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

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 induced by Pseudomonas aeruginosa. The imipenem and ceftazidime-susceptible strain (Pa39) and imipenem and ceftazidime-resistant strain (Pa238) were used. Ceftazidime pharmacokinetic and pharmacodynamic parameters were determined. The therapeutic efficacy and TNF-α and IL-10 levels were determined in murine models of PS and pneumonia induced by Pa39 and Pa238 and treated with LPC, imipenem or ceftazidime, alone or in combination. In the PS model, LPC+ceftazidime reduced spleen and lung Pa238 concentrations (−3.45 and −3.56log10CFU/g; P0.05). In the pneumonia model, LPC+ceftazidime or LPC+imipenem reduced the lung Pa238 concentrations (−2.37log10CFU/g, P=0.1, or −1.35log10CFU/g, P=0.75). For Pa39, no statistically significant difference was observed in the PS and pneumonia models between combined therapy and monotherapy. Moreover, LPC+imipenem and LPC+ceftazidime significantly decreased and increased the TNF-α and IL-10 levels, respectively, in comparison with the untreated controls and monotherapies. These results demonstrate the impact of immune response modification by LPC plus antibiotics on the prognosis of infections induced by ceftazidime-resistant P. aeruginosa. La estimulación de la respuesta inmunitaria podría ser adyuvante al tratamiento antimicrobiano. En este estudio, hemos evaluado el impacto de la modificación de la respuesta inmunitaria por la lisofosfatidilcolina (LPC), combinada con imipenem ó ceftazidima, en modelos murinos de sepsis peritoneal (SP) y de neumonía por Pseudomonas aeruginosa (P. aeruginosa). La cepa sensible a imipenem y ceftazidima (Pa39) y la cepa resistente a ambos antibióticos (Pa238) fueron usadas. Los parámetros farmacocinéticos/farmacodinámicos de ceftazidima fueron determinados. La eficacia terapéutica y los niveles de TNF-α and IL-10 fueron determinados en los modelos murinos de SP y de neumonía por Pa39 y Pa238 y tratados con LPC, imipenem o ceftazidima, en monoterapia ó en combinación. En el modelo de SP, LPC + ceftazidima redujo la concentración de Pa238 en el bazo y el pulmón (–3,45 y –3,56 log10 UFC/g; p < 0,05)