Dataset Information

Thermal Augmentation of Vancomycin Against Staphylococcal Biofilms.

ABSTRACT: Given the increasing evidence of safe application of elevated temperature in other clinical contexts, we consider the potential for supplemental hyperthermia to augment the effects of vancomycin against staphylococci, a major source of postoperative and posttraumatic sepsis. Laboratory reference strains and libraries of clinical blood isolates of Staphylococcus epidermidis and methicillin-resistant Staphylococcus aureus, both as planktonic cells and as established biofilms, were assessed for thermosensitivity and increased susceptibility to vancomycin in the setting of thermal treatment. In addition to viability measures, patterns of stress gene expression were assessed with quantitative polymerase chain reaction, and structural changes were measured using quantitative transmission electron microscopy. Laboratory strains of both species had reduced growth and biofilm viability at 45°C, a temperature commonly used in other domains such as adjuvant treatments of malignancy. Blood isolates of S. epidermidis were consistent in this regard as well, but significant between-isolate variability in thermosensitivity was seen in blood isolates of S. aureus. Expression profiling and ultrastructural measurements confirmed that elevated temperature was a substantial stressor with or without vancomycin treatment. Our findings suggest that temperature elevations shown to be tolerated in humans in other settings hold the potential to be used as an adjuvant to antibiotic therapy against staphylococcal biofilms.

SUBMITTER: Sturtevant RA

PROVIDER: S-EPMC4504807 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Thermal Augmentation of Vancomycin Against Staphylococcal Biofilms.

Sturtevant Rachael A RA Sharma Prannda P Pavlovsky Leonid L Stewart Elizabeth J EJ Solomon Michael J MJ Younger John G JG

Shock (Augusta, Ga.) 20150801 2

Given the increasing evidence of safe application of elevated temperature in other clinical contexts, we consider the potential for supplemental hyperthermia to augment the effects of vancomycin against staphylococci, a major source of postoperative and posttraumatic sepsis. Laboratory reference strains and libraries of clinical blood isolates of Staphylococcus epidermidis and methicillin-resistant Staphylococcus aureus, both as planktonic cells and as established biofilms, were assessed for the ...[more]

PMID: 25784524

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Project description:BackgroundLocal antimicrobial delivery through polymethylmethacrylate beads (PMMA), commonly vancomycin, is used for the treatment of contaminated open fractures but has limited activity against Staphylococcus aureus biofilms, which occur commonly in such fractures. Rifamycins have activity against biofilms and are an effective treatment for osteoarticular infections involving staphylococcal biofilms, but there are limited studies evaluating the activity of rifamycin derivatives, other than rifampin, against biofilms of S. aureus and evaluating incorporation of these drugs into PMMA for treatment of contaminated open fractures.Questions/purposes(1) Are rifamycin derivatives effective against established biofilms of clinical isolates of S. aureus? (2) Can PMMA be used as a carrier for rifamycin derivatives?MethodsBiofilms were developed and evaluated for susceptibility to a panel of antimicrobials in vitro using the minimum biofilm eradication concentration high-throughput model. Susceptibility was assessed by measuring bacterial recovery at 6 and 24 hours after antimicrobial treatment. Activity of rifamycin derivatives against intracellular bacteria was also evaluated using a gentamicin protection assay. Evaluation of PMMA as a carrier for rifampin and rifamycin derivatives was determined by assessing the curing time subsequent to loading of rifamycins and characterizing the release kinetics of rifamycins at daily intervals for 14 days from PMMA by performing bioassays.ResultsRifamycin derivatives between 1 and 8 µg/mL reduced bacteria within biofilms 5- to 9-logs and prevented bacterial recovery up to 24 hours post-treatment, indicating near to complete eradication of biofilms. Rifamycin derivatives at 32 µg/mL had activity against intracellular staphylococci, significantly reducing the number of internalized bacteria with limited effects on osteoblast viability. Rifampin was the only rifamycin observed to have a suitable release profile from PMMA, releasing 49% of the total antibiotic and maintaining a sustained released profile up to 14 days at a mean 28 ± 6 μg/mL.ConclusionsRifampin can be incorporated into PMMA and eluted at concentrations effective against biofilms and intracellular staphylococci.Clinical relevanceOur in vitro findings suggest that local delivery of rifampin may be an effective strategy for the prevention and/or treatment of open fractures where S. aureus biofilms might develop. Clinical studies are needed to characterize what role this approach might have in the prevention and treatment of infections involving biofilms.

Dataset Information

Thermal Augmentation of Vancomycin Against Staphylococcal Biofilms.

Publications

Thermal Augmentation of Vancomycin Against Staphylococcal Biofilms.

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