Severe Human Parainfluenza Virus Community- and Healthcare-Acquired Pneumonia in Adults at Tertiary Hospital, Seoul, South Korea, 2010-2019.

The characteristics of severe human parainfluenza virus (HPIV)-associated pneumonia in adults have not been well evaluated. We investigated epidemiologic and clinical characteristics of 143 patients with severe HPIV-associated pneumonia during 2010-2019. HPIV was the most common cause (25.2%) of severe virus-associated hospital-acquired pneumonia and the third most common cause (15.7%) of severe virus-associated community-acquired pneumonia. Hematologic malignancy (35.0%), diabetes mellitus (23.8%), and structural lung disease (21.0%) were common underlying conditions. Co-infections occurred in 54.5% of patients admitted to an intensive care unit. The 90-day mortality rate for HPIV-associated pneumonia was comparable to that for severe influenza virus-associated pneumonia (55.2% vs. 48.4%; p = 0.22). Ribavirin treatment was not associated with lower mortality rates. Fungal co-infections were associated with 82.4% of deaths. Clinicians should consider the possibility of pathogenic co-infections in patients with HPIV-associated pneumonia. Contact precautions and environmental cleaning are crucial to prevent HPIV transmission in hospital settings.

Whole blood transcriptome signature predicts severe forms of COVID-19: Results from the COVIDeF cohort study.

COVID-19 is associated with heterogeneous outcome. Early identification of a severe progression of the disease is essential to properly manage the patients and improve their outcome. Biomarkers reflecting an increased inflammatory response, as well as individual features including advanced age, male gender, and pre-existing comorbidities, are risk factors of severe COVID-19. Yet, these features show limited accuracy for outcome prediction. The aim was to evaluate the prognostic value of whole blood transcriptome at an early stage of the disease. Blood transcriptome of patients with mild pneumonia was profiled. Patients with subsequent severe COVID-19 were compared to those with favourable outcome, and a molecular predictor based on gene expression was built. Unsupervised classification discriminated patients who would later develop a COVID-19-related severe pneumonia. The corresponding gene expression signature reflected the immune response to the viral infection dominated by a prominent type I interferon, with IFI27 among the most over-expressed genes. A 48-genes transcriptome signature predicting the risk of severe COVID-19 was built on a training cohort, then validated on an external independent cohort, showing an accuracy of 81% for predicting severe outcome. These results identify an early transcriptome signature of severe COVID-19 pneumonia, with a possible relevance to improve COVID-19 patient management.

Drugs targeting CMPK2 inhibit pyroptosis to alleviate severe pneumonia caused by multiple respiratory viruses.

Severe pneumonia caused by respiratory viruses has become a major threat to humans, especially with the SARS-CoV-2 outbreak and epidemic. The aim of this study was to investigate the universal molecular mechanism of severe pneumonia induced by multiple respiratory viruses and to search for therapeutic strategies targeting this universal molecular mechanism. The common differential genes of four respiratory viruses, including respiratory syncytial virus (RSV), rhinovirus, influenza, and SARS-CoV-2, were screened by GEO database, and the hub gene was obtained by Sytohubba in Cytoscape. Then, the effect of hub genes on inflammasome and pyrodeath was investigated in the model of RSV infection in vitro and in vivo. Finally, through virtual screening, drugs targeting the hub gene were obtained, which could alleviate severe viral pneumonia in vitro and in vivo. The results showed that CMPK2 is one of the hub genes after infection by four respiratory viruses. CMPK2 activates the inflammasome by activating NLRP3, and promotes the releases of inflammatory factors interleukin (IL)-1ß and IL-18 to induce severe viral pneumonia. Z25 and Z08 can reduce the expression level of CMPK2 mRNA and protein, thereby inhibiting NLRP3 and alleviating the development of severe viral pneumonia. In conclusion, the inflammatory response mediated by CMPK2 is the common molecular mechanism of severe pneumonia induced by viral infection, and Z25 and Z08 can effectively alleviate viral infection and severe pneumonia through this mechanism.

Clinical application of bronchoalveolar lavage fluid metagenomics next-generation sequencing in cancer patients with severe pneumonia.

OBJECTIVE: Metagenomic next-generation sequencing (mNGS), as an emerging technique for pathogen detection, has been widely used in clinic. However, reports on the application of mNGS in cancer patients with severe pneumonia remain limited. This study aims to evaluate the diagnostic performance of bronchoalveolar lavage fluid (BALF) mNGS in cancer patients complicated with severe pneumonia. METHODS: A total of 62 cancer patients with severe pneumonia simultaneously received culture and mNGS of BALF were enrolled in this study. We systematically analyzed the diagnostic significance of BALF mNGS. Subsequently, optimization of anti-infective therapy based on the distribution of pathogens obtained from BALF mNGS was also assessed. RESULTS: For bacteria and fungi, the positive detection rate of mNGS was significantly higher than culture method (91.94% versus 51.61%, P < 0.001), especially for poly-microbial infections (70.97% versus 12.90%, P < 0.001). Compared with the culture method, mNGS exhibited a diagnostic sensitivity of 100% and a specificity of 16.67%, with the positive predictive value (PPV) and negative predictive value (NPV) being 56.14% and 100%, respectively. The agreement rate between these two methods was 59.68%, whereas kappa consensus analysis indicated a poor concordance (kappa = 0.171). After receipt of BALF mNGS results, anti-infective treatment strategies in 39 out of 62 cases (62.90%) were optimized. Moreover, anti-tumor therapy was a high-risk factor for mixed infections (87.18% versus 65.22%, P = 0.04). CONCLUSIONS: The present study showed that cancer patients with severe pneumonia, especially those received anti-tumor therapy, were more likely to have poly-microbial infections. BALF mNGS can provide a rapid and comprehensive pathogen distribution of pulmonary infection, making it a promising technique in clinical practice, especially for optimizing therapeutic strategies for cancer patients.

Validation of risk scores for prediction of severe pneumonia in kidney transplant recipients hospitalized with community-acquired pneumonia.

PURPOSE: Risk scores for community-acquired pneumonia (CAP) are widely used for standardized assessment in immunocompetent patients and to identify patients at risk for severe pneumonia and death. In immunocompromised patients, the prognostic value of pneumonia-specific risk scores seems to be reduced, but evidence is limited. The value of different pneumonia risk scores in kidney transplant recipients (KTR) is not known. METHODS: Therefore, we retrospectively analyzed 310 first CAP episodes after kidney transplantation in 310 KTR. We assessed clinical outcomes and validated eight different risk scores (CRB-65, CURB-65, DS-CRB-65, qSOFA, SOFA, PSI, IDSA/ATS minor criteria, NEWS-2) for the prognosis of severe pneumonia and in-hospital mortality. Risk scores were assessed up to 48 h after admission, but always before an endpoint occurred. Multiple imputation was performed to handle missing values. RESULTS: In total, 16 out of 310 patients (5.2%) died, and 48 (15.5%) developed severe pneumonia. Based on ROC analysis, sequential organ failure assessment (SOFA) and national early warning score 2 (NEWS-2) performed best, predicting severe pneumonia with AUC of 0.823 (0.747-0.880) and 0.784 (0.691-0.855), respectively. CONCLUSION: SOFA and NEWS-2 are best suited to identify KTR at risk for the development of severe CAP. In contrast to immunocompetent patients, CRB-65 should not be used to guide outpatient treatment in KTR, since there is a 7% risk for the development of severe pneumonia even in patients with a score of zero.

Clinical application of targeted next-generation sequencing in severe pneumonia: a retrospective review.

BACKGROUND: The precise identification of the underlying causes of infectious diseases, such as severe pneumonia, is essential, and the development of next-generation sequencing (NGS) has enhanced the effectiveness of pathogen detection. However, there is limited information on the systematic assessment of the clinical use of targeted next-generation sequencing (tNGS) in cases of severe pneumonia. METHODS: A retrospective analysis was conducted on 130 patients with severe pneumonia treated in the ICU from June 2022 to June 2023. The consistency of the results of tNGS, metagenomics next-generation sequencing (mNGS), and culture with the clinical diagnosis was evaluated. Additionally, the results for pathogens detected by tNGS were compared with those of culture, mNGS, and quantitative reverse transcription PCR (RT-qPCR). To evaluate the efficacy of monitoring severe pneumonia, five patients with complicated infections were selected for tNGS microbiological surveillance. The tNGS and culture drug sensitisation results were then compared. RESULTS: The tNGS results for the analysis of the 130 patients showed a concordance rate of over 70% with clinical diagnostic results. The detection of pathogenic microorganisms using tNGS was in agreement with the results of culture, mNGS, and RT-qPCR. Furthermore, the tNGS results for pathogens in the five patients monitored for complicated infections of severe pneumonia were consistent with the culture and imaging test results during treatment. The tNGS drug resistance results were in line with the drug sensitivity results in approximately 65% of the cases. CONCLUSIONS: The application of tNGS highlights its promise and significance in assessing the effectiveness of clinical interventions and providing guidance for anti-infection therapies for severe pneumonia.

Antimicrobial resistance prediction by clinical metagenomics in pediatric severe pneumonia patients.

BACKGROUND: Antimicrobial resistance (AMR) is a major threat to children's health, particularly in respiratory infections. Accurate identification of pathogens and AMR is crucial for targeted antibiotic treatment. Metagenomic next-generation sequencing (mNGS) shows promise in directly detecting microorganisms and resistance genes in clinical samples. However, the accuracy of AMR prediction through mNGS testing needs further investigation for practical clinical decision-making. METHODS: We aimed to evaluate the performance of mNGS in predicting AMR for severe pneumonia in pediatric patients. We conducted a retrospective analysis at a tertiary hospital from May 2022 to May 2023. Simultaneous mNGS and culture were performed on bronchoalveolar lavage fluid samples obtained from pediatric patients with severe pneumonia. By comparing the results of mNGS detection of microorganisms and antibiotic resistance genes with those of culture, sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: mNGS detected bacterial in 71.7% cases (86/120), significantly higher than culture (58/120, 48.3%). Compared to culture, mNGS demonstrated a sensitivity of 96.6% and a specificity of 51.6% in detecting pathogenic microorganisms. Phenotypic susceptibility testing (PST) of 19 antibiotics revealed significant variations in antibiotics resistance rates among different bacteria. Sensitivity prediction of mNGS for carbapenem resistance was higher than penicillins and cephalosporin (67.74% vs. 28.57%, 46.15%), while specificity showed no significant difference (85.71%, 75.00%, 75.00%). mNGS also showed a high sensitivity of 94.74% in predicting carbapenem resistance in Acinetobacter baumannii. CONCLUSIONS: mNGS exhibits variable predictive performance among different pathogens and antibiotics, indicating its potential as a supplementary tool to conventional PST. However, mNGS currently cannot replace conventional PST.

Time to recovery and its predictors among under-five children admitted with severe pneumonia in East Wallaga Zone public hospitals, western Ethiopia, 2023; a retrospective cohort study.

BACKGROUND: Globally, pneumonia is one of the leading causes of morbidity and mortality as well as hospitalization burden for under-five children. Despite significant initiatives implemented to reduce morbidity and mortality from pneumonia in under-five children, little is known regarding the time to recovery and its predictors among under-five children admitted with severe pneumonia in Ethiopia. Hence, this study intended to estimate the median time to recovery and its predictors among under-five children admitted with severe pneumonia in East Wallaga zone public hospitals, western Ethiopia; 2023. METHODS: An institution-based retrospective cohort study was conducted among 383 under-five children who were admitted with severe pneumonia in East Wallaga zone public hospitals from January 2017 to December 2022. A systematic sampling method was used to select eligible medical records. EpiData Version 4.6 was used to enter the data and analyzed using STATA Version 17.0. Cox-proportional hazard assumption test and model fitness were checked. Variables with P-value ˂ 0.25 at bivariable Cox regression analysis were selected for the multivariable Cox proportional model. A multivariable Cox regression model with 95% CI and Adjusted Hazard Ratio (AHR) was used to identify a significant predictor of time to recovery from severe pneumonia at a P-value < 0.05. RESULTS: At the end of the follow-up, 356 observations were developed an event (recovered) with the median time to recovery of 4 days with IQR of 3-5 days. The overall incidence rate of recovery was 22.26 per 100 (95% CI: 20.07-24.70) person-days observations. Being rural residency (AHR: 0.75, 95% CI: 0.60-0.93), late presenters for seeking care (AHR = 0.70, 95% CI: 0.53-0.93), presence of danger sign at admission (AHR = 1.46, 95% CI: 1.15-1.83), and presence of comorbidity (AHR = 1.63, 95% CI, 1.31-2.04) were found to have a statistically significant association with prolonged recovery time. CONCLUSION: The median time to recovery from severe pneumonia was long, and factors such as Residence, co-morbidity, presence of danger signs, and duration prior to seeking care were statistically significant predictors of recovery time from severe pneumonia. Hence, due attention has to be given to increasing the community's health-seeking behavior to visit health facility early and especial attention should be given for children with danger signs and comorbidity.

The Association between Anemia and Mortality of Severe Pneumonia COVID-19 Patients in the High Care Unit of a Tertiary Hospital in Jakarta.

BACKGROUND: Numerous studies explored the association between anemia and mortality in patients with severe pneumonia due to COVID-19. However, the findings were inconsistent. Therefore, this study was conducted to investigate the association between anemia at HCU admission and in-hospital mortality in severe pneumonia COVID-19 patients. METHODS: This retrospective cohort study obtained data on 110 COVID-19 patients with severe pneumonia who were admitted to the HCU between January, 1st 2021, and May 31st, 2021. Patients were categorized as anemic and non-anemic based on the World Health Organization (WHO) guidelines. The demographic and clinical characteristics of the subjects were described. The Chi-squared test was carried out followed by a logistic regression test to determine the association of anemia and mortality. RESULTS: Anemia was observed in 31% of 110 patients with severe pneumonia COVID-19. The source population consisted of 60.9% men and 39.1% women with a median age of 58 years. The most prevalent comorbidity was hypertension (38.2%), followed by diabetes mellitus (27.2%), renal diseases (19.1%) and heart diseases (10%). TAnemia on HCU admission was associated with in-hospital mortality in patients with severe pneumonia COVID-19 (RR: 2.794, 95% CI 1.470-5.312). After adjusting comorbidities as confounding factors, anemia was independently associated with mortality (RR: 2.204, 95% CI: 1.124-4.323, P < 0.021). The result also showed anemic patients had longer lengths of stay and higher levels of D-dimer than non-anemic patients. The median duration length of stay among the anemic and non-anemic was 16 (11-22) and 13 (9-17) days, respectively. The median D-dimer among the anemic and non-anemic was 2220 µg/ml and 1010 µg/ml, respectively. CONCLUSION: There is a significant association between anemia at HCU admission and mortality in patients with severe pneumonia COVID-19 during hospitalization.

[Meta-analysis and trial sequential analysis of Tanreqing Injection in treatment of severe pneumonia in elderly].

This study aimed to systematically evaluate the effectiveness and safety of Tanreqing Injection in the treatment of severe pneumonia in the elderly. Eighteen randomized controlled trials(RCTs) involving 1 457 elderly patients with severe pneumonia were included in the study after conducting searches in both Chinese and English databases as well as clinical trial registration platforms. The quality of the included studies was assessed using the Cochrane risk of bias assessment tool. Meta-analysis were conducted using RevMan 5.4 and Stata 17 software, and trial sequential analysis(TSA) was performed using TSA 0.9.5.10 beta software. Meta-analysis results showed that compared with conventional western medicine treatment, Tanreqing Injection + conventional western medical significantly improved the clinical effectiveness in elderly patients with severe pneumonia(RR=1.26, 95%CI[1.20, 1.32], P<0.000 01), arterial oxygen partial pressure(SMD=6.23, 95%CI[3.29, 9.18], P<0.000 1), oxygenation index(SMD=11.72, 95%CI[4.41, 19.04], P=0.002), reduce procalcitonin(SMD=-6.16, 95%CI[-8.10,-4.21], P<0.000 01), C-reactive protein(SMD=-8.50, 95%CI[-11.05,-5.96], P<0.000 01), white blood cell count(SMD=-4.56, 95%CI[-5.73,-3.39], P<0.000 01), and shortened the duration of fever(SMD=-3.12, 95%CI[-4.61,-1.63], P<0.000 1), cough(SMD=-4.84, 95%CI[-6.90,-2.79], P<0.000 01), lung rales(SMD=-0.99, 95%CI[-1.54,-0.44], P=0.000 4), and mechanical ventilation time(SMD=-3.26, 95%CI[-5.03,-1.50], P=0.000 3), increase CD4~+ T-cell levels(SMD=6.73, 95%CI[5.23, 8.23], P<0.000 01) and CD8~+ T-cell levels(SMD=7.47, 95% CI[5.32, 9.61], P<0.000 01) with no significant adverse reactions. TSA confirmed the stability and reliability of the results related to clinical effectiveness. This study suggests that Tanreqing Injection, as a Chinese medicinal preparation, has a significant therapeutic effect and good safety profile in the treatment of severe pneumonia in elderly patients. Due to the limited quality of the included studies, high-quality RCT is still needed to provide evidence support for the above conclusions.

Knock-down of IGFBP2 ameliorates lung fibrosis and inflammation in rats with severe pneumonia through STAT3 pathway.

OBJECTIVE: To observe the mechanism of IGFBP2 knock-down in improving lung fibrosis and inflammation through STAT3 pathway in rats with severe pneumonia. MATERIALS AND METHODS: First, SP rat model was established. Then rats were divided into the Control group, the SP group, the SP + Lv-vector shRNA group, the SP + Lv-IGFBP2 shRNA group, the SP + Lv-vector group, and the SP + Lv-IGFBP2 group. The mRNA and protein levels of IGFBP2, NOS, CD206 and Arg 1 were detected by RT-qPCR and Western blot. IHC was used to check the positive expression of IGFBP2 and MCP1. A fully automated blood gas analyzer was used to detected PaCO2, CO2 content, PaO2 and SaO2. HE and Masson staining were performed to observe the lung tissue injury and collagen deposition of rats in each group. ELISA assays were used to calculate the levels of inflammatory factors IL-1ß, IL-6, TNF-α, IL-4, and IL-10. Flow cytometry was conducted to acquire the ratio of M1-type AMs and M2-type AMs. RESULTS: Compared with the Control group, IGFBP2, iNOS, CD206, and Arg1 mRNA and protein expression levels, IGFBP2 and MCP1 positive expressions, PaCO2, p-STAT3/STAT3, p-JAK2/JAK2, IL-1ß, IL-6, and TNF-α levels, the number of AMs and neutrophils, the proportion of M1 type AMs and the expressions of α-SMA, Collagen-I, Collagen III, and Fibronectin were significantly increased in SP rats (p < 0.05), while PaCO2, CO2, and SaO2, IL-4 and IL-10 levels, and the proportion of M2 type AMs decreased (p < 0.05). However, the knockdown of IGFBP2 reversed the above index trends. CONCLUSION: Knock-down of IGFBP2 ameliorated lung injury in SP rats, inhibited inflammation and pulmonary fibrosis, and promoted M2-type transformation of AMs by activating the STAT3 pathway.

Association of subpleural ground-glass opacities with respiratory failure and RNAemia in COVID-19.

OBJECTIVES: To examine the radiological patterns specifically associated with hypoxemic respiratory failure in patients with coronavirus disease (COVID-19). METHODS: We enrolled patients with COVID-19 confirmed by qPCR in this prospective observational cohort study. We explored the association of clinical, radiological, and microbiological data with the development of hypoxemic respiratory failure after COVID-19 onset. Semi-quantitative CT scores and dominant CT patterns were retrospectively determined for each patient. The microbiological evaluation included checking the SARS-CoV-2 viral load by qPCR using nasal swab and serum specimens. RESULTS: Of the 214 eligible patients, 75 developed hypoxemic respiratory failure and 139 did not. The CT score was significantly higher in patients who developed hypoxemic respiratory failure than in those did not (median [interquartile range]: 9 [6-14] vs 0 [0-3]; p < 0.001). The dominant CT patterns were subpleural ground-glass opacities (GGOs) extending beyond the segmental area (n = 44); defined as "extended GGOs." Multivariable analysis showed that hypoxemic respiratory failure was significantly associated with extended GGOs (odds ratio [OR] 29.6; 95% confidence interval [CI], 9.3-120; p < 0.001), and a CT score > 4 (OR 12.7; 95% CI, 5.3-33; p < 0.001). The incidence of RNAemia was significantly higher in patients with extended GGOs (58.3%) than in those without any pulmonary lesion (14.7%; p < 0.001). CONCLUSIONS: Extended GGOs along the subpleural area were strongly associated with hypoxemia and viremia in patients with COVID-19. KEY POINTS: • Extended ground-glass opacities (GGOs) along the subpleural area and a CT score > 4, in the early phase of COVID-19, were independently associated with the development of hypoxemic respiratory failure. • The absence of pulmonary lesions on CT in the early phase of COVID-19 was associated with a lower risk of developing hypoxemic respiratory failure. • Compared to patients with other CT findings, the extended GGOs and a higher CT score were also associated with a higher incidence of RNAemia.

Comparison of endotracheal aspirate and bronchoalveolar lavage fluid metagenomic next-generation sequencing in severe pneumonia: a nested, matched case-control study.

OBJECTIVES: To compare clinical outcomes in patients with severe pneumonia according to the diagnostic strategy used. METHODS: In this retrospective, nested, case-control study, patients with severe pneumonia who had undergone endotracheal aspirate (ETA) metagenomic next-generation sequencing of (mNGS) testing (n = 53) were matched at a ratio of 1 to 2 (n = 106) by sex, age, underlying diseases, immune status, disease severity scores, and type of pneumonia with patients who had undergone bronchoalveolar lavage fluid (BALF) mNGS. The microbiological characteristics and patient's prognosis of the two groups were compared. RESULTS: An overall comparison between the two groups showed no significant differences in bacterial, fungal, viral, or mixed infections. However, subgroup analysis of 18 patients who received paired ETA and BALF mNGS showed a complete agreement rate for the two specimens of 33.3%. There were more cases for whom targeted treatment was initiated (36.79% vs. 22.64%; P = 0.043) and fewer cases who received no clinical benefit after mNGS (5.66% vs. 15.09%; P = 0.048) in the BALF group. The pneumonia improvement rate in the BALF group was significantly higher than in the ETA group (73.58% vs. 87.74%, P = 0.024). However, there were no significant differences in ICU mortality or 28-day mortality. CONCLUSIONS: We do not recommend using ETA mNGS as the first-choice method for analyzing airway pathogenic specimens from severe pneumonia patients.

Chlamydia psittaci Pneumonia in a patient with motor neuron disease: a case report.

BACKGROUND: Motor neuron disease (MND) is a fatal neurodegenerative disorder that leads to progressive loss of motor neurons. Chlamydia psittaci (C. psittaci) is a rare etiology of community-acquired pneumonia characterized primarily by respiratory distress. We reported a case of C. psittaci pneumonia complicated with motor neuron disease (MND). CASE PRESENTATION: A 74-year-old male was referred to the Shaoxing Second Hospital at January, 2022 complaining of fever and fatigue for 2 days. The patient was diagnosed of MND with flail arm syndrome 1 year ago. The metagenomic next-generation sequencing (mNGS) of sputum obtained through bedside fiberoptic bronchoscopy showed C. psittaci infection. Then doxycycline was administrated and bedside fiberoptic bronchoscopy was performed to assist with sputum excretion. Computed Tomography (CT) and fiberoptic bronchoscopy revealed a significant decrease in sputum production. On day 24 after admission, the patient was discharged with slight dyspnea, limited exercise tolerance. One month later after discharge, the patient reported normal respiratory function, and chest CT showed significant absorption of sputum. CONCLUSIONS: The mNGS combined with bedside fiberoptic bronchoscopy could timely detect C. psittaci infection. Bedside fiberoptic bronchoscopy along with antibiotic therapy may be effective for C. psittaci treatment.

Inhaled amikacin for pneumonia treatment and dissemination prevention: an experimental model of severe monolateral Pseudomonas aeruginosa pneumonia.

BACKGROUND: Pseudomonas aeruginosa pneumonia is commonly treated with systemic antibiotics to ensure adequate treatment of multidrug resistant (MDR) bacteria. However, intravenous (IV) antibiotics often achieve suboptimal pulmonary concentrations. We therefore aimed to evaluate the effect of inhaled amikacin (AMK) plus IV meropenem (MEM) on bactericidal efficacy in a swine model of monolateral MDR P. aeruginosa pneumonia. METHODS: We ventilated 18 pigs with monolateral MDR P. aeruginosa pneumonia for up to 102 h. At 24 h after the bacterial challenge, the animals were randomized to receive 72 h of treatment with either inhaled saline (control), IV MEM only, or IV-MEM plus inhaled AMK (MEM + AMK). We dosed IV MEM at 25 mg/kg every 8 h and inhaled AMK at 400 mg every 12 h. The primary outcomes were the P. aeruginosa burden and histopathological injury in lung tissue. Secondary outcomes included the P. aeruginosa burden in tracheal secretions and bronchoalveolar lavage fluid, the development of antibiotic resistance, the antibiotic distribution, and the levels of inflammatory markers. RESULTS: The median (25-75th percentile) P. aeruginosa lung burden for animals in the control, MEM only, and MEM + AMK groups was 2.91 (1.75-5.69), 0.72 (0.12-3.35), and 0.90 (0-4.55) log10 CFU/g (p = 0.009). Inhaled therapy had no effect on preventing dissemination compared to systemic monotherapy, but it did have significantly higher bactericidal efficacy in tracheal secretions only. Remarkably, the minimum inhibitory concentration of MEM increased to > 32 mg/L after 72-h exposure to monotherapy in 83% of animals, while the addition of AMK prevented this increase (p = 0.037). Adjunctive therapy also slightly affected interleukin-1ß downregulation. Despite finding high AMK concentrations in pulmonary samples, we found no paired differences in the epithelial lining fluid concentration between infected and non-infected lungs. Finally, a non-significant trend was observed for higher amikacin penetration in low-affected lung areas. CONCLUSIONS: In a swine model of monolateral MDR P. aeruginosa pneumonia, resistant to the inhaled AMK and susceptible to the IV antibiotic, the use of AMK as an adjuvant treatment offered no benefits for either the colonization of pulmonary tissue or the prevention of pathogen dissemination. However, inhaled AMK improved bacterial eradication in the proximal airways and hindered antibiotic resistance.

Impact of influenza virus infection on lung microbiome in adults with severe pneumonia.

BACKGROUND: Bacterial and viral infections are commonly implicated in the development of pneumonia. We aimed to compare the diversity and composition of lung bacteria among severe pneumonia patients who were influenza virus positive (IFVP) and influenza virus negative (IFVN). METHODS: Bronchoalveolar lavage fluid specimens were procured from patients diagnosed with severe pneumonia to investigate the microbiome utilizing 16S-rDNA sequencing. The alpha diversity of the microbiome was evaluated employing Chao1, Shannon, and Simpson indexes, while the beta diversity was assessed using principal component analysis and principal coordinate analysis. Linear discriminant analysis effect size (LEfSe) was employed to determine the taxonomic differences between the IFVP and IFVN groups. RESULTS: A total of 84 patients with 42 in the IFVP group and 42 in the IFVN group were enrolled. Slightly higher indexes of Shannon and Simpson were observed in the IFVP group without statistically significant difference. The dominant bacterial genera were Streptococcus, Klebsiella, Escherichia-Shigella in the IFVN group and Acinetobacter, Streptococcus, Staphylococcus in the IFVP group. Streptococcus pneumoniae and Acinetobacter baumannii were the most abundant species in the IFVN and IFVP groups, respectively. LEfSe analysis indicated a greater abundance of Klebsiella in the IFVN group. CONCLUSIONS: Individuals with severe pneumonia infected with IFV exhibit heightened susceptibility to certain bacteria, especially Acinetobacter baumannii, and the underlying mechanism of the interaction between IFV and Acinetobacter baumannii in the progression of pneumonia needs further investigation.

Diagnostic and prognostic value of deregulated long non-coding RNA RPPH1 in patients with severe community-acquired pneumonia: a retrospective cohort study.

BACKGROUND: Severe community-acquired pneumonia (SCAP) is one of the most common critical and acute diseases in the respiratory and acute medicine department. The expression and significance of lncRNA RPPH1 (RPPH1) in SCAP were assessed aiming to explore a biomarker assisting in the screening and management of SCAP. METHODS: This study is a retrospective study enrolled 97 SCAP patients, 102 mild community-acquired pneumonia (MCAP) patients, and 65 healthy individuals. The serum expression of RPPH1 of study subjects was evaluated using PCR. The diagnostic and prognostic significance of RPPH1 in SCAP was evaluated by ROC and Cox analyses. Meanwhile, the correlation of RPPH1 with patients' clinicopathological features was evaluated by spearman correlation analysis to evaluate its role in assessing disease severity. RESULTS: A significant downregulation of RPPH1 was observed in the serum of SCAP patients compared with MCAP and healthy individuals. RPPH1 was positively correlated with ALB (r = 0.74) and negatively correlated with C-reactive protein (r = -0.69), neutrophil-to-lymphocyte ratio (r = -0.88), procalcitonin (r = -0.74), and neutrophil (r = -0.84) of SCAP patients, which are associated with the development and severity of SCAP. Additionally, reduced RPPH1 was closely associated with the 28-day development-free survival of SCAP patients and served as an adverse prognostic indicator together with procalcitonin. CONCLUSIONS: Downregulated RPPH1 in SCAP could act as a diagnostic biomarker screening SCAP from healthy and MCAP individuals and act as a prognostic biomarker predicting patients' disease conditions and outcomes. The demonstrated significance of RPPH1 in SCAP could assist the clinical antibiotic therapies of SCAP patients.

Etiological and clinical characteristics of severe pneumonia in pediatric intensive care unit (PICU).

OBJECTIVE: To analyze the etiological distribution characteristics of pediatric patients with severe pneumonia admitted to the Pediatric Intensive Care Unit (PICU), in order to provide a reference for the rational use of clinical antimicrobial drugs. METHODS: A retrospective analysis of pediatric patients admitted to PICU with a diagnosis of severe pneumonia from January 2018 to December 2021 was performed and statistical analysis of pathogenic characteristics was performed. RESULTS: A total of 649 pathogens were detected in 515 children, with a positive detection rate of 77.48%. Bacteria were detected at the highest rate (40.52%), followed by viruses (34.35%), atypical pathogens (19.72%) and fungal (4.31%). Gram-positive infections were dominated by Staphylococcus aureus (39.56%) and Streptococcus pneumoniae (32.97%), and Gram-negative infections were dominated by Acinetobacter Bahmani (16.28%) and Haemophilus influenzae (15.12%), followed by Klebsiella pneumoniae (13.95%) and Pseudomonas aeruginosa (12.21%). Viral infections were dominated by respiratory syncytial virus (25.65%) and EB virus (20.43%), fungal infections were dominated by Candida albicans (50.0%). The proportion of children infected with single pathogen (49.62%) was comparable to that of those with mixed infections (50.38%). There were statistically significant differences in the distribution of children with single pathogen infection by gender (P < 0.05). The age distribution of children with single bacterial, single viral and single fungal infections was statistically different (P < 0.05). There was no significant difference in the distribution of onset season in children with single pathogen infections (P > 0.05), but the number of children with single viral infections was significantly higher in winter and spring than that in summer and autumn, and the difference was statistically significant (P < 0.05). A mixture of 2 pathogens (77.61%) accounted for the majority of mixed infections, there were statistical differences in the distribution of bacterial + viral infection in terms of gender, age, and onset season (P < 0.05), children with viral + mycoplasma infection in terms of gender and age (P < 0.05), and children with viral + fungal infection in terms of gender (P < 0.05), and children with bacterial + mycoplasma infection in terms of age and onset season (P < 0.05). Among the children infected with 3 pathogens, there were statistically significant differences in the distribution of bacterial + viral + fungal and viral + mycoplasma + fungal infections in terms of gender (P < 0.05), and children with bacterial + viral + mycoplasma infection in terms of age (P < 0.05), while there was no significant difference in the distribution of onset season (P > 0.05). There were no significant differences in the distribution of children infected with 4 pathogens in terms of gender, age and onset season (P > 0.05). CONCLUSION: The pathogens of pediatric patients with severe pneumonia in PICU commonly involves bacteria and viruses. As the age of children grows, the detection rate of bacteria shows a decreasing trend, and the pathogenic spectrum gradually changes from bacteria to mycoplasma and viruses, and the number of mixed infections gradually increase. Rational selection of antimicrobial drugs needs to consider pathogenic characteristics of different age, gender, and onset season in clinical practice.

The effect of low-molecular-weight heparin combined with amikacin on the coagulation function and bacterial clearance in the treatment of patients with severe senile pneumonia.

Objective: To analyze the effect of the combined low-molecular-weight heparin (LMWH) and amikacin treatment on the bacterial clearance and changes in coagulation function in patients with severe pneumonia (SP). Methods: A single-center retrospective observational study was conducted. Medical records of 526 elderly patients with SP admitted to the ICU Department of Shandong Provincial Third Hospital from February, 2018 to December, 2021 were reviewed and 342 patients were identified. The patients were divided into two groups according to the treatment records: the study group (175 patients received LMWH combined with amikacin) and the control group (167 patients received amikacin). Changes in coagulation indexes before and after the treatment, as well as bacterial clearance rate and clinical efficacy after the treatment were compared between the two groups. Results: There was no significant difference in prothrombin time (PT), D-Dimer (D-D), antithrombin III (AT-III) and fibrinogen (FIB) levels between the two groups before the treatment (P>0.05). After the treatment, levels of PT, D-D and FIB in the two groups decreased and the level of AT-III increased(P<0.05). Levels of PT, D-D and FIB in the study group were lower, and the level of AT-III was higher (P<0.05) that n in the control group. Bacterial clearance rate in the study group was (86.19%), higher than that in the control group (72.25%) (P<0.05). The total clinical effective rate of the study group (93.14%) was significantly higher than that of the control group (79.04%) (P<0.05). Conclusions: Combining LMWH with amikacin in the treatment of elderly SP patients can improve the coagulation function and bacterial clearance, can promote the recovery of patients and has a good clinical application value.

Respiratory viruses associated with severe mechanically ventilated pneumonia in children.

The burden of pneumonia, especially that caused by respiratory viruses, is markedly high in the pediatric age group. This study aimed to assess viral agents causing severe pneumonia among mechanically ventilated patients. Nonbronchoscopic bronchoalveolar lavage was performed for pediatric patients having severe pneumonia indicated for mechanical ventilation to be tested with a multiplex PCR immediate diagnosis of their etiologic pathogen. Among the 75 patients recruited, viral agents were detected in 73.4% of cases. Rhinovirus and respiratory syncytial virus (RSV) were the most common viruses detected in 32.1% and 29.5%, respectively. The rate of viral infection showed a clear increased incidence in the winter season. The mortality rate among viral-associated severe pneumonia reached 56.36%. Odds of mortality increased threefolds in presence of comorbid conditions and 10-folds with congenital heart disease. The study demonstrated the neglected importance of rhinovirus besides RSV in causing severe critical pneumonia in the pediatric age.