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      Micro-patterned surfaces reduce bacterial colonization and biofilm formation in vitro: Potential for enhancing endotracheal tube designs

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          Abstract

          Background

          Ventilator-associated pneumonia (VAP) is a leading hospital acquired infection in intensive care units despite improved patient care practices and advancements in endotracheal tube (ETT) designs. The ETT provides a conduit for bacterial access to the lower respiratory tract and a substratum for biofilm formation, both of which lead to VAP. A novel microscopic ordered surface topography, the Sharklet micro-pattern, has been shown to decrease surface attachment of numerous microorganisms, and may provide an alternative strategy for VAP prevention if included on the surface of an ETT. To evaluate the feasibility of this micro-pattern for this application, the microbial range of performance was investigated in addition to biofilm studies with and without a mucin-rich medium to simulate the tracheal environment in vitro.

          Methods

          The top five pathogens associated with ETT-related pneumonia, Methicillin-Resistant Staphylococcus aureus (MRSA) , Pseudomonas aeruginosa, Klebsiella pneumonia, Acinetobacter baumannii, and Escherichia coli, were evaluated for attachment to micro-patterned and un-patterned silicone surfaces in a short-term colonization assay. Two key pathogens, MRSA and Pseudomonas aeruginosa, were evaluated for biofilm formation in a nutrient rich broth for four days and minimal media for 24 hours, respectively, on each surface type. P. aeruginosa was further evaluated for biofilm formation on each surface type in a mucin-modified medium mimicking tracheal mucosal secretions. Results are reported as percent reductions and significance is based on t-tests and ANOVA models of log reductions. All experiments were replicated at least three times.

          Results

          Micro-patterned surfaces demonstrated reductions in microbial colonization for a broad range of species, with up to 99.9% ( p < 0.05) reduction compared to un-patterned controls. Biofilm formation was also reduced, with 67% ( p = 0.12) and 52% ( p = 0.05) reductions in MRSA and P. aeruginosa biofilm formation, respectively. Further, a 58% (p < 0.01) reduction was demonstrated on micro-patterned surfaces for P. aeruginosa biofilms under clinically-simulated conditions when compared to un-patterned controls.

          Conclusions

          This engineered micro-pattern reduces the colonization and biofilm formation of key VAP-associated pathogens in vitro. Future application of this micro-pattern on endotracheal tubes may prevent or prolong the onset of VAP without the need for antimicrobial agents.

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          Most cited references43

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          Clinical and economic consequences of ventilator-associated pneumonia: a systematic review.

          Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in critically ill patients. The clinical and economic consequences of VAP are unclear, with a broad range of values reported in the literature To perform a systematic review to determine the incidence of VAP and its attributable mortality rate, length of stay, and costs. Computerized PUBMED and MEDLINE search supplemented by manual searches for relevant articles, limited to articles published after 1990. English-language observational studies and randomized trials that provided data on the incidence of VAP were included. Matched cohort studies were included for calculation of attributable mortality rate and length of stay. Data were extracted on patient population, diagnostic criteria for VAP, incidence, outcome, type of intensive care unit, and study design. The cumulative incidence of VAP was calculated by combining the results of several studies using standard formulas for combining proportions, in which the weighted average and variance are calculated. Results from studies comparing intensive care unit and hospital mortality due to VAP, additional length of stay, and additional days of mechanical ventilation were pooled using a random effects model, with assessment of heterogeneity. Our findings indicate a) between 10% and 20% of patients receiving >48 hrs of mechanical ventilation will develop VAP; b) critically ill patients who develop VAP appear to be twice as likely to die compared with similar patients without VAP (pooled odds ratio, 2.03; 95% confidence interval, 1.16-3.56); c) patients with VAP have significantly longer intensive care unit lengths of stay (mean = 6.10 days; 95% confidence interval, 5.32-6.87 days); and d) patients who develop VAP incur > or = USD $10,019 in additional hospital costs. Ventilator-associated pneumonia occurs in a considerable proportion of patients undergoing mechanical ventilation and is associated with substantial morbidity, a two-fold mortality rate, and excess cost. Given these findings, strategies that effectively prevent VAP are urgently needed.
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            Guidelines for preventing health-care--associated pneumonia, 2003: recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee.

            This report updates, expands, and replaces the previously published CDC "Guideline for Prevention of Nosocomial Pneumonia". The new guidelines are designed to reduce the incidence of pneumonia and other severe, acute lower respiratory tract infections in acute-care hospitals and in other health-care settings (e.g., ambulatory and long-term care institutions) and other facilities where health care is provided. Among the changes in the recommendations to prevent bacterial pneumonia, especially ventilator-associated pneumonia, are the preferential use of oro-tracheal rather than naso-tracheal tubes in patients who receive mechanically assisted ventilation, the use of noninvasive ventilation to reduce the need for and duration of endotracheal intubation, changing the breathing circuits of ventilators when they malfunction or are visibly contaminated, and (when feasible) the use of an endotracheal tube with a dorsal lumen to allow drainage of respiratory secretions; no recommendations were made about the use of sucralfate, histamine-2 receptor antagonists, or antacids for stress-bleeding prophylaxis. For prevention of health-care--associated Legionnaires disease, the changes include maintaining potable hot water at temperatures not suitable for amplification of Legionella spp., considering routine culturing of water samples from the potable water system of a facility's organ-transplant unit when it is done as part of the facility's comprehensive program to prevent and control health-care--associated Legionnaires disease, and initiating an investigation for the source of Legionella spp. when one definite or one possible case of laboratory-confirmed health-care--associated Legionnaires disease is identified in an inpatient hemopoietic stem-cell transplant (HSCT) recipient or in two or more HSCT recipients who had visited an outpatient HSCT unit during all or part of the 2-10 day period before illness onset. In the section on aspergillosis, the revised recommendations include the use of a room with high-efficiency particulate air filters rather than laminar airflow as the protective environment for allogeneic HSCT recipients and the use of high-efficiency respiratory-protection devices (e.g., N95 respirators) by severely immunocompromised patients when they leave their rooms when dust-generating activities are ongoing in the facility. In the respiratory syncytial virus (RSV) section, the new recommendation is to determine, on a case-by-case basis, whether to administer monoclonal antibody (palivizumab) to certain infants and children aged <24 months who were born prematurely and are at high risk for RSV infection. In the section on influenza, the new recommendations include the addition of oseltamivir (to amantadine and rimantadine) for prophylaxis of all patients without influenza illness and oseltamivir and zanamivir (to amantadine and rimantadine) as treatment for patients who are acutely ill with influenza in a unit where an influenza outbreak is recognized. In addition to the revised recommendations, the guideline contains new sections on pertussis and lower respiratory tract infections caused by adenovirus and human parainfluenza viruses and refers readers to the source of updated information about prevention and control of severe acute respiratory syndrome.
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              Nosocomial infections in medical intensive care units in the United States. National Nosocomial Infections Surveillance System.

              To describe the epidemiology of nosocomial infections in medical intensive care units (ICUs) in the United States. Analysis of ICU surveillance data collected through the National Nosocomial Infections Surveillance (NNIS) System between 1992 and 1997. Medical ICUs in the United States. A total of 181,993 patients. Nosocomial infections were analyzed by infection site and pathogen distribution. Urinary tract infections were most frequent (31%), followed by pneumonia (27%) and primary bloodstream infections (19%). Eighty-seven percent of primary bloodstream infections were associated with central lines, 86% of nosocomial pneumonia was associated with mechanical ventilation, and 95% of urinary tract infections were associated with urinary catheters. Coagulase-negative staphylococci (36%) were the most common bloodstream infection isolates, followed by enterococci (16%) and Staphylococcus aureus (13%). Twelve percent of bloodstream isolates were fungi. The most frequent isolates from pneumonia were Gram-negative aerobic organisms (64%). Pseudomonas aeruginosa (21%) was the most frequently isolated of these. S. aureus (20%) was isolated with similar frequency. Candida albicans was the most common single pathogen isolated from urine and made up just over half of the fungal isolates. Fungal urinary infections were associated with asymptomatic funguria rather than symptomatic urinary tract infections (p < .0001). Certain pathogens were associated with device use: coagulase-negative staphylococci with central lines, P. aeruginosa and Acinetobacter species with ventilators, and fungal infections with urinary catheters. Patient nosocomial infection rates for the major sites correlated strongly with device use. Device exposure was controlled for by calculating device-associated infection rates for bloodstream infections, pneumonia, and urinary tract infections by dividing the number of device-associated infections by the number of days of device use. There was no association between these device-associated infection rates and number of hospital beds, number of ICU beds, or length of stay. There is a considerable variation within the distribution of each of these infection rates. The distribution of sites of infection in medical ICUs differed from that previously reported in NNIS ICU surveillance studies, largely as a result of anticipated low rates of surgical site infections. Primary bloodstream infections, pneumonia, and urinary tract infections associated with invasive devices made up the great majority of nosocomial infections. Coagulase-negative staphylococci were more frequently associated with primary bloodstream infections than reported from NNIS ICUs of all types in the 1980s, and enterococci were a more frequent isolate from bloodstream infections than S. aureus. Fungal urinary tract infections, often asymptomatic and associated with catheter use, were considerably more frequent than previously reported. Invasive device-associated infections were associated with specific pathogens. Although device-associated site-specific infection rates are currently our most useful rates for performing comparisons between ICUs, the considerable variation in these rates between ICUs indicates the need for further risk adjustment.
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                Author and article information

                Contributors
                Journal
                Clin Transl Med
                Clin Transl Med
                Clinical and Translational Medicine
                Springer
                2001-1326
                2014
                16 April 2014
                : 3
                : 8
                Affiliations
                [1 ]Sharklet Technologies, Inc., Aurora, 12635 E. Montview Blvd. Suite 155, CO 80045 Aurora, CO USA
                [2 ]Center for Biofilm Engineering, and the Department of Mathematical Sciences, Montana State University, Bozeman, MT, USA
                [3 ]Geisel School of Medicine at Dartmouth, Hanover, NH, USA
                [4 ]Department of Materials Science and Engineering, University of Florida, Gainesville, FL, USA
                Article
                2001-1326-3-8
                10.1186/2001-1326-3-8
                3996152
                24739529
                9e8761a9-74af-49f2-bc0c-a7537d2ffa67
                Copyright © 2014 May et al.; licensee Springer.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

                History
                : 19 December 2013
                : 10 March 2014
                Categories
                Research

                Medicine
                micro-pattern,sharklet,vap,endotracheal tube,biofilm inhibition
                Medicine
                micro-pattern, sharklet, vap, endotracheal tube, biofilm inhibition

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