Anti-inflammatory activity of lefamulin versus azithromycin and dexamethasone in vivo and in vitro in a lipopolysaccharide-induced lung neutrophilia mouse model

Häfner, Michael; Paukner, Susanne; Wicha, Wolfgang W; Hrvačić, Boška; Cedilak, Matea; Faraho, Ivan; Gelone, Steven P

doi:10.1371/journal.pone.0237659

Cited by 4 publications

(2 citation statements)

References 43 publications

(55 reference statements)

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“…L2880, Sigma, MO, USA) through an endotracheal tube (mouse 20G type, Zhongyanboji, Beijing, China). All rats were randomly assigned to six groups ( n = 12 each): control group (control), ALI model group (ALI), QBH low-dose group (ALI + QBH 1.5 mL/kg), QBH medium-dose group (ALI + QBH 3.0 mL/kg), QBH high-dose group (ALI + QBH 6.0 mL/kg), and dexamethasone-treated group (ALI + DXMS 0.42 mg/kg) [ 24 , 25 ]. Control group rats were given 60 μ L sterile saline through the trachea.…”

Section: Methodsmentioning

confidence: 99%

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Qinbaohong Zhike Oral Liquid Attenuates LPS-Induced Acute Lung Injury in Immature Rats by Inhibiting OLFM4

Zhang

Liu

et al. 2022

Oxidative Medicine and Cellular Longevity

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Acute respiratory infections (ARIs) are a common public safety threat with high morbidity and mortality in pediatric patients worldwide. Qinbaohong Zhike oral liquid (QBH), a marketed traditional Chinese medicine product, has been widely used to cure respiratory diseases. QBH is reported to have antitussive, expectorant, and antiasthmatic properties. However, its treatment effect against ARIs is not elucidated. This study aimed to explore the therapeutic efficacy of QBH in the treatment of ARIs-induced pneumonia. Network pharmacology was used to predict the possible targets of QBH against ARIs. Next, the tracheal lipopolysaccharide (LPS-)-induced acute lung injury (ALI) immature rat model was constructed to evaluate the therapeutic effect of QBH. Tandem mass tag (TMT-)-based quantitative proteomics was then used to screen the in-depth disease targets of QBH. QBH exerted a protective effect against LPS-induced ALI by inhibiting pulmonary pathological damage. QBH also reduced the levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and granulocyte macrophage colony-stimulating factor (GM-CSF) in the serum and IL-1β, IL-6, IL-8, TNF-α, IFN-γ, and GM-CSF in the lung tissue. Based on proteomic data, olfactomedin 4 (OLFM4) related to immunity and inflammation was selected as a potential target. Western blot analysis further confirmed the moderating effect of QBH downregulation on OLFM4 in the lung tissue. Our findings demonstrated that QBH alleviated lung tissue damage and inflammatory reaction via inhibiting OLFM4 expression in LPS-challenged immature rats. Our research indicates that QBH may have therapeutic potential for treating ARIs-related ALI in pediatric patients, which also serves as a candidate target for drug therapy of ALI by intervening OLFM-related signaling pathways.

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Section: Methodsmentioning

confidence: 99%

“…Oxidative Medicine and Cellular Longevity [24,25]. Control group rats were given 60 μL sterile saline through the trachea.…”

Section: Establishment Of Anmentioning

confidence: 99%

Qinbaohong Zhike Oral Liquid Attenuates LPS-Induced Acute Lung Injury in Immature Rats by Inhibiting OLFM4

Zhang

Liu

et al. 2022

Oxidative Medicine and Cellular Longevity

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Safety and Pharmacokinetics Following Oral or Intravenous Lefamulin in Adults With Cystic Fibrosis

Sawicki,

Wicha,

Hiley

et al. 2024

Clinical Therapeutics

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7-Year (2015–21) longitudinal surveillance of lefamulin in vitro activity against bacterial pathogens collected worldwide from patients with respiratory tract infections including pneumonia and characterization of resistance mechanisms

Paukner,

Mendes,

Arends

et al. 2023

Journal of Antimicrobial Chemotherapy

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Objectives Lefamulin (Xenleta™), a pleuromutilin antibiotic, was approved for the oral and IV treatment of community-acquired bacterial pneumonia (CABP) in adults in 2019/2020. This study evaluated the in vitro activity of lefamulin and comparators against 19 584 unique bacterial isolates collected from patients with community-acquired respiratory tract infections and hospitalized patients with pneumonia within the global SENTRY Antimicrobial Surveillance Program during 2015–21. Methods Isolates were susceptibility tested by the CLSI broth microdilution method, and resistance mechanisms were investigated in isolates with elevated lefamulin MICs. Results Lefamulin exhibited potent antibacterial activity against the most common and typical CABP pathogens tested, including Streptococcus pneumoniae [MIC50/90, 0.06/0.25 mg/L; 99.9% susceptible (S)], Staphylococcus aureus (MIC50/90, 0.06/0.12 mg/L; 99.6% S), Haemophilus influenzae (MIC50/90, 0.5/2 mg/L; 99.1% S) and Moraxella catarrhalis (MIC50/90, 0.06/0.12 mg/L; 100.0% S). Potent activity was also observed against the less common pneumonia pathogens: β-haemolytic (MIC50/90 of 0.03/0.06 mg/L) and viridans group Streptococcus spp. (MIC50/90 of 0.06/0.25 mg/L) and Haemophilus parainfluenzae (MIC50/90 of 1/4 mg/L). Lefamulin’s activity was not adversely affected by resistance to macrolides, penicillin, tetracyclines, fluoroquinolones and other resistance phenotypes. Non-susceptibility/resistance to lefamulin was rare and primarily determined by ribosomal protection through vga(A) variants in S. aureus, overexpression of AcrAB-TolC efflux pump in H. influenzae or modifications in L3, L4 and 23SrRNA in Streptococcus spp. Conclusions Based on the coverage of the most important CABP pathogens and lacking cross-resistance, lefamulin may represent a valuable empirical treatment option for ambulatory and hospitalized patients with CABP, particularly in settings with high prevalence of resistance.

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Anti-inflammatory activity of lefamulin versus azithromycin and dexamethasone in vivo and in vitro in a lipopolysaccharide-induced lung neutrophilia mouse model

Cited by 4 publications

References 43 publications

Qinbaohong Zhike Oral Liquid Attenuates LPS-Induced Acute Lung Injury in Immature Rats by Inhibiting OLFM4

Qinbaohong Zhike Oral Liquid Attenuates LPS-Induced Acute Lung Injury in Immature Rats by Inhibiting OLFM4

Safety and Pharmacokinetics Following Oral or Intravenous Lefamulin in Adults With Cystic Fibrosis

7-Year (2015–21) longitudinal surveillance of lefamulin in vitro activity against bacterial pathogens collected worldwide from patients with respiratory tract infections including pneumonia and characterization of resistance mechanisms

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