Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 61, Issue 6, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.00481-17
Keywords
antimicrobial combinations; biofilms; drug delivery; iron metabolism
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Funding
- Hospital Research Foundation, Woodville, Australia
- Department of Surgery, Otolaryngology Head and Neck Surgery, University of Adelaide, Adelaide, Australia
- Australian Government Research Training Program Scholarship
- National Health and Medical Research Council, Australia (NHMRC) [GNT1090898]
- Florey Medical Research Foundation, Adelaide, Australia
- Freemasons Foundation, Adelaide, Australia
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Many infectious diseases are associated with multidrug-resistant (MDR) bacteria residing in biofilms that require high antibiotic concentrations. While oral drug delivery is frequently ineffective, topical treatments have the potential to deliver higher drug concentrations to the infection site while reducing systemic side effects. This study determined the antibiofilm activity of a surgical wound gel loaded with the iron chelator deferiprone (Def) and the heme analogue gallium-protoporphyrin (GaPP), alone and in combination with ciprofloxacin. Activity against MDR Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Acinetobacter johnsonii biofilms was assessed in the colony biofilm and artificial wound model by enumeration of CFU and correlative light/electron microscopy. While Staphylococcus biofilms were equally susceptible to GaPP and Def-GaPP gels (log(10) reduction of 3.8 and 3.7, respectively), the Def-GaPP combination was crucial for significant activity against P. aeruginosa biofilms (log(10) reduction of 1.3 for GaPP and 3.3 for DefGaPP). When Def-GaPP gel was combined with ciprofloxacin, the efficacy exceeded the activity of the individual compounds. Def-GaPP delivered in a surgical wound gel showed significant antibiofilm activity against different MDR strains and could enhance the gel's wound-healing properties. Moreover, Def-GaPP indicated a potentiation of ciprofloxacin. This antibiofilm strategy has potential for clinical utilization as a therapy for topical biofilm-related infections.
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