Antibiotic-Loaded PLA Composites for Local Prevention of Implant-Associated Infections: Comparative Evaluation Against Reference Strains and Clinical Isolates

Background/Objectives: Implant-associated infections remain among the most severe and clinically challenging complications in contemporary orthopedics, largely due to the formation of persistent bacterial biofilms and the limited penetration of systemically administered antibiotics into the tissue–implant interface. In this context, local antibacterial functionalization of implantable materials represents a promising strategy for the prevention of early infectious complications. The objective of this study was to develop and comparatively evaluate the antimicrobial performance of PLA-based composites loaded with antibiotics from different pharmacological classes, with a view toward their potential application in individualized 3D-printed implants. Methods: Polylactic acid (PLA)-based composites incorporating gentamicin, ciprofloxacin, doxycycline, and vancomycin were fabricated using thermal processing under conditions compatible with extrusion and fused filament fabrication. Physicochemical characterization (FTIR, TGA, SEM) was performed to assess the structure and morphology of the composites, and in vitro antibiotic release studies were conducted. Antimicrobial activity was evaluated using an agar diffusion assay against ATCC reference strains and clinical isolates of methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA), Klebsiella pneumoniae, and Pseudomonas aeruginosa (n = 10 per species). The antibacterial performance of the composites was evaluated in comparison with standard commercial antibiotic disks used as qualitative reference controls. Results: Antibiotic-loaded PLA composites exhibited consistent and reproducible antibacterial activity, markedly exceeding that of neat PLA. The broadest activity spectrum was observed for PLA–ciprofloxacin (≈29–36 mm) and PLA–gentamicin (≈25–27 mm), which effectively inhibited both Gram-positive and Gram-negative clinical isolates, including MRSA and P. aeruginosa. PLA–vancomycin retained selective activity against staphylococci (≈14–15 mm), whereas PLA–doxycycline demonstrated limited efficacy against Gram-negative pathogens. Physicochemical analysis confirmed successful incorporation of antibiotics without detectable degradation of the polymer structure, while release studies demonstrated sustained antibiotic release from the composite materials. Importantly, the expected pharmacological activity profiles of the antibiotics were preserved after incorporation into the polymer matrix and subsequent high-temperature processing. Conclusions: The results demonstrate the feasibility of integrating clinically relevant antibiotics into a thermoplastic PLA matrix while preserving their selective antimicrobial activity following processing compatible with extrusion and additive manufacturing. The proposed PLA-based composites can be regarded as elements of a pharmacologically tunable antibacterial platform, offering a rationale for the development of context-dependent, biodegradable, 3D-printed implants for the local prevention of implant-associated infections in the setting of increasing antimicrobial resistance.