Duration of rifampin therapy is a key determinant of improved outcomes in early-onset acute prosthetic joint infection due to Staphylococcus treated with a debridement, antibiotics and implant retention (DAIR): a retrospective multicenter study in France

Abstract

Abstract. Introduction: In patients undergoing a « debridement, antibiotics, and implant retention » (DAIR) procedure for acute staphylococcal prosthetic joint infection (PJI), post-operative treatment with rifampin has been associated with a higher probability of success.(1,2) However, it is not known whether it is the total dose, delay of introduction or length of therapy with rifampin that is most strongly associated with the observed improved outcomes.Methods: A multicentric, retrospective cohort study of patients with acute staphylococcal hip and knee PJI treated with DAIR between January 2011 and December 2016. Failure of the DAIR procedure was defined as persistent infection, need for another surgery or death. We fitted logistic and Cox regression multivariate models to identify predictors of DAIR failure. We compared Kaplan-Meier estimates of failure probability in different levels of the 3 variables of interest - total dose, delay of introduction or length of therapy with rifampin - with the log-rank test.Results: 79 patients included (median age 71 years [63.5-81]; 55 men [70%]), including 54 (68%) DAIR successes and 25 (32%) DAIR failures. Patients observed for a median of 435 days [IQR 107.5-834]. Median ASA score significantly lower in DAIR successes than in DAIR failures (2 vs. 3, respectively p = 0.011). Bacterial cultures revealed 65 (82.3%) S. aureus and 16 (20.3%) coagulase negative staphylococci, with 2 patients being infected simultaneously with S. aureus and CNS. Among S. aureus isolates, 7 (10.8%) resistant to methicillin; 2 (3.1 %) resistant to rifampin. Median duration of antimicrobial therapy was 85 days [IQR 28.5-97.8]. Fifty-eight patients (73.4%) received rifampin at a median dose of 14.6 mg/kg/day |IQR 13-16.7], started at a median delay of 8.5 days [IQR, 4-7.5] after debridement surgery. Twenty-one patients (26.6%) developed a drug-related adverse event, leading to rifampin interruption in 6 of them (7.6% of total cohort). Determinants of DAIR failure were rifampin use (HR 0.17, IC [0.06, 0.45], p-value <0.001), association of rifampin with a fluoroquinolone (HR 0.19, IC [0.07, 0.53], p-value = 0.002) and duration of rifampin therapy (HR 0.97, IC [0.95, 1], p-value = 0.022). We did not observe a significant difference between DAIR successes and failures in rifampin use, dose and delay of introduction. In a multivariate Cox model, only duration of rifampin therapy was significantly associated with DAIR failure. Kaplan Meier estimate of DAIR failure probability was significantly higher in patients receiving less than 14 days of rifampin in comparison with those receiving more than 14 days of rifampin (p = 0.0017).Conclusion: Duration of rifampin therapy is a key determinant of improved outcomes in early-onset acute prosthetic joint infection due to Staphylococcus treated with DAIR.

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

“…In 3 studies, survival bias could be ruled out by excluding patients who failed early after debridement and before start of rifampicin [ 2 , 20 , 21 ], but survival bias was likely present in more studies. The positive association between duration of rifampicin and success rates after DAIR in the study of Becker et al [ 27 ] could be explained by survival bias and selectively excluding patients from the analysis who developed a failure while on rifampicin treatment [ 28 ]. Lora-Tamayo et al [ 2 ] described the strongest association between rifampicin use and outcome.…”

Comment on “Duration of rifampin therapy is a key determinant of improved outcomes in early-onset acute prosthetic joint infection due to Staphylococcus treated with a debridement, antibiotics and implant retention (DAIR): a retrospective multicenter study in France” by Becker et al. (2020)

“…The adjunctive role of rifampicin for staphylococcal prosthetic joint infection is an important and ongoing discussion. We compliment our colleagues for studying this important question in a multicenter collaboration (Becker et al, 2020). The authors conclude that prolonged duration of rifampicin therapy is a key determinant for improved outcomes in acute staphylococcal prosthetic joint infection treated with debridement, antibiotics and implant retention (DAIR).…”

To DAIR or not to DAIR: Decision-making in the management of acute prosthetic joint infection � A narrative review

“…Microbial etiology and the use of antibiotics with good activity against biofilm-embedded bacteria are certainly key factors for determining a given patient's prognosis. The benefits of using rifampin-based combinations to treat Staphylococcus aureus when the prosthesis is retained are well established in pre-clinical and clinical research, including a randomized clinical trial and several observational studies 55,58,[66][67][68][69] . Likewise, a dramatic improvement in prognosis has been shown using fluoroquinolones for infections caused by Gram-negative bacilli (GNB) [70][71][72][73] .…”