title: Hyperosmotic Agents and Antibiotics Affect Dissolved Oxygen and pH Concentration Gradients in Staphylococcus aureus Biofilms.
abstract: Biofilms on wound surfaces are treated topically with hyperosmotic agents, such as medical-grade honey and cadexomer iodine; in some cases, these treatments are combined with antibiotics. Tissue repair requires oxygen, and a low pH is conducive to oxygen release from red blood cells and epithelialization. We investigated the variation of dissolved oxygen concentration and pH with biofilm depth and the variation in oxygen consumption rates when biofilms are challenged with medical-grade honey or cadexomer iodine combined with vancomycin or ciprofloxacin. Dissolved oxygen and pH depth profiles inStaphylococcus aureusbiofilms were measured using microelectrodes. The presence of cadexomer iodine with vancomycin or ciprofloxacin on the surface of the biofilm permitted a measurable concentration of oxygen at greater biofilm depths (101.6 ± 27.3 μm,P= 0.02; and 155.5 ± 27.9 μm,P= 0.016, respectively) than in untreated controls (30.1 μm). Decreases in pH of ∼0.6 and ∼0.4 units were observed in biofilms challenged with medical-grade honey alone and combined with ciprofloxacin, respectively (P< 0.001 and 0.01, respectively); the number of bacteria recovered from biofilms was significantly reduced (1.26 log) by treatment with cadexomer iodine and ciprofloxacin (P= 0.002) compared to the untreated control. Combining cadexomer iodine and ciprofloxacin improved dissolved oxygen concentration and penetration depth into the biofilm, while medical-grade honey was associated with a lower pH; not all treatments established a bactericidal effect in the time frame used in the experiments.IMPORTANCEReports about using hyperosmotic agents and antibiotics against wound biofilms focus mostly on killing bacteria, but the results of these treatments should additionally be considered in the context of how they affect physiologically important parameters, such as oxygen concentration and pH. We confirmed that the combination of a hyperosmotic agent and an antibiotic results in greater dissolved oxygen and reduced pH within anS. aureusbiofilm.
authors.affiliation: The Gene and Linda Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, Washington, USA.
authors.forename: Mia Mae
authors.initials: MM
authors.lastname: Kiamco
authors.affiliation: The Gene and Linda Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, Washington, USA.
authors.forename: Erhan
authors.initials: E
authors.lastname: Atci
authors.affiliation: The Gene and Linda Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, Washington, USA.
authors.forename: Abdelrhman
authors.identifier: http://orcid.org/0000-0003-2132-0487
authors.initials: A
authors.lastname: Mohamed
authors.affiliation: The Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington, USA.
authors.forename: Douglas R
authors.identifier: http://orcid.org/0000-0001-6791-055X
authors.initials: DR
authors.lastname: Call
authors.affiliation: The Gene and Linda Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, Washington, USA beyenal@wsu.edu.
authors.forename: Haluk
authors.initials: H
authors.lastname: Beyenal
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D002939:Ciprofloxacin / Q000627:therapeutic use*; D003131:Combined Modality Therapy / Q000379:methods; D006722:Honey; D006863:Hydrogen-Ion Concentration; D007466:Iodophors / Q000627:therapeutic use*; D008826:Microbial Sensitivity Tests; D009997:Osmotic Pressure; D010100:Oxygen / Q000378:metabolism; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development*; D014640:Vancomycin / Q000627:therapeutic use*; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D007466:Iodophors; D002939:Ciprofloxacin; D014640:Vancomycin; C038634:cadexomer iodine; D010100:Oxygen
keywords: Staphylococcus aureus; biofilm; dissolved oxygen; hyperosmotic agent; pH