" a Randomized Pilot Study of the Benefit of Nebulized Amikacin in the Treatment of Gram-negative Bacillus Pneumonia Acquired During Mechanical Ventilation in Patients Receiving Extracorporeal Membrane Veno-arterial Oxygenation (ECMO-VA). "

Pneumonia are the most frequent infectious complication in patients on Extracorporeal Membrane Oxygenation Veno-arterial (ECMO-VA), with a treatment failure rate of around 40%, even though antibiotic therapy is tailored to the germs identified. One hypothesis to explain this particularly high failure rate is the reduced pulmonary blood flow associated with ECMO offloading of the heart. Although there are no data to date on the pulmonary penetration of antibiotics in patients undergoing VA-ECMO, this phenomenon of pulmonary hypoperfusion could contribute to altering the alveolocapillary diffusion of antibiotics, thereby reducing their concentration in the pulmonary parenchyma.
Our hypothesis is that amikacin nebulization could increase bacterial clearance and, ultimately, limit treatment failure or recurrence of gram-negative bacilli (GNB) pneumonia in patients undergoing VA-ECMO.

开始日期2024-11-15

申办/合作机构

Assistance Publique des Hôpitaux de Paris SA

CTRI/2024/07/070677 / Not yet recruiting临床2期

A Phase 1b/2a Open Label Bridging Safety, Pharmacokinetics and Tolerability Studies on Chloroquine Based HREZ Combination Regimens in Adults with Pulmonary Tuberculosis - NIL

开始日期2024-07-24

申办/合作机构

Foundation For Neglected Disease Research

NCT06135350 / Not yet recruiting临床2期IIT

A Randomized, Double-blind, Placebo Controlled Clinical Trial to Study the Efficacy and Safety of the Drug Fluorothiazinone (Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation) in Prophylaxis of Nosocomial Bacterial Infections With Participation of Patients on Mechanical Ventilation

This study is designed to evaluate the clinical and antibacterial efficacy, safety and pharmacokinetics of the drug Fluorothiazinone compared to placebo to prevent nosocomial gram-negative bacterial infections with participation of patients on mechanical ventilation.
The main objectives of this study are:
Evaluation of the clinical and antibacterial efficacy of the drug Fluorothiazinone in combination with standard measures for the prevention of nosocomial infections compared to placebo in combination with standard measures for the prevention of nosocomial infections for the prevention of nosocomial infections caused by bacterial gram-negative flora in patients on mechanical ventilation.
Evaluation of the safety and tolerability of the drug Fluorothiazinone in patients on mechanical ventilation.
Evaluation of the pharmacokinetics (in whole blood) of the drug Fluorothiazinone with a single daily dose of 2400 mg/day.
Researchers will compare results for the treatment and the placebo arms.

开始日期2023-11-01

申办/合作机构

Gamaleya Research Institute Of Epidemiology And Microbiology, Health Ministry Of The Russian Federation

100 项与革兰氏阴性菌肺炎相关的临床结果

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100 项与革兰氏阴性菌肺炎相关的转化医学

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0 项与革兰氏阴性菌肺炎相关的专利（医药）

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项与革兰氏阴性菌肺炎相关的文献（医药）

2024-11-01·Journal of the Formosan Medical Association

Microbial dynamics, risk factors and outcomes of secondary pneumonia in critically ill patients with COVID-19: A multicenter retrospective cohort study

Article

作者: Chung, Kuei-Pin ; Hu, Geng-Ning ; Liu, Wei-Lun ; Ruan, Sheng-Yuan ; Yu, Chong-Jen ; Chien, Jung-Yien ; Chang, Chia-Hao

BACKGROUNDSecondary pneumonia has a significant clinical impact on critically ill patients with COVID-19.AIMConsidering potential geographic variations, this study explores the clinical implications of secondary pneumonia within East Asian populations.METHODSThis multicenter, retrospective cohort study enrolled critical COVID-19 patients requiring intensive care units (ICUs) admission in Taiwan from December 31, 2020, to June 1, 2022.FINDINGSAmong the 187 critical COVID-19 patients, 80 (42.8%) developed secondary pneumonia. The primary causative pathogens were gram-negative bacilli (GNB) (76.8%). Gram-positive cocci and fungi were mainly observed during the initial two weeks of ICU stay. Notably, the incidence of pulmonary aspergillosis was 9.2% during the first week of ICU stay and all Staphylococcus aureus were susceptible to methicillin. Multi-drug resistant organisms (MDROs) were responsible for 28.3% of the cases, exhibiting significantly longer ICU stays compared to the non-MDRO group (median, 27 vs. 14 days, P < 0.001). In the multivariate analysis, Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores were associated with a significantly increased risk of secondary pneumonia. In-hospital mortality was significantly higher in patients with secondary pneumonia than in those without (37.7% vs. 16.7%, P = 0.02) and survival analysis demonstrated gram-negative bacilli-related secondary pneumonia contributed to a worse prognosis.CONCLUSIONSecondary pneumonia in critical COVID-19 patients significantly raised in-hospital mortality and extended hospital and ICU stays. Moreover, the presence of GNB notably predicted an unfavorable prognosis.

2024-03-01·International Immunopharmacology

NLRP3 knockout in mice provided protection against Serratia marcescens-induced acute pneumonia by decreasing PD-L1 and PD-1 expression in macrophages

Article

作者: Ferrandon, Dominique ; Liu, Meng-Ke ; Tang, Juan-Juan ; Chen, Xu-Yang ; Lai, Ke-Fang ; Liu, Zhi-Peng ; Chen, Kan-Yao ; Li, Zi ; Liu, Shu-Yan

Antibiotic-resistant Serratia marcescens (Sm) is known to cause bloodstream infections, pneumonia, etc. The nod-like receptor family, pyrin domain-containing 3 (NLRP3), has been implicated in various lung infections. Yet, its role in Sm-induced pneumonia was not well understood. In our study, we discovered that deletion of Nlrp3 in mice significantly improved Sm-induced survival rates, reduced bacterial loads in the lungs, bronchoalveolar lavage fluid (BALF), and bloodstream, and mitigated the severity of acute lung injury (ALI) compared to wild-type (WT) mice. Mechanistically, we observed that 24 h post-Sm infection, NLRP3 inflammasome activation occurred, leading to gasdermin D NH2-terminal (GSDMD-NT)-induced pyroptosis in macrophages and IL-1β secretion. The NLRP3 or NLRP3 inflammasome influenced the expression PD-L1 and PD-1, as well as the count of PD-L1 or PD-1-expressing macrophages, alveolar macrophages, interstitial macrophages, PD-L1-expressing neutrophils, and the count of macrophage receptors with collagenous structure (MARCO)-expressing macrophages, particularly MARCO⁺ alveolar macrophages. The frequency of MARCO⁺ alveolar macrophages, PD-1 expression, particularly PD-1⁺ interstitial macrophages were negatively or positively correlated with the Sm load, respectively. Additionally, IL-1β levels in BALF correlated with three features of acute lung injury: histologic score, protein concentration and neutrophil count in BALF. Consequently, our findings suggest that Nlrp3 deletion offers protection agaisnt acute Sm pneumonia in mice by inhibiting inflammasome activation and reducing Sm infection-induced PD-L1/PD-1 or MARCO expression, particularly in macrophages. This highlights potential therapeutic targets for Sm and other gram-negative bacteria-induced acute pneumonia.

2023-12-14·Journal of Medicinal Chemistry1区 · 医学

Structure–Interaction Relationship of Polymyxins with Lung Surfactant

1区 · 医学

Article

作者: Zhou, Fanfan ; Zhou, Qi Tony ; Wickremasinghe, Hasini ; Patil, Nitin A ; Li, Jian ; Xiao, Min ; Xu, Yuwen ; Velkov, Tony ; Thompson, Philip E ; Roberts, Kade D ; Jiang, Xukai ; Wang, Lushan

Multidrug-resistant Gram-negative bacteria present an urgent and formidable threat to the global public health. Polymyxins have emerged as a last-resort therapy against these 'superbugs'; however, their efficacy against pulmonary infection is poor. In this study, we integrated chemical biology and molecular dynamics simulations to examine how the alveolar lung surfactant significantly reduces polymyxin antibacterial activity. We discovered that lung surfactant is a phospholipid-based permeability barrier against polymyxins, compromising their efficacy against target bacteria. Next, we unraveled the structure-interaction relationship between polymyxins and lung surfactant, elucidating the thermodynamics that govern the penetration of polymyxins through this critical surfactant layer. Moreover, we developed a novel analog, FADDI-235, which exhibited potent activity against Gram-negative bacteria, both in the presence and absence of lung surfactant. These findings shed new light on the sequestration mechanism of lung surfactant on polymyxins and importantly pave the way for the rational design of new-generation lipopeptide antibiotics to effectively treat Gram-negative bacterial pneumonia.