Polymicrobial Infections in Orthopedic Surgery: A Marker of Clinical Complexity, a Contributor to Poor Outcomes, or Both?

Background. Polymicrobial post-surgical infections represent a clinically relevant component of orthopedic surgical infections and occur across a broad range of clinical settings, including implant-associated, surgical site, spinal, surgical oncology, and fracture-related infections. Objective. To characterize the epidemiological and clinical features of polymicrobial post-surgical infections across different settings and investigate their prognostic significance. Methods. A structured literature search was conducted using a scoping review-informed approach. Additional references were identified through reference-list screening and expert-informed selection. Evidence was synthesized narratively, integrating clinical, epidemiological, microbiological, and mechanistic perspectives. Results. Polymicrobial infections occur particularly in complex clinical scenarios involving foreign material, extensive tissue damage, complex reconstructive procedures, severe trauma, impaired host defenses, and compromised tissue perfusion, all of which can create opportunities for co-colonization by multiple microorganisms. Reported frequencies vary across populations, anatomical sites, surgical procedures, infection timing, microbial composition, and diagnostic methods. The microbiological spectrum is diverse, with Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus spp., Gram-negative bacteria, and anaerobes among the most commonly reported pathogens. Evidence on outcomes is heterogeneous: some cohorts associate polymicrobial infection with treatment failure, whereas others do not identify it as an independent risk factor. Conclusions. Polymicrobial post-surgical orthopedic infection may be regarded both as a marker of clinical and surgical complexity and, in selected settings, as a potential contributor to adverse outcomes. Its prognostic significance should therefore be interpreted within the clinical context and in light of the specific characteristics of each infection. The review also explores the potential of phytochemicals in interfering with interspecies communication and counteracting polymicrobial biofilms.