Review of ceftaroline fosamil microbiology: Integrated FOCUS studies

Cerexa, Inc., Oakland, CA 94612, USA.
Journal of Antimicrobial Chemotherapy (Impact Factor: 5.31). 04/2011; 66 Suppl 3(Supplement 3):iii45-51. DOI: 10.1093/jac/dkr098
Source: PubMed


Ceftaroline fosamil, the prodrug form of ceftaroline, is a novel broad-spectrum parenteral cephalosporin that exhibits antibacterial activity against typical respiratory pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and common Gram-negative pathogens. In particular, ceftaroline has activity against resistant Gram-positive cocci, including penicillin- and multidrug-resistant S. pneumoniae, as well as methicillin-resistant S. aureus. The activity of ceftaroline against these phenotypes is attributed to its ability to bind to modified penicillin-binding proteins with high affinity when compared with other β-lactams. The activity of ceftaroline is not compromised by the ability of H. influenzae to produce β-lactamase. Ceftaroline fosamil was compared with ceftriaxone for safety and efficacy in two randomized, double-blinded, controlled Phase III clinical trials for the treatment of community-acquired pneumonia (CAP). Microbiological assessments at baseline included respiratory specimen cultures, blood cultures, urinary antigen testing and atypical pathogen serology testing. By-subject and by-pathogen microbiological outcomes were assessed in the microbiologically evaluable population at the test-of-cure visit. The favourable microbiological response rates by subject for ceftaroline were 87.0% compared with 81.0% for ceftriaxone. The by-pathogen microbiological response rates of ceftaroline and ceftriaxone were 87.3% and 72.9% for S. pneumoniae, 83.3% and 85.0% for H. influenzae and 76.0% and 70.4% for S. aureus, respectively. Key baseline pathogens such as S. pneumoniae, H. influenzae and methicillin-susceptible S. aureus were susceptible to ceftaroline, with MIC(90)s of 0.03, 0.03 and 0.25 mg/L, respectively, supporting its utility as a promising new agent for treatment of CAP.

Download full-text


Available from: Hillel David Friedland, Oct 10, 2015
130 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Community-acquired pneumonia (CAP) is a serious condition associated with significant morbidity and potential long-term mortality. Although the majority of patients with CAP are treated as outpatients, the greatest proportion of pneumonia-related mortality and healthcare expenditure occurs among the patients who are hospitalized. There has been considerable interest in determining risk factors and severity criteria assessments to assist with site-of-care decisions. For both inpatients and outpatients, the most common pathogens associated with CAP include Streptococcus pneumoniae, Haemophilus influenzae, group A streptococci and Moraxella catarrhalis. Atypical pathogens, Gram-negative bacilli, methicillin-resistant Staphylococcus aureus (MRSA) and viruses are also recognized aetiological agents of CAP. Despite the availability of antimicrobial therapies, the recent emergence of drug-resistant pneumococcal and staphylococcal isolates has limited the effectiveness of currently available agents. Because early and rapid initiation of empirical antimicrobial treatment is critical for achieving a favourable outcome in CAP, newer agents with activity against drug-resistant strains of S. pneumoniae and MRSA are needed for the management of patients with CAP.
    Journal of Antimicrobial Chemotherapy 04/2011; 66 Suppl 3(supplement 3):iii3-9. DOI:10.1093/jac/dkr094 · 5.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Ceftaroline fosamil (ceftaroline) was recently approved for the treatment of community- acquired pneumonia (CAP) and complicated skin infections. This newly developed cephalosporin possesses a broad spectrum of activity against gram-positive and gram-negative bacteria. Most importantly, ceftaroline demonstrates potent in vitro antimicrobial activity against multi-drug resistant Streptococcus pneumoniae and methicillin-resistant strains of Staphylococcus aureus. In two Phase III, double-blinded, randomized, prospective trials (FOCUS 1 and FOCUS 2), ceftaroline was shown to be non-inferior to ceftriaxone for the treatment of CAP in hospitalized patients. Ceftaroline exhibits low resistance rates and a safety profile similar to that of other cephalosporins. In this review, we will evaluate the pharmacological characteristics, safety, antimicrobial properties, and efficacy of ceftaroline and its applications in the treatment of CAP.
    Infection and Drug Resistance 02/2012; 5(1):43-51. DOI:10.2147/IDR.S17433
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Drug resistance in Streptococcus pneumoniae, a frequent pathogen in community-acquired pneumonia, is increasing. Ceftaroline (active metabolite of ceftaroline fosamil) is a broad-spectrum intravenous cephalosporin with activity in vitro against drug-resistant Gram-positive organisms. We investigated ceftaroline at 600 mg every 12 h (q12h) (maximum concentration of the free, unbound drug in serum [fCmax] is 15.2 μg/ml, and half-life [T1/2] is 2.5 h) versus ceftriaxone at 1 g q24h (fCmax = 23 μg/ml, T1/2 = 8 h) against six clinical S. pneumoniae isolates in a one-compartment in vitro pharmacokinetic/pharmacodynamic 96-h model (starting inoculum of 107 CFU/ml). Differences in CFU/ml (at 24 to 96 h) were evaluated by analysis of variance with a Tukey's post hoc test. Bactericidal activity was defined as a ≥3 log10 CFU/ml decrease from the initial inoculum. Ceftaroline MICs were 0.06, 0.015, ≤0.008, 0.25, 0.25, and 0.5 μg/ml, and ceftriaxone MICs were 0.5, 0.25, 0.25, 4, 4, and 8 μg/ml for SP 1477, SP 669, SP 132, SP 211, SP 90, and SP 1466, respectively. Against the ceftaroline- and ceftriaxone-susceptible strain SP 1477, ceftaroline displayed sustained bactericidal activity (3 to 96 h, −5.49 log10 CFU/ml) and was significantly (P ≤ 0.012) better than ceftriaxone (72 to 96 h, −2.03 log10 CFU/ml). Against the ceftriaxone-resistant strains, ceftaroline displayed sustained bactericidal activity at 96 h and was significantly better than ceftriaxone (SP211 [−5.91 log10 CFU/ml, P ≤ 0.002], SP 90 [−5.26 log10 CFU/ml, P ≤ 0.008], and SP1466 [−5.14 log10 CFU/ml, P ≤ 0.042]). Ceftaroline was the more effective drug and displayed sustained bactericidal activity. Ceftaroline fosamil may provide a therapeutic option to treat ceftriaxone-resistant S. pneumoniae infections.
    Antimicrobial Agents and Chemotherapy 02/2012; 56(5):2691-5. DOI:10.1128/AAC.06185-11 · 4.48 Impact Factor
Show more