Therapeutic Efficacy of Lysophosphatidylcholine in Severe Infections Caused by Acinetobacter baumannii

Smani, Younes; Domínguez-Herrera, Juan; Ibáñez-Martínez, José; Pachón, Jerónimo

doi:10.1128/aac.04986-14

Cited by 45 publications

(58 citation statements)

References 25 publications

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“…Previous studies from our group demonstrated that preemptive LPC therapy protected mice from A. baumannii infections, reducing bacterial organ loads and bacteremia and increasing mouse survival to 40% (14), similar to the results obtained with both strains used in the present study. In addition, we showed that surviving mice had lower bacterial burdens in tissues than those in dead mice, which explains the observed improvement in survival.…”

Section: Discussionsupporting

confidence: 91%

“…A previously characterized murine model of peritoneal sepsis caused by A. baumannii was used (14). Briefly, animals were inoculated i.p.…”

Section: Methodsmentioning

confidence: 99%

“…Blood samples were collected from the periorbital plexuses of 30 anesthetized mice infected with the Ab9 and Ab186 strains at the MLD 100 , as previously described (14). Serum levels of tumor necrosis factor alpha (TNF-␣) and interleukin-10 (IL-10) were determined for mice at 0, 2, 4, 8, and 12 h postinfection by using an enzyme-linked immunosorbent assay (ELISA) (eBioscience).…”

Section: Methodsmentioning

confidence: 99%

“…We previously successfully demonstrated the efficacy of LPC as a preemptive treatment in murine peritoneal sepsis and pneumonia experimental models of infection caused by susceptible A. baumannii strains (14). From this study, we suggested the clinical application of LPC as an adjuvant pretreatment in combination with antimicrobial agents for the treatment of infections by A. baumannii, including MDR strains (14).…”

mentioning

confidence: 94%

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Efficacy of Lysophosphatidylcholine in Combination with Antimicrobial Agents against Acinetobacter baumannii in Experimental Murine Peritoneal Sepsis and Pneumonia Models

Parra-Millán

Sánchez-Encinales

et al. 2016

Antimicrob Agents Chemother

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bImmune response stimulation to prevent infection progression may be an adjuvant to antimicrobial treatment. Lysophosphatidylcholine (LPC) is an immunomodulator involved in immune cell recruitment and activation. In this study, we aimed to evaluate the efficacy of LPC in combination with colistin, tigecycline, or imipenem in experimental murine models of peritoneal sepsis and pneumonia. We used Acinetobacter baumannii strain Ab9, which is susceptible to colistin, tigecycline, and imipenem, and multidrug-resistant strain Ab186, which is susceptible to colistin and resistant to tigecycline and imipenem. Pharmacokinetic and pharmacodynamic parameters for colistin, tigecycline, and imipenem and the 100% minimal lethal dose (MLD 100 ) were determined for both strains. The therapeutic efficacies of LPC, colistin (60 mg/kg of body weight/day), tigecycline (10 mg/kg/day), and imipenem (180 mg/kg/day), alone or in combination, were assessed against Ab9 and Ab186 at the MLD 100 in murine peritoneal sepsis and pneumonia models. The levels of pro-and anti-inflammatory cytokines, i.e., tumor necrosis factor alpha (TNF-␣) and interleukin-10 (IL-10), were determined by enzyme-linked immunosorbent assay (ELISA) for the same experimental models after inoculating mice with the MLD of both strains. LPC in combination with colistin, tigecycline, or imipenem markedly enhanced the bacterial clearance of Ab9 and Ab186 from the spleen and lungs and reduced bacteremia and mouse mortality rates (P < 0.05) compared with those for colistin, tigecycline, and imipenem monotherapies. Moreover, at 4 h post-bacterial infection, Ab9 induced higher TNF-␣ and lower IL-10 levels than those with Ab186 (4 g/ml versus 3 g/ml [P < 0.05] and 2 g/ml versus 3.4 g/ml [P < 0.05], respectively). LPC treatment combined with colistin, tigecycline, or imipenem modestly reduced the severity of infection by A. baumannii strains with different resistance phenotypes compared to LPC monotherapy in both experimental models.A cinetobacter baumannii is a Gram-negative coccobacillus with high clinical relevance due to the different severe nosocomial infections that it causes, mainly in intensive care units, and its capacity to develop resistance to most of the antimicrobial agents used in clinical practice (1).A multidrug resistance pattern is commonly observed for A. baumannii isolates, raising the threat of impossible-to-treat infections (2). These multidrug-resistant (MDR) isolates are generally susceptible to polymyxins (colistin and polymyxin B) and resistant to imipenem and tigecycline (3, 4). The limited antimicrobial alternatives for the treatment of severe infections by MDR A. baumannii make the search for other therapeutic options urgent. Polymyxins have been used as a last resort to treat infections by MDR A. baumannii. In humans, suboptimal and optimal doses of colistin to treat ventilator-associated pneumonia due to MDR A. baumannii prevent mortality in only 38.1% and 62.5% of cases, respectively (5, 6). Recently, in a clinical trial at our hospital, treatm...

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Section: Discussionsupporting

confidence: 91%

“…A previously characterized murine model of peritoneal sepsis caused by A. baumannii was used (14). Briefly, animals were inoculated i.p.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 94%

See 2 more Smart Citations

Efficacy of Lysophosphatidylcholine in Combination with Antimicrobial Agents against Acinetobacter baumannii in Experimental Murine Peritoneal Sepsis and Pneumonia Models

Parra-Millán

Sánchez-Encinales

et al. 2016

Antimicrob Agents Chemother

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“…Although LPCs are typically regarded as pro-inflammatory mediators, they were increased in inflammatory diseases (27,28). A previous series of studies have demonstrated a protective effect of LPCs against diseases, including type 2 diabetes (29), cancer (30) and inflammatory diseases (31).…”

Section: Trend ------------------------------------------------------mentioning

confidence: 99%

Probiotic pre-administration reduces mortality in a mouse model of cecal ligation and puncture-induced sepsis

Chen

Gui

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. A number of clinical trials have demonstrated that the use of probiotics has the potential to prevent nosocomial infections. However, the mechanism underlying probiotic-induced anti-infection and sepsis remains to be investigated. In the present study, 200 µl/day of Lactobacillus rhamnosus GG (LGG) or normal saline (control) was orally administrated to 4-week-old C57BL6 mice 4 weeks prior to cecal ligation and puncture (CLP). A number of mice were sacrificed 24 h after CLP, and the remaining mice were used for survival studies. Ileum tissues were collected to evaluate the injury on the intestine. Blood samples were also obtained to investigate the changed metabolic pattern in mice that underwent different treatments using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). In the survival studies, the mortality of CLP-induced septic mice pretreated with LGG was significantly lower compared with untreated mice (P= 0.029). Ileum mucosal damage was evident in the control septic mice. Based on the data of UPLC-QTOF-MS, phosphatidylcholines were increased and lysophosphatidylcholines (LPCs) that contained polyunsaturated fatty acids were decreased in septic mice, whereas saturated fatty acid LPCs reveal no significant difference between septic and sham mice. In addition, the metabolic profile in the septic mice pretreated with LGG was much closer to that of sham mice compared with control septic mice. The results of the present study suggest that probiotic pre-administration reduces the mortality in septic mice by decreasing ileum mucosal damage, increasing the gut barrier integrity and altering global serum metabolic profiles.

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Metabolomic analysis for the protective effects of mangiferin on sepsis‐induced lung injury in mice

Wang¹,

Liu²,

Cao³

et al. 2018

Biomedical Chromatography

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This study aimed to investigate the efficacy of mangiferin, including its known antioxidant and anti-inflammatory effects on sepsis-induced lung injury induced by a classical cecal ligation and puncture (CLP) models in mouse using a metabolomics approach. A total of 24 mice were randomly divided into four groups: the sham group was given saline before sham operation. The CLP group received the CLP operation only. HMF and LMF groups were given mangiferin treatment of high dose and low dose of mangiferin, respectively, before the CLP operation. One week after treatment, the mice were sacrificed and their lungs were collected for metabolomics analysis. We developed ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry to perform lung metabolic profiling analysis. With the methods of principal component analysis and partial least squares discriminant analysis, 58 potential metabolites associated with amino acid metabolism, purine metabolism, lipid metabolism and energy regulation were observed to be increased or reduced in HMF and LMF groups compared with the CLP group. Conclusively, our results suggest that mangiferin plays a protective role in the moderation of sepsis-induced lung injury through reducing oxidative stress, regulating lipid metabolism and energy biosynthesis.

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Therapeutic Efficacy of Lysophosphatidylcholine in Severe Infections Caused by Acinetobacter baumannii

Cited by 45 publications

References 25 publications

Efficacy of Lysophosphatidylcholine in Combination with Antimicrobial Agents against Acinetobacter baumannii in Experimental Murine Peritoneal Sepsis and Pneumonia Models

Efficacy of Lysophosphatidylcholine in Combination with Antimicrobial Agents against Acinetobacter baumannii in Experimental Murine Peritoneal Sepsis and Pneumonia Models

Probiotic pre-administration reduces mortality in a mouse model of cecal ligation and puncture-induced sepsis

Metabolomic analysis for the protective effects of mangiferin on sepsis‐induced lung injury in mice

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