Evaluation of the In Vitro Activity of Ceftaroline Tested Against Clinical Bacterial Isolates from USA Hospitals: Results from 5 Years of the AWARE Surveillance Program (2011-2015)

Background: Ceftaroline (CPT) is a broad-spectrum cephalosporin with activity against S. aureus (SA), including methicillin-resistant SA (MRSA), multidrug-resistant (MDR) S. pneumoniae (SPN) and wild-type Enterobacteriaceae (ENT). CPT fosamil was approved for clinical use in the USA in October 2010, and the AWARE Program monitors its in vitro activity against clinical bacteria from various infection types. We evaluated the activity of CPT against prevalent Gram-positive and -negative species isolated in USA hospitals.

 

Methods: A total of 114,131 isolates were consecutively collected (one/patient) from 183 medical centers in 2011-2015 and tested for susceptibility (S) to CPT and comparator agents using CLSI broth microdilution methods.

 

Results: Isolates were mainly collected from skin/soft tissue (38,183; 33.5%), respiratory tract (33,553; 29.4% and bloodstream (17,298; 15.2%) infections. MRSA rates varied from a high of 50.0% in 2013 to a low of 44.9% in 2015 (48.7% overall). CPT inhibited all SA strains at ≤2 µg/mL and was very active against MRSA (MIC_50/90, 0.5/1 µg/mL; 97.2% S; Table). CPT was 16-fold more active than ceftriaxone (CRO) against methicillin-S SA (MSSA). CPT inhibited 99.99% of SPN at ≤0.5 µg/mL (only 1 non-S isolate of 11,696 had a CPT MIC of 1 µg/mL) and remained active against MDR SPN, including CRO-non-S (7.2% at ≥2 µg/mL) strains. SPN S rates to CRO (≤1 µg/mL) increased from 88.4% in 2011 to 98.1% in 2015. CPT activity against the most common ENT (MIC₅₀, 0.12 µg/mL; 78.8% S) was similar to CRO (MIC₅₀, ≤0.06 µg/mL; 85.8% S). The highest CPT MIC value among β-hemolytic streptococci was 0.06 µg/mL. ESBL phenotypes were observed in 13.4% of E. coli and 14.8% of Klebsiella spp., and all cephalosporins showed limited activity against ESBL-phenotype strains. H. influenzae (MIC₉₀, 0.03 µg/mL; 100.0% S), H. parainfluenzae (MIC₉₀, 0.03 µg/mL) and M. catarrhalis (MIC₉₀, 0.12 µg/mL) isolates were highly CPT-S, independent of β-lactamase production.

 

Conclusion: CPT demonstrated potent and consistent (2011-2015) activity against staphylococci, including MRSA, different streptococcal groups, and Haemophilus spp. CPT also had an activity against ENT most similar to that of currently available broad-spectrum cephalosporins.