Interim susceptibility testing for ceftaroline, a new MRSA-active cephalosporin: selecting potent surrogate β-lactam markers to predict ceftaroline activity against clinically indicated species

Abstract

Ceftaroline, the bio-active form of parenterally administered ceftaroline fosamil, is a unique broad-spectrum cephalosporin with in vitro and in vivo activity against methicillin-resistant Staphylococcus aureus and was approved for clinical use by the United States Food and Drug Administration in October 2010. In over a year since ceftaroline fosamil approval, no widely used commercial susceptibility test system has added this new compound to its product, therefore requiring use of alternative agar diffusion methods for clinical microbiology laboratories that want to test clinical isolates for ceftaroline susceptibility. An alternative strategy of applying a surrogate β-lactam class marker agent was assessed here, using results from 14,902 organisms (2008–2010) sampled in the USA. Very high and acceptable accuracy (≥99.75%) was observed for predicting ceftaroline susceptibility as follows: 1) use of imipenem or meropenem minimum inhibitory concentrations (MICs) at ≤8 μg/mL (susceptible and intermediate categories) when testing S. aureus; 2) use of ceftriaxone MIC at ≤2 μg/mL (susceptible and intermediate categories) when testing Streptococcus pneumoniae as well as other streptococci (S. pyogenes and S. agalactiae); and 3) use of ceftriaxone, or cefepime, or ceftazidime at ≤2 μg/mL (susceptible category) when testing Haemophilus influenzae. Only when testing indicated Enterobacteriaceae species using ceftriaxone susceptibility results did the ceftaroline-nonsusceptible errors increase (4.11%). These presented analyses offer a validated surrogate marker strategy for ceftaroline susceptibility testing, pending development and validation by the commonly used automated systems and agar diffusion commercial methods.