Control of pathogen growth and biofilm formation using a urinary catheter that releases antimicrobial nitrogen oxides

Kishikawa, Hiroaki; Ebberyd, Anette; Römling, Ute; Brauner, Annelie; Lüthje, Petra; Lundberg, Jon O.; Weitzberg, Eddie

doi:10.1016/j.freeradbiomed.2013.09.012

Cited by 28 publications

(29 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Remarkably, NO-np reduced the viability of biofilm-related bacteria formed by multiple S. aureus clinical isolates, suggesting that this gas can penetrate the EPM to deliver its bactericidal properties. Similar levels of NO efficacy against multidrug-resistant bacteria within biofilms using different synthetic compounds (e.g., N-diazeniumdiolates [21,25], nitrosothiols [24], and nitrosyl metal complexes [22]) have been described. However, these studies showed certain limitations, such as the inability to chemically stabilize and release NO in a controlled manner, safety issues, and perhaps most important, not using multiple strains of a specific bacterial genus to address the variability observed from strain to strain in these types of experiments, hindering the possibility that the methods can be exploited in biomedical applications.…”

Section: Discussionmentioning

confidence: 61%

“…Our group has previously characterized and extensively demonstrated the therapeutic potential of NO generated and delivered by a siliconbased nanoparticle platform (NO-np) for the treatment of diverse infectious diseases, including Gram-positive and -negative bacterial and fungal skin and soft tissue infections (16)(17)(18)(19)(20). While a number of NO-donating compounds have emerged, been evaluated in vitro, and shown efficacy against biofilm-forming pathogens, many suffer from various limitations ranging from inadequate release capacity to stability and safety concerns (21)(22)(23)(24)(25). A defining feature of the NO-np is that it is a true NO generator, not an NO-donating compound with potential cytotoxicity, such as is seen with diazeniumdiolates (21,25).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Sustained Nitric Oxide-Releasing Nanoparticles Interfere with Methicillin-Resistant Staphylococcus aureus Adhesion and Biofilm Formation in a Rat Central Venous Catheter Model

Mihu

Cabral

Pattabhi

et al. 2017

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Staphylococcus aureus is frequently isolated in the setting of infections of indwelling medical devices, which are mediated by the microbe's ability to form biofilms on a variety of surfaces. Biofilm-embedded bacteria are more resistant to antimicrobial agents than their planktonic counterparts and often cause chronic infections and sepsis, particularly in patients with prolonged hospitalizations. In this study, we demonstrate that sustained nitric oxide-releasing nanoparticles (NO-np) interfere with S. aureus adhesion and prevent biofilm formation on a rat central venous catheter (CVC) model of infection. Confocal and scanning electron microscopy showed that NO-np-treated staphylococcal biofilms displayed considerably reduced thicknesses and bacterial numbers compared to those of control biofilms in vitro and in vivo, respectively. Although both phenotypes, planktonic and biofilmassociated staphylococci, of multiple clinical strains were susceptible to NO-np, bacteria within biofilms were more resistant to killing than their planktonic counterparts. Furthermore, chitosan, a biopolymer found in the exoskeleton of crustaceans and structurally integrated into the nanoparticles, seems to add considerable antimicrobial activity to the technology. Our findings suggest promising development and translational potential of NO-np for use as a prophylactic or therapeutic against bacterial biofilms on CVCs and other medical devices.

show abstract

Section: Discussionmentioning

confidence: 61%

mentioning

confidence: 99%

Sustained Nitric Oxide-Releasing Nanoparticles Interfere with Methicillin-Resistant Staphylococcus aureus Adhesion and Biofilm Formation in a Rat Central Venous Catheter Model

Mihu

Cabral

Pattabhi

et al. 2017

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Over the past several decades, countless research has been conducted to develop effective NO-generating and releasing materials for clinical therapies in response to the continuous discoveries pertaining to NO's importance in physiology and pathophysiology. A great number of synthetic compounds (e.g., N-diazeniumdiolates [37], nitrosothiols [38], and nitrosyl metal complexes [39]) have been developed to chemically stabilize and release NO in a controlled manner and have been exploited in many biomedical applications. However, the translation of the therapeutic potential of NO to the bedside has been limited by its short biological lifetime, instability during storage, and potential toxicity associated with many of these platforms (40).…”

Section: Discussionmentioning

confidence: 99%

Sustained Nitric Oxide-Releasing Nanoparticles Induce Cell Death in Candida albicans Yeast and Hyphal Cells, Preventing Biofilm Formation In Vitro and in a Rodent Central Venous Catheter Model

Ahmadi

Lee

Sanchez

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Candida albicans is a leading nosocomial pathogen. Today, candidal biofilms are a significant cause of catheter infections, and such infections are becoming increasingly responsible for the failure of medical-implanted devices. C. albicans forms biofilms in which fungal cells are encased in an autoproduced extracellular polysaccharide matrix. Consequently, the enclosed fungi are protected from antimicrobial agents and host cells, providing a unique niche conducive to robust microbial growth and a harbor for recurring infections. Here we demonstrate that a recently developed platform comprised of nanoparticles that release therapeutic levels of nitric oxide (NO-np) inhibits candidal biofilm formation, destroys the extracellular polysaccharide matrices of mature fungal biofilms, and hinders biofilm development on surface biomaterials such as the lumen of catheters. We found NO-np to decrease both the metabolic activity of biofilms and the cell viability of C. albicans in vitro and in vivo. Many clinical manifestations are attributed to the human commensal fungus Candida albicans, especially to its ability to form biofilms on implanted medical devices (1). Biomaterials commonly used in clinical practice (e.g., central venous catheters [CVCs], dentures, and heart valves) are fertile grounds for C. albicans colonization and biofilm formation, thus establishing the onset and progression of disease (2, 3). Particularly, CVCs are a high risk for C. albicans biofilm-related infection by nature of direct contact with patient's bloodstream; it is therefore no surprise that this organism is the 4th leading cause of bloodstream infections in the United States (4, 5). Forty percent of patients with C. albicans biofilm-infected intravenous catheters develop fungemia, resulting in diverse outcomes ranging from focal disease to severe sepsis and death (6). Current guidelines for the treatment of catheter-associated candidemia advocate for line removal to facilitate more rapid clearance of the bloodstream and better prognosis (4). In contrast to removal of peripheral intravenous catheters, removal of larger CVCs is not always feasible, and replacement is expensive and associated with a procedural risk for the patient. The profound economic consequences of Candida infections is highlighted by the ϳ$1.7 billion spent annually on treating candidemia in the United States alone (7) and an estimated cost per infection of ϳ$34,508 to $56,000 (8, 9). In this scenario, there is a need for novel strategies to combat fungal contamination of prosthetic devices, especially biofilm-related infections that exacerbate morbidity, resulting in high mortality (6).Mature C. albicans biofilms consist of a unique niche for microbial growth, in which the fungus is highly equipped for survival as biofilms contain heterogeneous morphological forms, including yeasts, hyphae, and pseudohyphae, in a precise arrangement encased in an exogenous matrix that consists of carbohydrates and proteins (1). Cells within biofilms show different properties from their ...

show abstract

“…27,45 Additionally, some nanoparticles can cause production of antimicrobial reactive oxygen and nitrogen species by leukocytes in response to an infection. 46 Antimicrobial-coated indwelling devices are gaining acceptance, with up to 45% of hospitals using such technology. 47 Endotracheal (ET) tubes remain an important target for prevention of hospital-acquired pneumonia.…”

Section: Prophylaxismentioning

confidence: 99%

“…56 In a preclinical study, urinary catheters modified with a nitric oxide and acetic acid impeded bacterial growth and biofilms formation from clinically significant organisms, including P aeruginosa, K pneumoniae, and Enterococcus faecalis. 46 Orthopedic implant infections are associated with significant morbidity. Nanotechnology has been used to alter the surfaces of joint prostheses by means such as impregnation of chlorhexidine or covalently immobilizing antibiotics, such as vancomycin.…”

Section: Prophylaxismentioning

confidence: 99%

Advancing Technologies for the Diagnosis and Management of Infections

Heffernan

Fox

2014

Surgical Clinics of North America

View full text Add to dashboard Cite

Control of pathogen growth and biofilm formation using a urinary catheter that releases antimicrobial nitrogen oxides

Cited by 28 publications

References 34 publications

Sustained Nitric Oxide-Releasing Nanoparticles Interfere with Methicillin-Resistant Staphylococcus aureus Adhesion and Biofilm Formation in a Rat Central Venous Catheter Model

Sustained Nitric Oxide-Releasing Nanoparticles Interfere with Methicillin-Resistant Staphylococcus aureus Adhesion and Biofilm Formation in a Rat Central Venous Catheter Model

Sustained Nitric Oxide-Releasing Nanoparticles Induce Cell Death in Candida albicans Yeast and Hyphal Cells, Preventing Biofilm Formation In Vitro and in a Rodent Central Venous Catheter Model

Advancing Technologies for the Diagnosis and Management of Infections

Contact Info

Product

Resources

About