J Bone Jt Infect 2020; 5(1):28-34. doi:10.7150/jbji.40333

Research Paper

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

A. Becker1,2✉, L. Kreitmann3,4, C. Triffaut-Fillit1,2, F. Valour1,2,4,5, E. Mabrut2, E. Forestier6, O. Lesens7, C. Cazorla8, S. Descamps9, B. Boyer10, C. Chidiac1,2,4, S. Lustig2,4,11, E. Montbarbon12, C. Batailler2,4,11, T. Ferry1,2,4,5 on behalf of the IPASTAPH study group

1. Service des Maladies Infectieuses et Tropicales, Centre hospitalier universitaire (CHU) de la Croix Rousse, Hospices Civils de Lyon (HCL), Lyon (France)
2. Centre de Référence des Infections Ostéo-Articulaires Complexes (CRIOAc) de Lyon (France)
3. Service de Réanimation Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France
4. Université Claude Bernard Lyon 1, Lyon, France
5. Inserm U1111, Centre international de recherche en Infectiologie (CIRI), Université Claude-Bernard Lyon 1, Lyon, France
6. Service des Maladies Infectieuses et Tropicales, Centre hospitalier Métropole Savoie, Chambéry (France)
7. Service des Maladies Infectieuses et Tropicales, Centre hospitalier universitaire (CHU) Gabriel Montpied, Clermont-Ferrand (France)
8. Service des Maladies Infectieuses et Tropicales, Centre hospitalier universitaire (CHU) de Saint-Etienne (France)
9. Service de Chirurgie Orthopédique, Centre hospitalier universitaire (CHU) Gabriel Montpied, Clermont-Ferrand (France)
10. Service de Chirurgie Orthopédique, Centre hospitalier universitaire (CHU) de Saint-Etienne (France)
11. Service de Chirurgie Orthopédique, Centre hospitalier universitaire (CHU) de la Croix Rousse, Hospices Civils de Lyon (HCL), Lyon (France)
12. Service de Chirurgie Orthopédique, Centre hospitalier Métropole Savoie, Chambéry (France)

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Becker A, Kreitmann L, Triffaut-Fillit C, Valour F, Mabrut E, Forestier E, Lesens O, Cazorla C, Descamps S, Boyer B, Chidiac C, Lustig S, Montbarbon E, Batailler C, Ferry T. 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. J Bone Jt Infect 2020; 5(1):28-34. doi:10.7150/jbji.40333. Available from http://www.jbji.net/v05p0028.htm

File import instruction

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.

Keywords: debridement, antibiotics and implant retention (DAIR), prosthetic joint infection, rifampin, Staphylococcus aureus, coagulase negative staphylococci