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

Hashemi, Marjan M.; Rovig, John; Bateman, Jordan T; Holden, Brett S; Modelzelewski, Tomasz; Gueorguieva, Iliana; Dyck, Martin von; Bracken, Ronald; Genberg, Carl; Deng, Shenglou; Savage, Paul B.

doi:10.1093/jac/dkx347

Cited by 43 publications

(45 citation statements)

References 34 publications

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“…Nagent, et al, [9] conducted a biofilm study using confocal microscopy and their images revealed that ceragenins efficiently penetrated established biofilms and led to cell death without significant alterations to the extracellular matrix. Additionally, a recent study demonstrated prolonged inhibition of biofilm formation on endotracheal tube surfaces when the tubes were coated with a CSA-131-containing hydrogel [30].…”

Section: Resultsmentioning

confidence: 99%

Susceptibility of Multidrug-Resistant Bacteria, Isolated from Water and Plants in Nigeria, to Ceragenins

Hashemi

Mmuoegbulam

Holden

et al. 2018

IJERPH

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The continuous emergence of multidrug resistant pathogens is a major global health concern. Although antimicrobial peptides (AMPs) have shown promise as a possible means of combatting multidrug resistant strains without readily engendering resistance, costs of production and targeting by proteases limit their utility. Ceragenins are non-peptide AMP mimics that overcome these shortcomings while retaining broad-spectrum antimicrobial activity. To further characterize the antibacterial activities of ceragenins, their activities against a collection of environmental isolates of bacteria were determined. These isolates were isolated in Nigeria from plants and water. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of selected ceragenins and currently available antimicrobials against these isolates were measured to determine resistance patterns. Using scanning electron microscopy (SEM), we examined the morphological changes in bacterial membranes following treatment with ceragenins. Finally, we investigated the effectiveness of ceragenins in inhibiting biofilm formation and destroying established biofilms. We found that, despite high resistance to many currently available antimicrobials, including colistin, environmental isolates in planktonic and biofilm forms remain susceptible to ceragenins. Additionally, SEM and confocal images of ceragenin-treated cells confirmed the effective antibacterial and antibiofilm activity of ceragenins.

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Section: Resultsmentioning

confidence: 99%

Susceptibility of Multidrug-Resistant Bacteria, Isolated from Water and Plants in Nigeria, to Ceragenins

Hashemi

Mmuoegbulam

Holden

et al. 2018

IJERPH

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“…34,35 A recent preclinical study reported reduced colonization in ETTs coated with a hydrogel film eluting ceragenin CSA-131, a non-peptide small molecule mimicking innate immune defense antimicrobial peptides. 36 Another approach to prevent biofilm growth without the use of coatings is to alter the PVC surface of the ETT's internal lumen. ETTs are modified creating grooves or roughness on their inner surface; the hypothesis is that altered PVC physical properties could lead to reduced microbial adhesion or could facilitate secretion movement.…”

Section: Treatment Of Ett Surfacementioning

confidence: 99%

Non-Pharmacological Interventions to Prevent Ventilator-Associated Pneumonia: A Literature Review

Coppadoro

Bellani

2019

Respir Care

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Ventilator-associated pneumonia (VAP) is a well-known complication of invasive mechanical ventilation in critically ill patients. The presence of an endotracheal tube (ETT) is one of the major culprits for VAP development: air flow moves pathogens toward the distal airways, while clearance of the trachea is blunted due to reduced tracheal ciliary movement and impaired cough. Several measures are recognized as being useful to prevent VAP, and these are usually grouped in a VAP bundle (ie, avoiding intubation or re-intubation whenever possible; head of bed elevation; hand hygiene; shortening ventilation through sedation interruptions, spontaneous breathing trials, or thromboembolic prophylaxis). However, other interventions have been proposed to reduce VAP rate; some of these interventions have been reported in large clinical trials to be effective, some have been evaluated in small observational studies, and still others at a pre-clinical stage. Some strategies aim to improve the ETT design via a subglottic drainage system, with treatment of the ETT surface to reduce pathogen activity, or by modification of the cuff shape or cuff material to provide a better seal. Another proposed strategy is improving airway care through control of cuff pressure, cleaning the ETT, or use of closed suction systems. Other interventions target a patient's position in the bed to reduce aspiration of digestive content in the airways, or the use of probiotics to modulate gastric flora. Some of these measures are supported by strong evidence, but the impact on relevant outcomes such as duration of ventilation or mortality, as well as cost-benefit ratio, is still unclear, resulting in lack of widespread use.

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“…Not only are spores an obvious concern in a number of applied settings, but there is continued interest in the development of new agents that are active against a variety of growing bacteria, especially in view of the rise of antibiotic‐resistant organisms that cause human disease. One class of antimicrobial agents developed recently is the membrane‐active ceragenins (Niemirowicz et al ; Pogoda et al ; Piktel et al ,; Hashemi et al ). Generally, the most active member of this family is ceragenin CSA‐13 (hereafter CSA‐13) (Fig.…”

Section: Introductionmentioning

confidence: 99%

Effects of the microbicide ceragenin CSA‐13 on and properties ofBacillus subtilisspores prepared on two very different media

et al. 2019

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Aims To determine how the microbicide ceragenin‐13 (CSA‐13) kills Bacillus subtilis spores prepared on growth or sporulation media, and these spores’ properties. Methods and Results Spores made on Luria broth (LB) growth or double‐strength Schaeffer’s‐glucose (2xSG) sporulation plates found that spores made on LB plates have coat defects as evidenced by their lower hypochlorite resistance, faster germination with dodecylamine and slower germination with Ca2+‐dipicolinic acid (CaDPA) than 2xSG plate spores. CSA‐13 triggered CaDPA release from spores, an early step in germination, but only well at 70°C and better with spores made on LB than on 2xSG plates. Approximately 90% of spores with elevated levels of SpoVA proteins that form a CaDPA release channel, released CaDPA with CSA‐13 at 70°C, and faster with spores made on LB than 2xSG plates. Levels of CSA‐13 killing of spores made on LB and 2xSG plates were similar to levels of CaDPA release triggered by this agent. Conclusions CSA‐13 kills bacterial spores, but only at high concentrations and temperatures, and is preceded by CaDPA release. Significance and Impact of the Study CSA‐13 is not a direct sporicide as reported previously, but most likely germinates spores via activation of spores’ CaDPA channel, albeit inefficiently, and then killing the germinated spores.

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

Cited by 43 publications

References 34 publications

Susceptibility of Multidrug-Resistant Bacteria, Isolated from Water and Plants in Nigeria, to Ceragenins

Susceptibility of Multidrug-Resistant Bacteria, Isolated from Water and Plants in Nigeria, to Ceragenins

Non-Pharmacological Interventions to Prevent Ventilator-Associated Pneumonia: A Literature Review

Effects of the microbicide ceragenin CSA‐13 on and properties ofBacillus subtilisspores prepared on two very different media

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