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Activity analyses of staphylococcal isolates from pediatric, adult, and elderly patients: AWARE Ceftaroline
Helio S Sader1, Robert K Flamm, David J Farrell
1JMI Laboratories, North Liberty, Iowa 52317, USA. helio-sader@jmilabs.com
Abstract:
Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a broad-spectrum cephalosporin with bactericidal activity against resistant Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA), and common Gram-negative organisms. We evaluated the activity of ceftaroline and various antimicrobial agents against S. aureus isolates according to patient age. A total of 2143 consecutive unique patient strains of clinical significance were collected between January and December 2010 from 65 US medical centers as part of the Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) Program. Ceftaroline and various comparator agents were tested by reference Clinical and Laboratory Standards Institute broth microdilution methods. Ceftaroline was consistently active against methicillin-susceptible S. aureus (MSSA) (MIC(50), 0.25 μg/mL; MIC(90), 0.25 μg/mL; 100.0% susceptible) and MRSA (MIC(50), 0.50 μg/mL, MIC(90), 1 μg/mL; 98.4% susceptible) from all age groups. In general, resistance rates to erythromycin, clindamycin, and levofloxacin were higher in the population aged ≥ 65 years, whereas resistance rates to clindamycin and levofloxacin were lowest among isolates from patients aged 6-17 years. When tested against MSSA, levofloxacin resistance was higher among isolates from patients aged ≥ 65 years (16.1%) than among isolates from the other age groups (6.1%-10.5%), and ceftaroline was generally 16-fold more active than ceftriaxone (MIC(50), 4 μg/mL; MIC(90), 4 μg/mL; 97.9% susceptible overall). Ceftaroline (MIC(50), 0.50 μg/mL; MIC(/90), 1 μg/mL), daptomycin (MIC(50), 0.25 μg/mL; MIC(90), 0.5 μg/mL), linezolid (MIC(50), 1 μg/mL; MIC(90), 1 μg/mL), and vancomycin (MIC(50), 1 μg/mL(;) MIC(90), 1 μg/mL) were the most active compounds tested against MRSA strains, and the activity of these compounds did not vary significantly among the age groups. In contrast, susceptibility rates to clindamycin and levofloxacin varied from 94.0% and 60.7% (aged 6-17 years), respectively, to only 57.6% and 15.1% (aged ≥ 65 years), respectively, among MRSA strains. The results of this study showed major differences in the susceptibility rates to clindamycin and levofloxacin according to patient age group. The results also indicate that ceftaroline is highly active against MSSA and MRSA isolated from US medical centers, independent of patient age group.
Insights
Ceftaroline demonstrates consistent activity against methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) across all patient age groups. This study highlights significant age-related differences in susceptibility to other antibiotics like clindamycin and levofloxacin.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Antimicrobial resistance in Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), poses a significant global health threat.
- Understanding the activity of newer agents like ceftaroline against S. aureus across different patient demographics is crucial for effective treatment strategies.
Purpose of the Study:
- To evaluate the in vitro activity of ceftaroline and comparator antimicrobial agents against clinical isolates of Staphylococcus aureus.
- To assess the influence of patient age on the susceptibility patterns of S. aureus to various antibiotics, including ceftaroline.
Main Methods:
- Collected 2143 unique S. aureus patient strains from 65 US medical centers between January and December 2010.
- Determined antimicrobial susceptibility using Clinical and Laboratory Standards Institute (CLSI) broth microdilution methods.
- Analyzed susceptibility data stratified by patient age groups.
Main Results:
- Ceftaroline exhibited potent activity against both methicillin-susceptible S. aureus (MSSA) and MRSA isolates across all age groups (100% susceptibility for MSSA, 98.4% for MRSA).
- Resistance rates to erythromycin, clindamycin, and levofloxacin were generally higher in patients aged ≥ 65 years.
- Susceptibility to clindamycin and levofloxacin varied significantly by age group, particularly for MRSA isolates, with lower rates in older patients.
Conclusions:
- Ceftaroline demonstrates consistent and high in vitro activity against S. aureus, including MRSA, irrespective of patient age.
- Significant age-dependent variations in susceptibility were observed for clindamycin and levofloxacin, underscoring the importance of age stratification in resistance surveillance.
- Ceftaroline represents a valuable therapeutic option for S. aureus infections, including those caused by MRSA, across diverse patient populations.
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