Journal article
Zinc Pyrithione Improves the Antibacterial Activity of Silver Sulfadiazine Ointment
mSphere, Vol.1(5), p.e00194-16
09/01/2016
DOI: 10.1128/mSphere.00194-16
PMCID: PMC5023846
PMID: 27642637
Abstract
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.
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.
Details
- Title: Subtitle
- Zinc Pyrithione Improves the Antibacterial Activity of Silver Sulfadiazine Ointment
- Creators
- Catlyn Blanchard - Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USALauren Brooks - Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USAKatherine Ebsworth-Mojica - Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USALouis Didione - Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York, USABenjamin Wucher - Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USAStephen Dewhurst - Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USADamian Krysan - Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York, USAPaul M Dunman - Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USARachel A. F Wozniak - Department of Ophthalmology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
- Resource Type
- Journal article
- Publication Details
- mSphere, Vol.1(5), p.e00194-16
- DOI
- 10.1128/mSphere.00194-16
- PMID
- 27642637
- PMCID
- PMC5023846
- NLM abbreviation
- mSphere
- ISSN
- 2379-5042
- eISSN
- 2379-5042
- Publisher
- American Society for Microbiology
- Grant note
- AWD0000831 / American Society of Cataract and Refractive Surgery Research to Prevent Blindness (RPB) T90FR021985 / UR | University of Rochester Medical Center (URMC) AI103507 / HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) P30AI078498; AI094511 / UR | University of Rochester Medical Center (URMC)
- Alternative title
- Zinc Pyrithione Improves Silver Sulfadiazine Ointment
- Language
- English
- Date published
- 09/01/2016
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
- Record Identifier
- 9984093358402771
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