Analysis of Potential β-Lactam Surrogates To Predict In Vitro Susceptibility and Resistance to Ceftaroline for Clinical Isolates of Enterobacteriaceae.

Abstract

Ceftaroline fosamil was approved by the United States Food and Drug Administration in 2010 and by the European Medicines Agency in 2012. As of April 2017, only one commercial antimicrobial susceptibility testing device offered a Gram-negative panel that included ceftaroline. This circumstance is unfortunate, as many clinical microbiology laboratories rely solely on commercial devices to generate in vitro antimicrobial susceptibility testing results for common bacterial pathogens. In lieu of device-based testing of clinical isolates of Enterobacteriaceae, laboratories wishing to test ceftaroline must either opt for disk diffusion testing or use a gradient strip; however, both alternatives interrupt laboratory workflow and require additional labor and expense. Identification of a reliable surrogate β-lactam to predict in vitro susceptibility to ceftaroline may offer another interim solution as laboratories await availability of ceftaroline for testing on their commercial devices. We tested six β-lactams (aztreonam, ceftazidime, ceftriaxone, cefotaxime, cefoxitin, and cefpodoxime) as potential surrogates for ceftaroline against a collection of 543 clinical isolates of Enterobacteriaceae selected to approximate the distribution of ceftaroline MICs observed in AWARE global surveillance studies conducted in 2013. All six potential surrogates generated very major error rates of 16.3% to 56.6%, far exceeding the accepted limit of 1.5% set by the Clinical and Laboratory Standards Institute (CLSI) and the United States Food and Drug Administration (FDA) Center for Devices and Radiological Health. Failure to identify a reliable surrogate to predict in vitro susceptibility and resistance to ceftaroline for clinical isolates of Enterobacteriaceae underscores the need for expedited addition of newer antimicrobial agents to commercial antimicrobial susceptibility testing devices.