Rifampin combination therapy in staphylococcal prosthetic joint infections: a randomized controlled trial

Abstract

Background: The evidence supporting rifampin combination therapy in prosthetic joint infections (PJI) is limited due to the lack of controlled studies. The aim of this study is to evaluate the effect of adding rifampin to conventional antimicrobial therapy in early staphylococcal PJIs treated with debridement and retention of the implant (DAIR). Methods: In this multicenter randomized controlled trial, 99 patients with PJI after hip and knee arthroplasties were enrolled. They were randomly assigned to receive rifampin or not in addition to standard antimicrobial treatment with cloxacillin or vancomycin in case of methicillin resistance. The primary endpoint was no signs of infection after 2 years of follow-up. Results: Forty-eight patients were included in the final analyses. There were no differences in patient characteristics or comorbidities between the two groups. There was no significant difference in remission rate between the rifampin combination group (17 of 23 (74%)) and the monotherapy group (18 of 25 (72%), relative risk 1.03, 95% confidence interval 0.73 to 1.45, p = 0.88). Conclusion: This trial has not proven a statistically significant advantage by adding rifampin to standard antibiotic treatment in acute staphylococcal PJIs. Trial registration: The Regional Ethics Committee and the Norwegian Medicines Agency approved the study (EudraCT 2005-005494-29), and the study was registered at ClinicalTrials.gov at Jan 18, 2007 (NCT00423982).

Outcome of Debridement, Antibiotics, and Implant Retention for Staphylococcal Hip and Knee Prosthetic Joint Infections, Focused on Rifampicin Use: A Systematic Review and Meta-Analysis

“…From 1 study, comparing 2 historical groups and 1 prospective group, only the historical groups were included in the meta-analysis because these groups could be compared with each other while a control group for the prospective cohort was absent. The only included RCT in the meta-analysis (by Karlsen et al [ 8 ]) reported similar cure rates between the rifampicin group (74%) and the beta-lactam group (72%). The pooled risk ratio for rifampicin effectivity from 11 studies in the meta-analysis was 1.10 (95% CI, 1.00–1.22).…”

“…Except for 1 RCT, no studies compared baseline characteristics between patients treated and not treated with rifampicin. The study by Karlsen et al [ 8 ] was the only RCT that could be included in the meta-analysis. In this study, 48 patients with staphylococcal PJI were randomized between rifampicin combination therapy (23 patients) and beta-lactam monotherapy (25 patients).…”

Controversy about the Role of Rifampin in Biofilm Infections: Is It Justified?

“…In a study, in which 29 patients with acute PJI were treated with ciprofloxacin plus rifampin, the success rate was 83% [39]. Interestingly, in the mentioned Norwegian randomized trial, in which rifampin-combination therapy did not show superiority, another regimen has been used, namely cloxacillin or vancomycin with or without rifampin [8]. Possible reasons for the low success rates and the lack of improvement by the addition of rifampin are presented below.…”

“…The above mentioned RCT compared the outcome of patients with acute staphylococcal PJI treated with prosthesis retention and either monotherapy without rifampin or rifampin combination [8]. In this multicenter study conducted from 2006 to 2012 in eight centers, 48 patients with acute PJI were included in the final analysis.…”

“…Until recently, only one randomized controlled trial (RCT) existed, in which the added value of rifampin was shown in patients with orthopedic implant-associated staphylococcal infections [7]. In 2020, a second RCT in patients with periprosthetic joint infection (PJI) was published, using different combination therapy regimens, which did not show a better outcome with addition of rifampin to standard treatment [8]. These unexpected data may unsettle clinicians with limited experience in the field of implant-associated infections.…”