Development of EUCAST zone diameter breakpoints ...

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ceftaroline 5-μg disk QC range for S. aureus ATCC 29213 of 24–30 mm was also established by EUCAST. Introduction. Ceftaroline fosamil (ZINFORO™) is the ...

Eur J Clin Microbiol Infect Dis DOI 10.1007/s10096-014-2089-8


Development of EUCAST zone diameter breakpoints and quality control range for Staphylococcus aureus with ceftaroline 5-μg disk L. M. Koeth & E. Matuschek & G. Kahlmeter & R. A. Alm & J. E. Ambler

Received: 20 November 2013 / Accepted: 2 March 2014 # Springer-Verlag Berlin Heidelberg 2014

Abstract This ceftaroline MIC/disk comparison study for Staphylococcus aureus was performed for the purpose of establishing EUCAST zone diameter breakpoints. Ceftaroline susceptibility for a challenge set of 70 methicillin resistant- and 30 methicillin susceptible-S. aureus was determined by 5-μg disk diffusion and broth microdilution methods. Seventeen isolates were retested by disk and MIC, and the remaining 83 isolates were retested by MIC. Molecular testing was performed on 19 isolates with borderline susceptible ceftaroline MIC results to assess any differences in mecA and epidemiological correlation. An additional set of 101 consecutive clinical S. aureus isolates were tested using the 5-μg disk. S. aureus ATCC 29213 was tested by multiple sites and media for QC range determination. Replicate MIC results were within ±1 doubling dilution, with tendency for slightly lower repeat MICs, and there was minimal variation in replicate zone results. Based on susceptible breakpoints for MIC of ≤1 mcg/mL and for disk of >20 mm, there was 100 % categorical agreement for 30 MSSA and 92 % categorical agreement for 70 MRSA. There were no common MLST or PBP changes for strains with MICs of 1 and 2 mcg/mL. All ceftaroline disk results for the Electronic supplementary material The online version of this article (doi:10.1007/s10096-014-2089-8) contains supplementary material, which is available to authorized users. L. M. Koeth (*) Laboratory Specialists, Inc, 1651 A Crossings Parkway, Westlake, OH 44145, USA e-mail: [email protected] E. Matuschek : G. Kahlmeter EUCAST Laboratory for Antimicrobial Susceptibility Testing, Växjö, Sweden R. A. Alm : J. E. Ambler AstraZeneca Pharmaceuticals LP, Waltham, MA, USA

consecutively collected isolates were >20 mm. EUCAST selected the ceftaroline 5-μg disk breakpoint of Susceptible ≥20, Resistant 1 mg/L. A ceftaroline 5-μg disk QC range for S. aureus ATCC 29213 of 24–30 mm was also established by EUCAST.

Introduction Ceftaroline fosamil (ZINFORO™) is the prodrug of the active metabolite, ceftaroline, and was approved by the European Medicines Agency for treatment of adult patients with complicated skin and soft tissue infections or community-acquired pneumonia. Ceftaroline retains the broad spectrum activity of oxyimino cephalosporins with additional activity against methicillin-resistant staphylococci (including methicillinresistant Staphylococcus aureus) and streptococci (including penicillin-resistant Streptococcus pneumoniae). Its antiEnterobacteriaceae activity is constrained by lability to AmpC, extended spectrum, KPC and metallo β-lactamases and has no clinical utility against non-fermentative Gramnegative bacilli. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) established the ceftaroline S. aureus MIC (minimum inhibitory concentration) breakpoints (Susceptible ≤1, Resistant >1 mg/L) on the approval of ceftaroline fosamil in the European Union, and the S. aureus ATCC 29213 QC range (0.12–0.5 mg/L) was adopted from the CLSI document [1, 2]. For in vitro disk diffusion testing of ceftaroline, the 5-μg disk was selected by EUCAST. The purpose of this study was to establish and validate disk breakpoints and QC range for S. aureus ATCC 29213 for ceftaroline susceptibility testing using ceftaroline 5-μg disks and EUCAST methodology.

Eur J Clin Microbiol Infect Dis

Materials and methods These studies were a collaborative effort between EUCAST Laboratory for Antimicrobial Susceptibility Testing (ELAST, Växjö, Sweden) and Laboratory Specialists, Inc. (LSI, Westlake, OH, USA). Initial QC range testing was performed by ELAST and Statens Serum Institute (SSI, Copenhagen, Denmark) and validated by five European laboratories. Molecular testing of select isolates was performed at AstraZeneca (Waltham, MA, USA).

MIC-zone correlation A challenge set included 98 S. aureus, which were selected from cultures from a variety of clinical sources isolated worldwide in 2006–2012, and included 25 isolates from a 2010 European surveillance study [3] and two reference isolates (hVISA, ATCC 700698 and VISA, ATCC 700699). The set of study isolates included 70 MRSA and 30 MSSA (based on oxacillin MIC results). The study isolates were selected to include 67 with ceftaroline MICs of 1–8 mg/L (including five VISA) and 33 with ceftaroline MICs of

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