title: Efficacy of cecropin A-melittin peptides on a sepsis model of infection by pan-resistant Acinetobacter baumannii.
abstract: Pan-resistant Acinetobacter baumannii have prompted the search for therapeutic alternatives. We evaluate the efficacy of four cecropin A-melittin hybrid peptides (CA-M) in vivo. Toxicity was determined in mouse erythrocytes and in mice (lethal dose parameters were LD(0), LD(50), LD(100)). Protective dose 50 (PD(50)) was determined by inoculating groups of ten mice with the minimal lethal dose of A. baumannii (BMLD) and treating with doses of each CA-M from 0.5 mg/kg to LD(0). The activity of CA-Ms against A. baumannii was assessed in a peritoneal sepsis model. Mice were sacrificed at 0 and 1, 3, 5, and 7-h post-treatment. Spleen and peritoneal fluid bacterial concentrations were measured. CA(1-8)M(1-18) was the less haemolytic on mouse erythrocytes. LD(0) (mg/kg) was 32 for CA(1-8)M(1-18), CA(1-7)M(2-9), and Oct-CA(1-7)M(2-9), and 16 for CA(1-7)M(5-9). PD(50) was not achieved with non-toxic doses (≤ LD(0)). In the sepsis model, all CA-Ms were bacteriostatic in spleen, and decreased bacterial concentration (p < 0.05) in peritoneal fluid, at 1-h post-treatment; at later times, bacterial regrowth was observed in peritoneal fluid. CA-Ms showed local short-term efficacy in the peritoneal sepsis model caused by pan-resistant Acinetobacter baumannii.
authors.affiliation: Unidad Clínica de Enfermedades Infecciosas, Instituto de Biomedicina de Sevilla, IBIS/Hospital Universitario Virgen del Rocío/Universidad de Sevilla/CSIC Sevilla, 41013 Sevilla, Spain. rlopezrojas@hotmail.com
authors.forename: R
authors.initials: R
authors.lastname: López-Rojas
authors.forename: F
authors.initials: F
authors.lastname: Docobo-Pérez
authors.forename: M E
authors.initials: ME
authors.lastname: Pachón-Ibáñez
authors.forename: B G
authors.initials: BG
authors.lastname: de la Torre
authors.forename: M
authors.initials: M
authors.lastname: Fernández-Reyes
authors.forename: C
authors.initials: C
authors.lastname: March
authors.forename: J A
authors.initials: JA
authors.lastname: Bengoechea
authors.forename: D
authors.initials: D
authors.lastname: Andreu
authors.forename: L
authors.initials: L
authors.lastname: Rivas
authors.forename: J
authors.initials: J
authors.lastname: Pachón
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000254:growth & development; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D001202:Ascitic Fluid / Q000382:microbiology; D024881:Drug Resistance, Bacterial; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D007928:Lethal Dose 50; D008555:Melitten / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D023421:Models, Animal; D011993:Recombinant Fusion Proteins; D018805:Sepsis / Q000175:diagnosis* / Q000382:microbiology / Q000401:mortality; D013154:Spleen / Q000382:microbiology; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D011993:Recombinant Fusion Proteins; D008555:Melitten; C031161:cecropin A