1597. Evaluation of Ceftaroline Resistance (CPT-R) in Chile Across Time and a Comparison of CLSI vs. EUCAST Breakpoints in Methicillin-Resistant Staphylococcus aureus (MRSA)

Abstract

BackgroundCPT-R in MRSA is associated with clonal complex (CC) 5 lineages. Chile, with wide dissemination of the CC5 Chilean-Cordobes clone, has high MRSA rates. In 2019, CLSI revised the breakpoints (BPs) keeping susceptible (S, minimum inhibitory concentration [MIC mg/L] ≤1), added susceptible dose-dependent (SDD, MIC 2–4), removed intermediate (MIC 2); resistant (R) is now MIC ≥8. EUCAST S is MIC ≤ 1, but R differentiates among pneumonia (MIC > 1) and nonpneumonia (NP) isolates (MIC > 2). We evaluated CPT-R across time and agreement between agencies for broth microdilution (BMD), E-test and Disk Diffusion (DD)MethodsHospital- (HA; n = 320, 10 centers) and community-associated (CA, n = 37) clinical MRSA isolates collected between 1999 and 2018 were confirmed with MALDI-TOF, cefoxitin DD, and mecA PCR. CPT susceptibilities were evaluated by BMD, E-test and DD (5 and 30 mg) across revised and old CLSI or EUCAST BPs. We determined essential and categorical agreement (EA, CA), very major, major, and minor errors (VME, ME, MiE)ResultsThe MIC50/MIC90 of HA-MRSA with BMD was 2/2 mg/L (64% of isolates considered CPT non-susceptible) and 0.5/0.5 mg/L for CA-MRSA. MIC50/MIC90 was 1/1.5 with E-test. Strains collected in 1999–2008 (n = 161) and 2009–2018 (n = 159) both had a MIC50/MIC90 of 2/2. The EA of E-test with BMD was 82%; results of CA-VME-ME-MiE were 51-0-0-48% using the new CLSI BPs or 51-81-0-45% using EUCAST or old CLSI BPs. For BMD, CA-VME-ME-MiE between new CLSI and EUCAST was 95-0-0-5 with 100% CA for E-test. Under NP EUCAST BPs, R isolates increase from 5 to 21% by BMD and 0 to 8% by E-test. CA-VME-ME-MiE between new CLSI and NP EUCAST BPs for BMD is 79-0-0-21 and for E-test is 91-0-0-8. For DD vs. BMD, CA-VME-ME-MiE is 55-0-1-44 with new CLSI BPs, 53-63-1-43 with old CLSI and 36-6-35-51 with EUCAST. With EUCAST DD (5 μg CPT) as reference vs. CLSI DD (30ug CPT), CA-VME-ME-MiE is 25-70-0-38.ConclusionCPT nonsusceptibility is frequent in the CC5 HA-MRSA clone circulating in Chile across time. All methods had poor performance against BMD, but revision of CLSI BPs decreased error rates. E-test under called the MIC. CLSI DD (under called nonsusceptibility) and EUCAST DD (overcalled resistance) are drastically discordant. Respiratory isolates evaluated under NP BPs increased rates of resistance.Disclosures All authors: No reported disclosures.