In VitroActivity of Ceftaroline-Avibactam against Gram-Negative and Gram-Positive Pathogens Isolated from Patients in Canadian Hospitals from 2010 to 2012: Results from the CANWARD Surveillance Study

Abstract

ABSTRACTThein vitroactivities of ceftaroline-avibactam, ceftaroline, and comparative agents were determined for a collection of bacterial pathogens frequently isolated from patients seeking care at 15 Canadian hospitals from January 2010 to December 2012. In total, 9,758 isolates were tested by using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method (document M07-A9, 2012), with MICs interpreted by using CLSI breakpoints (document M100-S23, 2013). Ceftaroline-avibactam demonstrated potent activity (MIC90, ≤0.5 μg/ml) againstEscherichia coli,Klebsiella pneumoniae,Klebsiella oxytoca,Proteus mirabilis,Enterobacter cloacae,Enterobacter aerogenes,Serratia marcescens,Morganella morganii,Citrobacter freundii, andHaemophilus influenzae; >99% of isolates ofE. coli,K. pneumoniae,K. oxytoca,P. mirabilis,M. morganii,C. freundii, andH. influenzaewere susceptible to ceftaroline-avibactam according to CLSI MIC interpretative criteria for ceftaroline. Ceftaroline was less active than ceftaroline-avibactam against all species ofEnterobacteriaceaetested, with rates of susceptibility ranging from 93.9% (P. mirabilis) to 54.0% (S. marcescens). All isolates of methicillin-susceptibleStaphylococcus aureus(MIC90, 0.25 μg/ml) and 99.6% of methicillin-resistantS. aureusisolates (MIC90, 1 μg/ml) were susceptible to ceftaroline; the addition of avibactam to ceftaroline did not alter its activity against staphylococci or streptococci. All isolates ofStreptococcus pneumoniae(MIC90, 0.03 μg/ml),Streptococcus pyogenes(MIC90, ≤0.03 μg/ml), andStreptococcus agalactiae(MIC90, 0.015 μg/ml) tested were susceptible to ceftaroline. We conclude that combining avibactam with ceftaroline expanded its spectrum of activity to include most isolates ofEnterobacteriaceaeresistant to third-generation cephalosporins, including extended-spectrum β-lactamase (ESBL)- and AmpC-producingE. coliand ESBL-producingK. pneumoniae, while maintaining potent activity against staphylococci and streptococci.