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FDA Rationale for Recognition Decision: Ceftaroline fosamil

As of April 16, 2020, the FDA-recognized breakpoints for ceftaroline fosamil for Staphylococcus aureus (including methicillin resistant S. aureus (MRSA)) based on a dosing regimen of 600 mg administered intravenously every 12 hours (q12h) remain:

  • ≤1 mcg/mL (susceptible, “S”)
  • ≤1 mcg/mL (susceptible, “S”)
  • ≥4 mcg/mL (resistant, “R”)

On November 22, 2019, the Clinical and Laboratory Standards Institute (CLSI) submitted a comment to the open public docket, requesting recognition of revised ceftaroline breakpoints for S. aureus (including MRSA). (see: https://www.regulations.gov/document?D=FDA-2017-N-5925-0020). In this document, CLSI noted the following revisions in M100-S29:

  • Susceptible breakpoint of ≤1 mcg/mL based on a ceftaroline fosamil dosing regimen of 600 mg q12h.
  • A new “susceptible dose dependent breakpoint” (“SDD”) of 2 - 4 mcg/mL, supported by a dosing regimen of ceftaroline fosamil 600 mg q8h administered as a 2-hour intravenous infusion.

FDA has completed their review of the CLSI comment to the docket and provides additional information below regarding these breakpoints. The FDA reviewed the available clinical, microbiology and pharmacokinetic information and determined that no change is currently recommended for the ceftaroline fosamil breakpoints against S. aureus including MRSA. This is based on the following:

  • The susceptible breakpoint of ≤ 1 mcg/mL for S. aureus (including MRSA) is based on a ceftaroline fosamil dosing regimen of 600 mg q12h administered as a 5-60-minute IV infusion. Based on modeling and simulation analyses, the approved dose of ceftaroline fosamil of 600 mg q12h infused over 5-60 minutes, provides pharmacokinetic/pharmacodynamic (PK/PD) target attainment over 90% for S. aureus with MICs ≤ 2 mcg/mL. The corresponding zone diameters remain at ≥ 24 mm as susceptible, 21 – 23 mm as intermediate and ≤ 20 mm as resistant using the 30 mcg ceftaroline disk.
  • The proposed “SDD” of 2-4 mcg/mL and “R” of 8 mcg/mL based on a dose of 600 mg administered q8h over a 2-hour infusion is not recognized as this is not an FDA approved dosing regimen for ceftaroline fosamil.

In conclusion, the ceftaroline fosamil breakpoints against S. aureus including MRSA set by CLSI are not recognized by FDA. FDA identified and recognized breakpoints for ceftaroline fosamil can be found at www.fda.gov/stic.