Abstract
The stimulation of the immune response to prevent the progression of an infection may be an adjuvant to antimicrobial treatment. Here, we aimed to evaluate the efficacy of lysophosphatidylcholine (LPC) treatment in combination with colistin in murine experimental models of severe infections by Acinetobacter baumannii. We used the A. baumannii Ab9 strain, susceptible to colistin and most of the antibiotics used in clinical settings, and the A. baumannii Ab186 strain, susceptible to colistin but presenting a multidrug-resistant (MDR) pattern. The therapeutic efficacies of one and two LPC doses (25 mg/kg/d) and colistin (20 mg/kg/8 h), alone or in combination, were assessed against Ab9 and Ab186 in murine peritoneal sepsis and pneumonia models. One and two LPC doses combined with colistin and colistin monotherapy enhanced Ab9 and Ab186 clearance from spleen, lungs and blood and reduced mice mortality compared with those of the non-treated mice group in both experimental models. Moreover, one and two LPC doses reduced the bacterial concentration in tissues and blood in both models and increased mice survival in the peritoneal sepsis model for both strains compared with those of the colistin monotherapy group. LPC used as an adjuvant of colistin treatment may be helpful to reduce the severity and the resolution of the MDR A. baumannii infection.
Highlights
Acinetobacter baumannii is a Gram-negative bacterium with high clinical relevance owing to the increase in the number of nosocomial infections caused by this pathogen, as well as its ability to develop resistance to most antimicrobial agents used by physicians [1]
In many areas of the world that have a high prevalence of MDR A. baumannii, few options of treatment are present, and last resort treatments such as colistin are no longer effective in an increasing number of cases, leading to a 28-day mortality of 43% in hospitalized patients with bacteremia, ventilator-associated or hospital acquired pneumonia, or urosepsis [2]
We previously demonstrated the efficacy of lysophosphatidylcholine (LPC), a phospholipid involved in the recruitment and stimulation of immune cells [3,4,5,6], as a preemptive treatment in murine peritoneal sepsis and pneumonia experimental models by susceptible and MDR A. baumannii strains [7]
Summary
Acinetobacter baumannii is a Gram-negative bacterium with high clinical relevance owing to the increase in the number of nosocomial infections caused by this pathogen, as well as its ability to develop resistance to most antimicrobial agents used by physicians [1].Treatment of A. baumannii infections, especially those caused by multidrug-resistant (MDR)strains, is a major concern. Acinetobacter baumannii is a Gram-negative bacterium with high clinical relevance owing to the increase in the number of nosocomial infections caused by this pathogen, as well as its ability to develop resistance to most antimicrobial agents used by physicians [1]. Treatment of A. baumannii infections, especially those caused by multidrug-resistant (MDR). We previously demonstrated the efficacy of lysophosphatidylcholine (LPC), a phospholipid involved in the recruitment and stimulation of immune cells [3,4,5,6], as a preemptive treatment in murine peritoneal sepsis and pneumonia experimental models by susceptible and MDR A. baumannii strains [7]
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