Ceftaroline activity tested against bacterial isolates from pediatric patients: results from the assessing worldwide antimicrobial resistance and evaluation program for the United States (2011-2012)

Abstract

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.