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The in vitro antibacterial activity of ceftriaxone against Streptococcus pyogenes is unrelated to penicillin-binding
S Yan1, P M Mendelman, D L Stevens
1Department of Bacteriology, University of Idaho, Moscow.
Abstract:
The in vitro activities of penicillin and ceftriaxone were compared against 29 strains of Streptococcus pyogenes with the result that ceftriaxone showed greater activity than penicillin. The morphological changes induced by 1/2 and 1x MIC concentrations of penicillin and ceftriaxone, respectively, were very similar using scanning electron microscopy. Competitive binding studies using 'cold' penicillin or ceftriaxone as inhibitors of radiolabeled penicillin binding demonstrated that ceftriaxone had a very low affinity for penicillin binding protein (PBP) 4 compared to that of penicillin. Since ceftriaxone had greater antibacterial activity, this suggests that PBP 4 may not be important to the in vitro activity of ceftriaxone. In contrast, the IC50 for ceftriaxone was much lower (> 200 fold) for PBPs 2 and 3 compared to PBP 4, suggesting greater avidity of these high molecular mass PBPs for ceftriaxone. These data may at least in part explain the superior in vitro activity of ceftriaxone compared to penicillin against S. pyogenes. These data, together with the observation that PBP 1 was saturated at a lower concentration of penicillin than any of the other PBPs, suggest that the inhibition of PBPs 1, 2, and 3 mediates the bactericidal activity of beta-lactam antibiotics against group A streptococci.
Insights
Ceftriaxone demonstrates superior in vitro activity against Streptococcus pyogenes compared to penicillin. This enhanced efficacy is linked to ceftriaxone
Area of Science:
- Microbiology
- Pharmacology
- Biochemistry
Background:
- Streptococcus pyogenes is a significant human pathogen.
- Penicillin has been the standard treatment, but resistance is a concern.
- Ceftriaxone is a cephalosporin antibiotic with broad-spectrum activity.
Purpose of the Study:
- To compare the in vitro activity of penicillin and ceftriaxone against Streptococcus pyogenes.
- To investigate the underlying mechanisms of their differential activities.
- To identify key penicillin-binding proteins (PBPs) involved in beta-lactam antibiotic action.
Main Methods:
- In vitro susceptibility testing of 29 S. pyogenes strains.
- Scanning electron microscopy to observe morphological changes.
- Competitive binding assays using radiolabeled penicillin and unlabeled inhibitors.
Main Results:
- Ceftriaxone exhibited greater in vitro activity than penicillin against S. pyogenes.
- Morphological changes induced by both antibiotics were similar.
- Ceftriaxone showed significantly lower affinity for PBP 4 but higher avidity for PBPs 2 and 3 compared to penicillin.
- Penicillin binding protein 1 was saturated at lower concentrations of penicillin.
Conclusions:
- The superior activity of ceftriaxone against S. pyogenes may be attributed to its higher affinity for PBPs 2 and 3.
- PBP 4 appears less critical for ceftriaxone's in vitro efficacy.
- Inhibition of PBPs 1, 2, and 3 likely mediates the bactericidal effect of beta-lactams against group A streptococci.