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J Bone Jt Infect. 2019 Jan 1;4(1):1-9. doi: 10.7150/jbji.29711. eCollection 2019.

Determination of Tobramycin and Vancomycin Exposure Required to Eradicate Biofilms on Muscle and Bone Tissue In Vitro.

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School of Biological & Health Systems Engineering, Arizona State University, Tempe, AZ, USA.
Sonoran Biosciences, Chandler, AZ, USA.
University of Arizona College of Medicine, Phoenix, AZ, USA.


Background: Bacterial biofilms cause chronic orthopaedic infections. Surgical debridement to remove biofilm can be ineffective without adjuvant local antimicrobials because undetected biofilm fragments may remain in the wound and reestablish the infection if untreated. However, the concentrations and duration of antimicrobial exposure necessary to eradicate bacteria from clinical biofilms remain largely undefined. In this study, we determined the minimum biofilm eradication concentration (MBEC) of tobramycin and vancomycin for bacterial biofilms grown on bone and muscle in vitro. Methods: Biofilms of pathogens found in musculoskeletal infections (S. aureus, S. epidermidis, E. faecalis, P. aeruginosa, and E. coli) were established for 72 hr on rabbit muscle and bone specimens in vitro and characterized by SEM imaging and CFU counts. Biofilm-covered tissue specimens were exposed to serial log2 dilutions (4000-31.25 µg/mL) of tobramycin, vancomycin, or a 1:1 combination of both drugs for 6, 24, or 72 hr. Tissues were subcultured following antimicrobial exposure to determine bacterial survival. The breakpoint concentration with no surviving bacteria was defined as the MBEC for each pathogen-antimicrobial-exposure time combination. Results: All tested pathogens formed biofilm on tissue. Tobramycin/vancomycin (1:1) was the most effective antimicrobial regimen with MBEC on muscle (10/10 pathogens) or bone (7/10 pathogens) generally in the range of 100-750 µg/mL with 24 or 72 hr exposure. MBEC decreased with exposure time for 53.3% of biofilms between 6 and 24 hr, 53.3% of biofilms between 24 and 72 hr, and for 76.7% of biofilms between 6 and 72 hr. MBECs on bone were significantly higher than corresponding MBECs on muscle tissue (p < 0.05). In most cases, tissue MBECs were lower compared to previously published MBECs for the same pathogens on polystyrene tissue-culture plates. Conclusions: The majority of MBECs for orthopaedic infections on bone and muscle are on the order of 100-750 µg/mL of vancomycin+tobramycin when sustained for at least 24 hr, which may be clinically achievable using high-dose antimicrobial-loaded bone cement (ALBC).


antimicrobial susceptibility; biofilm susceptibility; bone and joint infection; local antimicrobial delivery; minimum biofilm eradication concentration; surgical site infection

Conflict of interest statement

Competing Interests: DO and AM own stock in Sonoran Biosciences, which is developing sustained release antimicrobial formulations for treatment and prevention of biofilm-based infections. DO, VB, RM and JH are or have been employees of Sonoran Biosciences. AM has served as a paid consultant to Sonoran Biosciences.

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