Guidelines from the Infectious Diseases Society of America (IDSA) recommend oral rifampin plus a fluoroquinolone as a second-line option for native vertebral osteomyelitis (NVO) caused by Staphylococci (drug susceptible or resistant). This recommended regimen is levofloxacin PO 500-750 mg q24h plus rifampin PO 600 mg q24h for 6 weeks. Rifampin plus doxycycline (for at least 3 months) has also been shown to be successful for treating Brucellar NVO. [1]
A 2024 systematic review and meta-analysis evaluated the efficacy and safety of rifampin-based therapy in patients with Staphylococcus aureus native vertebral osteomyelitis (NVO) using 13 studies (N= 679). Two randomized controlled trials were included and the rest were observational cohort studies. Rifampin-based regimens were associated with a reduced risk of clinical failure compared to standard therapy (risk difference, -14%; 95% CI, -19% to -8%; p<0.001; relative risk, 0.58; 95% CI, 0.37 to 0.92; p= 0.02). Subgroup analysis did not reveal significant differences based on methicillin resistance, but an exploratory analysis suggested a lower risk of failure in cases where rifampin was combined with fluoroquinolones. However, significant limitations, including high or unclear risk of bias across all studies and very low certainty in evidence, preclude definitive conclusions. Only one study reported adverse events, limiting safety assessments. The findings highlight the potential benefit of adjunctive rifampin in S. aureus NVO treatment, but randomized trials are needed to substantiate these observations. [2]
Research from the 1980s demonstrated enhanced osteomyelitis cure rates when vancomycin was combined with rifampin as opposed to vancomycin alone. This prompted clinical trials comparing nafcillin alone to nafcillin with rifampin for chronic Staphylococcus aureus osteomyelitis, with the combination showing higher cure rates. Similar results were observed in trials where oxacillin or vancomycin combined with rifampin led to fewer clinical failures compared to placebo in S. aureus infections. Spurring interest in rifampin as an adjunct for bone and joint infections, subsequent retrospective and randomized controlled trials found improved treatment outcomes in osteomyelitis using oral rifampin combinations compared to traditional intravenous therapies. Combinations included rifampin with trimethoprim-sulfamethoxazole, linezolid, clindamycin, and fluoroquinolones. A small trial with orthopedic device-associated staphylococcal infections showed superior outcomes with ciprofloxacin plus rifampin over ciprofloxacin alone. However, evidence supporting rifampin's benefit for osteomyelitis without prosthetic involvement is less conclusive. While a retrospective study indicated higher rifampin use in cured S. aureus vertebral osteomyelitis cases, another review found similar cure rates with or without rifampin in oral regimens. Although adding rifampin to fluoroquinolones for S. aureus osteomyelitis appears beneficial due to poor outcomes with fluoroquinolone monotherapy, the general value of rifampin adjunct therapy in non-prosthetic osteomyelitis remains unclear. An ongoing study (VA INTREPID; NCT03012529) aims to clarify rifampin's role in diabetic foot osteomyelitis without prosthetic infections; this randomized, double-blind, placebo-controlled trial is estimated to be completed by the end of September 2025. It will compare adjunctive rifampin 600 mg daily versus placebo added to backbone antibacterial therapy for 6 weeks. [3], [4]