J. Li,1 D. A. Melnick,2 J. Ambler1; 1AstraZeneca LP, Waltham, MA, 2AstraZeneca LP, Wilmington, DE
BACKGROUND: A prospective clinical trial has demonstrated the superiority of CPT-F 600 mg every 12 h (q12h) to ceftriaxone 2 g every 24 h in treating Asian patients with CAP. Data from the study were used to calculate PTAs at the 90th percentile (MIC90) for S. pneumoniae, S. aureus and Enterobacteriaceae from ceftaroline (CPT) surveillance studies of Asia Pacific region isolates collected in 2010, 2011 and 2012, and at the CPT clinical breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in 2012.
METHODS: Simulations for PTAs for CPT-F 600 mg q12h were performed using an updated population PK model of CPT and CPT-F including data from Asian and Western healthy volunteers and patients with infection including CAP, together with PK/PD targets of the primary CAP pathogens defined in a neutropenic murine thigh infection model, and MIC90s of those pathogens collected in the 2010, 2011 and 2012 Asia Pacific surveillance.
RESULTS: For S. pneumoniae, >90% PTA is predicted at the CPT MIC90 (≤0.5 mg/L) observed for all years and at stasis, 1 log10 and 2 log10 kill PK/PD targets. PTA for S. aureus (including methicillin-susceptible and -resistant strains) was 100% at the CPT MIC90 (≤2 mg/L) for all years at the stasis and 1 log10 kill targets. For ceftazidime-susceptible E. coli or K. pneumoniae, >90% PTA is predicted at CPT MIC90 (≤0.5 mg/L) of these pathogens observed from 2010 and 2011 surveillance. The PTAs for CAP pathogens at susceptible EUCAST breakpoints are all greater than 90%.
CONCLUSION: Consistent with the clinical outcomes, high PTAs are predicted for CPT-F 600 mg q12h dose regimen for Asian patients with CAP, covering the MIC90s of primary CAP pathogens in the Asia Pacific region, and CPT susceptible breakpoints established by EUCAST.