Harry S Courtney

Publications of Harry S Courtney

• Cis-2-decenoic Acid Inhibits S. aureus Growth and Biofilm In Vitro: A Pilot Study.

  Authors: Jessica Amber Jennings, Harry S Courtney, Warren O Haggard

  Clinical orthopaedics and related research. 05/2012;

  BACKGROUND: Cis-2 decenoic acid (C2DA) disperses biofilm in many strains of microorganisms. However, whether C2DA inhibits bacterial growth or has potential to boost the actions of antibiotics isBACKGROUND: Cis-2 decenoic acid (C2DA) disperses biofilm in many strains of microorganisms. However, whether C2DA inhibits bacterial growth or has potential to boost the actions of antibiotics is unknown. QUESTIONS/PURPOSES: We asked whether (1) C2DA inhibited MRSA growth and biofilm, (2) antibiotics increased inhibitory effects, (3) inhibitory concentrations of C2DA were cytotoxic to human cells, and (4) effective concentrations could be delivered from a chitosan sponge drug delivery device. METHODS: Broth containing seven concentrations of C2DA and six concentrations of either daptomycin, vancomycin, or linezolid was inoculated with a clinical isolate of MRSA and added to a total of 504 coated microtiter plate wells in triplicate (n = 3) for turbidity bacterial growth and crystal violet biofilm mass quantification. We used fibroblast cell viability assays of six C2DA concentrations (n = 4) to evaluate preliminary biocompatibility. We measured the elution of C2DA from a chitosan sponge drug delivery device with two representative loading concentrations (n = 3). RESULTS: C2DA at concentrations of 500 μg/mL and above inhibited growth, while 125 μg/mL C2DA inhibited biofilm. Combination with antibiotics increased these effects. At concentrations up to 500 μg/mL, there were no cytotoxic effects on fibroblasts. Chitosan sponges loaded with 100 mg of C2DA eluted concentrations at or above biofilm-inhibitory concentrations for 5 days. CONCLUSIONS: C2DA inhibited biofilm formation by MRSA at biocompatible concentrations, with increasing biofilm reduction with added antibiotics. Elution of C2DA from a chitosan sponge can be modified through adjusting loading concentration. CLINICAL RELEVANCE: By inhibiting biofilm formation on implant surfaces, C2DA may reduce the number of infections in musculoskeletal trauma.

• Evaluation of two sources of calcium sulfate for a local drug delivery system: a pilot study.

  Authors: Ashley C Parker, J Keaton Smith, Harry S Courtney, Warren O Haggard

  Clinical orthopaedics and related research. 05/2011; 469(11):3008-15.

  Local drug delivery has substantial potential to prevent infections compared with systemic delivery. Although calcium sulfate (CaSO(4)) has been studied for local drug delivery and two types areLocal drug delivery has substantial potential to prevent infections compared with systemic delivery. Although calcium sulfate (CaSO(4)) has been studied for local drug delivery and two types are commercially available, it is unknown whether they differentially release antibiotics. We determined the differences between two sources of CaSO(4) and the K(2)SO(4) catalyst's presence on the degradation, daptomycin elution, and activity against Staphylococcus aureus. We formed pellets from synthetic and naturally sourced (from gypsum) CaSO(4) and loaded with 5% daptomycin and 3% or 0% K(2)SO(4). We used in vitro experiments to determine the daptomycin concentration and degradation profiles over 10 days. Turbidity assays were used to evaluate the activity of the daptomycin eluates against S. aureus. All pellets exhibited a bolus release with the highest daptomycin concentration on Day 1 with the sourced CaSO(4) pellets. The synthetic CaSO(4) pellets with 3% K(2)SO(4) exhibited a slower drug release compared with the synthetic CaSO(4) pellets with 0% K(2)SO(4), which degraded and eluted daptomycin too quickly to inhibit S. aureus. Turbidity assays demonstrated that all CaSO(4) pellets inhibit S. aureus for expected lengths of time. Our preliminary in vitro data suggest differences in the degradation, elution, and activity properties between sourced and synthetic CaSO(4) pellets. The addition of K(2)SO(4) appeared beneficial when using synthetic CaSO(4). Synthetic CaSO(4) may be effective when slow degradation and longer elution times are needed. Local delivery of eluted daptomycin can be tailored through material selection and K(2)SO(4) addition.

• Chitosan coatings deliver antimicrobials from titanium implants: a preliminary study.

  Authors: Peter A Norowski, Harry S Courtney, Jegdish Babu, Warren O Haggard, Joel D Bumgardner

  Implant dentistry. 02/2011; 20(1):56-67.

  Chitosan was investigated as a coating for local delivery of antimicrobials for prevention of acute implant infection. The objectives of this study were to (1) measure the release of 2 antimicrobialsChitosan was investigated as a coating for local delivery of antimicrobials for prevention of acute implant infection. The objectives of this study were to (1) measure the release of 2 antimicrobials from chitosan coatings, (2) determine efficacy of eluted antimicrobials against bacteria, in vitro, and (3) evaluate toxicity of eluted drugs to host cells/tissues. Chitosan coatings (80.7% deacetylated, 108 kDa) containing 20% tetracycline or 0.02% chlorhexidine digluconate were bonded to titanium via silane reactions. After elution in culture medium for 7 days, eluates were tested against model pathogens Actinobacillus actinomycetemcomitans and Staphylococcus epidermidis in turbidity tests and in 24-hour cytotoxicity tests using human osteoblasts and fibroblasts. Finally, antibiotic-loaded chitosan-coated titanium pins were implanted for 7 days in muscle of Sprague-Dawley rats to evaluate the initial tissue response. Coatings released 89% of tetracycline in 7 days and 100% chlorhexidine in 2 days. Released tetracycline inhibited growth (95%-99.9%) of pathogens for up to 7 days with no cytotoxicity to human cells. Released chlorhexidine was active against pathogens for 1 to 2 days (56%-99.5% inhibition) but was toxic to cells on the first day of elution. Typical acute inflammatory response was observed to antimicrobial-loaded chitosan coatings similar to unloaded coatings. These preliminary data support the hypothesis that chitosan coatings have the potential to locally deliver antimicrobials to inhibit bacteria without being toxic to host cells/tissues and warrant additional studies to evaluate the ability of the coatings to prevent/resist infection and promote osseointegration.

• Antibiotic-loaded chitosan film for infection prevention: A preliminary in vitro characterization.

  Authors: J Keaton Smith, Joel D Bumgardner, Harry S Courtney, Mark S Smeltzer, Warren O Haggard

  Journal of biomedical materials research. Part B, Applied biomaterials. 07/2010; 94(1):203-11.

  The growing infection rate by methicillin-resistant Staphylococcus aureus, especially with bone fracture fixation implants, is a major concern in extremity musculoskeletal wound treatment. ThisThe growing infection rate by methicillin-resistant Staphylococcus aureus, especially with bone fracture fixation implants, is a major concern in extremity musculoskeletal wound treatment. This preliminary investigation evaluates the ability of chitosan film to be loaded with daptomycin and vancomycin in the operating room, in situ loading, and applied to musculoskeletal fixation devices to lessen or prevent infection. Films with 61, 71, and 80% degrees of deacetylation (DDA) made using lactic or acetic acid solvents were analyzed for their antibiotic uptake, elution, and activity along with film swelling ratio, ultimate tensile strength, Young's modulus, adhesive strength, and degradation. Chitosan films after 1 min of rehydration were able in a simulated, clinical setting to maintain mechanical integrity and adhesive strength to be applied to bone fracture fixation devices or implant surfaces. The film percent degradation increased with DDA increasing from 61 to 80%, but film degradation rate decreased in the presence of antibiotics. Eighty percent DDA chitosan films were optimal for absorbing and eluting antibiotics. Antibiotics eluted by the films were active against Staphylococcus aureus. These findings indicate that an 80% DDA chitosan film is potentially advantageous as a clinically adjunctive treatment in musculoskeletal injuries to lessen or prevent infections.

• Chitosan sponges to locally deliver amikacin and vancomycin: a pilot in vitro evaluation.

  Authors: Scott P Noel, Harry S Courtney, Joel D Bumgardner, Warren O Haggard

  Clinical orthopaedics and related research. 03/2010; 468(8):2074-80.

  Open orthopaedic wounds are ideal sites for infection. Preventing infection in these wounds is critical for reducing patient morbidity and mortality, controlling antimicrobial resistance and loweringOpen orthopaedic wounds are ideal sites for infection. Preventing infection in these wounds is critical for reducing patient morbidity and mortality, controlling antimicrobial resistance and lowering the cost of treatment. Localized drug delivery has the potential to overcome the challenges associated with traditional systemic dosing. A degradable, biocompatible polymer sponge (chitosan) that can be loaded with clinician-selected antibiotics at the point of care would provide the patient and clinician with a desirable, adjunctive preventive modality. We asked (1) if an adaptable, porous chitosan matrix could absorb and elute antibiotics for 72 hours for potential use as an adjunctive therapy to débridement and lavage; and (2) if the sponges could elute levels of antibiotic that would inhibit growth of Staphylococcus aureus and Pseudomonas aeruginosa? We fabricated a degradable chitosan sponge that can be loaded with antibiotics during a 60-second hydration in drug-containing solution. In vitro evaluation determined amikacin and vancomycin release from chitosan sponges at six time points. Activity tests were used to assess the release of inhibitory levels of amikacin and vancomycin. Amikacin concentration was 881.5 microg/mL after 1 hour with a gradual decline to 13.9 microg/mL after 72 hours. Vancomycin concentration was 1007.4 microg/mL after 1 hour with a decrease to 48.1 microg/mL after 72 hours. Zone of inhibition tests were used to verify inhibitory levels of drug release from chitosan sponges. A turbidity assay testing activity of released amikacin and vancomycin indicated inhibitory levels of elution from the chitosan sponge. Chitosan sponges may provide a potential local drug delivery device for preventing musculoskeletal infections.

• An Approach for determining antibiotic loading for a physician-directed antibiotic-loaded PMMA bone cement formulation.

  Authors: Gladius Lewis, Jennifer L Brooks, Harry S Courtney, Yuan Li, Warren O Haggard

  Clinical orthopaedics and related research. 02/2010; 468(8):2092-100.

  When a physician-directed antibiotic-loaded polymethylmethacrylate (PMMA) bone cement (ALBC) formulation is used in total hip arthroplasties (THAs) and total knee arthroplasties (TKAs), currentWhen a physician-directed antibiotic-loaded polymethylmethacrylate (PMMA) bone cement (ALBC) formulation is used in total hip arthroplasties (THAs) and total knee arthroplasties (TKAs), current practice in the United States involves arbitrary choice of the antibiotic loading (herein defined as the ratio of the mass of the antibiotic added to the mass of the cement powder). We suggest there is a need to develop a rational method for determining this loading. We propose a new method for determining the antibiotic loading to use when preparing a physician-directed ALBC formulation and illustrate this method using three in vitro properties of an ALBC in which the antibiotic was daptomycin. Daptomycin was blended with the powder of the cement using a mechanical mixer. We performed fatigue, elution, and activity tests on three sets of specimens having daptomycin loadings of 2.25, 4.50, and 11.00 wt/wt%. Correlational analyses of the results of these tests were used in conjunction with stated constraints and a nonlinear optimization method to determine the daptomycin loading to use. With an increase in daptomycin loading, the estimated mean fatigue limit of the cement decreased, the estimated elution rate of the antibiotic increased, and the percentage inhibition of staphylococcal growth by the eluate remained unchanged at 100%. For a daptomycin-loaded PMMA bone cement we computed the optimum amount of daptomycin to mechanically blend with 40 g of cement powder is 1.36 g. We suggest an approach that may be used to determine the amount of antibiotic to blend with the powder of a PMMA bone cement when preparing a physician-directed ALBC formulation, and highlighted the attractions and limitations of this approach. When a physician-directed ALBC formulation is selected for use in a TKA or THA, the approach we detail may be employed to determine the antibiotic loading to use rather than the empirical approach that is taken in current clinical practice.

• Preliminary in vitro evaluation of an adjunctive therapy for extremity wound infection reduction: Rapidly resorbing local antibiotic delivery.

  Authors: Stephanie R Jackson, Kelly C Richelsoph, Harry S Courtney, Joseph C Wenke, Joanna G Branstetter, Joel D Bumgardner, Warren O Haggard

  Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 01/2009;

  Despite the continuing advances in treatment of open fractures and musculoskeletal wounds, infection remains a serious complication. Current treatments to prevent infection utilize surgicalDespite the continuing advances in treatment of open fractures and musculoskeletal wounds, infection remains a serious complication. Current treatments to prevent infection utilize surgical debridement and irrigation, and high doses of systemic antimicrobial therapy. The aim of this work was to evaluate, in vitro, the potential of a fast-resorbing calcium sulfate pellet loaded with an antibiotic. The pellet could be used as an adjunctive therapy at the time of debridement and irrigation to reduce bacterial wound contamination. Small pellets containing a binder and calcium sulfate were engineered to resorb rapidly (within 24 h) and deliver high local doses of antibiotic (amikacin, gentamicin, or vancomycin) to the wound site while minimizing systemic effects. Results from dissolution, elution, and biological activity tests against P. aeruginosa and S. aureus were used to compare the performance of antibiotic-loaded, rapidly resorbing calcium sulfate pellets to antibiotic-loaded crushed conventional calcium sulfate pellets. Antibiotic-loaded rapidly resorbing pellets dissolved in vitro in deionized water in 12-16 h and released therapeutic antibiotic levels in phosphate buffered saline that were above the minimal inhibitory concentration for P. aeruginosa and S. aureus, completely inhibiting the growth of these bacteria for the life of the pellet. Crushed conventional calcium sulfate pellets dissolved over 4-6 days, but the eluates only contained sufficient antibiotic to inhibit growth for the first 4 h. These data indicate that fast-resorbing pellets can release antibiotics rapidly and at therapeutic levels. Adjunctive therapy with fast-acting pellets is promising and warrants further in vivo studies. Published by Wiley Periodicals, Inc. J Orthop Res.

• Daptomycin eluted from calcium sulfate appears effective against Staphylococcus.

  Authors: Nathan D Webb, Jonathan D McCanless, Harry S Courtney, Joel D Bumgardner, Warren O Haggard

  Clinical orthopaedics and related research. 07/2008; 466(6):1383-7.

  The emergence of resistant strains of Gram-positive organisms in osteomyelitis creates treatment challenges. Daptomycin is an antibiotic that shows promise for treating some resistant strains ofThe emergence of resistant strains of Gram-positive organisms in osteomyelitis creates treatment challenges. Daptomycin is an antibiotic that shows promise for treating some resistant strains of Gram-positive infections; however, it has not been widely used clinically for the treatment of osteomyelitis. We determined whether daptomycin eluted from calcium sulfate-a local delivery vehicle used for the treatment of osteomyelitis-retained activity against Gram-positive bacteria. Daptomycin was mixed with calcium sulfate hemihydrate, with both laboratory powder and a commercial kit, to form a hardened pellet. Daptomycin was eluted from calcium sulfate and retained its ability to inhibit bacterial growth of Staphylococcus aureus and Staphylococcus epidermidis for eluates gathered up to 28 days. Our preliminary data demonstrates sterilized pellets with daptomycin retained their ability to inhibit bacterial growth of certain strains of Gram-positive organisms.