Risk factors for developing ventilator-associated lower respiratory tract infection in patients with severe COVID-19: a multinational, multicentre study, prospective, observational study.

Around one-third of patients diagnosed with COVID-19 develop a severe illness that requires admission to the Intensive Care Unit (ICU). In clinical practice, clinicians have learned that patients admitted to the ICU due to severe COVID-19 frequently develop ventilator-associated lower respiratory tract infections (VA-LRTI). This study aims to describe the clinical characteristics, the factors associated with VA-LRTI, and its impact on clinical outcomes in patients with severe COVID-19. This was a multicentre, observational cohort study conducted in ten countries in Latin America and Europe. We included patients with confirmed rtPCR for SARS-CoV-2 requiring ICU admission and endotracheal intubation. Only patients with a microbiological and clinical diagnosis of VA-LRTI were included. Multivariate Logistic regression analyses and Random Forest were conducted to determine the risk factors for VA-LRTI and its clinical impact in patients with severe COVID-19. In our study cohort of 3287 patients, VA-LRTI was diagnosed in 28.8% [948/3287]. The cumulative incidence of ventilator-associated pneumonia (VAP) was 18.6% [610/3287], followed by ventilator-associated tracheobronchitis (VAT) 10.3% [338/3287]. A total of 1252 bacteria species were isolated. The most frequently isolated pathogens were Pseudomonas aeruginosa (21.2% [266/1252]), followed by Klebsiella pneumoniae (19.1% [239/1252]) and Staphylococcus aureus (15.5% [194/1,252]). The factors independently associated with the development of VA-LRTI were prolonged stay under invasive mechanical ventilation, AKI during ICU stay, and the number of comorbidities. Regarding the clinical impact of VA-LRTI, patients with VAP had an increased risk of hospital mortality (OR [95% CI] of 1.81 [1.40-2.34]), while VAT was not associated with increased hospital mortality (OR [95% CI] of 1.34 [0.98-1.83]). VA-LRTI, often with difficult-to-treat bacteria, is frequent in patients admitted to the ICU due to severe COVID-19 and is associated with worse clinical outcomes, including higher mortality. Identifying risk factors for VA-LRTI might allow the early patient diagnosis to improve clinical outcomes.Trial registration: This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.

How and when to manage respiratory infections out of hospital.

Lower respiratory infections include acute bronchitis, influenza, community-acquired pneumonia, acute exacerbation of COPD and acute exacerbation of bronchiectasis. They are a major cause of death worldwide and often affect the most vulnerable: children, elderly and the impoverished. In this paper, we review the clinical presentation, diagnosis, severity assessment and treatment of adult outpatients with lower respiratory infections. The paper is divided into sections on specific lower respiratory infections, but we also dedicate a section to COVID-19 given the importance of the ongoing pandemic. Lower respiratory infections are heterogeneous entities, carry different risks for adverse events, and require different management strategies. For instance, while patients with acute bronchitis are rarely admitted to hospital and generally do not require antimicrobials, approximately 40% of patients seen for community-acquired pneumonia require admission. Clinicians caring for patients with lower respiratory infections face several challenges, including an increasing population of patients with immunosuppression, potential need for diagnostic tests that may not be readily available, antibiotic resistance and social aspects that place these patients at higher risk. Management principles for patients with lower respiratory infections include knowledge of local surveillance data, strategic use of diagnostic tests according to surveillance data, and judicious use of antimicrobials.

Combined exploration of the mechanism of Sang Xing Decoction in the treatment of smoke-induced acute bronchitis from protein and metabolic levels.

Sang Xing decoction (SXD) is a typical prescription for treating "warm dryness" in traditional Chinese medicine (TCM), which is equivalent to respiratory diseases such as acute bronchitis in modern medicine. However, its mechanism of action remains unclear. In this study, the representative components of SXD were characterized using liquid chromatography-tandem mass spectrometry (LC-MS). The key targets, signaling pathways, and metabolic pathways associated with SXD in the treatment of acute bronchitis were identified via network prediction and metabolomics. A rat model of acute bronchitis was also established using mixed smoke, systematic in vivo experiments such as histopathological analyses, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, immunohistochemistry and western blotting were conducted to evaluate the network prediction results. An in-depth analysis of the targeted quantitative results was performed using the SIMCA software and MetaboAnalyst website. The results revealed that 50 active compounds and 45 key targets were screened and clustered with 20 approved drugs. The NF-κB signaling pathway, oxidative stress, and glutamine metabolism were associated with the therapeutic mechanism of SXD in acute bronchitis. In vivo experiments showed that SXD may maintain the production of inflammatory factors by regulating the PI3K/Akt/NF-κB signaling pathway, improving the metabolism of glutamine and glutamate to reduce oxidative stress, and inhibiting apoptosis. Simultaneously, the possibility of using SXD as an adjuvant drug for COVID-19 treatment was also revealed. This research will lay the foundation for the modern clinical application of SXD and promote the promotion and innovation of TCM.

Operationalising outpatient antimicrobial stewardship to reduce system-wide antibiotics for acute bronchitis.

BACKGROUND: Antibiotics are not recommended for treatment of acute uncomplicated bronchitis (AUB), but are often prescribed (85% of AUB visits within the Veterans Affairs nationally). This quality improvement project aimed to decrease antibiotic prescribing for AUB in community-based outpatient centres from 65% to <32% by April 2020. METHODS: From January to December 2018, community-based outpatient clinics' 6 months' average of prescribed antibiotics for AUB and upper respiratory infections was 63% (667 of 1054) and 64.6% (314 of 486) when reviewing the last 6 months. Seven plan-do-study-act (PDSA) cycles were implemented by an interprofessional antimicrobial stewardship team between January 2019 and March 2020. Balancing measures were a return patient phone call or visit within 4 weeks for the same complaint. Χ2 tests and statistical process control charts using Western Electric rules were used to analyse intervention data. RESULTS: The AUB antibiotic prescribing rate decreased from 64.6% (314 of 486) in the 6 months prior to the intervention to 36.8% (154 of 418) in the final 6 months of the intervention. No change was seen in balancing measures. The largest reduction in antibiotic prescribing was seen after implementation of PDSA 6 in which 14 high prescribers were identified and targeted for individualised reviews of encounters of patients with AUB with an antimicrobial steward. CONCLUSIONS: Operational implementation of successful stewardship interventions is challenging and differs from the traditional implementation study environment. As a nascent outpatient stewardship programme with limited resources and no additional intervention funding, we successfully reduced antibiotic prescribing from 64.6% to 36.8%, a reduction of 43% from baseline. The most success was seen with targeted education of high prescribers.