Accuracy of the Thermo Fisher Scientific (Sensititre?) dry-form broth microdilution MIC product when testing ceftaroline

摘要

Ceftaroline is the active metabolite of a new parenteral cephalosporin (ceftaroline fosamil) having potent activity against multidrug-resistant (MDR) Gram-positive cocci including methicillin-resistant Staphylococcus aureus (MRSA) and ceftriaxone-resistant Streptococcus pneumoniae (Flamm et al., 2014; Jones et al., 2013b; Livermore et al., 2014; Moisan et al., 2010; Pfaller et al., 2014). Applying a dosing schedule justified by pharmacokinetic-pharmacodynamic analysis (Van Wart et al., 2014), ceftaroline clinical trials in hospitalized patients were successful against complicated skin and soft tissue infections and community-acquired pneumonia (Frampton, 2013), and those results were confirmed by postapproval effectiveness/safety evaluations (Casapao et al., 2014; Santos et al., 2013; Teflaro?, 2012).New and novel antimicrobials are urgently needed to address infections caused by emerging MDR species (Boucher et al., 2009), and ceftaroline has activity against staphylococci having reduced susceptibility to daptomycin, linezolid, and vancomycin (Sader et al., 2013). To measure ceftaroline activity in clinical microbiology laboratories, quality diagnostic devices are required to recognize its utility as strains of staphylococci have been reported with elevated (>2 ug/mL) ceftaroline MIC values (Mendes et al., 2012). In this presentation, we present a multisite evaluation/validation of a quantitative, dry-form broth microdilution test (Sensititre?; Thermo Fisher, Cleveland, OH, USA) to expand ceftaroline susceptibility tests beyond disk and stable gradient agar diffusion methods (CLSI, 2008) or the use of surrogate marker testing (Jones et al., 2013a).All ceftaroline MIC values were compared over the <0.004-64 ug/mL dilution range in the dry-form Sensititre commercial and the frozen-form reference panels (CLSI, 2012; 2014). The MIC endpoints were read manually (CLSI, 2014) and by the Sensititre automated device. Five quality control (QC) organisms were used: S. aureus ATCC 29213, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, S. pneumoniae ATCC 49619, and Haemophilus influenzae ATCC 49247; all QC results were within published limits (CLSI, 2014) with 67.0% of the MIC values at the midpoint of the QC ranges. Colony counts to monitor the inoculum concentrations across the 3 laboratories and 5 QC strains demonstrated an average density of 3.1 x 105 CFU/mL (range, 1.5-5.2 x 105 CFU/mL), i.e., acceptable inoculum preparations.