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Ceftaroline fosamil: a novel broad-spectrum cephalosporin with expanded anti-Gram-positive activity.
J Antimicrob Chemother. 2010 Nov; 65 Suppl 4:iv9-16.JA

Abstract

Ceftaroline fosamil is a novel cephalosporin with broad-spectrum activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Streptococcus pneumoniae, and common Gram-negative organisms. The activity of ceftaroline against MRSA is attributed to its ability to bind to penicillin-binding protein (PBP) 2a with high affinity and inhibit the biochemical activity of PBP 2a more efficiently than other presently available β-lactams. The activity of ceftaroline against MRSA and the β-haemolytic streptococci makes it an attractive monotherapy agent for the treatment of complicated skin and skin structure infections (cSSSIs). Recent profiling and surveillance studies have shown that ceftaroline is active against contemporary skin pathogens collected from US and European medical centres in 2008. The mean free drug %T > MIC (percentage of time the drug concentration remains above the MIC) needed for stasis ranged from 26% for S. aureus to 39% for S. pneumoniae in the murine thigh infection model. Pharmacokinetic and pharmacodynamic target attainment predictions for 600 mg of ceftaroline fosamil every 12 h showed that the mean %T > MICs for which plasma free-drug concentrations exceeded an MIC of 1 and 2 mg/L were 71% and 51% of the dosing interval, respectively. For a 40% T > MIC target, the predicted attainments for infections due to pathogens for which ceftaroline MICs were 1 or 2 mg/L were 100% and 90%, respectively. Clinical and microbiological successes of ceftaroline fosamil in treating cSSSIs were demonstrated in two Phase III clinical studies, in which 96.8% of all baseline cSSSI isolates from the microbiologically evaluable population were inhibited by ceftaroline at ≤ 2 mg/L. Ceftaroline fosamil is a promising broad-spectrum agent for the treatment of cSSSIs.

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Authors+Show Affiliations

Biek D
Cerexa, Inc., Oakland, CA 94612, USA. ronald-jones@jmilabs.com
Critchley IA
No affiliation info available
Riccobene TA
No affiliation info available
Thye DA
No affiliation info available

MeSH

AnimalsAnti-Bacterial AgentsCephalosporinsClinical Trials, Phase III as TopicDrug Resistance, BacterialGram-Negative BacteriaGram-Positive BacteriaHumansMethicillin-Resistant Staphylococcus aureusMiceMicrobial Sensitivity TestsSkin Diseases, BacterialSoft Tissue InfectionsTreatment Outcome

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

21115457

Citation

Biek, Donald, et al. "Ceftaroline Fosamil: a Novel Broad-spectrum Cephalosporin With Expanded anti-Gram-positive Activity." The Journal of Antimicrobial Chemotherapy, vol. 65 Suppl 4, 2010, pp. iv9-16.
Biek D, Critchley IA, Riccobene TA, et al. Ceftaroline fosamil: a novel broad-spectrum cephalosporin with expanded anti-Gram-positive activity. J Antimicrob Chemother. 2010;65 Suppl 4:iv9-16.
Biek, D., Critchley, I. A., Riccobene, T. A., & Thye, D. A. (2010). Ceftaroline fosamil: a novel broad-spectrum cephalosporin with expanded anti-Gram-positive activity. The Journal of Antimicrobial Chemotherapy, 65 Suppl 4, iv9-16. https://doi.org/10.1093/jac/dkq251
Biek D, et al. Ceftaroline Fosamil: a Novel Broad-spectrum Cephalosporin With Expanded anti-Gram-positive Activity. J Antimicrob Chemother. 2010;65 Suppl 4:iv9-16. PubMed PMID: 21115457.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ceftaroline fosamil: a novel broad-spectrum cephalosporin with expanded anti-Gram-positive activity. AU - Biek,Donald, AU - Critchley,Ian A, AU - Riccobene,Todd A, AU - Thye,Dirk A, PY - 2010/12/1/entrez PY - 2010/12/9/pubmed PY - 2011/3/15/medline SP - iv9 EP - 16 JF - The Journal of antimicrobial chemotherapy JO - J Antimicrob Chemother VL - 65 Suppl 4 N2 - Ceftaroline fosamil is a novel cephalosporin with broad-spectrum activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Streptococcus pneumoniae, and common Gram-negative organisms. The activity of ceftaroline against MRSA is attributed to its ability to bind to penicillin-binding protein (PBP) 2a with high affinity and inhibit the biochemical activity of PBP 2a more efficiently than other presently available β-lactams. The activity of ceftaroline against MRSA and the β-haemolytic streptococci makes it an attractive monotherapy agent for the treatment of complicated skin and skin structure infections (cSSSIs). Recent profiling and surveillance studies have shown that ceftaroline is active against contemporary skin pathogens collected from US and European medical centres in 2008. The mean free drug %T > MIC (percentage of time the drug concentration remains above the MIC) needed for stasis ranged from 26% for S. aureus to 39% for S. pneumoniae in the murine thigh infection model. Pharmacokinetic and pharmacodynamic target attainment predictions for 600 mg of ceftaroline fosamil every 12 h showed that the mean %T > MICs for which plasma free-drug concentrations exceeded an MIC of 1 and 2 mg/L were 71% and 51% of the dosing interval, respectively. For a 40% T > MIC target, the predicted attainments for infections due to pathogens for which ceftaroline MICs were 1 or 2 mg/L were 100% and 90%, respectively. Clinical and microbiological successes of ceftaroline fosamil in treating cSSSIs were demonstrated in two Phase III clinical studies, in which 96.8% of all baseline cSSSI isolates from the microbiologically evaluable population were inhibited by ceftaroline at ≤ 2 mg/L. Ceftaroline fosamil is a promising broad-spectrum agent for the treatment of cSSSIs. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/21115457/Ceftaroline_fosamil:_a_novel_broad_spectrum_cephalosporin_with_expanded_anti_Gram_positive_activity_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkq251 DB - PRIME DP - Unbound Medicine ER -