Impact of the immune response modification by lysophosphatidylcholine in the efficacy of antibiotic therapy of experimental models of peritoneal sepsis and pneumonia by Pseudomonas aeruginosa: LPC therapeutic effect in combined therapy

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.

Effects of Lysophosphatidylcholine on Jejuna Morphology and Its Potential Mechanism

“…Parra-Millan et al reported that LPC could trigger innate and specific humoral-mediated immunity as LPC administration regulated the immune response in the prognosis of ceftazidime-resistant Pseudomonas -induced infections ( 6 ). Moreover, in monocyte-derived dendritic cells, LPC could upregulate the CD86, HLA-DR , and CD40 genes expression ( 6 ).…”

“…Parra-Millan et al reported that LPC could trigger innate and specific humoral-mediated immunity as LPC administration regulated the immune response in the prognosis of ceftazidime-resistant Pseudomonas -induced infections ( 6 ). Moreover, in monocyte-derived dendritic cells, LPC could upregulate the CD86, HLA-DR , and CD40 genes expression ( 6 ). LPC increased the relative weights of bursa and thymus, and improved antibody production titers against Newcastle disease virus and sheep red blood cells in broilers ( 7 ).…”

IgM-enriched immunoglobulin improves colistin efficacy in a pneumonia model by Pseudomonas aeruginosa

“…Other approaches to immunomodulation, different to immunoglobulins, have also been reported. In murine experimental models infected with ceftazidime-resistant P. aeruginosa , a combination of lysophosphatidylcholine—a modulator of the immune system—with ceftazidime and/or imipenem led to a greater decrease in the bacterial concentration in tissues compared with when these antibiotics were used as monotherapies ( Parra-Millán et al, 2020 ). Modulation of the immune system might circumvent antibacterial resistance, leading to an efficacious treatment of these infections ( Chiang et al, 2018 ), does not disrupt microbiota ( Schubert et al, 2015 ), and protects against reinfection ( Quintin et al, 2012 ).…”

Efficacy of Lysophosphatidylcholine as Direct Treatment in Combination with Colistin against Acinetobacter baumannii in Murine Severe Infections Models

“…Of note, LPC preemptive treatment in combination with colistin, tigecycline or imipenem has improved the in vivo antibacterial activity of these antimicrobials in murine experimental peritoneal sepsis and pneumonia by drug-susceptible and MDR A. baumannii [ 8 ]. In the same line, preemptive LPC treatment in combination with ceftazidime has potentiated the in vivo antibacterial activity of ceftazidime in these severe infection models by MDR Pseudomonas aeruginosa [ 9 ]. Recently, Yadav et al reported that LPC in vitro potentiated the effect of a nonbactericidal concentration of polymexin B against the growth of Pseudomonas aeruginosa and Klebsiella pneumoniae [ 10 ].…”