title: Methodological agreement on the in vitro activity of ceftaroline against cefotaxime-susceptible and -resistant pneumococci.
abstract: Ceftaroline reportedly has lower minimum inhibitory concentrations (MICs) than established cephalosporins for Streptococcus pneumoniae. We further evaluated this activity using 155 pneumococci chosen by serotype and cefotaxime MIC. MICs were determined by agar dilution on Mueller-Hinton agar and Iso-Sensitest agar and by Etest. Inhibition zones were measured for 5 μg and 30 μg ceftaroline discs using both CLSI/EUCAST and BSAC methodology. Ceftaroline was more active than cefotaxime, with MICs 2-8-fold lower for isolates with cefotaxime MICs of ≤1 mg/L and mostly in the range 0.125-0.5 mg/L for those with cefotaxime MICs of 2 mg/L to ≥16 mg/L. Twelve isolates belonging to serotypes 14 (n=2), 19A (n=6) and 19F (n=4) were ceftaroline-resistant, with MICs of 0.5-1 mg/L. Essential agreement between MIC methods was excellent, with values on Iso-Sensitest agar and Mueller-Hinton agar identical ±1 doubling dilution in all cases, and with 154/155 values identical ±1 doubling dilution between agar dilution and Etest. Nevertheless, 5/11 isolates with agar dilution MICs of 0.5 mg/L (i.e. just resistant) 'had' MICs of 0.25 mg/L (just susceptible) by Etest. Inhibition zones also correlated with MICs, but discrimination around the breakpoint MICs was poor irrespective of method and disc type. In summary, the results confirm the good activity of ceftaroline against pneumococci, but susceptibility testing will present challenges in routine laboratories, with discs poorly discriminatory and with Etest prone to give susceptible results for isolates with MICs one doubling dilution above the breakpoint.
authors.affiliation: Antimicrobial Resistance & Healthcare-Associated Infections Reference Unit, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK. Electronic address: d.livermore@uea.ac.uk.
authors.forename: David M
authors.initials: DM
authors.lastname: Livermore
authors.affiliation: Antimicrobial Resistance & Healthcare-Associated Infections Reference Unit, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.
authors.forename: Marina
authors.initials: M
authors.lastname: Warner
authors.affiliation: Antimicrobial Resistance & Healthcare-Associated Infections Reference Unit, Public Health England, 61 Colindale Avenue, London NW9 5EQ, UK.
authors.forename: Shazad
authors.initials: S
authors.lastname: Mushtaq
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002439:Cefotaxime / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification / Q000187:drug effects*; D018440:beta-Lactam Resistance; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D002439:Cefotaxime; D002511:Cephalosporins; D000097583:Ceftaroline
keywords: CLSI; Disc diffusion; EUCAST; Etest; Streptococcus pneumoniae