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.

Highlights

  • 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] 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

  • Determinants of treatment failure were diabetes mellitus (HR 2.17, IC [0.82, 5.72], p-value = 0.118), active smoking (HR 2.26, IC [0.85, 6.04], p-value = 0.103), Charlson comorbidity index (HR 1.10, IC [0.97, 1.26], p-value = 0.130), ASA score (HR 2.07, IC [1.07, 4.03], p-value = 0.031), Staphylococcus aureus (HR 4.03, IC [0.54, 30.27], p-value 0.175), MRSA (HR 2.56, IC [0.73, 8.94], p-value = 0.140), total duration of antibiotic therapy (HR 0.98, IC [0.97, 0.99], p-value = 0.002), rifampin use (HR 0.17, IC [0.06, 0.45], p-value

  • The aim of the study was to evaluate the impact of rifampin on the outcome of patients treated with debridement, antibiotics and retention (DAIR) according to current guidelines, to investigate whether it is the total dose, duration of therapy and/or delay of introduction of rifampin that have the most significant impact on the DAIR procedure probability of success

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Summary

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] 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. A « debridement, antibiotics, and implant retention » (DAIR) procedure is indicated in patients with a short duration of symptoms (< 30 days), a stable implant and no sinus tract [4]. This strategy is attractive because it can preserve implant function and bone mass, while it reduces the need for further surgical intervention [8]

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