Preprint Article Version 1 This version is not peer-reviewed

Impact of the Immune Response Modification by Lysophosphatidylcholine in the Efficacy of Antibiotic Therapy of Experimental Sepsis and Pneumonia by Pseudomonas aeruginosa

Version 1 : Received: 12 February 2020 / Approved: 13 February 2020 / Online: 13 February 2020 (12:48:49 CET)

How to cite: Parra-Millán, R.; Jiménez-Mejías, M.E.; Ayerbe-Algaba, R.; Domínguez-Herrera, J.; Díaz-Navarro, C.; Pérez del Palacio, J.; Pachón, J.; Smani, Y. Impact of the Immune Response Modification by Lysophosphatidylcholine in the Efficacy of Antibiotic Therapy of Experimental Sepsis and Pneumonia by Pseudomonas aeruginosa. Preprints 2020, 2020020171 (doi: 10.20944/preprints202002.0171.v1). Parra-Millán, R.; Jiménez-Mejías, M.E.; Ayerbe-Algaba, R.; Domínguez-Herrera, J.; Díaz-Navarro, C.; Pérez del Palacio, J.; Pachón, J.; Smani, Y. Impact of the Immune Response Modification by Lysophosphatidylcholine in the Efficacy of Antibiotic Therapy of Experimental Sepsis and Pneumonia by Pseudomonas aeruginosa. Preprints 2020, 2020020171 (doi: 10.20944/preprints202002.0171.v1).

Abstract

Immune response stimulation may be an adjuvant to antimicrobial treatment. Here, we evaluated the impact of immune response modification by lysophosphatidylcholine (LPC) combined with imipenem or ceftazidime in murine models of peritoneal sepsis (PS) and pneumonia by Pseudomonas aeruginosa. Imipenem and ceftazidime-susceptible strain (Pa39), and imipenem and ceftazidime-resistant strain (Pa238) were used. Ceftazidime pharmacokinetic and pharmacodynamic parameters were determined. Therapeutic efficacy, and TNF-α and IL-10 levels were determined in murine models of PS and pneumonia by Pa39 and Pa238 treated with LPC, imipenem or ceftazidime, alone or in combination. In PS model, LPC+ceftazidime reduced spleen and lungs Pa238 concentrations (-3.45 and -3.56 log10 CFU/g; P<0.05) than ceftazidime monotherapy, while LPC+imipenem maintained the imipenem efficacy (-1.66 and -1.45 log10 CFU/g; P>0.05). In pneumonia model, LPC+ceftazidime or LPC+imipenem reduced lungs Pa238 concentrations (-2.37 log10 CFU/g, P=0.1, or -1.35 log10 CFU/g, P=0.75). For Pa39 no statistically significant difference has been observed in PS and pneumonia models between combined therapy and monotherapy. Moreover, LPC+imipenem and LPC+ceftazidime decreased and increased significantly TNF-α and IL-10 levels, respectively, in comparison with untreated controls and monotherapies. These results demonstrate the impact of immune response modification by LPC plus antibiotics on the prognosis of infections by ceftazidime-resistant P. aeruginosa.

Subject Areas

Lysophosphatidylcholine; combined antimicrobial treatment; immune response; peritoneal sepsis model; pneumonia model; Pseudomonas aeruginosa

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