Treatment of Methicillin-Susceptible Staphylococcus aureus Osteoarticular and Prosthetic Joint Infections: Using the Oxacillin Minimum Inhibitory Concentration to Guide Appropriate Ceftriaxone Use

TO THE EDITOR—Methicillin-susceptible Staphylococcus aureus (MSSA) prosthetic joint infection (PJI) is difficult to treat even with surgical debridement and antimicrobial therapy. The antimicrobial agents of choice for MSSA are typically oxacillin, nafcillin, and cefazolin [1]. The use of ceftriaxone for MSSA PJI is controversial, as mentioned in the recently published Infectious Diseases Society of America (IDSA) guidelines on PJI management [2], in which it is recommended that ceftriaxone be dosed 1–2 g every 24 hours. We believe 2 g/day is appropriate but 1 g/day may give inadequate drug levels; thus, a higher risk for failure given ceftriaxone minimum inhibitory concentration (MIC) 90 values against MSSA is 4 μg/mL [3] (Table 1). Current US Food and Drug Administration (FDA)–recommended ceftriaxone dosage for MSSA is 2–4 g/day [4]. This recommendation is based on pharmacokinetic-pharmacodynamic (PK/PD) analysis demonstrating that ceftriaxone 2 g/ day will attain 25% free-drug time above MIC with 90% probability for a MIC at ≤4 μg/mL after considering ceftriaxone’s >90% protein binding, leading to lower drug level in tissue compared to serum [5]. Ceftriaxone given at 1 g daily will attain a target MIC at ≤2 μg/mL, but only 8% of MSSA in the SENTRYAntimicrobial Surveillance Program database in the United States has these MIC results (Table 1). Clinical studies generally support a ceftriaxone dose of at least 2 g/day for osteoarticular and PJI infections. The IDSA PJI guidelines cited 2 cohort studies [6, 7] and 1 registry trial [8] to support its ceftriaxone recommendation. On closer examination, both Tice et al and Guglielmo et al [6, 7] used a ceftriaxone dosage of 2 g/day whereas Wynn et al [8] reported a mean of 1.85 g/day. A recent retrospective controlled study with a large number of MSSA PJIs, not cited by the guidelines, suggests that ceftriaxone 2 g/day and oxacillin 2 g every 6 hours have similar cure rates [9].