Polymyxin B/Pulmonary Surfactant Mixtures Have Increased Resistance to Inactivation by Meconium and Reduce Growth of Gram-Negative Bacteria In Vitro

Abstract

Pulmonary surfactant is inactivated in meconium aspiration syndrome and neonatal pneumonia. Development of an exogenous surfactant less sensitive to inactivation might be useful for treating these diseases. We investigated in vitro whether addition of the cationic cyclic membrane cross-linking peptide polymyxin B (PxB) and/or calcium chloride (CaCl 2 ) to modified porcine surfactant Curosurf increases resistance to meconium-induced inactivation of surface activity while antimicrobial activity of PxB is maintained. To study bacterial proliferation, Escherichia coli, group B streptococci (GBS), or Staphylococcus aureus were incubated 0 -5 h in saline or in meconium in the presence or absence of Curosurf with or without PxB. PxB and CaCl 2 improved spreading and adsorption of Curosurf. Curosurf plus CaCl 2 /PxB needed a 4-fold increase of meconium concentration to increase dynamic surface tension significantly compared with Curosurf plus CaCl 2 alone, indicating that PxB further increases the resistance of Curosurf to meconium-induced inactivation. Meconium alone like meconium/Curosurf promoted growth of E. coli and GBS, but addition of Curosurf/PxB or PxB alone significantly reduced the growth of E. coli. Biophysical and antibacterial properties of Curosurf and PxB may be combined into a useful adjunct in the treatment of neonatal Gram-negative pneumonia and/or meconium aspiration syndrome.

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

“…However, our previous studies demonstrated that addition of PxB to modified pSF increases resistance to surfactant inactivation and maintains antimicrobial activity of PxB (6).…”

“…Our group previously found that addition of PxB to modified porcine surfactant (pSF) increases resistance to meconiuminduced surfactant inactivation in vitro while the antimicrobial function of PxB is maintained (6). Thus, the combination of PxB and surfactant might be useful in clinical conditions such as neonatal Gram-negative pneumonia, MAS, or ARDS.…”

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

“…We previously showed that addition of PxB to porcine SF in vitro resulted in maintained antimicrobial activity and improved surface activity [8]. In addition, PxB accelerates SF exocytosis in isolated cultured rat alveolar type II cells [9].…”

“…The use of SF as a vector for topical pulmonary drug administration is a concept that has been evaluated for mixtures with antibiotics [6,7], including polymyxin B (PxB) [8]. Polymyxins and SF-specific proteins B and C have some similar properties.…”

What’s new in surfactant?

“…Moreover, a group of additives capable of decreasing surfactant inactivation is under investigation, showing promising results. These include chitosan [153], hyaluronan [91,92,141], dextran [108] and polymyxin B [27,130]. The potential of these additives lies in their use in RDS and meconium aspiration syndrome (MAS), where inactivation of surfactant by albumin and meconium respectively decreases its efficiency.…”