" 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.

Start Date15 Nov 2024

Sponsor / Collaborator

Assistance Publique des Hôpitaux de Paris SA

CTRI/2024/07/070677

/ Not yet recruitingPhase 2

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

Start Date24 Jul 2024

Sponsor / Collaborator

Foundation For Neglected Disease Research

NCT06135350

/ Not yet recruitingPhase 2IIT

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.

Start Date01 Nov 2023

Sponsor / Collaborator

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

100 Clinical Results associated with Gram Negative Pneumonia

100 Translational Medicine associated with Gram Negative Pneumonia

0 Patents (Medical) associated with Gram Negative Pneumonia

389

Literatures (Medical) associated with Gram Negative Pneumonia

01 Jan 2025·Journal of Ethnopharmacology

How can traditional Chinese medicine enhance the efficacy of antibiotics in the treatment of MRSA-infected pneumonia: An experimental study on the combination of Reyanning mixture (RYN) and linezolid

Article

Author: Zhang, Xin-Yu ; Wang, Xin-Ran ; Lu, Yang ; Dou, Min-Hang ; Chen, Wan-Ling ; Li, Peng-Yue ; Fan, Xiao-Yu ; Du, Shou-Ying ; Huang, Jia-Yi ; Yang, Tian-Zi ; Bai, Jie

ETHNOPHARMACOLOGICAL RELEVANCEThe Reyanning Mixture (RYN) is a Chinese patent medicine widely used in the treatment of respiratory inflammatory diseases in China and has potential in the treatment of bacteria-infected pneumonia.AIM OF THE STUDYThe present study aimed to demonstrate the therapeutic potential of RYN in combination with linezolid for the treatment of MRSA-infected pneumonia and to explore the mechanisms of action and active components.MATERIALS AND METHODSThe pharmacodynamics of RYN alone and in combination with linezolid was investigated in a rat model of MRSA-induced pneumonia. Transcriptomics, ELISA, Western blot and qRT-PCR were used to explore and verify the pharmacological mechanism of the anti-inflammatory effect of RYN. UPLC-MS and molecular docking were used to explore the anti-inflammatory components of RYN for the treatment of MRSA-infected pneumonia.RESULTSIn vivo, RYN reduced lung injury and inflammation in rats with pneumonia. In particular, the combination of RYN and linezolid enhanced the therapeutic effect compared to that of either treatment alone. Further research suggests that the synergistic therapeutic effect of the combination may be related to the inhibition of the inflammatory response by RYN and the enhancement of linezolid inhibition and clearance of MRSA in lung tissues by RYN. RYN plays an anti-inflammatory role in MRSA-infected pneumonia by inhibiting the TLR2/NF-κB/NLRP3 pathway, with 7 active components that may play a dominant role.CONCLUSIONSThese results indicate that RYN may serve as an adjuvant drug to antibiotics for the treatment of MRSA-associated pneumonia. Exploration of its mechanisms and active components is conducive to the clinical application and quality improvement of RYN. More importantly, this study showed that the synergistic therapeutic effect of the combination of traditional Chinese medicine and antibiotics may be a valuable therapeutic strategy.

01 Nov 2024·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

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

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.

01 Nov 2024·Clinical Pharmacokinetics

Impact of Continuous Infusion Meropenem PK/PD Target Attainment on C-Reactive Protein Dynamics in Critically Ill Patients With Documented Gram-Negative Hospital-Acquired or Ventilator-Associated Pneumonia

Article

Author: van Hasselt, Coen ; Siniscalchi, Antonio ; Rinaldi, Matteo ; Cojutti, Pier Giorgio ; Pea, Federico ; Tonetti, Tommaso ; Viale, Pierluigi ; Troisi, Carla

BACKGROUND AND OBJECTIVEPopulation pharmacokinetic/pharmacodynamic (PK/PD) modelling of antibiotics including C-reactive protein (C-RP) dynamics could be helpful in predicting the efficacy of antimicrobials. We developed a PK/PD model for assessing the impact of continuous infusion (CI) meropenem PK/PD target attainment on C-RP dynamics in critically ill patients with documented Gram-negative hospital- (HAP) or ventilator-acquired pneumonia (VAP).METHODSPatients were grouped according to the type of antibiotic treatment received [meropenem monotherapy; meropenem plus empirical anti-MRSA (methicillin-resistant Staphylococcus aureus) therapy; meropenem in combination with another anti-Gram-negative active agent; meropenem plus a targeted anti-MRSA therapy]. A one-compartment population PK model of CI meropenem was developed by including all patients. A full C-RP production inhibition model was developed for fitting the PD data by including only patients receiving meropenem monotherapy or meropenem plus empirical anti-MRSA therapy. Monte Carlo simulations explored the relationship between the type of PK/PD target attainment of CI meropenem, defined as optimal (steady-state plasma concentration [C_ss] to minimum inhibitory concentration [MIC] ratio = 4-8), quasi-optimal (C_ss/MIC = 1-4) and sub-optimal (C_ss/MIC < 1) and the magnitude of C-RP production inhibition over time.RESULTSA total of 64 patients providing 211 meropenem concentrations were included in the PK analysis, whereas 47 patients providing 328 C-RP data were included in the PD model. Simulations showed that optimal PK/PD target attainment was associated with the highest and most rapid C-RP production inhibition (44% and 56% at days 2 and 4, respectively). Conversely, sub-optimal PK/PD target attainment was shown to be almost ineffective (< 5% at day 4 and < 10% at day 10).CONCLUSIONOur PK/PD model predicted that attaining optimal PK/PD target with CI meropenem may grant prompt and intense C-RP decrease among critically ill patients receiving targeted monotherapy for Gram-negative HAP/VAP, thus anticipating efficacy.

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