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. Indwelling medical devices are a major source of nosocomial infections. In particular, patients requiring mechanical ventilation (intubation with an endotracheal tube [ETT]) face a high probability of contracting one of the most prevalent nosocomial infections, ventilator-associated pneumonia (VAP) (1-3). Neonatal and pediatric populations are at especially high risk for VAP because the current standard of care involves prolonged intubation without ETT exchange or tracheostomy, both common practice in adult patients. In neonates and infants, the inner diameter of the ETT is often 2.5 to 3.5 mm (the size of a thin straw), which complicates suctioning of secretions and confounds attempts to maintain patency. Despite aggressive bedside hygiene, Pseudomonas aeruginosa remains one of the most common causes of VAP in intubated children (2,4,5).P. aeruginosa, often found on indwelling devices such as ETTs, forms a biofilm which serves as an ideal environment for antibiotic resistance, making VAP difficult to treat (6, 7). Biofilm on ETTs is considered to be a reservoir for infecting pathogens derived from oropharyngeal flora and gastric microaspiration and is highly correlated with lower airway infection and subsequent VAP (8-11). To date, few side-by-side studies have compared killing activity (defined as 99.9% kill) of tobramycin to that of polymyxin E against P. aeruginosa, especially in the context of ETT biofilm and VAP (12-15). The eff...

Microbial profiling of dental plaque from mechanically ventilated patients

“…Previous studies have suggested Pseudomonas aeruginosa to be a predominant colonizer of dental plaque during MV and a causative pathogen of VAP (Parker et al , 2008; Raad et al , 2011; Tarquinio et al , 2014). Current microbiological analysis relies on cost effective, readily available and reproducible microbial culture.…”

Real-time monitoring of Pseudomonas aeruginosa biofilm formation on endotracheal tubes in vitro

“…As a consequence, ETT-associated biofilm increases the risk of upper respiratory tract infections, as well as device occlusion and wound infections, among other complications [ 7 , 8 ]. Biofilm on ETT is recognized to be one of the main causes of ventilator-associated pneumonia (VAP) [ 9 , 10 ]. The latter is commonly caused by the opportunistic pathogen Pseudomonas aeruginosa ( P. aeruginosa ) [ 11 ] .…”

Individual and Combined Effects of Engineered Peptides and Antibiotics on Pseudomonas aeruginosa Biofilms

“…As a consequence, combination therapy is pursued for the treatment of biofilm-related infections [ 7 , 10 , 11 ]. In particular, combinations of colistin + doripenem [ 12 , 13 ], colistin + tobramycin [ 14 , 15 ], and colistin + tigecycline [ 16 ] showed promising results under various disease conditions. Colistin, which is considered the last resort for treating the P. aeruginosa infections, is usually included in these combined treatments.…”