Evaluation of Ceftaroline and Levofloxacin against Staphylococci Using Serum from Patients with Community-Acquired Pneumonia

Abstract

Purpose: Currently, no clinical data exists comparing ceftaroline to a "respiratory" fluoroquinolone in patients with community-acquired bacterial pneumonia (CABP). The purpose of this study was to compare time-kill assays of ceftaroline and levofloxacin against clinical isolates of Staphylococcus aureus using sera from hospitalized patients with a diagnosis CABP. Methods:A total of 12 patients were equally randomized to receive ceftaroline (600 mg q12h) or levofloxacin (750 mg q24h) for treatment of presumptive CABP. Blood samples were obtained on day 3 at 2, 6 and 12h after the initiation of the antibiotic infusion and serum levels were measured using a LC/MS/MS assay. Time-Kill curves were performed using these patient sera against selected clinical isolates of S. aureus with levofloxacin MICs ranging from 0.5 mg/L to 4 mg/L. Findings:Both agents exhibited bactericidal activity (≥3 log kill at 24h) against methicillin-sensitive S. aureus (MSSA) strains with levofloxacin MICs=0.5 and 1.0 mg/L. Only ceftaroline produced bactericidal activity against MSSA isolates with levofloxacin MICs=2.0 and 4.0 mg/L. Similar results were observed against methicillin-resistant S. aureus (MRSA) strains for levofloxacin but bactericidal activity was not observed for ceftaroline against all MRSA isolates. Bacterial regrowth was observed with 6 and 12h serum samples against MRSA strains with ceftaroline MICs > 0.25 mg/L. Implications:In summary, our study results found that clinical concentrations of ceftaroline exhibited bactericidal activity against strains of S. aureus that were both susceptible as well as non-susceptible to levofloxacin, but did not produce bactericidal activity against all strains of MRSA.