Effectiveness of rifampicin combination therapy for orthopaedic implant-related infections: A systematic review and meta-analysis

•A systematic review and meta-analysis was performed to analyse the effectiveness of rifampicin combination therapy in patients with whole orthopaedic implant-related infections.•A total of 27 studies were included in the meta-analysis, including two RCTs and 25 cohort studies.•Rifampicin combination therapy had a significant overall effect on the cure rate in patients with orthopaedic implant-related infection in cohort studies, but not in RCTs.•Subgroup analyses showed that rifampicin combination therapy was significantly effective in patients who underwent DAIR and one-stage revision and in patients infected with Cutibacterium, Staphylococcus, and Streptococcus species.•Fluoroquinolones are desirable as a combination drug with rifampicin for implant-related infections. In vitro, animal, and clinical comparative studies have revealed that combinations of rifampicin with antibacterial agents are effective in the treatment of biofilm-associated infections. This study aimed to assess the effectiveness of rifampicin combination therapies compared with monotherapies without rifampicin in patients with orthopaedic implant-related infections. The clinical literature was comprehensively searched for studies assessing the effectiveness of rifampicin combination therapy in patients with orthopaedic implant-related infection. Identified studies were screened based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses flow diagram. The primary outcome was the cure rate and the secondary outcome was the incidence of adverse events. Subgroup analyses were performed based on causative organisms, antibacterial agents, and types of surgical intervention. Twenty-seven studies were identified, including two randomized controlled trials (RCTs) and 25 cohort studies. Rifampicin combinations were associated with significantly higher cure rates than monotherapies in cohort studies, but not in RCTs. Subgroup analyses showed that rifampicin combinations were effective in patients infected with Cutibacterium and Staphylococcus spp.; in patients who underwent debridement, antibiotics, implant retention procedures; and in patients with one-stage revision. Moreover, combinations of rifampicin and fluoroquinolones were more effective than fluoroquinolones alone, while combinating rifampicin with other antibacterial agents showed no significant benefit. Combination treatment did not significantly affect adverse events in either RCTs or observational studies. Risk o