Elution kinetics and antimicrobial efficacy of high-dose gram-negative antibiotic-loaded acrylic cement: an in vitro and in vivo study.

backgroundHigh-dose antibiotic-loaded acrylic cement is routinely employed for the management of skeletal infections when implant fixation or local structural support is required. However, no established consensus or clinical guidelines currently exist regarding the selection of antibiotics in acrylic cement, particularly those targeting Gram-negative bacteria. This study aimed to systematically evaluate, through both in vitro and animal experiments, the efficacy of high-dose antibiotic-loaded acrylic cement in controlling periprosthetic skeletal infections caused by Gram-negative bacteria following orthopedic implant placement.

methodsHigh doses (4 g) of tobramycin, meropenem, piperacillin, ceftazidime, ciprofloxacin, and aztreonam were individually incorporated into acrylic cement (40 g). The elution profiles (n = 6 per group), antimicrobial efficacy (n = 5 per test), and compressive mechanical properties (n = 8 per group) were characterized in vitro over 28 days. The composite demonstrating the most favorable overall performance was selected for subsequent in vivo evaluation in a rat model of periprosthetic joint infection induced by Pseudomonas aeruginosa (P. aeruginosa) (n = 15 per group).

resultsThe incorporation of antibiotics resulted in a reduction in the mechanical strength of all tested cement composites compared with plain cement; however, all formulations except piperacillin-containing cement maintained compressive strengths above 70 MPa. After 28 days of elution, compressive strength increased in all groups except piperacillin‑cement; ciprofloxacin‑cement exhibited the highest post‑elution compressive strength among the antibiotic‑loaded cements (99.57 ± 2.64 MPa). Tobramycin-cement demonstrated the highest cumulative antibiotic release over the 28-day period (7.867 ± 0.295%). The other five antibiotics were released predominantly within the first 7 days, with peak release occurring on the first day, particularly for piperacillin. Through in vitro antibacterial assays, meropenem-loaded cement exhibited the strongest antimicrobial activity against the tested strains, while tobramycin- and ciprofloxacin-loaded cements also maintained antibacterial efficacy throughout the 28-day testing period. Meropenem was selected for in vivo testing based on its overall superior in vitro performance. In a rat model of periprosthetic joint infection induced by P. aeruginosa, animals treated with meropenem-loaded cement showed significantly lower bacterial loads in all periarticular tissues compared with antibiotic‑free cement (P < 0.01) and less severe bone destruction. The in vivo study compared meropenem‑cement only with antibiotic‑free cement, not with other antibiotic‑loaded formulations. Microbial cultures of the retrieved meropenem-cement specimens revealed no bacterial growth.

conclusionsBoth in vitro and in vivo findings indicate that meropenem-loaded acrylic cement offers distinct advantages in terms of mechanical properties, elution characteristics, and sustained antimicrobial activity against Gram-negative bacteria. Meropenem-cement may therefore represent a promising candidate for local antimicrobial delivery in the management of Gram-negative skeletal infections, warranting further clinical investigation. However, the potential selection pressure for carbapenem-resistant organisms must be carefully managed in any clinical translation of this approach.