Reply to Eisen and Denholm, Dauchy et al, Fierer, and Nguyen and Jones.

We appreciate the opportunity to reply to the letters of Fierer [1], Eisen and Denholm [2], Dauchy et al [3], and Nguyen and Jones [4]. We are also glad that the publication of the Infectious Diseases Society of America (IDSA) guidelines on prosthetic joint infection (PJI) has prompted additional discussion and hope that this eventually manifests as further research [5]. Fierer [1] raises the important question of rifampin dosing in PJI due to susceptible staphylococci treated with debridement and retention. We recommended the dose as outlined in the only randomized clinical trial to address this issue [6]. In that trial, a dose of 450 mg orally twice daily was used initially and decreased to 300 mg orally twice daily if toxicity occurred that did not require drug discontinuation. With oral rifampin doses of 300 mg or 450 mg, peak concentrations of 4.0 μg/mL or 6 μg/mL, respectively, are reached. The trough level of both doses is >0.25 μg/mL at 12 hours (half-life: 2.5 hours). The 600-mg dose results in a peak of 10 μg/mL, with a trough level at 24 hours of about 0.08 μg/ mL (half-life: 3 hours) [7]. In view of the minimum inhibitory concentration (MIC) values of Staphylococcus aureus (0.008–0.15 μg/mL, MIC 90% [MIC90]: 0.015 μg/mL) and Staphylococcus epidermidis (0.004–0.15 μg/mL, MIC90: 0.015 μg/mL), all these regimens may be adequate [8]. The dose of 300–450 mg orally twice daily as well as 600 mg orally once daily was also recently recommended in