Ceftaroline: An Alternative Broad Spectrum Antibiotic for Pediatric Infections

Marcia L. Buck, PharmD, FCCP, FPPAG, BCPPS

Disclosures

Pediatr Pharm. 2017;23(6) 

In This Article

Mechanism of Action and Spectrum of Activity

Ceftaroline is the active metabolite of the prodrug ceftaroline fosamil.[1–3] The prodrug is converted to active ceftaroline by plasma phosphate enzymes. As with other cephalosporins, the antibacterial activity of ceftaroline is the result of binding to essential penicillin-binding proteins (PBPs) to inhibit bacterial cell wall synthesis. Ceftaroline exhibits enhanced activity for mutated PBPs, including the mecA gene-encoded mutant PBP2a seen in MRSA, PBP2x associated with multi-drug resistant Strep. pneumoniae, PBP1A, and PBP2b. The resulting efficacy of ceftaroline, particularly in treating MRSA and beta-lactam resistant Strep. pneumoniae, has led some authors to refer to it as the first "5th generation" cephalosporin.[1]

Ceftaroline is indicated for the treatment of ABSSI cause by methicillin-sensitive and methicillin-resistant strains of Staph. aureus, Strep. pyogenes, Strep. agalactiae, E. coli, Klebsiella pneumoniae, and Klebsiella oxytoca. It is approved for CABP caused by Strep. pneumoniae, methicillin-sensitive Staph. aureus, E. coli, Haemophilus influenzae, Klebsiella pneumonia, and Klebsiella oxytoca. Criteria for interpreting susceptibility based on minimum inhibitory concentrations and disk diffusion zone diameters is available in the manufacturer's prescribing information.[3,4]

In vitro testing suggests that ceftaroline may also be effective against Strep. dysgalactiae, Citrobacter koseri, Citrobacter freundii, Enterobacter cloacae, Enterobacter aerogenes, Moraxella catarrhalis, Morganella morganii, Proteus mirabilis, and Haemophilus parainfluenzae; however, there are not adequate clinical studies to support their use in these infections at this time. Ceftaroline is not active against Gram negative bacteria that produce extended spectrum beta-lactamases (ESBLs).[3,4]

The development of ceftaroline-resistant MRSA isolates has been documented in several case reports in adults. In 2016, Cannavino and colleagues reported a case of ceftaroline-resistant MRSA in a 4-year-old girl with cystic fibrosis (CF) after 22 ceftaroline courses over a period of 30 months.[5] The authors hypothesize that subinhibitory concentrations of the drug in the thick mucus of the airways in patients with CF may have supported the development of genetic mutations leading to resistance.

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