Zinc Pyrithione Improves the Antibacterial Activity of Silver Sulfadiazine Ointment

ABSTRACT Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus are commonly associated with biofilm-associated wound infections that are recalcitrant to conventional antibiotics. As an initial means to identify agents that may have a greater propensity to improve clearance of wo...

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Autores principales:	Catlyn Blanchard, Lauren Brooks, Katherine Ebsworth-Mojica, Louis Didione, Benjamin Wucher, Stephen Dewhurst, Damian Krysan, Paul M. Dunman, Rachel A. F. Wozniak
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Acinetobacter baumannii Pseudomonas aeruginosa Staphylococcus aureus biofilm silver sulfadiazine wound Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2d09b8abe8ff45cda0ab06908007efd5
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spelling	oai:doaj.org-article:2d09b8abe8ff45cda0ab06908007efd52021-11-15T15:21:29ZZinc Pyrithione Improves the Antibacterial Activity of Silver Sulfadiazine Ointment10.1128/mSphere.00194-162379-5042https://doaj.org/article/2d09b8abe8ff45cda0ab06908007efd52016-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00194-16https://doaj.org/toc/2379-5042ABSTRACT Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus are commonly associated with biofilm-associated wound infections that are recalcitrant to conventional antibiotics. As an initial means to identify agents that may have a greater propensity to improve clearance of wound-associated bacterial pathogens, we screened a Food and Drug Administration-approved drug library for members that display bactericidal activity toward 72-h-established P. aeruginosa biofilms using an adenylate kinase reporter assay for bacterial cell death. A total of 34 compounds displayed antibiofilm activity. Among these, zinc pyrithione was also shown to reduce levels of A. baumannii and S. aureus biofilm-associated bacteria and exhibited an additive effect in combination with silver sulfadiazine, a leading topical therapeutic for wound site infections. The improved antimicrobial activity of zinc pyrithione and silver sulfadiazine was maintained in an ointment formulation and led to improved clearance of P. aeruginosa, A. baumannii, and S. aureus in a murine model of wound infection. Taken together, these results suggest that topical zinc pyrithione and silver sulfadiazine combination formulations may mitigate wound-associated bacterial infections and disease progression. IMPORTANCE Topical antimicrobial ointments ostensibly mitigate bacterial wound disease and reliance on systemic antibiotics. Yet studies have called into question the therapeutic benefits of several traditional topical antibacterials, accentuating the need for improved next-generation antimicrobial ointments. Yet the development of such agents consisting of a new chemical entity is a time-consuming and expensive proposition. Considering that drug combinations are a mainstay therapeutic strategy for the treatment of other therapeutic indications, one alternative approach is to improve the performance of conventional antimicrobial ointments by the addition of a well-characterized and FDA-approved agent. Here we report data that indicate that the antimicrobial properties of silver sulfadiazine ointments can be significantly improved by the addition of the antifungal zinc pyrithione, suggesting that such combinations may provide an improved therapeutic option for the topical treatment of wound infections.Catlyn BlanchardLauren BrooksKatherine Ebsworth-MojicaLouis DidioneBenjamin WucherStephen DewhurstDamian KrysanPaul M. DunmanRachel A. F. WozniakAmerican Society for MicrobiologyarticleAcinetobacter baumanniiPseudomonas aeruginosaStaphylococcus aureusbiofilmsilver sulfadiazinewoundMicrobiologyQR1-502ENmSphere, Vol 1, Iss 5 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Acinetobacter baumannii Pseudomonas aeruginosa Staphylococcus aureus biofilm silver sulfadiazine wound Microbiology QR1-502
spellingShingle	Acinetobacter baumannii Pseudomonas aeruginosa Staphylococcus aureus biofilm silver sulfadiazine wound Microbiology QR1-502 Catlyn Blanchard Lauren Brooks Katherine Ebsworth-Mojica Louis Didione Benjamin Wucher Stephen Dewhurst Damian Krysan Paul M. Dunman Rachel A. F. Wozniak Zinc Pyrithione Improves the Antibacterial Activity of Silver Sulfadiazine Ointment
description	ABSTRACT Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus are commonly associated with biofilm-associated wound infections that are recalcitrant to conventional antibiotics. As an initial means to identify agents that may have a greater propensity to improve clearance of wound-associated bacterial pathogens, we screened a Food and Drug Administration-approved drug library for members that display bactericidal activity toward 72-h-established P. aeruginosa biofilms using an adenylate kinase reporter assay for bacterial cell death. A total of 34 compounds displayed antibiofilm activity. Among these, zinc pyrithione was also shown to reduce levels of A. baumannii and S. aureus biofilm-associated bacteria and exhibited an additive effect in combination with silver sulfadiazine, a leading topical therapeutic for wound site infections. The improved antimicrobial activity of zinc pyrithione and silver sulfadiazine was maintained in an ointment formulation and led to improved clearance of P. aeruginosa, A. baumannii, and S. aureus in a murine model of wound infection. Taken together, these results suggest that topical zinc pyrithione and silver sulfadiazine combination formulations may mitigate wound-associated bacterial infections and disease progression. IMPORTANCE Topical antimicrobial ointments ostensibly mitigate bacterial wound disease and reliance on systemic antibiotics. Yet studies have called into question the therapeutic benefits of several traditional topical antibacterials, accentuating the need for improved next-generation antimicrobial ointments. Yet the development of such agents consisting of a new chemical entity is a time-consuming and expensive proposition. Considering that drug combinations are a mainstay therapeutic strategy for the treatment of other therapeutic indications, one alternative approach is to improve the performance of conventional antimicrobial ointments by the addition of a well-characterized and FDA-approved agent. Here we report data that indicate that the antimicrobial properties of silver sulfadiazine ointments can be significantly improved by the addition of the antifungal zinc pyrithione, suggesting that such combinations may provide an improved therapeutic option for the topical treatment of wound infections.
format	article
author	Catlyn Blanchard Lauren Brooks Katherine Ebsworth-Mojica Louis Didione Benjamin Wucher Stephen Dewhurst Damian Krysan Paul M. Dunman Rachel A. F. Wozniak
author_facet	Catlyn Blanchard Lauren Brooks Katherine Ebsworth-Mojica Louis Didione Benjamin Wucher Stephen Dewhurst Damian Krysan Paul M. Dunman Rachel A. F. Wozniak
author_sort	Catlyn Blanchard
title	Zinc Pyrithione Improves the Antibacterial Activity of Silver Sulfadiazine Ointment
title_short	Zinc Pyrithione Improves the Antibacterial Activity of Silver Sulfadiazine Ointment
title_full	Zinc Pyrithione Improves the Antibacterial Activity of Silver Sulfadiazine Ointment
title_fullStr	Zinc Pyrithione Improves the Antibacterial Activity of Silver Sulfadiazine Ointment
title_full_unstemmed	Zinc Pyrithione Improves the Antibacterial Activity of Silver Sulfadiazine Ointment
title_sort	zinc pyrithione improves the antibacterial activity of silver sulfadiazine ointment
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/2d09b8abe8ff45cda0ab06908007efd5
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Zinc Pyrithione Improves the Antibacterial Activity of Silver Sulfadiazine Ointment

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