Abstract
Antibiotic-tolerant bacterial biofilms are notorious in causing PJI. Antibiotic loaded calcium sulfate bead (CSB) bone void fillers and PMMA cement and powdered vancomycin (VP) have been used to achieve high local antibiotic concentrations; however, the effect of drainage on concentration is poorly understood. We designed an in vitro flow reactor which provides post-surgical drainage rates after knee revision surgery to determine antibiotic concentration profiles. Tobramycin and vancomycin concentrations were determined using LCMS, zones of inhibition confirmed potency and the area under the concentration–time curve (AUC) at various time points was used to compare applications. Concentrations of antibiotcs from the PMMA and CSB initially increased then decreased before increasing after 2 to 3 h, correlating with decreased drainage, demonstrating that concentration was controlled by both release and flow rates. VP achieved the greatest AUC after 2 h, but rapidly dropped below inhibitory levels. CSB combined with PMMA achieved the greatest AUC after 2 h. The combination of PMMA and CSB may present an effective combination for killing biofilm bacteria; however, cytotoxicity and appropriate antibiotic stewardship should be considered. The model may be useful in comparing antibiotic concentration profiles when varying fluid exchange is important. However, further studies are required to assess its utility for predicting clinical efficacy.
Highlights
IntroductionPeriprosthetic joint infections (PJI) present many challenges for orthopedic surgeons as the economic burden and incidence rate increases [1]
Introduction conditions of the Creative CommonsPeriprosthetic joint infections (PJI) present many challenges for orthopedic surgeons as the economic burden and incidence rate increases [1]
InInour ourstudy, study,we weintroduce introducea acontinuous continuousflow-through flow-throughreactor reactorsystem systemdesigned designedbased based on drainage in the human knee following revision surgery, to study the antibiotic on drainage in the human knee following PJI revision surgery, to study the antibiotic conconcentration profile over time based elution from antibiotic loaded bone centration profile over time based onon thethe elution from antibiotic loaded bone cecement, absorbable and as a single bolus added in powder form
Summary
Periprosthetic joint infections (PJI) present many challenges for orthopedic surgeons as the economic burden and incidence rate increases [1]. These infections lengthen hospitalizations and increase the risk of mortality and morbidity [2]. Due to a higher tolerance to antibiotics compared with planktonic cells, biofilms require extended or repeated high concentrations of exposure [4,5]. To treat bacterial biofilm PJIs, antibiotics such as vancomycin and the aminoglycosides tobramycin and gentamicin are often mixed into bone cement to provide locally high concentrations and broad spectrum coverage against Gram positive and negative pathogens [6]. Broad spectrum antibiotics are used because culture data may not identify the infecting bacteria or this information may not be available at the time of operation [7,8]
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