Background: Ceftaroline, the active form of ceftaroline fosamil, is a cephalosporin with broad-spectrum bactericidal activity against resistant Gram-positive organisms, including methicillin-resistant Staphylococcus aureus, ceftriaxone-resistant Streptococcus pneumoniae and many Enterobacteriaceae species. Ceftaroline fosamil is approved in the United States for treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia in adults.
Methods: A total of 5291 consecutive unique pediatric patient strains of clinical significance were collected from 157 US medical centers. The isolates were identified locally and forwarded to a central monitoring laboratory for reference antimicrobial susceptibility testing. S. pneumoniae isolates from the 2011 to 2012 respiratory season were serotyped. Susceptibility results were analyzed according to patient age as follows: ≤1 years old (yo; 1857 strains); 2–5 (1342); 6–12 (1281) and 13–17 (811).
Results: Methicillin-resistant Staphylococcus aureus rates were slightly lower in isolates from patients 13–17 yo (39.9%) compared with other age groups (48.2–51.5%), and ceftaroline was consistently active against S. aureus isolates from all 4 age groups [minimal inhibitory concentration (MIC50/90): 0.25–05/1 μg/mL; 99.8–100.0% susceptible]. Overall, 99.8% of methicillin-resistant Staphylococcus aureus were ceftaroline susceptible (MIC50/90: 0.5/1 μg/mL). All S. pneumoniae strains (1178) were ceftaroline susceptible (MIC50/90: ≤0.015/0.12 μg/mL), whereas ceftriaxone susceptibility varied from only 84.8 (≤1 yo) to 89.7% (13–17 yo). 19A was the most frequent serotype identified among S. pneumoniae and these isolates exhibited low susceptibility to ceftriaxone (42.4%) and most other antimicrobials tested. The highest ceftaroline MIC among Haemophilus influenzae (587 strains) was 0.12 μg/mL (100.0% susceptible), and β-lactamase production rates varied from 24.2 (13–17 yo) to 30.1% (6–12 yo); 27.9% overall. Ceftaroline was also active against β-hemolytic streptococci (556 strains, highest MIC, 0.06 μg/mL). Extended-spectrum β-lactamase (ESBL)-phenotype rates among Escherichia coli/Klebsiella spp. were 6.0/5.1, 11.0/11.5, 5.1/8.3 and 11.4/14.7% for the ≤1, 2–5, 6–12 and 13–17 yo age groups, respectively. Ceftaroline exhibited good activity against non-ESBL phenotype strains of E. coli and Klebsiella spp. (MIC90: 0.25 μg/mL for both organisms), but had limited activity against ESBL-producing strains.
Conclusion: Ceftaroline demonstrated potent in vitro activity when tested against S. aureus, S. pneumoniae, H. influenzae, β-hemolytic streptococci and non-ESBL-phenotype E. coli and Klebsiella spp. strains isolated from pediatric patients, independent of patient age.
From the JMI Laboratories, North Liberty, IA
Accepted for publication January 26, 2014.
This study was supported by Forest Laboratories, Inc. Forest Laboratories, Inc., was involved in the design of the study, but had no involvement in the collection, analysis, and interpretation of data, Scientific Therapeutics Information, Inc., provided editorial coordination, which was funded by Forest Research Institute, Inc.
The authors have no other funding or conflicts of interest to disclose.
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Address for correspondence: Helio S. Sader, MD, PhD, JMI Laboratories, 345 Beaver Kreek Ctr, Ste A, North Liberty, IA 52317. E-mail: firstname.lastname@example.org.