Efficacy and Safety of Tetracyclines in Bone and Joint Infections: A Literature Review

Abstract Introduction Bone and joint infections (BJIs) are complex and difficult to eradicate, and have high relapse rates and limited oral treatment options. Tetracyclines combine favorable bone penetration, oral bioavailability, and activity against multidrug-resistant (MDR) pathogens, but their clinical role in BJIs remains unclear. Objectives This study aimed to summarize experimental and clinical evidence on tetracyclines in the management of BJIs, including pharmacology, antimicrobial activity, clinical efficacy, and guideline recommendations. Methods We performed a literature review of PubMed® (1960–2024) for animal, pharmacokinetic, and clinical studies evaluating tetracyclines in BJIs. Data on bone distribution, anti-biofilm activity, clinical outcomes, tolerability, and recommendations were extracted and synthesized. Results Tetracyclines display strong bone affinity but inconsistent tissue concentrations in experimental models. In vitro and in vivo studies suggest anti-biofilm activity, particularly in combination with rifampicin, although monotherapy is insufficient. Two randomized controlled trials reported inferior outcomes compared with standard regimens. Observational studies of minocycline and tigecycline demonstrated variable efficacy (40–80%), with better outcomes in salvage therapy for MDR infections, but frequent gastrointestinal intolerance. Data on omadacycline remain limited to a single small cohort. Tetracyclines are recommended in guidelines for zoonotic infections (e.g., Brucella) and as long-term suppressive therapy in selected prosthetic joint infections, but evidence is weak compared with other agents, especially fluoroquinolones. Conclusions Tetracyclines may provide therapeutic options for refractory or MDR-related BJIs, and for suppressive therapy when surgical or antibiotic alternatives are limited. However, available data are heterogeneous and largely observational. Robust prospective studies are needed to clarify their role, particularly for newer agents such as omadacycline and eravacycline.