Antibiotics | Clinical Application of Combination Antibiotic Therapy for Orthopedic Infections

This article systematically reviews the application of combination antibiotic therapy for orthopedic infections, including complex infection types such as fracture-related infections, post-arthroplasty joint infections, spinal implant infections, and anterior cruciate ligament reconstruction-associated infections. It summarizes indications for combination therapy, recommended regimens, and guideline variations across countries, providing critical references for clinical practice.

 

Literature Overview
This article, 'Combination Antibiotic Therapy for Orthopedic Infections', published in the journal Antibiotics, systematically reviews current guideline recommendations for combination antibiotic therapy in orthopedic infections. It analyzes clinical scenarios warranting combination therapy by integrating in vitro and animal study data, emphasizing its role in empirical treatment, drug-resistant infections, biofilm-related infections, and resistance risk reduction. Potential adverse effects, including toxicity and drug interactions, are also highlighted.

Background Knowledge
Orthopedic infections (e.g., fracture-related infections, prosthetic joint infections, spinal implant infections) often involve bacterial biofilm formation, complicating clinical management, particularly with drug-resistant pathogens. Conventional monotherapy may inadequately cover all potential pathogens or effectively combat biofilms. Combination antibiotic therapy has been proposed as a strategy to enhance antimicrobial activity, broaden pathogen coverage, improve bactericidal efficacy, and reduce resistance risks. However, guidelines from different countries and institutions show variability in recommending combination therapy, and high-quality clinical evidence remains limited. This review aims to provide clinicians with evidence-based indications and regimens for combination therapy while advocating for further clinical research.

 

 

Research Methods and Experiments
The study reviews indications and recommended regimens for combination antibiotic therapy in orthopedic infections based on existing clinical guidelines, in vitro, and animal experimental data. It covers various infection types, including fracture-related infections (FRI), prosthetic joint infections (PJI), spinal implant infections, and anterior cruciate ligament reconstruction infections (ACLRI), with a focus on pathogen-specific recommendations for Staphylococcus, Enterococcus, Enterobacteriaceae, and Pseudomonas species.

Key Conclusions and Perspectives

• Combination therapy is primarily indicated for empirical coverage, biofilm-associated infections, drug-resistant pathogens, and resistance risk mitigation.
• In FRI, recommended regimens include amoxicillin-clavulanate or ampicillin-sulbactam combined with vancomycin or daptomycin to cover gram-positive and anaerobic bacteria.
• For PJI, guidelines recommend vancomycin or linezolid combined with broad-spectrum β-lactams such as cefepime or meropenem.
• Spinal implant infections typically require combinations of gram-positive agents (e.g., vancomycin) and gram-negative agents (e.g., meropenem or ceftazidime).
• Empirical treatment for ACLRI recommends ampicillin-sulbactam or cefuroxime combined with daptomycin; daptomycin monotherapy is an option for allergic patients.
• Rifampin, fluoroquinolones, fosfomycin, and aminoglycosides are used to enhance biofilm penetration and synergistic bactericidal effects but require monitoring for toxicity and resistance.
• While combination therapy offers theoretical advantages, clinical evidence remains limited, necessitating more randomized controlled trials.

Research Significance and Prospects
This review provides clinicians with reference strategies for combination antibiotic therapy in complex orthopedic infections, underscoring the importance of individualized treatment. Future research should evaluate efficacy across infection types and resistance profiles, and explore novel antibiotic combinations and delivery systems to optimize therapeutic outcomes.

 

 

Conclusion
The application of combination antibiotic therapy in orthopedic infections remains controversial, particularly in the absence of high-quality clinical evidence. This article synthesizes current guideline recommendations and analyzes combination therapy strategies across infection types and pathogen profiles. While combination regimens offer advantages in broadening antimicrobial coverage and reducing resistance risks, their clinical efficacy requires further validation. Future studies should integrate individualized treatment approaches, resistance surveillance, and advanced antibiotic delivery systems to refine management protocols.

 

Eric Bonnet and Julie Lourtet-Hascoët. Combination Antibiotic Therapy for Orthopedic Infections. Antibiotics.