Preclinical testing of a broad-spectrum antimicrobial endotracheal tube coated with an innate immune synthetic mimic.

BACKGROUND: Endotracheal tubes provide an abiotic surface on which bacteria and fungi form biofilms, and the release of endotoxins and planktonic organisms can cause damaging inflammation and infections. OBJECTIVES: Ceragenins are small molecule mimics of antimicrobial peptides with broad-spectrum antibacterial and antifungal activity, and a ceragenin may be used to provide antimicrobial protection to the abiotic surface of an endotracheal tube. METHODS: A hydrogel film, containing CSA-131, was generated on endotracheal tubes. Elution of CSA-131 was quantified in drip-flow and static systems, antifungal and antibacterial activity was measured with repeated inoculation in growth media, biofilm formation was observed through electron microscopy, safety was determined by intubation of pigs with coated and uncoated endotracheal tubes. RESULTS: Optimized coatings containing CSA-131 provided controlled elution of CSA-131, with concentrations released of less than 1 µg/mL. The eluting ceragenin prevented fungal and bacterial colonization of coated endotracheal tubes for extended periods, while uncoated tubes were colonized by bacteria and fungi. Coated tubes were well tolerated in intubated pigs. CONCLUSIONS: Thin films containing CSA-131 provide protection against microbial colonization of endotracheal tubes. This protection prevents fungal and bacterial biofilm formation on the tubes and reduces endotoxin associated with tubes. This coating is well suited for decreasing the adverse effects of intubation associated with infection and inflammation.

Economic burden of ventilator-associated pneumonia based on total resource utilization.

OBJECTIVES: To characterize the current economic burden of ventilator-associated pneumonia (VAP) and to determine which services increase the cost of VAP in North American hospitals. DESIGN AND SETTING: We performed a retrospective, matched cohort analysis of mechanically ventilated patients enrolled in the North American Silver-Coated Endotracheal Tube (NASCENT) study, a prospective, randomized study conducted from 2002 to 2006 in 54 medical centers, including 45 teaching institutions (83.3%). METHODS: Case patients with microbiologically confirmed VAP (n = 30)were identified from 542 study participants with claims data and were matched by use of a primary diagnostic code, and subsequently by the Acute Physiology and Chronic Health Evaluation II score, to control patients without VAP (n = 90). Costs were estimated by applying hospital-specific cost-to-charge ratios based on all-payer inpatient costs associated with VAP diagnosis-related groups. RESULTS: Median total charges per patient were $198,200 for case patients and $96,540 for matched control patients (P < .001); corresponding median hospital costs were $76,730 for case patients and $41,250 for control patients (P = .001). After adjusting for diagnosis-related group payments, median losses to hospitals were $32,140 for case patients and $19,360 for control patients (P = .151). The median duration of intubation was longer for case patients than for control patients (10.1 days vs 4.7 days; P < .001), as were the median duration of intensive care unit stay (18.5 days vs 8.0 days; P < .001) and the median duration of hospitalization (26.5 days vs 14.0 days; P < .001). Examples of services likely to be directly related to VAP and having higher median costs for case patients were hospital care (P < .05) and respiratory therapy (P < .05). CONCLUSIONS: VAP was associated with increased hospital costs, longer duration of hospital stay, and a higher number of hospital services being affected, which underscores the need for bundled measures to prevent VAP. TRIAL REGISTRATION: NASCENT study ClinicalTrials.gov Identifier: NCT00148642.

Activity of a silver-coated endotracheal tube in preclinical models of ventilator-associated pneumonia and a study after extubation.

OBJECTIVE: To elucidate the mechanism of action of the silver-coated endotracheal tube in models of the early pathogenesis of ventilator-associated pneumonia. DESIGN: Open-labeled, prospective, controlled, sequentially conducted, preclinical studies, and in vitro assessment of tubes from patients. SETTING: Microbiology laboratory of a device manufacturer, animal research facility of a university, and a tertiary medical center. INTERVENTIONS: Endotracheal tubes were similar except for the silver coating. In the 21-day in vitro elution model, tube samples were incubated in saline solution at 37.8 degrees C. In the in vitro adherence model, coated and uncoated tubes were exposed to 21 respiratory isolates of radiolabeled microorganisms for 2-4 hrs. In the animal model, 12 healthy white rabbits were intubated for 16 hrs with noncuffed silver-coated or uncoated tubes and challenged with buccal administration of Pseudomonas aeruginosa. In the in vitro assessment, tubes from 16 patients underwent quantitative culture assessment and qualitative confocal laser scanning microscopy. MEASUREMENTS AND MAIN RESULTS: After in vitro incubation, the mean residual silver concentration was 2.6 microg/cm, confirming that the coating was not entirely depleted. In vitro adherence to the silver-coated endotracheal tube was less than that of the uncoated tube for 12 of 21 isolates and equivalent for seven. For example, adherence to the silver-coated endotracheal tube was reduced >90% for all five isolates of P. aeruginosa (p < .05). In rabbits, P. aeruginosa colonization on the silver-coated endotracheal tube was reduced 99.9% compared with that on the uncoated tube (p < .0001); colonization in the tracheal and lung tissue was reduced > or =99% (p < .05). In the in vitro assessment, pathogens were detected on none of nine silver-coated tubes from patients and three of seven control tubes (p > .05). CONCLUSIONS: : The collective findings of this series of studies demonstrated that the silver-coated endotracheal tube was active in models designed to mimic the early pathogenesis of ventilator-associated pneumonia.