surgery prophylaxis, and methicillin-sensitive staph aureus. Cephalosporins as a whole are known potential inducers of hemolytic anemia; however, mechanism of action is primarily autoimmune, and compared to other drugs, cefazolin is the least common., Methods: A rare case report of cefazolin-induced hemolytic anemia "CIHA" and a systematic review of CIHA articles in English literature. Two authors performed review of publications and articles were selected based on inclusion and exclusion criteria. A systematic search of the literature yielded 768 entries with five case reports on cefazolin-induced hemolytic anemia., Case Presentation/results: An 80-year-old female with methicillin-sensitive Staphylococcus aureus "MSSA" endocarditis. The patient was started on intravenous "IV" cefazolin that that resulted in hemolytic anemia and eosinophilia. Switching to vancomycin improved hemoglobin level and resolved eosinophilia. Four cefazolin-induced hemolytic anemia case reports and one population-based article with a case reported were analyzed with respect to direct antiglobulin test "DAT" (also known as the direct Coombs test) results, prior penicillin sensitivity, and acute anemia causes exclusion., Conclusions: CIHA is a rare cause of clinically significant anemia. The diagnosis of drug-induced anemia is one of exclusion. It is important to consider DAT results and prior penicillin sensitivity when evaluating a patient for cefazolin-induced hemolytic anemia. However, the frequency of cefazolin use and resultant anemia necessitates early recognition of hemolytic anemia and prompt discontinuation of cefazolin, especially with long-term use., (© 2021. The Author(s).)

The mortality rates among patients who initially survive sepsis are, in part, associated with a high risk of secondary lung infections and respiratory failure. Given that phagolysosomes are important for intracellular killing of pathogenic microbes, we investigated how severe lung infections associated with post-sepsis immunosuppression affect phagolysosome biogenesis. In mice with P. aeruginosa-induced pneumonia, we found a depletion of both phagosomes and lysosomes, as evidenced by decreased amounts of microtubule associated protein light chain 3-II (LC3-II) and lysosomal-associated membrane protein (LAMP1). We also found a loss of transcription factor E3 (TFE3) and transcription factor EB (TFEB), which are important activators for transcription of genes encoding autophagy and lysosomal proteins. These events were associated with increased expression of ZKSCAN3, a repressor for transcription of genes encoding autophagy and lysosomal proteins. Zkscan3 -/- mice had increased expression of genes involved in the autophagy-lysosomal pathway along with enhanced killing of P. aeruginosa in the lungs, as compared to wild-type mice. These findings highlight the involvement of ZKSCAN3 in response to severe lung infection, including susceptibility to secondary bacterial infections due to immunosuppression., (© 2021. The Author(s), under exclusive licence to United States and Canadian Academy of Pathology.)

The FilmArray Pneumonia Panel has proven to be an effective tool for rapid detection of main respiratory pathogens. However, its rational use needs appropriate knowledge and formation regarding its indication and interpretation. Herein, we provide some advices to help with success of its daily routine use, particularly in critically ill ventilated COVID-19 patients. Clinical Trial registration number: NCT04453540., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The aim of this study is to review bacterial isolates from respiratory samples of patients with severe COVID-19 disease during the first 2 months of the first wave in our hospital. A single-center retrospective observational study in critically ill adult patients was performed. A total of 1251 respiratory samples from 1195 patients were processed. Samples from 66 patients (5.52%) were determined to be microbiologically significant by a semi-quantitative culture. All patients received broad spectrum antibiotherapy as an empirical treatment. The isolated bacteria were mainly Enterobacterales followed by Staphylococcus aureus and Pseudomonas aeruginosa. Bacterial co-infections in ICU stay could seem not dependent on the virus that has produced the viral pneumonia similarly as with other respiratory viruses such as Influenza virus., Competing Interests: Declaration of competing interest None., (Copyright © 2021. Published by Elsevier Inc.)

Among critically ill COVID-19 patients, bacterial coinfections may occur, and timely appropriate therapy may be limited with culture-based microbiology due to turnaround time and diagnostic yield challenges (e.g. antibiotic pre-exposure). We performed a systematic review and meta-analysis of the impact of BioFire® FilmArray® Pneumonia Panel in detecting bacteria and clinical management among critically ill COVID-19 patients admitted to the ICU. Seven studies with 558 patients were included. Antibiotic use before respiratory sampling occurred in 28-79% of cases. The panel incidence of detections was 33% (95% CI 0.25 to 0.41, I 2 =32%) while culture yielded 18% (95% CI 0.02 to 0.45; I 2 =93%). The panel was associated with approximately a 1 and 2 day decrease in turnaround for identification and common resistance targets, respectively. The panel may be an important tool for clinicians to improve antimicrobial use in critically ill COVID-19 patients., Competing Interests: Declaration of competing interest T.T. Timbrook and K.D. Hueth are employees of BioFire Diagnostics; C.C. Ginocchio is an employee of bioMérieux and BioFire Diagnostics. Authors report no other conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Pleural sepsis stems from an infection within the pleural space typically from an underlying bacterial pneumonia leading to development of a parapneumonic effusion. This effusion is traditionally divided into uncomplicated, complicated, and empyema. Poor clinical outcomes and increased mortality can be associated with the development of parapneumonic effusions, reinforcing the importance of early recognition and diagnosis. Management necessitates a multimodal therapeutic strategy consisting of antimicrobials, catheter/tube thoracostomy, and at times, video-assisted thoracoscopic surgery., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Sepsis induces gut barrier dysfunction characterized by increased gut epithelial apoptosis and increased intestinal permeability. The cytokine IL-22 has been demonstrated to regulate gut barrier function. Type-3 innate lymphoid cells (ILC3) are the predominate source of IL-22 in the GI tract. We hypothesized that sepsis may cause changes to the gut ILC3/IL-22 axis., Materials and Methods: Sepsis was induced in WT and IL-22 KO mice by Pseudomonas aeruginosa pneumonia. Changes in gut-associated leukocyte populations were determined by flow-cytometry and ILC-associated transcripts were measured by RT-PCR. The effect of sepsis on gut permeability, pulmonary microbial burden, gut epithelial apoptosis, and survival was compared between WT and IL-22-/- mice., Results: Sepsis resulted in a significant decrease in the number of ILC3 in the gut, with a reciprocal increase in type-1 ILC (ILC1). Consistent with prior reports, sepsis was associated with increased gut permeability; however there was no difference in gut permeability, gut epithelial apoptosis, pulmonary microbial burden, or survival between WT and IL-22-/- mice., Conclusions: Septic pneumonia causes a decrease in gut-associated ILC3 and an associated reciprocal increase in ILC1. This may reflect inflammation-induced conversion of ILC3 to ILC1. Constitutive systemic IL-22 deficiency does not alter sepsis-induced gut barrier dysfunction., Competing Interests: Decleration of competing interest The authors declare no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Abstract: Although pulmonary mycobacterial infection is associated with acute respiratory distress syndrome (ARDS) in critically ill patients, its clinical implication on patients with ARDS has not been clearly elucidated. The aim of study was to investigate the clinical significance of pulmonary mycobacterial infection in patients with ARDS.Between January 2014 and April 2019, medical records of 229 patients with ARDS who met the Berlin criteria and received invasive mechanical ventilation in medical intensive care unit were reviewed. Clinical characteristics and the rate of mortality between patients with and without pulmonary mycobacterial infection were compared. Factors associated with a 28-day mortality were analyzed statistically.Twenty two (9.6%) patients were infected with pulmonary mycobacteria (18 with tuberculosis and 4 with non-tuberculous mycobacteria). There were no differences in baseline characteristics, the severity of illness scores. Other than a higher rate of renal replacement therapy required in those without pulmonary mycobacterial infection, the use of adjunctive therapy did not differ between the groups. The 28- day mortality rate was significantly higher in patients with pulmonary mycobacterial infection (81.8% vs 58%, P = .019). Pulmonary mycobacterial infection was significantly associated with 28-day mortality (hazard ratio 1.852, 95% confidence interval 1.108-3.095, P = .019).Pulmonary mycobacterial infection was associated with increased 28-day mortality in patients with ARDS., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by acute hypoxaemia, and few studies have reported the incidence of deep vein thrombosis (DVT) in direct ARDS caused by bacterial pneumonia. We performed a study to evaluate the prevalence, risk factors, prognosis and potential thromboprophylaxis strategies of DVT in these patients., Methods: Ninety patients were included. Demographic, and clinical data, laboratory data and outcome variables were obtained, and comparisons were made between the DVT and non-DVT groups., Results: Of the 90 patients, 40 (44.4%) developed lower extremity DVT. Compared with non-DVT patients, DVT patients had higher systemic inflammatory response syndrome (SIRS) scores, lower serum creatinine levels, higher D-dimer levels, and higher rates of sedative therapy and invasive mechanical ventilation (IMV). Multivariate analysis showed an association between the SIRS score (OR 3.803, P = 0.027), level of serum creatinine (OR 0.988, P = 0.001), IMV (OR 5.822, P = 0.002) and DVT. The combination of SIRS score, serum creatinine level and IMV has a sensitivity of 80.0% and a specificity of 74.0% for screening for DVT. The survival rate within 28 days after ARDS in the DVT group was significantly lower than that in the non-DVT group (P = 0.003). There was no difference in the prevalence of DVT between the 41 patients who received thromboprophylaxis and the 49 patients who did not receive thromboprophylaxis (41.5% vs 46.9%; P = 0.603)., Conclusions: The prevalence of DVT is high in hospitalized patients with direct ARDS caused by bacterial pneumonia and may be associated with adverse outcomes. The current thromboprophylaxis strategies may need to be further optimized., (© 2021. The Author(s).)

Rationale: Mucinous cystadenoma is a benign tumor that is commonly found in the pancreas, ovaries, or appendix, but is rarely encountered in the lungs. Worldwide, only a few reported cases of these tumors originate in the lungs. Herein, we analyzed the imaging features of a case of pulmonary mucinous cystadenoma (PMCA). To the best of our knowledge, this is the first reported case of PMCA complicated by significant infection., Patient Concerns: A 57-year-old man was admitted to our hospital with blood in sputum for more than 2 months. Serum laboratory examination showed significantly elevated leukocyte and tumor marker, carcinoembryonic antigen. Enhanced thoracic computed tomography and whole-body positron emission tomography/computed tomography showed a cystic-solid ill-defined mass in the right upper lung., Diagnosis: The tumor was considered malignant, both clinically and radiologically., Interventions: The patient underwent right upper lobe tumor resection and mediastinal lymph node dissection., Outcomes: Postoperative specimen pathology was diagnosed as PMCA with infection. The patient was not administered any further treatment. The patient was alive without any recurrence or metastasis of the tumor after 2 years of follow-up., Lessons: Preoperative diagnosis of PMCA with atypical imaging and clinical manifestations is extremely difficult. This is the first reported case of PMCA complicated by a significant infection that was misdiagnosed preoperatively as a malignancy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

We present the case of a 19 year old female presenting to the Emergency Department with signs of pneumonia and sepsis, with her clinical status deteriorating rapidly to septic shock and respiratory failure. Her pneumonia was complicated by formation of an empyema and a bronchopleural fistula. Bronchopleural fistula (BPF) is a fistula between pleural space and a bronchus. It is an uncommon complication of lung surgery, endobronchial interventions or chest trauma. They are sometimes formed secondary to postoperative pneumonia. Management of BPF requires surgical or bronchoscopic intervention with supportive care. Since a BPF can cause physiological tension pneumothorax, it can lead to significant worsening of respiratory status of these patients. Ventilator settings need to be adjusted to reduce the Positive end expiratory pressure and tidal volume to support these patients. With this case we highlight the importance of recognizing and diagnosing a BPF and timely management of a BPF in the emergency setting to help patients get to the definitive treatment of the fistula., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The etiology of Kawasaki Disease (KD), the most common cause of acquired heart disease in children in developed countries, remains elusive, but could be multifactorial in nature as suggested by the numerous environmental and infectious exposures that have previously been linked to its epidemiology. There is still a lack of a comprehensive model describing these complex associations. We present a Bayesian disease model that provides insight in the spatiotemporal distribution of KD in Canada from 2004 to 2017. The disease model including environmental factors had improved Watanabe-Akaike information criterion (WAIC) compared to the base model which included only spatiotemporal and demographic effects and had excellent performance in recapitulating the spatiotemporal distribution of KD in Canada (98% and 86% spatial and temporal correlations, respectively). The model suggests an association between the distribution of KD and population composition, weather-related factors, aeroallergen exposure, pollution, atmospheric concentration of spores and algae, and the incidence of healthcare encounters for bacterial pneumonia or viral intestinal infections. This model could be the basis of a hypothetical data-driven framework for the spatiotemporal distribution of KD. It also generates novel hypotheses about the etiology of KD, and provides a basis for the future development of a predictive and surveillance model., (© 2021. The Author(s).)

Competing Interests: None declared.

Background: Acute respiratory distress syndrome (ARDS) often requires controlled ventilation, yielding high mechanical power and possibly further injury. Veno-venous extracorporeal membrane oxygenation (VV-ECMO) can be used as a bridge to recovery, however, if this fails the end result is destroyed lung parenchyma. This condition is fatal and the only remaining alternative is lung transplantation. In the case study presented in this paper, lung transplantation was not an option given the critically ill state and the presence of HLA antibodies. Airway pressure release ventilation (APRV) may be valuable in ARDS, but APRV settings recommended in various patient and clinical studies are inconsistent. The Time Controlled Adaptive Ventilation (TCAV™) method is the most studied technique to set and adjust the APRV mode and uses an extended continuous positive airway pressure (CPAP) Phase in combination with a very brief Release Phase. In addition, the TCAV™ method settings are personalized and adaptive based on changes in lung pathophysiology. We used the TCAV™ method in a case of severe ARDS, which enabled us to open, stabilize and slowly heal the severely damaged lung parenchyma., Case Presentation: A 43-year-old woman presented with Staphylococcus Aureus necrotizing pneumonia. Progressive respiratory failure necessitated invasive mechanical ventilation and VV-ECMO. Mechanical ventilation (MV) was ultimately discontinued because lung protective settings resulted in trivial tidal volumes. She was referred to our academic transplant center for bilateral lung transplantation after the remaining infection had been cleared. We initiated the TCAV™ method in order to stabilize the lung parenchyma and to promote tissue recovery. This strategy was challenged by the presence of a large bronchopleural fistula, however, APRV enabled weaning from VV-ECMO and mechanical ventilation. After two months, following nearly complete surgical closure of the remaining bronchopleural fistulas, the patient was readmitted to ICU where she had early postoperative complications. Since other ventilation modes resulted in significant atelectasis and hypercapnia, APRV was restarted. The patient was then again weaned from MV., Conclusions: The TCAV™ method can be useful to wean challenging patients with severe ARDS and might contribute to lung recovery. In this particular case, a lung transplantation was circumvented.

Sepsis is a leading cause of mortality in intensive care unit worldwide, it's accompanied by immune cell dysfunction induced by multiple factors. However, little is known about the specific alterations in immune cells in the dynamic pathogenesis of sepsis secondary to bacterial pneumonia. Here, we used single cell RNA sequencing (scRNA-seq) to profile peripheral blood mononuclear cells (PBMCs) in a healthy control and two patients with sepsis secondary to bacterial pneumonia, including acute, stable and recovery stage. We analyzed the quantity and function of immune cells. During disease course, interferon gamma response was upregulated; T/NK cell subtypes presented activation and exhaustion properties, which might be driven by monocytes through IL-1β signaling pathways; The proportion of plasma cells was increased, which might be driven by NK cells through IFN signaling pathways; Additionally, interferon gamma response was upregulated to a greater degree in sepsis secondary to pneumonia induced by SARS-COV-2 compared with that induced by influenza virus and bacteria., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Among 197 COVID-19 patients hospitalized in ICU, 88 (44.7%) experienced at least one bacterial infection, with pneumonia (39.1%) and bloodstream infections (15,7%) being the most frequent. Unusual findings include frequent suspicion of bacterial translocations originating from the digestive tract as well as bacterial persistence in the lungs despite adequate therapy., Competing Interests: The authors have declared that no competing interests exist.

Background: Over the past decades, Klebsiella pneumoniae (K. pneumoniae) infections have been increasing and affected immunocompromised patients nosocomially and communally, with extended-spectrum β-lactamase (ESBL) production becoming a major concern. Patients with rheumatic autoimmune diseases, mostly receiving immunosuppressive therapy, are vulnerable to various infections, including K. pneumoniae. However, few have investigated K. pneumoniae infections in this specific population. This study aimed to identify factors associated with ESBL production and mortality of K. pneumoniae pneumonia among patients with rheumatic autoimmune diseases in the Emergency Department., Methods: We retrospectively investigated patients with rheumatic diseases who were diagnosed with K. pneumoniae pneumonia. The diagnosis of K. pneumoniae pneumonia was based on clinical manifestations, radiological findings and microbiological testing results. Prognostic factors and risk factors for ESBL production were determined with univariate and multivariate logistic regression analysis. Empirical therapy and antimicrobial susceptibility data were also collected., Results: Of 477 K. pneumoniae pneumonia patients, 60 were enrolled into this study. The in-hospital mortality was 28.3%. Septic shock, ICU admission, the need for mechanical ventilation and change of antibiotics due to clinical deterioration, all related to mortality, were included as unfavorable clinical outcomes. Multivariate analysis suggested that ESBL production (OR, 6.793; p = 0.012), initial PCT ≥ 0.5 ng/ml (OR, 5.024; p = 0.033) and respiratory failure at admission (OR, 4.401; p = 0.046) predicted increased mortality. ESBL production was significantly associated with dose of corticosteroids (OR, 1.033; p = 0.008) and CMV viremia (OR, 4.836; p = 0.032) in patients with rheumatic autoimmune diseases. Abnormal leukocyte count (OR, 0.192; p = 0.036) was identified as a protective factor of ESBL-producing K. pneumoniae pneumonia. The most commonly used empirical antibiotic was ceftazidime, while most isolates showed less resistance to carbapenems and amikacin in susceptibility testing., Conclusions: K. pneumoniae pneumonia could be life-threatening in patients with rheumatic autoimmune diseases. Our findings suggested that ESBL production, initial PCT ≥ 0.5 ng/ml and respiratory failure at admission were independent factors associated with poor prognosis. Dose of corticosteroids and CMV viremia, predicting ESBL production in K. pneumoniae pneumonia, may help make individualized antibiotic decisions in clinical practice.

Clinical Presentation: A 52-year-old man presented with hemoptysis of 2 weeks' duration. He had been experiencing hoarseness, right-sided pleuritic chest pain, subjective fevers, chills, night sweats, and 10 pounds weight loss for the previous 2 months. He additionally reported severe frontal headaches, nasal congestion, and intermittent epistaxis, which had been present for a year before his current presentation. He had worked in construction and denied tobacco or illicit drug use., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Infections within intensive care unit (ICU) are a persistent problem among the critically ill. Viral pneumonias have already been established as having a season variations. We attempt to evaluate the seasonal variations of pneumonia among the traumatically injured and the critically ill., Materials and Methods: A retrospective cohort study among traumatized patients admitted from 1997 to 2017 to an ICU within the state of Florida was performed who were diagnosed with pneumonia. A multivariate regression analysis was performed to adjust for confounders. Time periods were divided into seasons: summer, winter, spring, and fall. A subset analysis of geriatric patients (>65 years) was also performed., Results: A total of 869 553 patients were identified. The most common viral infection was influenza with adenovirus the least. The most common bacterial pneumonia was Staphylococcus aureus with Bordetella pertussis the least. Pneumonias had a seasonal variation. Compared to summer, winter had a higher likelihood of pneumonia overall (Adjusted Odds Ratio (AOR)1.13). This was seen in the spring (AOR 1.04) but not in fall (AOR 1.00). Viral infections were more pronounced (AOR 3.79) in all other seasons, while bacterial showed increased likelihood during winter (AOR 1.05). In geriatrics, pneumonia was again more likely in the winter (AOR 1.22) with both viral and bacterial infections being more pronounced during winter (AOR 4.79, AOR 1.09)., Discussion: Pneumonias are seen more frequently within the ICU during the winter for the traumatized patient. This held true with the critically ill geriatric population as well. This effect was observed in both viral and bacterial pneumonias.

Background: Hemoptysis is a frequent and sometimes fatal complication of non-tuberculous mycobacterial (NTM) lung disease. The risk factors for hemoptysis are not well understood. In the current study, potential risk factors for hemoptysis were investigated in patients with Mycobacterium avium complex (MAC) lung disease, which is the most common NTM in Japan., Methods: Medical records from the Kinki-Chuo Chest Medical Center were reviewed. Consecutive patients with MAC lung disease diagnosed in 2014 and followed up for more than 1 year in the hospital were included in the study. Hemoptysis was confirmed between 2014 and 2016. The characteristics of patients with hemoptysis and non-hemoptysis at the time of the initial diagnosis of MAC lung disease were obtained from the medical records, and the two groups were compared. The radiological findings assessed included nodules, infiltration shadows, cavities, and bronchiectasis. Each was classified and scored individually in six lung fields, and these data were used to generate radiological scores., Results: The study included 82 patients with MAC lung disease, 18 with hemoptysis and 64 without. Higher total radiological severity score at the time of the initial diagnosis of MAC was associated with an increased risk of hemoptysis. Among the radiological scores, infiltration and cavities were marginally associated with the risk of hemoptysis., Conclusions: The radiological severity score at the time of initial diagnosis of MAC lung disease was associated with hemoptysis., Competing Interests: Conflict of interest The authors declare that there are no conflicts of interest., (Copyright © 2020 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Many antibiotics require dosage adjustments in patients with renal impairment. In Phase III studies, omadacycline was non-inferior to moxifloxacin and linezolid in adults with community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI), respectively. This analysis evaluated efficacy and safety measures from three omadacycline studies by patient renal function., Methods: Patients were stratified as having normal renal function (creatinine clearance >89 mL/min), mild renal impairment (creatinine clearance 60-89 mL/min) or moderate renal impairment (creatinine clearance <60 mL/min); creatine clearance ≤30 mL/min (severe renal impairment) was an exclusion criterion. Efficacy endpoints were clinical success at the early clinical response (ECR) and post-treatment evaluation (PTE) time-points. Safety was evaluated as treatment-emergent adverse events (TEAEs) and laboratory measures., Results: This subgroup analysis included 773 patients with CABP and 1339 patients with ABSSSI in intent-to-treat (ITT) and modified ITT populations, respectively. Clinical success rates were high at ECR and PTE across the studies (CABP 75-90%; ABSSSI 74-95%), and broadly similar between treatments, irrespective of renal function. Rates of TEAEs in patients with ABSSSI ranged from 33% to 52%, and were similar across renal function groups. In patients with CABP, higher rates were observed in patients with moderate renal impairment (56-61%) compared with patients with normal renal function or mild renal impairment (35-49%). The most common TEAEs were nausea and vomiting., Conclusions: Clinical success was similar across renal function groups, indicating no notable difference in the efficacy of omadacycline in patients with mild or moderate renal impairment. Omadacycline and comparators displayed similar safety profiles. CLINICALTRIALS., Gov Registry: OPTIC (NCT02531438); OASIS-1 (NCT02378480); OASIS-2 (NCT02877927)., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A 47-year-old man was referred for ongoing workup of an enlarging lung mass. Extensive workup of the mass had been unrevealing for several months until cultures grew Nocardia beijingensis He was successfully treated with trimethoprim/sulfamethoxazole and then doxycycline with near-complete resolution of the mass on follow-up. This case presents a rare species of N. beijingensis It highlights the importance of considering nocardiosis in immunocompetent adults and the challenge in initiating targeted treatment due to delayed culture results., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junctions that leads to fluctuating weakness and disabling fatigability. Due to difficulty in breathing caused by weakness of the respiratory muscles, patients with MG are more susceptible to pneumonia and other respiratory infections. As many patients with MG are given immunosuppressive therapy, this makes them more prone to infections. However, coinfection with 3 pathogens is very rare., Patient Concerns: Here, we report the case of a 41-year-old gentleman with MG who was receiving long-term steroid therapy. He presented with a cough with pale brown expectoration that occurred without obvious inducement, severe pain in the scapula, as well as swelling and weakness of both legs. Despite undergoing treatment, but his symptoms did not improve, prompting two additional hospital admissions over a period of several months., Diagnosis: Bronchoscopy and bronchoalveolar lavage (BAL) were performed, revealing the presence of Pneumocystis jirovecii , Nocardia brasiliensis, and Mycobacterium tuberculosis (MTB). N brasiliensis was identified by positive modified acid-fast Kinyoun staining as well as a positive colony culture identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry from the BAL sample. MTB was confirmed using GeneXpert, and due to the limitations of the culture conditions, methenamine silver stain was used to confirm Pneumocystis jirovecii. Next-generation sequencing (NGS) assay of the BAL samples also confirmed these pathogens., Interventions: The patient was transferred to a designated tuberculosis hospital and received anti-infective and anti-TB treatment., Outcomes: During treatment at the designated hospital, the patient developed gastrointestinal bleeding and impaired liver function. One month later, he developed multiple organ failure, consolidation of the left lower lung, and pan-drug resistant bacteremia. He refused further treatment and was discharged., Conclusion: In conclusion, physicians should be aware of the predisposition of MG patients to co-infections, especially patients with metabolic disorders, to avoid inadequate treatment and poor patient outcomes. Due to the limitations of culture conditions, NGS should be considered as a new technique for identifying pathogens., Competing Interests: All authors have no potential conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

We are presenting an interesting case of Pneumonia, who after good initial response deteriorated with recurrent hemoptysis. On culture of bronchial aspirate, patient had coexisting fungal infection and on repeat bronchoscopy showed a unique and rare picture. There was a dancing ball in RUL which was moving. Patient was initially managed conservatively but finally had to undergo lobectomy to achieve permanent cure., Competing Interests: Conflicts of interest The authors have none to declare., (Copyright © 2020 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Background: The routine use of empiric combination therapy with aminoglycosides during critical illness is associated with uncertain benefit and increased risk of acute kidney injury. This study aimed to assess the benefits of aminoglycosides in immunocompromised patients with suspected bacterial pneumonia and sepsis., Methods: Secondary analysis of a prospective multicenter study. Adult immunocompromised patients with suspected bacterial pneumonia and sepsis or septic shock were included. Primary outcome was hospital mortality. Secondary outcomes were needed for renal replacement therapy (RRT). Mortality was also assessed in neutropenic patients and in those with confirmed bacterial pneumonia. Results were further analyzed in a cohort matched on risk of receiving aminoglycosides combination., Results: Five hundred thirty-five patients were included in this analysis, of whom 187 (35%) received aminoglycosides in addition to another antibiotic effective against gram-negative bacteria. Overall hospital mortality was 59.6% (58.3% vs. 60.3% in patients receiving and not receiving combination therapy; P = 0.71). Lack of association between mortality and aminoglycosides was confirmed after adjustment for confounders and center effect (adjusted OR 1.14 [0.69-1.89]) and in a propensity matched cohort (adjusted OR = 0.89 [0.49-1.61]). No association was found between aminoglycosides and need for RRT (adjusted OR = 0.83 [0.49-1.39], P = 0.477), nor between aminoglycoside use and outcome in neutropenic patients or in patients with confirmed bacterial pneumonia (adjusted OR 0.66 [0.23-1.85] and 1.25 [0.61-2.57], respectively)., Conclusion: Aminoglycoside combination therapy was not associated with hospital mortality or need for renal replacement therapy in immunocompromised patients with pulmonary sepsis.

Case Presentation: A 60-year-old non-smoker white woman presented with a new episode of hemoptysis. She reported recurrent hemoptoic sputum in the past month. She had no relevant medical history, except presumed resolved bacterial pneumonia 1 year ago. She denied taking immunosuppressive treatment and was not exposed to lung irritants. She had not traveled recently. General health status was good. She denied fever, dyspnea, chest pain, and extra-pulmonary symptoms., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: To appraise the epidemiological features of bacterial pneumonia and its impact on lung suitability for donation in brain-dead patients managed with protective ventilatory settings., Design: Retrospective observational study., Setting: Six ICUs from two university-affiliated hospitals., Patients: Brain-dead adult patients managed in the participating ICUs over a 4-year period., Interventions: None., Measurements and Main Results: Among the 231 included patients, 145 (62.8%) were classified as ideal or extended-criteria potential lung donors at ICU admission and the remaining 86 patients having baseline contraindication for donation. Culture-proven aspiration pneumonia and early-onset ventilator-associated pneumonia occurred in 54 patients (23.4%) and 15 patients (6.5%), respectively (overall pneumonia incidence, 29.9%). Staphylococcus aureus and Enterobacterales were the most common pathogens. Using mixed-effects Cox proportional hazard models, age (adjusted hazard ratio, 0.98; 95% CI [0.96-0.99]), anoxic brain injury (3.55 [1.2-10.5]), aspiration (2.29 [1.22-4.29]), and not receiving antimicrobial agents at day 1 (3.56 [1.94-6.53]) were identified as independent predictors of pneumonia occurrence in the whole study population. Analyses restricted to potential lung donors yielded similar results. Pneumonia was associated with a postadmission decrease in the PaO2/FIO2 ratio and lower values at brain death, in the whole study population (estimated marginal mean, 294 [264-323] vs 365 [346-385] mm Hg in uninfected patients; p = 0.0005) as in potential lung donors (299 [248-350] vs 379 [350-408] mm Hg; p = 0.04; linear mixed models). Lungs were eventually retrieved in 31 patients (34.4%) among the 90 potential lung donors with at least one other organ harvested (pneumonia prevalence in lung donors (9.7%) vs nondonors (49.2%); p = 0.0002)., Conclusions: Pneumonia occurs in one-third of brain-dead patients and appears as the main reason for lung nonharvesting in those presenting as potential lung donors. The initiation of antimicrobial prophylaxis upon the first day of the ICU stay in comatose patients with severe brain injury could enlarge the pool of actual lung donors.

Background: Bacterial community-acquired atypical pneumonia is sometimes complicated by a myositis or by a renal parenchymal disease. Available reviews do not mention the concurrent occurrence of both myositis and acute kidney injury., Methods: In order to characterize the link between bacterial community-acquired atypical pneumonia and both myositis and a renal parenchymal disease, we reviewed the literature (United States National Library of Medicine and Excerpta Medica databases)., Results: We identified 42 previously healthy subjects (35 males and 7 females aged from 2 to 76, median 42 years) with a bacterial atypical pneumonia associated both with myositis (muscle pain and creatine kinase ≥5 times the upper limit of normal) and acute kidney injury (increase in creatinine to ≥1.5 times baseline or increase by ≥27 μmol/L above the upper limit of normal). Thirty-six cases were caused by Legionella species (N = 27) and by Mycoplasma pneumoniae (N = 9). Further germs accounted for the remaining 6 cases. The vast majority of cases (N = 36) presented a diffuse myalgia. Only a minority of cases (N = 3) were affected by a calf myositis. The diagnosis of rhabdomyolysis-associated kidney injury was retained in 37 and that of acute interstitial nephritis in the remaining 5 cases., Conclusion: Bacterial atypical pneumonia may occasionally induce myositis and secondary kidney damage., (Copyright © 2020. Published by Elsevier Ltd.)

We present here a case of a 29-year-old woman with a medical history of GATA-2 deficiency, who was under treatment for Mycobacterium avium intracellulare pneumonia. She presented with worsening dyspnoea with cough and fever. It was initially thought she had pneumonia but she was later diagnosed with Pulmonary Alveolar Proteinosis (PAP)., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is an emerging opportunistic infection, but basic epidemiological data are lacking in most regions. We have investigated epidemiology and diagnostic and treatment practices in five EU countries (United Kingdom, Spain, Italy, France, Germany; EU5) and Japan., Study Design: and methods: Annual prevalence in each country was established using a 2-round Delphi method in combination with a regional prevalence-estimation model that incorporated data obtained from a blinded physician screening survey (3154 physicians) and a real-world NTM-PD treating-physician/patient-chart observational study (619 physicians - 1429 patient charts)., Results: The annual prevalence of NTM-PD was estimated at 6.2/100,000 in the EU5 and 24.9/100,000 in Japan. Overall prevalence between the EU5 was comparable, while differences in regional prevalence were found to be pronounced in France and The United Kingdom. Regional differences were also found in Japan, with the majority of cases in Chubu and Kanto regions., Conclusion: This new methodology for obtaining often missing regional-level epidemiological data reveals dramatic variations in NTM-PD annual prevalence and helps pinpoint areas that may merit special preventative and treatment focus., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Lipopolysaccharide (LPS), a component of the outer membrane of gram-negative bacteria, disrupts the alveolar-capillary barrier, triggering pulmonary vascular leak thus inducing acute lung injury (ALI). Extracellular purines, adenosine and ATP, protected against ALI induced by purified LPS. In this study, we investigated whether these purines can impact vascular injury in more clinically-relevant E.coli (non-sterile LPS) murine ALI model. Mice were inoculated with live E. coli intratracheally (i.t.) with or without adenosine or a non-hydrolyzable ATP analog, adenosine 5'-(γ-thio)-triphosphate (ATPγS) added intravenously (i.v.). After 24 h of E. coli treatment, we found that injections of either adenosine or ATPγS 15 min prior or adenosine 3 h after E.coli insult significantly attenuated the E.coli-mediated increase in inflammatory responses. Furthermore, adenosine prevented weight loss, tachycardia, and compromised lung function in E. coli-exposed mice. Accordingly, treatment with adenosine or ATPγS increased oxygen saturation and reduced histopathological signs of lung injury in mice exposed to E. coli. Lastly, lung-targeting gene delivery of adenosine or ATPγS downstream effector, myosin phosphatase, significantly attenuated the E. coli-induced compromise of lung function. Collectively, our study has demonstrated that adenosine or ATPγS mitigates E. coli-induced ALI in mice and may be useful as an adjuvant therapy in future pre-clinical studies.

Complicated community-acquired pneumonia in a previously well child is a severe illness characterised by combinations of local complications (eg, parapneumonic effusion, empyema, necrotising pneumonia, and lung abscess) and systemic complications (eg, bacteraemia, metastatic infection, multiorgan failure, acute respiratory distress syndrome, disseminated intravascular coagulation, and, rarely, death). Complicated community-acquired pneumonia should be suspected in any child with pneumonia not responding to appropriate antibiotic treatment within 48-72 h. Common causative organisms are Streptococcus pneumoniae and Staphylococcus aureus. Patients have initial imaging with chest radiography and ultrasound, which can also be used to assess the lung parenchyma, to identify pleural fluid; CT scanning is not usually indicated. Complicated pneumonia is treated with a prolonged course of intravenous antibiotics, and then oral antibiotics. The initial choice of antibiotic is guided by local microbiological knowledge and by subsequent positive cultures and molecular testing, including on pleural fluid if a drainage procedure is done. Information from pleural space imaging and drainage should guide the decision on whether to administer intrapleural fibrinolytics. Most patients are treated by drainage and more extensive surgery is rarely needed; in any event, in low-income and middle-income countries, resources for extensive surgeries are scarce. The clinical course of complicated community-acquired pneumonia can be prolonged, especially when patients have necrotising pneumonia, but complete recovery is the usual outcome., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Klebsiella ( K .) pneumoniae is a common cause of pneumonia-derived sepsis in human and is associated with high morbidity and mortality. The microbiota promotes and maintains host immune homeostasis during bacterial infections. However, the mechanisms by which the gut microbiota affects immune responses in the lung still remain poorly understood. Here, we performed cecal metabolomics sequencing and fecal 16s rRNA sequencing in K. pneumoniae -infected mice and uninfected controls and showed that K. pneumoniae infection led to profound alterations in the gut microbiome and thus the cecal metabolome. We observed that the levels of Lactobacillus reuteri and Bifidobacterium pseudolongum were significantly decreased in K. pneumoniae -infected mice. Spearman correlation analysis showed that alterations in the richness and composition of the gut microbiota were associated with profound changes in host metabolite concentrations. Further, short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, were detected in cecal contents and serum by gas chromatography-mass spectrometry (GC-MS). We observed that the concentrations of these three SCFAs were all lower in the infected groups than in the untreated controls. Lastly, oral supplementation with these three SCFAs reduced susceptibility to K. pneumoniae infections, as indicated by lower bacterial burdens in the lung and higher survival rates. Our data highlight the protective roles of gut microbiota and certain metabolites in K. pneumoniae -pneumonia and suggests that it is possible to intervene in this bacterial pneumonia by targeting the gut microbiota., (Copyright © 2020 Wu, Xu, Su, Li, Lv, Liu, Gao, Lan and Li.)

Objective: To study the bacterial pathogen, the optimal plan of antibacterial drugs and the prognostic factors in patients with liver cirrhosis combined with bacterial pneumonia. Methods: Data of 324 cases with liver cirrhosis from the Department of Traditional and Western Medical Hepatology, the Third Hospital of Hebei Medical University were collected, including 217 cases of bacterial pneumonia. Baseline characteristics of the patients, factors affecting the efficacy of antibacterial treatment and prognosis were compared and analyzed. Logistic regression analysis was used to screen and predict the antibacterial efficacy indicators and a prediction model was established. Receiver operating characteristic curve was used to evaluate the value of the established model and Child-Turcortte-Pugh, model for end-stage liver disease, and model for end-stage liver disease combined with serum sodium concentration predict the therapeutic efficacy. Results: Chronic HBV and HCV infections were the main causes of cirrhosis, followed by cryptogenic cirrhosis and alcoholic cirrhosis. Diabetes, cardio-cerebrovascular and chronic obstructive pulmonary disease were susceptible factors for bacterial pneumonia. As infection occurred, the ratio of neutrophils to lymphocytes, serum C-reactive protein, procalcitonin, alanine aminotransferase, and total bilirubin levels had increased significantly. The results of pathogenic analysis showed that the top three pathogenic bacteria were Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus aureus. The resistance rate of Klebsiella pneumoniae to ceftriaxone was 50.0%, and that of ceftazidime, cefepime, and cefoperazone sulbactam were 27.8%. Imipenem and piperacillin tazobactam containing β-lactamase inhibitors were the most effective antibacterial therapies. Regression analysis showed that age, procalcitonin, and albumin was significantly correlated with antibacterial effects. The PAA model was established and had predicted the efficacy of Child-Turcortte-Pugh, model for end-stage liver disease, and model for end-stage liver disease combined with serum sodium. The specificity and sensitivity of the PAA was confirmed to be 94.12% and 93.62%, which was significantly higher than other models. Conclusion: The main common pathogenic bacterium of cirrhosis combined with bacterial pneumonia is Klebsiella pneumonia (G-bacilli). In addition, gram positive cocci (Staphylococcus aureus) and other are also visible. The elderly, diabetics and patients using hormones are prone to secondary fungal infections. Age, procalcitonin and serum albumin can accurately predict the antibacterial effect, guide clinical treatment and judge the prognosis of the established PAA model.

Background: Pneumonia is the leading cause of death among children and young people (CYP) with severe cerebral palsy (CP). Only a few studies used nomogram for assessing risk factors and the probability of pneumonia. Therefore, we aimed to identify risk factors and devise a nomogram for identifying the probability of severe pneumonia in CYP with severe CP., Methods: This retrospective nationwide population-based cohort study examined CYP with newly diagnosed severe CP before 18 years old between January 1st, 1997 and December 31st, 2013 and followed them up through December 31st, 2013. The primary endpoint was defined as the occurrence of severe pneumonia with ≥ 5 days of hospitalization. Logistic regression analysis was used for determining demographic factors and comorbidities associated with severe pneumonia. These factors were assigned integer points to create a scoring system to identify children at high risk for severe pneumonia., Results: Among 6,356 CYP with newly diagnosed severe CP, 2,135 (33.59%) had severe pneumonia. Multivariable logistic regression analysis revealed that seven independent predictive factors, namely age <3 years, male sex, and comorbidities of pressure ulcer, gastroesophageal reflux, asthma, seizures, and perinatal complications. A nomogram was devised by employing these seven significant predictive factors. The prediction model presented favorable discrimination performance., Conclusions: The nomogram revealed that age, male sex, history of pressure ulcer, gastroesophageal reflux, asthma, seizures, and perinatal complications were potential risk factors for severe pneumonia among CYP with severe CP., Competing Interests: The authors have declared that no competing interests exist.

Methemoglobinemia is a rare disorder of the blood in which there is an increase in methemoglobin, which occurs when hemoglobin is present in the oxidized form. Methemoglobin impairs hemoglobin's ability to transport oxygen, produces functional anemia, and leads to tissue hypoxia. We report the successful management of a case of refractory hypoxia due to acutely acquired methemoglobinemia in a patient undergoing treatment for coronavirus disease 2019 (COVID-19) pneumonia. The cause of methemoglobinemia in this patient remains unknown. Hypoxia and methemoglobinemia did not respond to methylene blue and required administration of packed red blood cell transfusions.