title: Prophylactic intratracheal polymyxin B/surfactant prevents bacterial growth in neonatal Escherichia coli pneumonia of rabbits.
abstract: In neonatal pneumonia, the surface activity of pulmonary surfactant is impaired and microorganisms may invade by passing the air-liquid interface. Previously, we have shown that addition of the antimicrobial peptide polymyxin B (PxB) to modified porcine surfactant (pSF) improves resistance to surfactant inactivation in vitro while antimicrobial activity of PxB is maintained. In this study, we investigated pSF/PxB in vivo. Neonatal near-term rabbits were treated with intratracheal pSF and/or PxB. Rabbits treated with only saline served as controls. Animals were ventilated with standardized tidal volumes and received ∼10(7) Escherichia coli intratracheally. Plethysmographic pressure-volume curves were recorded every 30 min. After 240 min, animals were killed, the right lung and left kidney were excised, and bacterial growth was determined. The left lung was used for histologic analysis. Intratracheal administration of PxB ± pSF significantly reduced the growth of E. coli compared with control animals or animals receiving only pSF. This was accompanied by reduction of severe inflammatory tissue destruction and significantly reduced bacterial translocation to the left kidney. Animals receiving pSF + PxB had no difference in lung compliance compared with the pSF- or PxB-treated group. Mixtures of PxB and pulmonary surfactant show antimicrobial effects in neonatal rabbits and prevent systemic spreading of E. coli.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Sweden. stichtenoth@paedia.ukl.mu-luebeck.de
authors.forename: Guido
authors.initials: G
authors.lastname: Stichtenoth
authors.forename: Bim
authors.initials: B
authors.lastname: Linderholm
authors.forename: Marie Hägerstrand
authors.initials: MH
authors.lastname: Björkman
authors.forename: Gabi
authors.initials: G
authors.lastname: Walter
authors.forename: Tore
authors.initials: T
authors.lastname: Curstedt
authors.forename: Egbert
authors.initials: E
authors.lastname: Herting
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004926:Escherichia coli / Q000254:growth & development*; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D011112:Polymyxin B / Q000008:administration & dosage* / Q000627:therapeutic use; D011663:Pulmonary Surfactants / Q000008:administration & dosage* / Q000627:therapeutic use; D011817:Rabbits; D014132:Trachea
chemical_list: D011663:Pulmonary Surfactants; D011112:Polymyxin B