Exogenous Pulmonary Surfactant as a Vehicle for Antimicrobials: Assessment of Surfactant-Antibacterial InteractionsIn Vitro

Abstract

Owing to its unique surface-active properties, an exogenous pulmonary surfactant may become a promising drug delivery agent, in particular, acting as a vehicle for antibiotics in topical treatment of pneumonia. The purpose of this study was to assess a mutual influence of natural surfactant preparation and three antibiotics (amikacin, cefepime, and colistimethate sodium) in vitro and to identify appropriate combination(s) for subsequent in vivo investigations of experimental surfactant/antibiotic mixtures. Influence of antibiotics on surface-active properties of exogenous surfactant was assessed using the modified Pattle method. Effects of exogenous surfactant on antibacterial activity of antimicrobials against Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa were evaluated using conventional microbiologic procedures. Addition of amikacin or cefepime to surfactant had no significant influence on surface-active properties of the latter. Obvious reduction of surface-active properties was confirmed for surfactant/colistimethate composition. When suspended with antibiotics, surfactant either had no impact on their antimicrobial activity (amikacin) or exerted mild to moderate influence (reduction of cefepime bactericidal activity and increase of colistimethate bacteriostatic activity against S. aureus and P. aeruginosa). Considering favorable compatibility profile, the surfactant/amikacin combination is advisable for subsequent investigation of joint surfactant/antibacterial therapy in animals with bacterial pneumonia.

Seventy-Five Years of Research on Protein Binding

“…Furthermore, the data demonstrate that contradictory results were generated in studies which have used different surfactant preparations. For example, the bactericidal action of aminoglycosides was completely abolished in one study (141), whereas surfactant did not affect the activities of tobramycin (142) and amikacin (143). Likewise, the activity of colistin was reduced in one study (144) but moderately increased in another study (143).…”

“…For example, the bactericidal action of aminoglycosides was completely abolished in one study (141), whereas surfactant did not affect the activities of tobramycin (142) and amikacin (143). Likewise, the activity of colistin was reduced in one study (144) but moderately increased in another study (143). Furthermore, the effect of identical surfactant preparations on the bacteriostatic activity of ciprofloxacin seems to be species specific: while surfactant reduced its activity against P. aeruginosa and A. baumannii, it increased its activity against K. pneumoniae (145).…”

Antimicrobial and Biophysical Properties of Surfactant Supplemented with an Antimicrobial Peptide for Treatment of Bacterial Pneumonia

“…The general characteristics of surfactant and positive findings of exogenous surfactant therapy led to a number of laboratory studies to investigate the possibility of exogenous surfactant as a pulmonary delivery vehicle for other drugs (12)(13)(14)(15)(16). The rationale for this approach is that the spreading properties of surfactant would improve therapeutic distribution throughout the lung, while opening collapsed lung regions to improve drug availability directly at the site of an infection (8).…”

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

“…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.…”