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Identifying alternative antibiotics that elute from calcium sulfate beads for treatment of orthopedic infections.

ABSTRACT: There has been increasing interest in the use of a synthetic absorbable calcium sulfate (CaSO₄ ) for local antibiotic delivery in orthopaedic infections. The purpose of this study was to quantify elution kinetics of six antibiotics (amikacin, meropenem, fosfomycin, minocycline, cefazolin, and dalbavancin) from a clinically relevant CaSO₄ bead model and compare elution and antimicrobial activity to the current clinical gold standards: vancomycin and tobramycin. Antibiotic-loaded synthetic CaSO₄ beads were immersed in phosphate buffered saline and incubated at 37°C. Eluent was harvested at eight time points over 28 days. Antibiotic concentrations were measured by high performance liquid chromatography to quantify elution rates. CaSO₄ beads demonstrated burst release kinetics. Dalbavancin, cefazolin, and minocycline all demonstrated similar elution profiles to vancomycin. Amikacin and meropenem demonstrated favorable elution profiles and durations of above-minimum inhibitory concentration when compared to tobramycin. Clinical Significance: This study provides important novel data regarding the utility of amikacin, meropenem and dalbavancin as alternative choices to place in CaSO₄ carriers when treating orthopaedic infections.

SUBMITTER: Levack AE

PROVIDER: S-EPMC8716667 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Identifying alternative antibiotics that elute from calcium sulfate beads for treatment of orthopedic infections.

Levack Ashley E AE Turajane Kathleen K Driscoll Daniel A DA Yang Xu X Miller Andy O AO Bostrom Mathias P MP Wellman David S DS Carli Alberto V AV

Journal of orthopaedic research : official publication of the Orthopaedic Research Society 20210712 5

There has been increasing interest in the use of a synthetic absorbable calcium sulfate (CaSO<sub>4</sub> ) for local antibiotic delivery in orthopaedic infections. The purpose of this study was to quantify elution kinetics of six antibiotics (amikacin, meropenem, fosfomycin, minocycline, cefazolin, and dalbavancin) from a clinically relevant CaSO<sub>4</sub> bead model and compare elution and antimicrobial activity to the current clinical gold standards: vancomycin and tobramycin. Antibiotic-lo ...[more]

PMID: 34191350

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Project description:IntroductionAdult spinal deformity (ASD) surgery patients are at higher risk for surgical site infections (SSIs) due to large incisions, high blood loss, long surgical duration, and extensive instrumentation. The use of vancomycin powder has demonstrated inconsistent results in ASD surgery. Antibiotic-impregnated calcium sulfate beads have been used in arthroplasty and foot and ankle surgery with promising results. The purpose of this study was to provide preliminary data on the use of vancomycin-impregnated calcium sulfate beads in the prevention of SSI following ASD surgery and provide comparisons to the use of vancomycin powder.MethodsA retrospective chart review was performed for 95 consecutive surgical ASD patients at a tertiary care center from January 2017 until March 2020. Patients received either vancomycin powder (powder group) or vancomycin-impregnated calcium sulfate beads (bead group) intrawound prior to closure. Patient demographics, operative course, and incidence of postoperative infections were recorded. A two-tailed chi-squared test was performed to compare infection rates.ResultsNinety-five patients were included for review. Forty-two patients were in the powder group and 53 patients were in the bead group. The bead group was older (59.8 vs 67.8 years, p < 0.01) with similar BMI and rates of diabetes, smoking, and length of surgery. There were four postoperative SSI in the powder group requiring operative irrigation and debridement and one SSI in the bead group (9.5% vs 1.9%, p = 0.09). All infections occurred in the first 90 days of the postoperative period.ConclusionPreliminary examination of the use of vancomycin-impregnated calcium sulfate beads demonstrated a 1.9% surgical site infection rate in adult spinal deformity surgical patients, which was not significantly different compared with the 9.5% infection rate in patients who received vancomycin powder. Prospective study is needed to determine if the differences found are significant in a larger number of patients.

Project description:Introduction: Bacterial biofilms are an important virulence factor in chronic periprosthetic joint infection (PJI) and other orthopedic infection since they are highly tolerant to antibiotics and host immunity. Antibiotics are mixed into carriers such as bone cement and calcium sulfate bone void fillers to achieve sustained high concentrations of antibiotics required to more effectively manage biofilm infections through local release. The effect of antibiotic diffusion from antibiotic-loaded calcium sulfate beads (ALCS-B) in combination with PMMA bone cement spacers on the spread and killing of Pseudomonas aeruginosa Xen41 (PA-Xen41) biofilm was investigated using a "large agar plate" model scaled for clinical relevance. Methods: Bioluminescent PA-Xen41 biofilms grown on discs of various orthopedic materials were placed within a large agar plate containing a PMMA full-size mock "spacer" unloaded or loaded with vancomycin and tobramycin, with or without ALCS-B. The amount of biofilm spread and log reduction on discs at varying distances from the spacer was assessed by bioluminescent imaging and viable cell counts. Results: For the unloaded spacer control, PA-Xen41 spread from the biofilm to cover the entire plate. The loaded spacer generated a 3 cm zone of inhibition and significantly reduced biofilm bacteria on the discs immediately adjacent to the spacer but low or zero reductions on those further away. The combination of ALCS-B and a loaded PMMA spacer greatly reduced bacterial spread and resulted in significantly greater biofilm reductions on discs at all distances from the spacer. Discussion: The addition of ALCS-B to an antibiotic-loaded spacer mimic increased the area of antibiotic coverage and efficacy against biofilm, suggesting that a combination of these depots may provide greater physical antibiotic coverage and more effective dead space management, particularly in zones where the spread of antibiotic is limited by diffusion (zones with little or no fluid motion).

Dataset Information

Identifying alternative antibiotics that elute from calcium sulfate beads for treatment of orthopedic infections.

Publications

Identifying alternative antibiotics that elute from calcium sulfate beads for treatment of orthopedic infections.

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