Antibiotic Elution from PMMA Over 60 Days: an in vitro Study of 21 antibiotic combinations against C. acnes and Coagulase Negative Staph. (CNS).

Abstract

Periprosthetic Joint Infection (PJI) of the shoulder differs from that of other joints due a prevalence of C. acnes and Coagulase Negative Staph. The ideal antibiotic combination for 2-stage revision is not fully known. The purpose of this study was to evaluate numerous different antibiotic eluates over a 60 day period against multiple strains of common pathogens found in shoulder PJI. PMMA beads loaded with antibiotic were made in triplicate using a silicone mold. Vancomycin (V), Ertapenam (E), Doxycycline, Ceftriaxone (CX), Cefazolin (CZ), Rifampin (R) were tested separately and in combination for a total of 21 conditions. Beads were suspended in phosphate buffered saline (PBS) and agitated at 37°C. Eluate was collected at 11 timepoints over 60 days. The biological activity of eluate samples was measured against 4 bacterial strains from clinically proven infection: 2 CNS strains and 2 C. acnes strains. Bacterial colonies were inoculated onto 96-well plates. For each well, 250μL of eluate and 50μL of culture were introduced and incubated for 48 hours at 37°C. The optical density (OD) of each well was read at 600nm to determine bacterial growth. In vitro analysis revealed that numerus antibiotic combinations induce full bacterial suppression for the full 60-day elution period. Vancomycin paired with Cefazolin and Ceftriaxone displays full 60-day suppression in some but not all strains. Ceftriaxone plus Doxycycline induces full suppression in ¾ of strains. Cefazolin plus Doxycycline also induces full suppression in 3/4 of strains. Five antibiotic admixtures with PMMA induced full growth suppression for all 4 strains including: R, V+D, R+V, R +CZ, R+CX, R+D. (OD difference range: 0.38-0.53, P=0.0005) DISCUSSION/CONCLUSIONS: This study evaluates antibiotic/PMMA combinations in a time release model against common organisms in shoulder PJI. Rifampin alone and combined with most tested antibiotics produced full inhibition over 60 days of CNS and C. acnes strains. Vancomycin plus doxycycline powerfully suppressed in all strains over 60 days. Ceftriaxone and cefazolin plus vancomycin suppressed most strains of C. acnes and CNS with earlier breakthrough in CNS strains. Recent studies show rifampin's effect on the structural integrity of PMMA can be mitigated, making it an intriguing antibiotic candidate for shoulder PJI treatment for its high efficacy in vitro and bactericidal capabilities against microorganisms living in biofilm. Further study and consideration should be given to the antibiotic candidates that fully suppressed growth in all strains over 60 days.