|
 
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| DRUG REVIEW |
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| Year : 2016 | Volume
: 18
| Issue : 2 | Page : 72-73 |
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Ceftaroline Fosamil: An update
Manju K Nair1, Saritha Narayanan Kutty2
1 Department of Pharmacology, Government Medical College, Paripally, Kollam, Kerala, India
2 Department of Microbiology, Government Medical College, Paripally, Kollam, Kerala, India
| Date of Web Publication | 30-Nov-2016 |
Correspondence Address:
Dr. Saritha Narayanan Kutty
Department of Microbiology, Government Medical College, Paripally, Kollam, Kerala
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0972-1282.194923
How to cite this article:
Nair MK, Kutty SN. Ceftaroline Fosamil: An update. J Acad Clin Microbiol 2016;18:72-3 |
| Introduction | |  |
Microbial pathogens have an extraordinary capacity to develop resistance to antimicrobial agents.[1] Methicillin-resistant Staphylococcus aureus (MRSA) is a prominent nosocomial pathogen causing community-acquired pneumonia (CAP) and complicated skin and soft tissue infections (SSTIs). Cephalosporins are a class of Beta-lactam antibiotics with a broad spectrum of activity, proven efficacy and favourable safety profile, making it one of the most commonly prescribed classes of antimicrobials.[2] However, all the four generations are inactive against MRSA. Ceftaroline Fosamil, a fifth-generation Cephalosporin,[3] was synthesised by Takeda Pharmaceutical Co., Ltd and developed by Cerexa, Inc. and Forest Laboratories, Inc.,[2],[4] and it gained the FDA approval in 2010. The Clinical and Laboratory Standards Institute, however, has considered it under a new subclass 'Cephalosporins with anti-methicillin-resistant Staphylococcus aureus activity'.[2],[5] The 1, 3 thiazole ring attached to three-position of Cephalosporin nucleus and Oxime group in C7 Acyl moiety confers enhanced activity against MRSA.[2]
| Mechanism of Action | | |
The bactericidal action is mediated by binding to all forms of penicillin-binding proteins (PBPs; PBP2a and PBP2b, 2×, 1a), causing bacterial cell wall irregularities and eventually bacterial cell death. Activity on PBP2a and PBP2× confers increased activity against S. aureus and Streptococcus pneumoniae, respectively.[6]
| Antibacterial Spectrum | | |
It is effective against resistant Gram-positive bacteria (e.g., S. aureus including MRSA, Methicillin-susceptible S. aureus, Vancomycin-resistant S. aureus, Vancomycin-intermediate S. aureus, coagulase-negative Staphylococcus epidermidis, Streptococcus agalactiae, S. pneumoniae, Streptococcus viridans, Streptococcus pyogenes), Gram-negative bacteria (e.g., Moraxella More Details catarrhalis, Haemophilus influenza, Pasteurella multocida) and a few anaerobes (Propionibacterium spp., Peptostreptococcus spp., non-difficile Clostridium spp., etc.). However, it is inactive against Enterococcus faecium, extended-spectrum β-lactamase and carbapenemase-producing strains, strains with stable de-repressed AmpC β-lactamase production, Pseudomonas spp. and most β-lactamase-producing Gram-negative anaerobes, including Bacteroides fragilis and Prevotella spp.[1],[2],[6]
| Pharmacokinetic and Pharmacodynamic Profile | | |
It is a water-soluble prodrug, rapidly dephosphorylated to the active form, Ceftaroline, in plasma. Less than 20% of the drug is plasma protein bound. Elimination half-life is about 2.7 h, the maximum observed concentration is 21 μg/mL and the area under the concentration-time curve is 56 μg h/mL, with no appreciable accumulation. It is excreted through kidneys and dosage adjustment is recommended for patients with creatinine clearance ≤50 mL/min. Not metabolised by cytochrome P450 enzymes, so less propensity for drug-drug interactions. It exhibits time-dependent killing. The amount of time the serum concentration remains above the minimum inhibitory concentration represents the main pharmacodynamic predictor of efficacy.[6]
| Preparations, Dosage and Uses | | |
It is available as 400 and 600 mg single-use vials of sterile powder. The reconstituted solution should be used within 6 h if stored at room temperature or within 24 h if refrigerated.[2] It is used in community-acquired bacterial pneumonia (600 mg intravenous [IV] over 1 h every 12 h for 5-7 days) and acute bacterial skin and skin structure infections including those caused by MRSA (600 mg IV over 1 h every 12 h for 5-14 days).[6]
| Adverse Effects | | |
Diarrhoea, nausea, headache, rash and pruritus are the adverse effects. Data are incomplete regarding use in children and are considered as a category B drug in pregnancy.[1],[2]
| Clinical Trials | | |
CANVAS I and II trials (randomised, double-blind, multinational Phase III trials) evaluated the efficacy of Ceftaroline for the treatment of SSTIs among 1378 subjects comparing Ceftaroline to Vancomycin ± Aztreonam in 2007. It was found that for treating SSTI, Ceftaroline (600 mg IV every 12 h) was non-inferior to Vancomycin (1 g IV every 12 h) plus Aztreonam (1 g IV every 8 h) administered for 5-14 days. In FOCUS I and II trials (randomised, double-blind, multicentric Phase III trials), 1228 hospitalised adults with moderate to severe CAP were randomised to Ceftaroline (600 mg IV every 12 h) or Ceftriaxone (1 g IV daily) for 5-7 days. The overall clinical and microbiological response rates were similar, demonstrating Ceftaroline to be efficacious, well tolerated and comparable in efficacy and adverse effects to Ceftriaxone in the treatment of CAP.[1]
| Conclusion | | |
Ceftaroline Fosamil, a new, broad spectrum Cephalosporin, is a promising approach towards combating MRSA-mediated infections and has been approved for use in CAP and complicated SSTIs.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Duplessis C, Crum-Cianflone NF. Ceftaroline: A New cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA). Clin Med Rev Ther 2011;3. pii: A2466.  |
| 2. | Laudano JB. Ceftaroline fosamil: A new broad-spectrum cephalosporin. J Antimicrob Chemother 2011;66 Suppl 3:iii11-8. |
| 3. | Kollef MH. New antimicrobial agents for methicillin-resistant Staphylococcus aureus. Crit Care Resusc 2009;11:282-6. |
| 4. | Parish D, Scheinfeld N. Ceftaroline fosamil, a cephalosporin derivative for the potential treatment of MRSA infection. Curr Opin Investig Drugs 2008;9:201-9. |
| 5. | Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing: Twentieth Informational Supplement M 100-S20. Wayne, PA, USA: CLSI; 2010. |
| 6. | Shirley DA, Heil EL, Johnson JK. Ceftaroline fosamil: A brief clinical review. Infect Dis Ther 2013;2:95-110. |
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