zithromax and Pneumonia--Ventilator-Associated

Anti-virulence strategies have not been evaluated for the prevention of bacterial infections. Prolonged colonization of intubated patients with Pseudomonas aeruginosa isolates producing high-levels of the quorum sensing (QS)-regulated virulence factor rhamnolipids has been associated with ventilator-associated pneumonia (VAP). In this pathogen, azithromycin reduces QS-regulated virulence. We aimed to assess whether azithromycin could prevent VAP in patients colonized by rhamnolipids producing isolates.. In a randomized, double-blind, multicenter trial, intubated colonized patients received either 300 mg/day azithromycin or placebo. Primary endpoint was the occurrence of P. aeruginosa VAP. We further identified those patients persistently colonized by isolates producing high-levels of rhamnolipids and therefore at the highest risk to develop VAP linked to this QS-dependent virulence factor.. Ninety-two patients were enrolled; 43 azithromycin-treated and 42 placebo patients were eligible for the per-protocol analysis. In the per-protocol population, the occurrence of P. aeruginosa VAP was reduced in the azithromycin group but without reaching statistical significance (4.7 vs. 14.3 % VAP, p = 0.156). QS-dependent virulence of colonizing isolates was similarly low in both study groups, and only five patients in each arm were persistently colonized by high-level rhamnolipids producing isolates. In this high-risk subgroup, the incidence of VAP was reduced fivefold in azithromycin versus placebo patients (1/5 vs. 5/5 VAP, p = 0.048).. There was a trend towards reduced incidence of VAP in colonized azithromycin-treated patients. In addition, azithromycin significantly prevented VAP in those patients at high risk of rhamnolipid-dependent VAP, suggesting that virulence inhibition is a promising anti-microbial strategy.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Double-Blind Method; Female; Glycolipids; Humans; Male; Middle Aged; Pilot Projects; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections; Quorum Sensing; Virulence

Topics: Acinetobacter Infections; Aged; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Azithromycin; Bacteremia; Candidemia; COVID-19 Drug Treatment; Enzyme Inhibitors; Female; Gram-Negative Bacterial Infections; Humans; Hydroxychloroquine; Italy; Klebsiella Infections; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Pneumonia, Ventilator-Associated; Protective Factors; Pseudomonas Infections; Respiration, Artificial; SARS-CoV-2; Staphylococcal Infections; Superinfection; Teicoplanin

Invasive mechanical has been associated with high mortality in COVID-19. Alternative therapy of high flow nasal therapy (HFNT) has been greatly debated around the world for use in COVID-19 pandemic due to concern for increased healthcare worker transmission.This was a retrospective analysis of consecutive patients admitted to Temple University Hospital in Philadelphia, Pennsylvania, from 10 March 2020 to 24 April 2020 with moderate-to-severe respiratory failure treated with HFNT. Primary outcome was prevention of intubation. Of the 445 patients with COVID-19, 104 met our inclusion criteria. The average age was 60.66 (+13.50) years, 49 (47.12 %) were female, 53 (50.96%) were African-American, 23 (22.12%) Hispanic. Forty-three patients (43.43%) were smokers. Saturation to fraction ratio and chest X-ray scores had a statistically significant improvement from day 1 to day 7. 67 of 104 (64.42%) were able to avoid invasive mechanical ventilation in our cohort. Incidence of hospital-associated/ventilator-associated pneumonia was 2.9%. Overall, mortality was 14.44% (n=15) in our cohort with 13 (34.4%) in the progressed to intubation group and 2 (2.9%) in the non-intubation group. Mortality and incidence of pneumonia was statistically higher in the progressed to intubation group. CONCLUSION: HFNT use is associated with a reduction in the rate of invasive mechanical ventilation and overall mortality in patients with COVID-19 infection.

Topics: Adrenal Cortex Hormones; Aged; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Azithromycin; Betacoronavirus; Black or African American; Cannula; Comorbidity; Coronavirus Infections; COVID-19; Diabetes Mellitus; Female; Healthcare-Associated Pneumonia; Heart Diseases; Hispanic or Latino; Humans; Hydroxychloroquine; Hypertension; Hypoxia; Immunoglobulins, Intravenous; Immunologic Factors; Intubation, Intratracheal; Lung Diseases; Male; Middle Aged; Oxygen Inhalation Therapy; Pandemics; Philadelphia; Pneumonia, Ventilator-Associated; Pneumonia, Viral; Pulse Therapy, Drug; Renal Insufficiency, Chronic; Respiratory Insufficiency; Retrospective Studies; SARS-CoV-2; Severity of Illness Index; Smoking; White People

Acinetobacter baumannii is one of the main pathogens that cause ventilator-associated pneumonia (VAP). Hypersecretion of mucin in the airway is associated with the onset of VAP. Furthermore, macrolides are known to accelerate the resolution of VAP. However, this mechanism has not been elucidated. We examined whether macrolides inhibit MUC5AC production that is induced by multidrug-resistant A. baumannii (MDRAB). MUC5AC production in bronchial cells after MDRAB stimulation was analyzed by enzyme-linked immunosorbent assay and quantitative reverse transcription-polymerase chain reaction. For the inhibition study, cells were treated with azithromycin (AZM) or clarithromycin (CAM) simultaneously along with MDRAB stimulation. Western blotting was performed was performed to determine potential rules for signal modules. MDRAB induced MUC5AC production and gene expression. The EGFR-ERK/JNK-NF-κB pathway was involved in MDRAB-induced MUC5AC production. AZM but not CAM inhibited MUC5AC production. AZM suppressed the phosphorylation of ERK/JNK and the nuclear translocation of NF-κB. Our results suggest that the efficacy of macrolides against VAP may be due to the inhibition of mucin production.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Azithromycin; Blotting, Western; Bronchi; Cells, Cultured; Clarithromycin; Drug Resistance, Multiple, Bacterial; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Gene Expression Regulation; Humans; Mucin 5AC; Pneumonia, Ventilator-Associated; Reverse Transcriptase Polymerase Chain Reaction

Acinetobacter baumannii is one of the main pathogens that cause ventilator-associated pneumonia (VAP) and is associated with a high rate of mortality. Little is known about the efficacy of macrolides against A. baumannii. In order to confirm the efficacy of azithromycin (AZM) against VAP caused by multidrug-resistant A. baumannii (MDRAB), we used a mouse model that mimics VAP by placement of a plastic tube in the bronchus. AZM (10 and 100 mg/kg of body weight) was administered subcutaneously every 24 h beginning at 3 h after inoculation. Phosphate-buffered saline was administered as the control. Survival was evaluated over 7 days. At 48 h postinfection, mice were sacrificed and the numbers of viable bacteria in lungs and bronchoalveolar lavage fluid were compared. Histopathological analysis of lung specimens was also performed. The treatment groups displayed significantly longer survival than the control group (P < 0.05). AZM did not have an antimicrobial effect. Histopathological examination of lung specimens indicated that the progression of lung inflammation was prevented in the AZM-treated groups. Furthermore, total cell and neutrophil counts, as well as cytokine levels, in bronchoalveolar lavage fluid were significantly decreased (P < 0.05) in the AZM-treated groups. AZM may have a role for the treatment of VAP with MDRAB because of its anti-inflammatory effects.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Azithromycin; Bacterial Load; Disease Models, Animal; Drug Administration Schedule; Drug Evaluation, Preclinical; Drug Resistance, Multiple, Bacterial; Lung; Male; Mice; Microbial Viability; Pneumonia; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Survival Analysis

Topics: Azithromycin; Female; Glycolipids; Humans; Male; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Pseudomonas Infections