Hydrocortisone in Severe Community-Acquired Pneumonia.

BACKGROUND: Whether the antiinflammatory and immunomodulatory effects of glucocorticoids may decrease mortality among patients with severe community-acquired pneumonia is unclear. METHODS: In this phase 3, multicenter, double-blind, randomized, controlled trial, we assigned adults who had been admitted to the intensive care unit (ICU) for severe community-acquired pneumonia to receive intravenous hydrocortisone (200 mg daily for either 4 or 7 days as determined by clinical improvement, followed by tapering for a total of 8 or 14 days) or to receive placebo. All the patients received standard therapy, including antibiotics and supportive care. The primary outcome was death at 28 days. RESULTS: A total of 800 patients had undergone randomization when the trial was stopped after the second planned interim analysis. Data from 795 patients were analyzed. By day 28, death had occurred in 25 of 400 patients (6.2%; 95% confidence interval [CI], 3.9 to 8.6) in the hydrocortisone group and in 47 of 395 patients (11.9%; 95% CI, 8.7 to 15.1) in the placebo group (absolute difference, -5.6 percentage points; 95% CI, -9.6 to -1.7; P = 0.006). Among the patients who were not undergoing mechanical ventilation at baseline, endotracheal intubation was performed in 40 of 222 (18.0%) in the hydrocortisone group and in 65 of 220 (29.5%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.40 to 0.86). Among the patients who were not receiving vasopressors at baseline, such therapy was initiated by day 28 in 55 of 359 (15.3%) of the hydrocortisone group and in 86 of 344 (25.0%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.43 to 0.82). The frequencies of hospital-acquired infections and gastrointestinal bleeding were similar in the two groups; patients in the hydrocortisone group received higher daily doses of insulin during the first week of treatment. CONCLUSIONS: Among patients with severe community-acquired pneumonia being treated in the ICU, those who received hydrocortisone had a lower risk of death by day 28 than those who received placebo. (Funded by the French Ministry of Health; CAPE COD ClinicalTrials.gov number, NCT02517489.).

Systemic corticosteroid use and cardiovascular risk in patients hospitalized for pneumonia.

BACKGROUND: Limited data are available concerning cardiovascular risk with respect to adjunctive corticosteroid use in patients with pneumonia. We aimed to assess the associations between systemic corticosteroid use and the occurrence of major adverse cardiovascular events (MACEs) in patients hospitalized for pneumonia. METHODS: Among study participants enrolled via surveillance for severe acute respiratory infection from July 2016 to January 2017, the clinical course of patients with pneumonia was retrospectively investigated until December 2019. We evaluated the occurrence of in-hospital and after-discharge MACEs according to steroid use during hospitalization. RESULTS: Of the 424 patients hospitalized for pneumonia, 118 (28.8%) received systemic corticosteroids during hospitalization. The most common reason for steroid use was acute exacerbation of chronic lung disease (75.4%). Systemic steroid use was significantly associated with an increased risk of in-hospital MACEs; it was not associated with after-discharge MACEs. The risk of in-hospital MACEs was significantly greater in patients with more comorbidities, more severe pneumonia, and a higher inflammatory marker level; moreover, it was positively associated with duration and cumulative dose of steroid treatment. CONCLUSION: Systemic corticosteroid use was associated with an increased risk of in-hospital MACEs in patients hospitalized for pneumonia.

Bioactive metabolites of Streptomyces misakiensis display broad-spectrum antimicrobial activity against multidrug-resistant bacteria and fungi.

Background: Antimicrobial resistance is a serious threat to public health globally. It is a slower-moving pandemic than COVID-19, so we are fast running out of treatment options. Purpose: Thus, this study was designed to search for an alternative biomaterial with broad-spectrum activity for the treatment of multidrug-resistant (MDR) bacterial and fungal pathogen-related infections. Methods: We isolated Streptomyces species from soil samples and identified the most active strains with antimicrobial activity. The culture filtrates of active species were purified, and the bioactive metabolite extracts were identified by thin-layer chromatography (TLC), preparative high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) spectroscopy, and gas chromatography-mass spectrometry (GC-MS). The minimum inhibitory concentrations (MICs) of the bioactive metabolites against MDR bacteria and fungi were determined using the broth microdilution method. Results: Preliminary screening revealed that Streptomyces misakiensis and S. coeruleorubidus exhibited antimicrobial potential. The MIC50 and MIC90 of S. misakiensis antibacterial bioactive metabolite (ursolic acid methyl ester) and antifungal metabolite (tetradecamethylcycloheptasiloxane) against all tested bacteria and fungi were 0.5 µg/ml and 1 µg/mL, respectively, versus S. coeruleorubidus metabolites: thiocarbamic acid, N,N-dimethyl, S-1,3-diphenyl-2-butenyl ester against bacteria (MIC50: 2 µg/ml and MIC90: 4 µg/mL) and fungi (MIC50: 4 µg/ml and MIC90: 8 µg/mL). Ursolic acid methyl ester was active against ciprofloxacin-resistant strains of Streptococcus pyogenes, S. agalactiae, Escherichia coli, Klebsiella pneumoniae, and Salmonella enterica serovars, colistin-resistant Aeromonas hydrophila and K. pneumoniae, and vancomycin-resistant Staphylococcus aureus. Tetradecamethylcycloheptasiloxane was active against azole- and amphotericin B-resistant Candida albicans, Cryptococcus neoformans, C. gattii, Aspergillus flavus, A. niger, and A. fumigatus. Ursolic acid methyl ester was applied in vivo for treating S. aureus septicemia and K. pneumoniae pneumonia models in mice. In the septicemia model, the ursolic acid methyl ester-treated group had a significant 4.00 and 3.98 log CFU/g decrease (P < 0.05) in liver and spleen tissue compared to the infected, untreated control group. Lung tissue in the pneumonia model showed a 2.20 log CFU/g significant decrease in the ursolic acid methyl ester-treated group in comparison to the control group. The haematological and biochemical markers in the ursolic acid methyl ester-treated group did not change in a statistically significant way. Moreover, no abnormalities were found in the histopathology of the liver, kidneys, lungs, and spleen of ursolic acid methyl ester-treated mice in comparison with the control group. Conclusion: S. misakiensis metabolite extracts are broad-spectrum antimicrobial biomaterials that can be further investigated for the potential against MDR pathogen infections. Hence, it opens up new horizons for exploring alternative drugs for current and reemerging diseases.

Delayed organising pneumonia in an immunocompromised host after a mild COVID-19 infection.

Organising pneumonia after a mild COVID-19 infection has been increasingly reported and poses a diagnostic challenge to physicians especially in immunocompromised patients. We report a patient with a background of lymphoma in remission on rituximab who presented with prolonged and persistent fever after recovering from a mild COVID-19 infection. The initial workup showed bilateral lower zone lung consolidation; however, the infective and autoimmune workup were unremarkable. Subsequently, a bronchoscopy with transbronchial lung biopsy confirmed the diagnosis of organising pneumonia. A tapering glucocorticoid regimen was commenced with prompt resolution of the patient's clinical symptoms, and subsequent resolution of biochemical markers and radiological lung changes 3 months later. This case highlights the importance of early recognition of the diagnosis of organising pneumonia in immunocompromised populations after a mild COVID-19 infection as it shows promising response to glucocorticoid therapy.

Anti-inflammatory actions of Pentosan polysulfate sodium in a mouse model of influenza virus A/PR8/34-induced pulmonary inflammation.

Introduction: There is an unmet medical need for effective anti-inflammatory agents for the treatment of acute and post-acute lung inflammation caused by respiratory viruses. The semi-synthetic polysaccharide, Pentosan polysulfate sodium (PPS), an inhibitor of NF-kB activation, was investigated for its systemic and local anti-inflammatory effects in a mouse model of influenza virus A/PR8/1934 (PR8 strain) mediated infection. Methods: Immunocompetent C57BL/6J mice were infected intranasally with a sublethal dose of PR8 and treated subcutaneously with 3 or 6 mg/kg PPS or vehicle. Disease was monitored and tissues were collected at the acute (8 days post-infection; dpi) or post-acute (21 dpi) phase of disease to assess the effect of PPS on PR8-induced pathology. Results: In the acute phase of PR8 infection, PPS treatment was associated with a reduction in weight loss and improvement in oxygen saturation when compared to vehicle-treated mice. Associated with these clinical improvements, PPS treatment showed a significant retention in the numbers of protective SiglecF+ resident alveolar macrophages, despite uneventful changes in pulmonary leukocyte infiltrates assessed by flow cytometry. PPS treatment in PR8- infected mice showed significant reductions systemically but not locally of the inflammatory molecules, IL-6, IFN-g, TNF-a, IL-12p70 and CCL2. In the post-acute phase of infection, PPS demonstrated a reduction in the pulmonary fibrotic biomarkers, sICAM-1 and complement factor C5b9. Discussion: The systemic and local anti-inflammatory actions of PPS may regulate acute and post-acute pulmonary inflammation and tissue remodeling mediated by PR8 infection, which warrants further investigation.

Top-ten papers in pneumonia (2020-2021).

Despite the fact that the last year has been marked by the SARS-CoV-2 pandemic, there have been many articles published on non-COVID pneumonia. Making the selection has not been easy, having based on those articles that we think can bring us some novelty and help in clinical practice. We have divided the selection into seven sections: patient severity, diagnosis, treatment, ventilation, novelties in the guidelines, fungal infection and organ donation.

Severe community-acquired pneumonia.

Severe community-acquired pneumonia is the most life-threatening form of community-acquired pneumonia, characterised by intensive care unit admission and high morbidity and mortality. In this review article, we cover in depth six aspects of severe community-acquired pneumonia that are still controversial: use of PCR molecular techniques for microbial diagnosis; the role of biomarkers for initial management; duration of treatment, macrolides or quinolones in the initial empirical antibiotic therapy; the use of prediction scores for drug-resistant pathogens to modify initial empiric therapy; the use of noninvasive mechanical ventilation and high-flow nasal oxygen; and the use of corticosteroids as adjunctive therapy in severe community-acquired pneumonia.

Efficacy and safety of Jinhua Qinggan granules in the treatment of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis.

OBJECTIVE: To evaluate, using meta-analysis, the efficacy and safety profile of Jinhua Qinggan granules (JHQG) in the treatment of novel coronavirus pneumonia. METHODS: We screened multiple publication databases (PubMed, Embase, The Cochrane Library, Web of Science, CNKI, WanFang, and VIP), using parameters designed to identify articles detailing randomized controlled trials relating to the treatment of novel coronavirus pneumonia with JHQG. The inclusion period for each search was the point of database inception to November 2022. Each piece of literature identified in our initial screening was independently reviewed by 2 researchers, who extracted the relevant data and evaluated the bias risk associated with the study. The data was split in 2: the control group (containing patients who had received routine treatment or placebo) and the experimental group (containing patients treated with JHQG). The meta-analysis was performed using Revman 5.4 software. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Four articles were selected for this study and combined included a total of 582 patients, which were subdivided into experimental (n = 347) and control (n = 235) groups. The results showed that treatment with JHQG could significantly: enhance the improvement rate of primary symptoms [relative ratio (RR) = 1.26,95% confidence interval (CI) (1.07, 1.49), P = .007] and fever [RR = 1.48, 95% CI (1.07, 2.04), P = .02]; decrease the viral nucleic acid in patients with coronavirus disease 2019 (COVID-19) [RR = 2.04, 95% CI (1.15, 3.62), P = .02] and reduce the progression of pneumonia [RR = 0.34, 95% CI (0.17, 0.67), P = .002]. However, there was no significant difference between the 2 groups with regards to: the improvement rate of cough, nausea and vomiting, fatigue, computed tomography, or frequency of adverse reactions. CONCLUSIONS: Current evidence indicates that JHQG is effective in treating COVID-19, increasing the rate of improvement for fever, increasing the negative rate of viral nucleic acid in patients with COVID-19 and reducing the aggravation rate of pneumonia. These conclusions need to be verified by further rigorous studies, as the existing results were limited by the number and quality of the included studies.

A review of organizing pneumonia.

ABSTRACT: Organizing pneumonia is a clinical and pathological syndrome that describes a lung injury caused by an inflammatory reaction in the alveolar connective tissue. Classified as an interstitial lung disease, it can be secondary to infection, drug toxicity, connective tissue disorders, inhalation injuries (cocaine), organ transplant, or radiotherapy, and also can be idiopathic. Although organizing pneumonia is not a new phenomenon, it has been noted to be a complication of COVID-19, and should be considered in patients who have had COVID-19 and have atypical chest imaging, because treatment includes corticosteroids instead of antimicrobials.

IMPACT OF STATINS ON THE CLINICAL COURSE OF COVID-19-ASSOCIATED PNEUMONIA IN UNVACCINATED PATIENTS WITH ARTERIAL HYPERTENSION.

OBJECTIVE: The aim: To assess the impact of statins on the severity and lethality rate in hypertensive patients with COVID-19-associated pneumonia. PATIENTS AND METHODS: Materials and methods: 106 unvaccinated hypertensive patients were enrolled in the study. 29 (27.4%) patients took statins. RESULTS: Results: Statins were not associated with reduced risks of lethality (relative risk (RR), 0.24; [95%CI, 0.03-1.79], p=0.16), decline in oxygen saturation <92% during the inpatient stay (RR, 0.70 [95%CI, 0.39-1.28], p=0.25) and need for supplemental oxygen (RR, 0.84; [95%CI, 0.51-1.37], p=0.48). There was no significant difference in the median length of in-hospital stay between the patients taking statins (14.0 [10.0-15.0] days) and patients, which didn't take statins (13.0 [9.0-18.0] days) (p=0.76). However, subgroup analysis showed that statins reduced the risk of decline in oxygen saturation <92% in patients aged 65 years and older with body mass index $ 25.0 kg/m2 (RR, 0.33 [95%CI, 0.11-0.92], p=0.03). CONCLUSION: Conclusions: Statins didn't a#ect the severity and lethality rate in hypertensive patients with COVID-19-associated pneumonia. Subgroup analysis showed that statin use was associated with a decrease in morbidity of patients aged 65 years and older with BMI $25.0 kg/m2 hospitalized for COVID-19-associated pneumonia.

Efficacy and safety of AP-Bio®(KalmCold®) in participants with uncomplicated upper respiratory tract viral infection (common cold) - A phase III, double-blind, parallel group, randomized placebo-controlled trial.

INTRODUCTION: Kalmegh (Andrographis paniculata) is commonly used for treating uncomplicated Upper Respiratory Tract Infection (URTI) in complementary and alternative system of medicine. AP-Bio®(KalmCold®) is a standardized extract derived from the leaves of A. paniculata. This study was proposed to evaluate its efficacy using validated scales and objective measures. METHODS: Participants were randomized in a ratio of 1:1:1 to receive either AP-Bio® 200 mg/day, AP-Bio® 400 mg/day or placebo for 7 days. The primary outcome measure was Wisconsin Upper Respiratory Symptom Survey (WURSS-21) score. The secondary outcome measures were nasal mucous weight, nasal muco-ciliary clearance function and Interleukin-8 in nasal wash, as well as safety and tolerability. RESULTS: A total of n = 331 participants were screened and N = 300 participants were enrolled. The absolute WURSS-21 global score [mean (Standard Deviation - SD)] in the AP-Bio® 400 mg group [5.70 (5.31)] was less than the AP-Bio® 200 mg group [5.81 (4.83)] on Day-3. However, it was much higher in the placebo group [9.55 (14.27)]. AP-Bio® 400 mg group (Mean Difference - MD [Standard Error - SE] = -3.85 [1.52]; 95% CI = -6.85, - 0.85; adjusted p = 0.034) and 200 mg group (MD [SE] = -3.74 [1.51]; 95% CI = -6.73, - 0.76; adjusted p = 0.038) had significantly lower score than placebo. Similarly, on Day-3, the change in global score from baseline was significantly better in the AP-Bio® 400 mg group (MD [SE] = -3.91; [1.82] 95% CI = -7.50, - 0.32; adjusted p = 0.038) and AP-Bio® 200 mg group (MD [SE] = -3.84 [1.97]; 95% CI = -7.72, - 0.04; adjusted p = 0.044) in comparison to the placebo group. Nasal mucous weight, tissue paper counts used, and interleukin-8 showed a trend towards AP-Bio® groups having a favourable outcome when compared with placebo but did not reach statistical significance due to a small sample size. None of the study participants complained of any adverse physical symptoms. However, incident eosinophilia was noted in n = 20 participants on day 3. (n = 6 in AP-Bio® 200 mg group, n = 7 in Ap-Bio® 400 mg group and n = 13 in placebo group; p = 0.181). CONCLUSIONS: Participants in both the AP-Bio® dose groups showed positive tendency towards resolution of URTI symptoms when compared with placebo on Day-3 but not on Day-5 and Day-7.

Trial of antibiotic restraint in presumed pneumonia: A Surgical Infection Society multicenter pilot.

BACKGROUND: Pneumonia is the most common intensive care unit-acquired infection in the trauma and emergency general surgery population. Despite guidelines urging rapid antibiotic use, data supporting immediate antibiotic initiation in cases of suspected infection are limited. Our hypothesis was that a protocol of specimen-initiated antibiotic initiation would have similar compliance and outcomes to an immediate initiation protocol. METHODS: We devised a pragmatic cluster-randomized crossover pilot trial. Four surgical and trauma intensive care units were randomized to either an immediate initiation or specimen-initiated antibiotic protocol for intubated patients with suspected pneumonia and bronchoscopically obtained cultures who did not require vasopressors. In the immediate initiation arm, antibiotics were started immediately after the culture regardless of patient status. In the specimen-initiated arm, antibiotics were delayed until objective Gram stain or culture results suggested infection. Each site participated in both arms after a washout period and crossover. Outcomes were protocol compliance, all-cause 30-day mortality, and ventilator-free alive days at 30 days. Standard statistical techniques were applied. RESULTS: A total of 186 patients had 244 total cultures, of which only the first was analyzed. Ninety-three patients (50%) were enrolled in each arm, and 94.6% were trauma patients (84.4% blunt trauma). The median age was 50.5 years, and 21% of the cohort was female. There were no differences in demographics, comorbidities, sequential organ failure assessment, Acute Physiology and Chronic Health Evaluation II, or Injury Severity Scores. Antibiotics were started significantly later in the specimen-initiated arm (0 vs. 9.3 hours; p < 0.0001) with 19.4% avoiding antibiotics completely for that episode. There were no differences in the rate of protocol adherence, 30-day mortality, or ventilator-free alive days at 30 days. CONCLUSION: In this cluster-randomized crossover trial, we found similar compliance rates between immediate and specimen-initiated antibiotic strategies. Specimen-initiated antibiotic protocol in patients with a suspected hospital-acquired pneumonia did not result in worse clinical outcomes compared with immediate initiation. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II.

Treatment of infection and inflammation associated with COVID-19, multi-drug resistant pneumonia and fungal sinusitis by nebulizing a nanosilver solution.

Solutions containing Ag0 nanoclusters, Ag+1, and higher oxidation state silver, generated from nanocrystalline silver dressings, were anti-inflammatory against porcine skin inflammation. The dressings have clinically-demonstrated broad-spectrum antimicrobial activity, suggesting application of nanosilver solutions in treating pulmonary infection. Nanosilver solutions were tested for antimicrobial efficacy; against HSV-1 and SARS-CoV-2; and nebulized in rats with acute pneumonia. Patients with pneumonia (ventilated), fungal sinusitis, burns plus COVID-19, and two non-hospitalized patients with COVID-19 received nebulized nanosilver solution. Nanosilver solutions demonstrated pH-dependent antimicrobial efficacy; reduced infection and inflammation without evidence of lung toxicity in the rat model; and inactivated HSV-1 and SARS-CoV-2. Pneumonia patients had rapidly reduced pulmonary symptoms, recovering pre-illness respiratory function. Fungal sinusitis-related inflammation decreased immediately with infection clearance within 21 days. Non-hospitalized patients with COVID-19 experienced rapid symptom remission. Nanosilver solutions, due to anti-inflammatory, antiviral, and antimicrobial activity, may be effective for treating respiratory inflammation and infections caused by viruses and/or microbes.