Linezolid Exerts Greater Bacterial Clearance but No Modification of Host Lung Gene Expression Profiling: A Mouse MRSA Pneumonia Model

Chen, Jiwang; Feng, Gang; Song, Yang; Wardenburg, Juliane Bubeck; Lin, Simon; Inoshima, Ichiro; Otto, Michael; Wunderink, Richard G.

doi:10.1371/journal.pone.0067994

Cited by 5 publications

(9 citation statements)

References 37 publications

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“…Akinnusi et al (2011) did not observe a significant difference in IL-6 or MCP-1 concentration in BALF between LZD- and vancomycin-treated mice. Chen et al (2013) found that LZD therapy significantly decreased BALF protein concentration and levels of cytokines, including IL-6, IL-1β, IFN-γ, and IL-17. With LZD treatment, no abscesses formed, less lung edema occurred, and fewer inflammatory cells were observed compared with the control group.…”

Section: Introductionmentioning

confidence: 92%

Linezolid and Its Immunomodulatory Effect: In Vitro and In Vivo Evidence

et al. 2019

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Recent studies have explored the effects of some antibacterial agents on various aspects of the immune response to infection in addition to their bactericidal effects. As a synthetic oxazolidinone class of antibacterial agent, linezolid (LZD) exhibits activity against a broad range of Gram-positive bacteria. In the present review, we summarized the effects of LZD on the immune response and new approaches that can exploit such interactions for the treatment of bacterial infections. In vitro and pre-clinical evidence demonstrate that LZD suppresses the phagocytic ability, cytokine synthesis, and secretion of immune cells as well as the expressions of immune-related genes at the mRNA level under the stimulation of endotoxin or pathogens. Immunomodulatory effects of LZD can not only reduce the inflammatory damage induced by exaggerated or prolonged release of pro-inflammatory cytokines during infections but can also be applied to alleviate the symptoms of non-infectious inflammatory conditions. Further research is necessary to explore the molecular mechanisms involved and confirm these findings in clinical practice.

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Section: Introductionmentioning

confidence: 92%

Linezolid and Its Immunomodulatory Effect: In Vitro and In Vivo Evidence

et al. 2019

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“…Linezolid inhibits the secretion of proinflammatory mediators resulting in diminished chemotaxis of immune cells into the airways [96][97][98]. In particular, neutrophil migration, which is a hallmark of ARDS, is inhibited [97,99]. Additionally, linezolid restores neutrophil effector mechanisms like phagocytosis and killing of pathogens while it suppresses phagocytosis in macrophages [100,101].…”

Section: Mechanism Of Actionmentioning

confidence: 99%

“…Additionally, linezolid restores neutrophil effector mechanisms like phagocytosis and killing of pathogens while it suppresses phagocytosis in macrophages [100,101]. Neutrophil apoptosis, which in combination with efferocytosis constitutes a crucial step toward ARDS resolution and is usually delayed in ARDS, is increased by linezolid [99].…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Antibiotics as immunomodulators: a potential pharmacologic approach for ARDS treatment

et al. 2021

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First described in the mid-1960s, acute respiratory distress syndrome (ARDS) is a life-threatening form of respiratory failure with an overall mortality rate of approximately 40%. Despite significant advances in the understanding and treatment of ARDS, no substantive pharmacologic therapy has proven to be beneficial, and current management continues to be primarily supportive. Beyond their antibacterial activity, several antibiotics such as macrolides and tetracyclines exert pleiotropic immunomodulatory effects that might be able to rectify the dysregulated inflammatory response present in patients with ARDS. This review aims to provide an overview of preclinical and clinical studies that describe the immunomodulatory effects of antibiotics in ARDS. Moreover, the underlying mechanisms of their immunomodulatory properties will be discussed. Further studies are necessary to investigate their full therapeutic potential and to identify ARDS phenotypes which are most likely to benefit from their immunomodulatory effects.

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“…The first group received colistin (125,000 UI/kg, every 6 h; 500,000 UI/ kg/day) 30 . The second group received linezolid (50 mg/kg, every 12 h) 31 . The third group received the combination of colistin (125,000 UI/kg, every 6 h) and linezolid (50 mg/kg, every 12 h).…”

Section: Study Groupsmentioning

confidence: 99%

In vivo bactericidal effect of colistin–linezolid combination in a murine model of MDR and XDR Acinetobacter baumannii pneumonia

Guo

et al. 2020

Sci Rep

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Recently, paradoxical combinations of colistin with anti-Gram-positive bacterial agents were introduced as a treatment alternative for multidrug-resistant Acinetobacter baumannii (MDRAB) infection. We assessed the therapeutic efficacy of the colistin–linezolid combination regimen in vitro and in a murine model of Acinetobacter baumannii pneumonia. A multidrug-resistant clinical strain (MDRAB31) and an extensively drug-resistant clinical strain (XDRAB78) were used in this study. The survival rates of mice and bacterial counts in lung tissue were used to assess the effects of colistin–linezolid combination. The survival rates of colistin–linezolid combination groups significantly increased compared with colistin groups for MDRAB31 (72% versus 32%, P = 0.03) and for XDRAB78 (92% versus 68%, P = 0.031). The colistin–linezolid combination groups significantly reduced the bacterial counts in lung tissue compared with colistin groups for MDRAB31 and for XDRAB78 (P < 0.05). The colistin–linezolid combination had a bactericidal and synergistic effect compared with colistin alone in time-kill assay and in murine model of pneumonia. Our data demonstrated the synergistic effect of colistin–linezolid combination regimen as a treatment alternative for the severe pulmonary infection caused by MDRAB and XDRAB.

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Linezolid Exerts Greater Bacterial Clearance but No Modification of Host Lung Gene Expression Profiling: A Mouse MRSA Pneumonia Model

Cited by 5 publications

References 37 publications

Linezolid and Its Immunomodulatory Effect: In Vitro and In Vivo Evidence

Linezolid and Its Immunomodulatory Effect: In Vitro and In Vivo Evidence

Antibiotics as immunomodulators: a potential pharmacologic approach for ARDS treatment

In vivo bactericidal effect of colistin–linezolid combination in a murine model of MDR and XDR Acinetobacter baumannii pneumonia

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