Efficacy of Lysophosphatidylcholine in Combination with Antimicrobial Agents against Acinetobacter baumannii in Experimental Murine Peritoneal Sepsis and Pneumonia Models
| Autor: | J. Pérez del Palacio, R. Parra Millán, L. F. López Cortés, Younes Smani, Caridad Díaz, V. Sánchez Encinales, R. Ayerbe Algaba, M. E. Pachón Ibáñez, M. E. Jiménez Mejías, A. Gutiérrez Valencia, Jerónimo Pachón |
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| Přispěvatelé: | Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), European Commission, Red Española de Investigación en Patología Infecciosa, Fundación MEDINA, [Parra Millan, R.] Univ Seville, CSIC, Hosp Univ Virgen Rocio, Inst Biomed Sevilla IBiS, Seville, Spain, [Jimenez Mejias, M. E.] Univ Seville, CSIC, Hosp Univ Virgen Rocio, Inst Biomed Sevilla IBiS, Seville, Spain, [Sanchez Encinales, V.] Univ Seville, CSIC, Hosp Univ Virgen Rocio, Inst Biomed Sevilla IBiS, Seville, Spain, [Ayerbe Algaba, R.] Univ Seville, CSIC, Hosp Univ Virgen Rocio, Inst Biomed Sevilla IBiS, Seville, Spain, [Gutierrez Valencia, A.] Univ Seville, CSIC, Hosp Univ Virgen Rocio, Inst Biomed Sevilla IBiS, Seville, Spain, [Pachon Ibanez, M. E.] Univ Seville, CSIC, Hosp Univ Virgen Rocio, Inst Biomed Sevilla IBiS, Seville, Spain, [Lopez Cortes, L. F.] Univ Seville, CSIC, Hosp Univ Virgen Rocio, Inst Biomed Sevilla IBiS, Seville, Spain, [Pachon, J.] Univ Seville, CSIC, Hosp Univ Virgen Rocio, Inst Biomed Sevilla IBiS, Seville, Spain, [Smani, Y.] Univ Seville, CSIC, Hosp Univ Virgen Rocio, Inst Biomed Sevilla IBiS, Seville, Spain, [Diaz, C.] Fdn MEDINA, Fdn Ctr Excelencia Invest Medicamentos Innovadore, Granada, Spain, [Perez del Palacio, J.] Fdn MEDINA, Fdn Ctr Excelencia Invest Medicamentos Innovadore, Granada, Spain, Ministerio de Economia y Competitividad, Instituto de Salud Carlos III, Spanish Network for Research in Infectious Diseases, Fundacion MEDINA, Merck Sharp & Dohme de Espana S.A./Universidad de Granada/Junta de Andalucia, European Development Regional Fund |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Acinetobacter baumannii Imipenem Cells 030106 microbiology Enzyme-Linked Immunosorbent Assay Minocycline Tigecycline Microbial Sensitivity Tests Microbiology Sepsis 03 medical and health sciences Mice medicine polycyclic compounds Animals Experimental Therapeutics Pharmacology (medical) Multidrug-resistant Pharmacology biology business.industry Colistin Tumor Necrosis Factor-alpha Lysophosphatidylcholines Pneumonia biochemical phenomena metabolism and nutrition medicine.disease Antimicrobial biology.organism_classification bacterial infections and mycoses Anti-Bacterial Agents Interleukin-10 Infectious Diseases Bacteremia Critically-ill patients lipids (amino acids peptides and proteins) Rifampin business Infection Immune-responses medicine.drug |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | Immune 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 (MLD100) 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 MLD100 in murine peritoneal sepsis and pneumonia models. The levels of pro- and anti-inflammatory cytokines, i.e., tumor necrosis factor alpha (TNF-α) 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-α and lower IL-10 levels than those with Ab186 (4 μg/ml versus 3 μg/ml [P < 0.05] and 2 μg/ml versus 3.4 μg/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. This study was supported by the Instituto Carlos III, Proyectos de Investigación en Salud (grant PI13/01744). Y.S. was funded by the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III, cofinanced by the European Development Regional Fund (“A way to achieve Europe”), by the Spanish Network for Research in Infectious Diseases (grant REIPI RD12/00015/0001), and by the Subprograma Miguel Servet Tipo I from the Ministerio de Economia y Competitividad of Spain (grant CP15/01358). The MEDINA authors disclose the receipt of financial support from Fundación MEDINA, a public-private partnership of Merck Sharp & Dohme de España S.A./Universidad de Granada/Junta de Andalucía. |
| Databáze: | OpenAIRE |
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