A prospective phase IIA multicenter double-blinded randomized placebo-controlled clinical trial evaluating the efficacy and safety of inhaled Tobramycin in patients with ventilator-associated pneumonia (iToVAP).

OBJECTIVE: Treatment of ventilated pneumonia is often unsuccessful, even when patients are treated according to current guidelines. Therefore, we aimed to investigate the efficacy of the adjunctive inhaled Tobramycin in patients with pneumonia caused by Gram-negative pathogens in addition to the standard systemic treatment. DESIGN: Prospective, multicenter, double-blinded, randomized, placebo-controlled clinical trial. SETTING: 26 patients in medical and surgical ICUs. PATIENTS: Patients with ventilator-associated pneumonia caused by Gram-negative pathogens. MEASUREMENT AND MAIN RESULTS: Fourteen patients were assigned to the Tobramycin Inhal group and 12 patients to the control group. The microbiological eradication of the Gram-negative pathogens was significantly higher in the intervention group than in the control group (p < 0.001). The probability of eradication was 100% in the intervention group [95% Confidence Interval: 0.78-1.0] and 25% in the control group [95% CI: 0.09-0.53]. The increased eradication frequency was not associated with increased patient survival. CONCLUSION: Inhaled aerosolized Tobramycin demonstrated clinically meaningful efficacy in patients with Gram-negative ventilator-associated pneumonia. The probability of eradication in the intervention group was 100%. However, the successful eradication was not associated with a reduction in systemic anti-infective therapy, a shorter ICU stay, or even a survival benefit. In the presence of multidrug-resistant Gram-negative pathogens that are sensitive only to colistin and/or aminoglycosides, supplemental inhaled therapy with nebulizers suitable for this purpose should be considered in addition to systemic antibiotic therapy.

Echocardiographic Evaluation of Right Ventricular (RV) Performance over Time in COVID-19-Associated ARDS-A Prospective Observational Study.

(1) Background: To evaluate time-dependent right ventricular (RV) performance in patients with COVID-19-associated acute respiratory distress syndrome (ARDS) undergoing intensive care (ICU) treatment. (2) Methods: This prospective observational study included 21 ICU patients with COVID-19-associated ARDS in a university hospital in 2020 (first wave). Patients were evaluated by transthoracic echocardiography at an early (EE) and late (LE) stage of disease. Echocardiographic parameters describing RV size and function as well as RV size in correlation to PaO2/FiO2 ratio were assessed in survivors and nonsurvivors. (3) Results: Echocardiographic RV parameters were within normal range and not significantly different between EE and LE. Comparing survivors and nonsurvivors revealed no differences in RV performance at EE. Linear regression analysis did not show a correlation between RV size and PaO2/FiO2 ratio over all measurements. Analysing EE and LE separately showed a significant increase in RV size correlated to a lower PaO2/FiO2 ratio at a later stage of COVID-19 ARDS. (4) Conclusion: The present study reveals neither a severe RV dilatation nor an impairment of systolic RV function during the initial course of COVID-19-associated ARDS. A trend towards an increase in RV size in correlation with ARDS severity in the second week after ICU admission was observed.