In Vitro Ceftriaxone Susceptibility in Methicillin-Susceptible Staphylococcus aureus

LETTER

Staphylococcus aureus is a leading cause of invasive infections in both hospital and community settings. Beta-lactams, specifically oxacillin, nafcillin, and cefazolin, are the drugs of choice against methicillin-susceptible Staphylococcus aureus (MSSA). At our institution, ceftriaxone is commonly used for infections due to MSSA and susceptible Gram-negative organisms, in view of the convenient once-daily dosing schedule (1, 2). However, routine susceptibility testing for S. aureus is performed only for oxacillin, and the results are extrapolated to other beta-lactams, including ceftriaxone.

We were alerted to the potential lack of concordance between susceptibilities to oxacillin and ceftriaxone in S. aureus; 60% of MSSA bloodstream isolates were reported to be resistant to ceftriaxone (3). The publication was subsequently retracted because the testing method used (Etest) was not FDA cleared for testing against S. aureus. In addition, the authors' findings were not consistent with an independent study using a standard broth microdilution method (4).

We report the results of our investigations completed in the interim period. Ceftriaxone (USP) powder was purchased from Sigma-Aldrich (St. Louis, MO). A stock solution was prepared, aliquoted, and stored at −70°C. For each susceptibility test, an aliquot of the drug was thawed and diluted to desired concentrations. Seventeen clinical MSSA bloodstream isolates (oxacillin MIC ≤ 0.5 μg/ml) and 1 methicillin-resistant S. aureus bloodstream isolate (MRSA) (oxacillin MIC = 64 μg/ml) from our institution were evaluated in this study. The isolates were subcultured twice on 5% blood agar plates (Hardy Diagnostics, Santa Maria, CA) prior to each experiment. MICs were determined in cation-adjusted Mueller-Hinton II broth (BBL, Sparks, MD) using a broth dilution method. A standard wild-type isolate, ATCC 29213 (American Type Culture Collection, Manassas, VA), was used as the reference control. The studies were conducted in triplicate and repeated at least once on a separate day.

All 17 MSSA isolates were found to be susceptible to ceftriaxone according to 2012 CLSI interpretive criteria (5), with a MIC range of 1 to 8 μg/ml. In comparison, the ceftriaxone MIC for the MRSA isolate was 32 μg/ml. We found a complete categorical concordance between oxacillin and ceftriaxone susceptibilities in S. aureus. In our experience, ceftriaxone susceptibility may be reasonably inferred based on the testing using oxacillin, as recommended by the 2014 CLSI guidelines (6).