Prophylactic Intratracheal Polymyxin B/Surfactant Prevents Bacterial Growth in Neonatal Escherichia coli Pneumonia of Rabbits

Abstract

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 ϳ107 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 Ϯ 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 ϩ 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. (Pediatr Res 67: 369-374, 2010)

Comparison of Polymyxin E and Polymyxin B as an Additive to Pulmonary Surfactant in Escherichia coli Pneumonia of Ventilated Neonatal Rabbits

“…In the present study, the addition of PxE or PxB to SF decreased the bacterial load of lungs, which agrees with previous studies on SF/PxB [14]. In a direct comparison, SF/PxE reduces the bacterial load more effectively than SF/PxB.…”

Joint Intratracheal Surfactant-Antibacterial Therapy in Experimental Pseudomonas-Induced Pneumonia

“…(4) Significantly reduced bacterial growth in lung tissue, restriction of inflammatory tissue destruction, and considerable reduction of bacterial translocation were demonstrated when polymyxin B combined with modified porcine surfactant was intratracheally administered to neonatal near-term rabbits to prevent Escherichia coli-induced pneumonia. (5) Our study provides additional data on the effects of surfactant-antibacterial therapy for the treatment of respiratory infections. To our best knowledge, this is the first study to utilize a multi-method assessment of therapeutic effects of intratracheal surfactant-antimicrobial instillations in animals with induced pneumonia, involving bacteriological methods, morphological methods, and evaluation of surface activity alterations.…”

“…Despite theoretical benefits of natural pulmonary surfactant as a vehicle for intratracheally instilled antibiotics, the evidence of experimental studies in this field is still insufficient to advance the method to clinical practice. (3)(4)(5)(6)10) The ability of exogenous surfactant to increase airspace deposition and improve the distribution uniformity of intratracheally instilled antibiotic (pentamidine) was demonstrated by Kharasch et al in healthy hamsters. (3) Later on, a group from The Netherlands conducted a series of experiments to assess the interactive effects of surfactant and several antibacterials when mixed in vitro.…”

“…(3)(4)(5)(6) However, an integrated in vivo assessment of surfactant-enhanced antibacterial therapy in acute pneumonia is yet to be done.…”

Properties of modified natural surfactant after exposure to fibrinogen in vitro and in an animal model of respiratory distress syndrome

“…Evaluation of surface activity by CBS. Surface activity of surfactant samples was measured by CBS; developed and built by Schürch and Bachofen (19) as previously described (20,21). The test chamber was initially filled with 10% sucrose in saline.…”