In Vitro Activity of Ceftaroline Tested Against Recent Clinical Isolates from the United States (USA)

Susceptibility Testing: The isolates were tested for susceptibility to ceftaroline and many comparator agents by reference broth microdilution or agar dilution (Neisseria gonorrhoeae only) tests followed by confirmatory techniques that included CLSI M100-S19 criteria. S. pneumoniae was tested in Mueller-Hinton broth supplemented with 3-5% lysed horse blood, and Haemophilus influenzae was tested in Haemophilus Test Media while S. aureus was tested in cation-adjusted Mueller-Hinton broth. Results: CPT was very active against staphylococci, including strains R to oxacillin (OXA), vancomycin (VAN), mupirocin or linezolid. Against streptococci, including 40 S. pneumoniae with a penicillin MIC of ≥8 µg/mL (highest CPT MIC, 0.5 µg/mL) and other R subsets, CPT was highly potent. The highest CPT MIC for MRSA was 2 µg/mL (MIC 50/90 , 0.5/1 µg/mL). VAN-R did not affect CPT activity against E. faecalis (MIC 50/90 , 2/8 µg/mL). CPT was very active against non-ESBL, non-AmpC hyperproducer Enterobacteriaceae (MIC 50/90 , 0.12/2 µg/mL). E. coli, Klebsiella spp., Enterobacter spp., Citrobacter spp. P. mirabilis, Salmonella spp. and Shigella spp. were S to CPT (MIC 90 , 0.25-0.5 µg/mL), while indole-positive Proteae and Serratia spp. exhibited slightly higher CPT MIC values. CPT was very active against H. influenzae, including 104 ampicillin-R (β-lactamase(βL)-producing and βL- negative (BLNAR; MIC 90 , 0.12 µg/mL) strains. MIC 90 for H. parainfluenzae (24 strains), M. catarrhalis (101), Pasteurella multocida (51) and N. meningitidis (20) were 0.06, 0.12, 0.03 and ≤0.008 µg/mL, respectively. CPT showed limited activity against Acinetobacter spp. and P. aeruginosa. • Ceftaroline was active against S. aureus (325 strains) including MSSA, MRSA, and strains with decreased susceptibility to vancomycin (hVISA, VISA, and VRSA), linezolid (MIC, ≥8 µg/mL), quinupristin/dalfopristin (MIC, ≥2 µg/mL), and/or mupirocin (MIC, >256 µg/mL; Tables 1 and 2) • Against MRSA, all isolates were inhibited at a ceftaroline MIC of ≤2 µg/mL (MIC 50/90 , 0.5/1 µg/mL). Ceftaroline MIC results varied from 0.25 to 2 µg/mL for the hVISA/VISA/VRSA subset (MIC 50/90 , 1/2 µg/mL), from 0.5 to 2 µg/mL among the linezolid-resistant subset (MIC 50 , 1/2 µg/mL), from 0.06 to 1 µg/mL among quinupristin/dalfopristin nonsusceptible strains (MIC 50 , 0.5/1 µg/mL), and from 0.25 to 2 µg/mL among mupirocin-resistant strains (MIC 50 , 0.5/1 µg/mL; Table 2) • Ceftaroline (MIC 50/90 , 0.25 µg/mL) was 16-fold more active than ceftriaxone (MIC 50/90 , 4 µg/mL) and 8- to 16-fold more active than cefepime (MIC 50/90 , 2/4 µg/mL) against MSSA. The highest ceftaroline MIC value was only 0.5 µg/mL (Table 2) • Ceftaroline was slightly more active against coagulase-negative staphylococci (CoNS) compared to S. aureus. Against oxacillin-susceptible Staphylococcus epidermidis (MIC 50/90 , 0.06/0.12 µg/mL), ceftaroline was 16-fold more active than ceftriaxone and 8-fold more active than cefepime (MIC 50/90 , 1/2 µg/mL for ceftriaxone and 0.5/1 µg/mL for cefepime). Staphylococcus capitis (MIC 50/90 , 0.06/0.5 µg/mL), Staphylococcus hominis (MIC 50/90 , 0.5/1 µg/mL), Staphylococcus haemolyticus (MIC 50/90 , 1/2 µg/mL), as well as CoNS strains having reduced susceptibility to linezolid (MIC 50/90 , 0.5/1 µg/mL), were very susceptible to ceftaroline (Table 2) ≤0.25 ≤0.25 ≤0.25 - 0.5 100.0 / 0.0 Ceftriaxone ≤0.5 ≤0.5 ≤0.5 - 1 100.0 / 0.0 Oxacillin-susceptible (100) Amoxicillin/clavulanate ≤1 ≤1 ≤1 - 2 100.0 / 0.0 Cefepime 0.25 0.5 ≤0.12 - 1 100.0 / 0.0 Ceftaroline 0.06 0.12 ≤0.008 - 1 - / - Penicillin-intermediate (MIC, 0.12 - 1 µg/mL; 102) Penicillin 0.06 0.12 ≤0.015 - 2 95.1 / 0.0 Ceftriaxone 1 2 ≤0.5 - 16 98.0 / 0.0 Ceftaroline 0.03 0.06 ≤0.008 - 0.12 - / -