title: Activities of tobramycin and polymyxin E against Pseudomonas aeruginosa biofilm-coated medical grade endotracheal tubes.
abstract: Indwelling medical devices have become a major source of nosocomial infections, especially Pseudomonas aeruginosa infections, which remain the most common cause of ventilator-associated pneumonia (VAP) in neonates and children. Using medical grade polyvinyl chloride endotracheal tubes (ETTs), the activity of tobramycin and polymyxin E was quantified in a simulated prevention and treatment static time-kill model using biofilm-forming P. aeruginosa. The model simulated three clinical conditions: (i) planktonic bacteria grown in the presence of antibiotics (tobramycin and polymyxin E) without ETTs, (ii) planktonic bacteria grown in the presence of P. aeruginosa, antibiotic, and ETTs (simulating prevention), and (iii) a 24-h-formed P. aeruginosa biofilm grown on ETTs prior to antibiotic exposure (simulating treatment). In the model simulating "prevention" (conditions 1 and 2 above), tobramycin alone or in combination with polymyxin E was more bactericidal than polymyxin E alone at 24 h using a concentration of greater than 2 times the MIC. However, after a 24-h-old biofilm was allowed to form on the ETTs, neither monotherapy nor combination therapy over 24 h exhibited bactericidal or bacteriostatic effects. Against the same pathogens, tobramycin and polymyxin E, alone or in combination, exhibited bactericidal activity prior to biofilm attachment to the ETTs; however, no activity was observed once biofilm formed on ETTs. These findings support surveillance culturing to identify pathogens for a rapid and targeted approach to therapy, especially when P. aeruginosa is a potential pathogen.
authors.affiliation: Pediatric Critical Care Medicine, Hasbro Children's Hospital, Rhode Island Hospital, Providence, Rhode Island, USA.
authors.forename: Keiko
authors.initials: K
authors.lastname: Tarquinio
authors.forename: Kelsey
authors.initials: K
authors.lastname: Confreda
authors.forename: James
authors.initials: J
authors.lastname: Shurko
authors.forename: Kerry
authors.initials: K
authors.lastname: LaPlante
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D004359:Drug Therapy, Combination; D006801:Humans; D007442:Intubation, Intratracheal / Q000009:adverse effects / Q000295:instrumentation*; D008826:Microbial Sensitivity Tests; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy; D011113:Polymyxins / Q000008:administration & dosage / Q000494:pharmacology*; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D014031:Tobramycin / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D011113:Polymyxins; D014031:Tobramycin