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Ceftaroline Activity Against Staphylococci and Characterization of S. aureus with Elevated Ceftaroline MIC Values: Results from the Ceftaroline Surveillance Program

Helio Silva Sader, D P Biek, Ian A. Critchley

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Abstract

Results: 56.8 and 27.2% of SA were MRSA in the USA and EU, respectively. CPT was very active against oxacillin-S SA (MSSA), MRSA and CoNS with MIC 90 s of 0.25-0.5, 1-2 and 0.5-1 µg/mL, respectively. CPT was 16-fold more potent than ceftriaxone against MSSA. All MRSA were inhibited at ≤2 µg/mL of CPT except 4 strains from a Greek hospital with a CPT MIC of 4 µg/mL. These 4 clonal strains had no change in mecR1, mecA promoter and ribosomal binding site, but showed 3 amino acid (AA) mutations (N→K 146/204 ; E→K 150 ) in the non-penicillin binding domain (nPBD) of PBP2a. mecI could not be detected on these 4 strains, all of which were PVL negative, SCCmec III and related to the ST-239 / spa t037 clone. Amended Abstract • The highest ceftaroline MIC value among methicillin-susceptible S. aureus (MSSA) strains was only 1 µg/mL (1 isolate (0.03%)), and 88.4 to 90.3% of strains were inhibited at a ceftaroline MIC of ≤0.25 µg/mL (Table 1). Ceftaroline (MIC 50/90 , 0.25 µg/mL) was 16- fold more active than ceftriaxone (MIC 50/90 , 4 µg/mL), 8- to 16-fold more active than cefepime (MIC 50 , 2 µg/mL and MIC 90 , 4 µg/mL), and 8-fold more active than linezolid (MIC 50/90 , 2 µg/mL) when tested against MSSA (Tables 2 and 3). • Against MRSA, all isolates were inhibited at a ceftaroline MIC of ≤2 µg/mL, except for 4 isolates (0.06% of S. aureus and 0.13% of MRSA tested) that had ceftaroline MICs of 4 µg/mL (Table 1). These four MRSA isolates were from a single medical center located in Greece and showed a dominant PFGE pattern (83.8% similarity; Figure 1).

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Results: 56.8 and 27.2% of SA were MRSA in the USA and EU, respectively. CPT was very active against oxacillin-S SA (MSSA), MRSA and CoNS with MIC 90 s of 0.25-0.5, 1-2 and 0.5-1 µg/mL, respectively. CPT was 16-fold more potent than ceftriaxone against MSSA. All MRSA were inhibited at ≤2 µg/mL of CPT except 4 strains from a Greek hospital with a CPT MIC of 4 µg/mL. These 4 clonal strains had no change in mecR1, mecA promoter and ribosomal binding site, but showed 3 amino acid (AA) mutations (N→K 146/204 ; E→K 150 ) in the non-penicillin binding domain (nPBD) of PBP2a. mecI could not be detected on these 4 strains, all of which were PVL negative, SCCmec III and related to the ST-239 / spa t037 clone. Amended Abstract • The highest ceftaroline MIC value among methicillin-susceptible S. aureus (MSSA) strains was only 1 µg/mL (1 isolate (0.03%)), and 88.4 to 90.3% of strains were inhibited at a ceftaroline MIC of ≤0.25 µg/mL (Table 1). Ceftaroline (MIC 50/90 , 0.25 µg/mL) was 16- fold more active than ceftriaxone (MIC 50/90 , 4 µg/mL), 8- to 16-fold more active than cefepime (MIC 50 , 2 µg/mL and MIC 90 , 4 µg/mL), and 8-fold more active than linezolid (MIC 50/90 , 2 µg/mL) when tested against MSSA (Tables 2 and 3). • Against MRSA, all isolates were inhibited at a ceftaroline MIC of ≤2 µg/mL, except for 4 isolates (0.06% of S. aureus and 0.13% of MRSA tested) that had ceftaroline MICs of 4 µg/mL (Table 1). These four MRSA isolates were from a single medical center located in Greece and showed a dominant PFGE pattern (83.8% similarity; Figure 1).

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Available abstract

Results: 56.8 and 27.2% of SA were MRSA in the USA and EU, respectively. CPT was very active against oxacillin-S SA (MSSA), MRSA and CoNS with MIC 90 s of 0.25-0.5, 1-2 and 0.5-1 µg/mL, respectively. CPT was 16-fold more potent than ceftriaxone against MSSA. All MRSA were inhibited at ≤2 µg/mL of CPT except 4 strains from a Greek hospital with a CPT MIC of 4 µg/mL. These 4 clonal strains had no change in mecR1, mecA promoter and ribosomal binding site, but showed 3 amino acid (AA) mutations (N→K 146/204 ; E→K 150 ) in the non-penicillin binding domain (nPBD) of PBP2a. mecI could not be detected on these 4 strains, all of which were PVL negative, SCCmec III and related to the ST-239 / spa t037 clone. Amended Abstract • The highest ceftaroline MIC value among methicillin-susceptible S. aureus (MSSA) strains was only 1 µg/mL (1 isolate (0.03%)), and 88.4 to 90.3% of strains were inhibited at a ceftaroline MIC of ≤0.25 µg/mL (Table 1). Ceftaroline (MIC 50/90 , 0.25 µg/mL) was 16- fold more active than ceftriaxone (MIC 50/90 , 4 µg/mL), 8- to 16-fold more active than cefepime (MIC 50 , 2 µg/mL and MIC 90 , 4 µg/mL), and 8-fold more active than linezolid (MIC 50/90 , 2 µg/mL) when tested against MSSA (Tables 2 and 3). • Against MRSA, all isolates were inhibited at a ceftaroline MIC of ≤2 µg/mL, except for 4 isolates (0.06% of S. aureus and 0.13% of MRSA tested) that had ceftaroline MICs of 4 µg/mL (Table 1). These four MRSA isolates were from a single medical center located in Greece and showed a dominant PFGE pattern (83.8% similarity; Figure 1).

Key concepts: Microbiology, Minimum inhibitory concentration, Ceftriaxone, Cephalosporin, Staphylococcus aureus, Linezolid, Cefepime, Chemistry

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Ceftaroline Activity Against Staphylococci and Characterization of S. aureus with Elevated Ceftaroline MIC Values: Results from the Ceftaroline Surveillance Program — Research Paper | ScholarLens