Cefazolin is a first-generation cephalosporin for parenteral administration that is indicated for the treatment of a number of bacterial infections including urinary tract infections. 1
In February and March 2020, respectively, the United States Committee on Antimicrobial Susceptibility Testing (USCAST) and the Clinical and Laboratory Standards Institute (CLSI) submitted rationale documents to establish cefazolin as a surrogate agent for predicting the activity of orally administered cephalosporins, including cefaclor, cefdinir, cefpodoxime, cefprozil, cefuroxime, cephalexin, and locarbacef for treatment of uncomplicated urinary tract infections (uUTI) due to Enterobacterales.
Specifically, a cefazolin MIC ≤ 16 mcg/mL was proposed as a surrogate susceptible breakpoint for urine Enterobacterales isolates to predict the cross-susceptibility to oral cephalosporins listed above. This susceptible breakpoint was suggested because peak urine concentrations following standard dosing of cefaclor, cefdinir, cefpodoxime, cefprozil, cefuroxime, cephalexin, and locarbacef are multiple times the proposed breakpoint, and a susceptible result for cefazolin at a breakpoint of ≤ 16 mcg/mL was predictive of a susceptible result for the oral cephalosporins when testing E. coli, K. pneumoniae, and P. mirabilis.
No clinical studies were provided that evaluated the efficacy of cefazolin or oral cephalosporins in the treatment of uUTI based on the proposed urine-specific breakpoint for Enterobacterales. The submitted materials included studies reviewing the microbiologic and clinical outcomes of uUTI when treated with oral cephalosporins without specifying the distribution of MICs of the urinary pathogens nor the association of MICs with the microbiological or clinical outcomes. No decision support logic was provided using urinary drug exposure-antibacterial response relationships nor probability of target attainment analyses in patients with uUTI.
FDA has determined that there are insufficient data at this time to support the proposed cefazolin susceptible MIC breakpoint of ≤16 mg/L as a surrogate for determining breakpoints for oral cephalosporins for the treatment of uUTIs due to Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis. Therefore, no changes are recommended on the FDA STIC website.
1 U.S. Food and Drug Administration. Ancef Prescribing Information.