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

Abstract

Background: Ascending maternofetal bacterial infections often result in premature birth and neonatal respiratory distress. These neonates are treated with exogenous pulmonary surfactant (SF) and systemic antibiotics. Polymyxins are antimicrobiotic peptides that may bind to SF phospholipids. Objectives: Does topical administration of SF/polymyxin reduce bacterial growth in neonatal rabbit pneumonia and improve pulmonary function? Methods: Neonatal rabbits were tracheotomized and treated intratracheally with mixtures of porcine SF, SF/polymyxin E (PxE), or polymyxin B (PxB). Control animals received saline. Animals were then inoculated with Escherichia coli and ventilated for 4 h. During the experiment, peak insufflation pressures, dynamic lung compliance, and ECG were recorded. Pulmonary and renal bacterial load were determined. Lung histology was performed. Lung and kidney IL-8 were measured in subgroups. Results: Eighty-five animals were included in 2 experimental series, of which 78% survived 4 h of ventilation. E. coli inoculation caused severe neonatal pneumonia with median IL-8 levels of 2.2 ng/g in the lungs compared to a median of 0.2 ng/g in the lungs of the saline controls (p < 0.01). Lung compliance after 4 h was significantly increased at a mean of 0.48 ml/(kg·cm H₂O) in the SF group and 0.43 in the SF + PxE group compared to 0.35 in the E. coli group (p < 0.01). In direct comparison, bacterial growth found in the E. coli group was reduced 20-fold in the SF + PxB group compared to 75-fold in the SF + PxE group. Conclusion: Addition of polymyxin to SF effectively promotes antimicrobial treatment and improves lung function in neonatal pneumonia of rabbits.

The Perturbation of Pulmonary Surfactant by Bacterial Lipopolysaccharide and Its Reversal by Polymyxin B: Function and Structure

“…The favourable in vitro effect of PxB is explained by its ability to bridge PL membranes, making it easier to develop more-resistant multilayer structures [ 10 ]. PxB also increases the resistance of the surfactant to meconium, and combined treatment with PSUR/PxB is effective against the systemic spread of E. coli [ 12 , 13 ].…”

“…We have previously shown that the addition of PxB improves the surface properties of exogenous surfactants and increases the resistance to inactivation with plasma albumin that enters the airspaces and interferes with pulmonary surfactants in the case of alveolar–capillary membrane damage [ 11 ]. The combination of surfactant/PxB or PxE mixtures was also tested in other models of surfactant inhibition, as in meconium aspiration syndrome or neonatal pneumonia [ 12 , 13 ].…”

Polymyxin B-Enriched Exogenous Lung Surfactant: Thermodynamics and Structure

“…Prophylactic intratracheal treatment of neonatal rabbits with PxB–EPS prevents the growth of bacterial E. coli and improves lung function in neonatal pneumonia of rabbits . Encouraging results were reported in a similar model of pneumonia with polymyxin E, where the mixing of polymyxin with the surfactant increased its bactericidal effect .…”