P-1526. <i>In vitro</i> Activity of Ceftobiprole Against Prominent Methicillin-resistant <i>Staphylococcus aureus</i> Clonal Groups Collected Through the SENTRY Antimicrobial Surveillance Program

Abstract Background Ceftobiprole (BPR), an advanced generation cephalosporin, was recently (April 2024) approved by the US FDA for treating Staphylococcus aureus bacteremia (SAB), community-acquired bacterial pneumonia (CABP), and acute bacterial skin and skin structure infections (ABSSSI). This study examined the activity of BPR and the comparator agent ceftaroline (CPT) against a contemporary (2018-2019) collection of methicillin-resistant S. aureus (MRSA) isolates from major pandemic lineages. Genomic features and susceptibility profile of MRSA isolates stratified by clonal group and subgroups. Methods 150 MRSA collected from 38 hospitals in 18 countries were susceptibility (S) tested against BPR and CPT using CLSI broth microdilution methods; FDA breakpoints were applied. Total genomic DNA was extracted and sequenced. Assembled genomes were used to determine multi-locus sequence type (ST), clonal complex (CC), spa (not shown) and SCCmec types; results of typing methods were used to assign clonal group (CG). Results Twenty-four CGs, including subdivisions, were identified; 3 isolates could not be assigned a CG. Prominent CGs were USA300 (n=53, 35.3%), UK-EMRSA-15 (n=33, 22.0%), USA100 (n=28, 18.7%), and USA800 (n=15, 10.0%); rare CGs (≤ 3 isolates; n=21) totaled 14.0% (TABLE). Against all MRSA, 97.3% were BPR-S and 85.3% were CPT-S. BPR was more active than CPT across CGs and subdivisons: USA300, 100.0% BPR-S/94.3% CPT-S; UK-EMRSA-15, 93.9% BPR-S/69.7% CPT-S; USA100, 96.4% BPR-S/75.0% CPT-S; USA800, 100.0% BPR-S/CPT-S. Against rare or unknown CGs, 95.2% were BPR-S and 90.5% were CPT-S. Four (2.7%) and 22 (14.7%) isolates were BPR- and CPT-NS, respectively; all BPR-NS isolates were CPT-NS whereas 81.8% of CPT-NS isolates were BPR-S. No CG feature united BPR-NS isolates (n=2 UK-EMRSA-15, CC22/ST22/SCCmec-IV(2B); USA100-Swiss, CC5/ST105/SCCmec-II(2A); Hungarian-Brazilian; CC8/ST239/SCCmec-III(3A)), whereas 19/22 (86.4%) CPT-NS isolates were from subgroups of UK-EMRSA-15, USA100, or Hungarian-Brazilian CGs. Conclusion This study reports the potent activity of BPR against a global collection of MRSA from prominent pandemic lineages. The low frequency of BPR-NS isolates, particularly among highly represented CGs including UK-EMRSA and USA100, and its activity against CPT-NS isolates, support the use of BPR in the treatment of MRSA-associated SAB, ABSSSI, and CABP. Disclosures Rodrigo E. Mendes, PhD, GSK: Grant/Research Support Jennifer Smart, PhD, Basilea Pharmaceutica International Ltd: Employee|Basilea Pharmaceutica International Ltd: Stocks/Bonds (Public Company) Mark E. Jones, PhD, Basilea Pharmaceutica International Ltd: Employee|Basilea Pharmaceutica International Ltd: Stocks/Bonds (Public Company)