Antibiotic elution from polymethylmethacrylate cement over 60 days: an in vitro study of 21 antibiotic combinations against Cutibacterium acnes and coagulase-negative Staphylococcus

Background: Periprosthetic joint infection (PJI) of the shoulder differs from that of other joints because of the prevalence of Cutibacterium acnes and coagulase-negative Staphylococcus (CNS). 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. Methods: Polymethylmethacrylate cement (PMMA) beads loaded with antibiotic were made in triplicate using a silicone mold. Vancomycin (V), ertapenem (E), doxycycline (D), ceftriaxone (CX), cefazolin (CZ), and rifampin (R) were tested separately and in combination for a total of 21 conditions. Beads were suspended in phosphate-buffered saline and agitated at 37°C. Eluate was collected at 11 time points 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 600 nm to determine bacterial growth. Results: In vitro analysis revealed that numerus antibiotic combinations induced full bacterial suppression for the full 60-day elution period. Vancomycin paired with cefazolin and ceftriaxone displayed full 60-day suppression in some but not all strains. Ceftriaxone plus doxycycline induced full suppression in three-fourths of strains. Cefazolin plus doxycycline also induced full suppression in three-fourths 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, and R+D (OD difference range: 0.38-0.53, P = .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 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 that 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 the micro-organisms living in biofilm. Further consideration should be given to the antibiotic candidates that fully suppressed growth in all strains over 60 days.