Efficacy of lysophosphatidylcholine as direct treatment in combination with colistin against Acinetobacter baumannii in murine severe infections models

Abstract

ABSTRACTObjectivesThe stimulation of the immune response to prevent the progression of the infection may be an adjuvant to antimicrobial treatment. Previously, we showed that preemptive treatment with lysophosphatidylcholine (LPC) in combination with colistin improved the therapeutic efficacy of colistin against MDR Acinetobacter baumannii. In this study, we aimed to evaluate the efficacy of direct treatment with LPC in combination with colistin in murine experimental models of severe infections by A. baumannii.MethodsWe used A. baumannii strain Ab9, which is susceptible to colistin and most of the antibiotics used in clinical settings, and A. baumannii strain Ab186, which is susceptible to colistin but presents a MDR pattern. The therapeutic efficacies of one and two doses of LPC (25 mg/kg/d) and colistin (20 mg/kg/8h), alone or in combination, were assessed against Ab9 and Ab186 in murine peritoneal sepsis and pneumonia models.ResultsOne and two doses of LPC in combination with colistin and colistin monotherapy enhanced bacterial clearance of Ab9 and Ab186 from spleen, lungs and blood and reduced mortality rates compared with those of the non-treated mice group in both experimental models (P<0.05). Moreover, one and two doses of LPC reduced the bacterial concentration in tissues and blood in both models, and increased mice survival in peritoneal sepsis model for both strains compared with those of colistin monotherapy group.ConclusionsLPC used as an adjuvant of colistin treatment may be helpful to reduce the severity and the resolution of the infection by MDR A. baumannii.