Development of a broad spectrum polymer‐released antimicrobial coating for the prevention of resistant strain bacterial infections

Sinclair, Kristofer D.; Pham, Theresa; Farnsworth, Ryan W.; Williams, Dustin L.; Loc-Carrillo, Catherine; Horne, L. A.; Ingebretsen, S. H.; Bloebaum, Roy D.

doi:10.1002/jbm.a.34209

Cited by 30 publications

(28 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, this low-molecular-mass compound has potent activity against bacterial biofilms (32,33). Some previous studies undertook evaluations of CSA-13 activity using in vitro systems and different experimental settings dedicated to evaluation of activity against resistant strains (31,34), in different body fluids (32), in the presence of different polyelectrolytes (35,36), or using drug release systems and antimicrobial coating (32,37,38). However, only a few studies have evaluated the activity of CSA-13 in cell cultures or animal models (13,39,40).…”

Section: Discussionmentioning

confidence: 99%

Bactericidal Activity of Ceragenin CSA-13 in Cell Culture and in an Animal Model of Peritoneal Infection

Bucki

Niemirowicz

Wnorowska

et al. 2015

Antimicrob Agents Chemother

View full text Add to dashboard Cite

e Ceragenins constitute a novel family of cationic antibiotics characterized by a broad spectrum of antimicrobial activities, which have mostly been assessed in vitro. Using a polarized human lung epithelial cell culture system, we evaluated the antibacterial activities of the ceragenin CSA-13 against two strains of Pseudomonas aeruginosa (PAO1 and Xen5). Additionally, the biodistribution and bactericidal activity of a CSA-13-IRDye 800CW derivate were assessed using an animal model of peritoneal infection after PAO1 challenge. In cell culture, CSA-13 bactericidal activities against PAO1 and Xen5 were higher than the activities of the human cathelicidin peptide LL-37. Increased CSA-13 activity was observed in polarized human lung epithelial cell cultures subjected to butyric acid treatment, which is known to increase endogenous LL-37 production. Eight hours after intravenous or intraperitoneal injection, the greatest CSA-13-IRDye 800CW accumulation was observed in mouse liver and kidneys. CSA-13-IRDye 800CW administration resulted in decreased bacterial outgrowth from abdominal fluid collected from animals subjected to intraperitoneal PAO1 infection. These observations indicate that CSA-13 may synergistically interact with antibacterial factors that are naturally present at mucosal surfaces and it maintains its antibacterial activity in the infected abdominal cavity. Cationic lipids such as CSA-13 represent excellent candidates for the development of new antibacterial compounds.

show abstract

Section: Discussionmentioning

confidence: 99%

Bactericidal Activity of Ceragenin CSA-13 in Cell Culture and in an Animal Model of Peritoneal Infection

Bucki

Niemirowicz

Wnorowska

et al. 2015

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Recently, the in vitro performance of CSA-13 embedded in silicone polymer for challenges against methicillin-resistant Staphylococcus aureus (MRSA) was investigated [254]. A weight-to-weight ( w / w ) concentration of 18% CSA-13 in silicone eliminated 5 × 10 8 CFU of MRSA within 8 h [254].…”

Section: The Antimicrobial Supramolecular Assembliesmentioning

confidence: 99%

“…A weight-to-weight ( w / w ) concentration of 18% CSA-13 in silicone eliminated 5 × 10 8 CFU of MRSA within 8 h [254]. A review on immobilization of antimicrobial agents both for medical and food preservation applications discussed the avoidance of toxicity allowed by immobilized biocides and the compatibility and reservoir limitations common to elutable agents [255].…”

Section: The Antimicrobial Supramolecular Assembliesmentioning

confidence: 99%

Cationic Antimicrobial Polymers and Their Assemblies

Carmona-Ribeiro

Carrasco

2013

IJMS

442

328

View full text Add to dashboard Cite

Cationic compounds are promising candidates for development of antimicrobial agents. Positive charges attached to surfaces, particles, polymers, peptides or bilayers have been used as antimicrobial agents by themselves or in sophisticated formulations. The main positively charged moieties in these natural or synthetic structures are quaternary ammonium groups, resulting in quaternary ammonium compounds (QACs). The advantage of amphiphilic cationic polymers when compared to small amphiphilic molecules is their enhanced microbicidal activity. Besides, many of these polymeric structures also show low toxicity to human cells; a major requirement for biomedical applications. Determination of the specific elements in polymers, which affect their antimicrobial activity, has been previously difficult due to broad molecular weight distributions and random sequences characteristic of radical polymerization. With the advances in polymerization control, selection of well defined polymers and structures are allowing greater insight into their structure-antimicrobial activity relationship. On the other hand, antimicrobial polymers grafted or self-assembled to inert or non inert vehicles can yield hybrid antimicrobial nanostructures or films, which can act as antimicrobials by themselves or deliver bioactive molecules for a variety of applications, such as wound dressing, photodynamic antimicrobial therapy, food packing and preservation and antifouling applications.

show abstract

“…Preliminary in vitro experimentation 22 suggested the CSA-13 antimicrobial was eluted from the implant at a rate of approximately 14.84 6 1.21 lg/mL over a 24-h period; well above the recorded MIC of 2.5 lg/mL.…”

Section: Csa-13 Combination Coatingmentioning

confidence: 99%

Model development for determining the efficacy of a combination coating for the prevention of perioperative device related infections: A pilot study

Sinclair

Pham

Williams

et al. 2013

J. Biomed. Mater. Res

View full text Add to dashboard Cite

Antibiotic resistant bacterial infections are a growing problem in patient care. These infections are difficult to treat and severely affect the patient's quality of life. The goal of this translational experiment was to investigate the antimicrobial potential of cationic steroidal antimicrobial-13 (CSA-13) for the prevention of perioperative device-related infections in vivo. It was hypothesized that when incorporated into a polymeric device coating, the release of CSA-13 could prevent perioperative device-related infection without inhibiting skeletal attachment. To test this hypothesis, 12 skeletally mature sheep received a porous coated titanium implant in the right femoral condyle. Group 1 received the titanium implant and an inoculum of 5 × 10(8) CFU of methicillin-resistant Staphylococcus aureus (MRSA). Group 2 received a CSA-13 coated implant and the MRSA inoculum. Group 3 received only the CSA-13 coated implant and Group 4 received only the implant-without the CSA-13 coating or MRSA inoculum. In conclusion, the CSA-13 combination coating demonstrated bactericidal potential without adversely affecting skeletal attachment. The CSA-13 containing groups exhibited no evidence of bacterial infection at the conclusion of the 12 week study and established skeletal attachment consistent with Group 4. In contrast, all of the Group 1 animals became infected and required euthanasia within 6-10 days. The significance of this finding is that this combination coating could be applied to implanted devices to prevent perioperative device-related infections. This method may facilitate significantly reduced incidences of device-related infections as well as a new method to treat and prevent resistant strain bacterial infections.

show abstract

Development of a broad spectrum polymer‐released antimicrobial coating for the prevention of resistant strain bacterial infections

Cited by 30 publications

References 25 publications

Bactericidal Activity of Ceragenin CSA-13 in Cell Culture and in an Animal Model of Peritoneal Infection

Bactericidal Activity of Ceragenin CSA-13 in Cell Culture and in an Animal Model of Peritoneal Infection

Cationic Antimicrobial Polymers and Their Assemblies

Model development for determining the efficacy of a combination coating for the prevention of perioperative device related infections: A pilot study

Contact Info

Product

Resources

About