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Ceftaroline Activity Against Multidrug-Resistant Streptococcus pneumoniae from U.S. Medical Centers (2014) and
Michael A Pfaller1,2, Rodrigo E Mendes1, Robert K Flamm1
11 JMI Laboratories , North Liberty, Iowa.
Abstract:
Streptococcus pneumoniae isolates (2,614) were collected from patients at 135 U.S. Medical Centers during 2014. Isolates were evaluated for multidrug resistance to penicillin, ceftriaxone, erythromycin, tetracycline, trimethoprim-sulfamethoxazole, and levofloxacin. A single isolate (853008) demonstrated a ceftaroline nonsusceptible minimal inhibitory concentration (MIC) value, and it was subjected to molecular characterization. Ceftaroline (MIC50/90, ≤0.015/0.12 μg/ml) was eightfold more potent than ceftriaxone (MIC50/90, ≤0.06/1 μg/ml) against all isolates. For multidrug-resistant (MDR) isolates (28.8% of tested strains), ceftaroline (MIC50/90, 0.06/0.25 μg/ml; 99.9% susceptible) was the most active agent tested, being eightfold more active than ceftriaxone (MIC50/90, 0.25/2 μg/ml; 81.5% susceptible at MIC, ≤1 μg/ml) and 16-fold more active than penicillin (MIC50/90, 0.25/4 μg/ml; 78.5% susceptible at MIC, ≤2 μg/ml). Isolate 853008 was a single locus variant of sequence type 377 and serotype 35B. It had multiple substitutions in the penicillin-binding proteins (PBPs), mainly PBP2x, when compared with reference sequences from the R6 strain. Isolate 853008 showed 31 amino acid alterations in MurM. The in vitro data presented here confirm that ceftaroline potency against S. pneumoniae to be higher than other β-lactams, including against those isolates demonstrating ceftriaxone nonsusceptible and MDR phenotypes.
Insights
Ceftaroline demonstrates superior in vitro activity against Streptococcus pneumoniae, including multidrug-resistant strains. This new cephalosporin shows higher potency than other beta-lactams, offering a promising option for treating resistant pneumococcal infections.
Area of Science:
- Clinical Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Streptococcus pneumoniae is a leading cause of bacterial infections, with increasing antimicrobial resistance posing a significant public health threat.
- Multidrug resistance (MDR) in S. pneumoniae necessitates the development and evaluation of novel antimicrobial agents.
- Ceftriaxone and penicillin are commonly used beta-lactam antibiotics, but resistance is a growing concern.
Purpose of the Study:
- To evaluate the in vitro activity of ceftaroline against a contemporary U.S. collection of Streptococcus pneumoniae isolates.
- To compare the potency of ceftaroline with other beta-lactam antibiotics, including ceftriaxone and penicillin, particularly against MDR strains.
- To investigate the molecular characteristics of a ceftaroline-nonsusceptible isolate.
Main Methods:
- Antimicrobial susceptibility testing (MIC determination) was performed on 2,614 S. pneumoniae isolates collected from 135 U.S. medical centers in 2014.
- Isolates were tested against penicillin, ceftriaxone, erythromycin, tetracycline, trimethoprim-sulfamethoxazole, and levofloxacin.
- A single ceftaroline-nonsusceptible isolate (853008) underwent molecular characterization, including analysis of penicillin-binding proteins (PBPs) and MurM.
Main Results:
- Ceftaroline exhibited potent in vitro activity against all S. pneumoniae isolates, with MIC50/90 values of ≤0.015/0.12 μg/ml, outperforming ceftriaxone (MIC50/90, ≤0.06/1 μg/ml).
- Against MDR isolates (28.8% of strains), ceftaroline (MIC50/90, 0.06/0.25 μg/ml) demonstrated 99.9% susceptibility and was significantly more active than ceftriaxone and penicillin.
- The ceftaroline-nonsusceptible isolate (853008) was a single locus variant of ST377 and serotype 35B, with multiple amino acid substitutions in PBP2x and MurM.
Conclusions:
- Ceftaroline demonstrates superior in vitro potency against Streptococcus pneumoniae compared to other beta-lactams, including against ceftriaxone-nonsusceptible and MDR phenotypes.
- The findings support ceftaroline as a valuable therapeutic option for invasive pneumococcal diseases, even in the context of emerging resistance.
- Molecular analysis of resistant isolates provides insights into resistance mechanisms, aiding in the ongoing surveillance and management of pneumococcal infections.