A Multicenter Study To Evaluate Ceftaroline Breakpoints: Performance in an Area with High Prevalence of...

Area of Science:

• Microbiology
• Clinical Infectious Diseases
• Antimicrobial Resistance

Background:

• Ceftaroline (CPT) is a broad-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA).
• The ST5 Chilean-Cordobés clone, linked to CPT nonsusceptibility, is prevalent in Chile, a country with high MRSA infection rates.

Purpose of the Study:

• To assess the in vitro activity of CPT against MRSA isolates from Chile.
• To evaluate the performance of different antimicrobial susceptibility testing (AST) methodologies for CPT.

Main Methods:

• Analysis of 361 MRSA isolates collected from 1999-2018 in Santiago, Chile.
• In vitro susceptibility testing using broth microdilution (BMD), Etest, and disk diffusion.
• Comparison of results against CLSI and EUCAST breakpoints.

Main Results:

• Hospital-associated MRSA isolates showed higher CPT MIC distributions (MIC50/90 = 2 mg/L) than community isolates (MIC50/90 = 0.5 mg/L).
• 64% of isolates were CPT nonsusceptible, irrespective of CPT use in Chile.
• Etest underestimated CPT MICs compared to BMD (MIC50/90 = 1/1.5 mg/L), with low categorical agreement (CA) across breakpoints.
• Disk diffusion showed poor performance, with low CA and high very major errors (VMEs) compared to BMD.

Conclusions:

• CPT-nonsusceptible MRSA are dominant in Chilean clinical settings.
• Current AST methodologies exhibit poor agreement for CPT, necessitating reevaluation of breakpoints.
• Standardization of AST methods is crucial for accurate CPT susceptibility reporting.