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Activity of glycopeptides against vancomycin-resistant gram-positive bacteria
T I Nicas1, C T Cole, D A Preston
1Lilly Research Laboratories, Eli Lilly & Co., Indianapolis, Indiana 46285-0438.
Abstract:
Gram-positive bacteria resistant to vancomycin are rare; but they include members of the genera Leuconostoc, Lactobacillus, and Pediococcus, as well as recently emerging vancomycin-resistant strains of Enterococcus faecium and Enterococcus faecalis. Vancomycin, teicoplanin, and several vancomycin derivatives were tested for their activities against vancomycin-resistant gram-positive bacteria. Vancomycin-resistant E. faecium and E. faecalis were generally cross-resistant to other glycopeptides, but some N-substituted vancomycin derivatives were active against the resistant strains, with MICs of 2 to 32 micrograms/ml. These vancomycin derivatives also had significant levels of activity against intrinsically vancomycin-resistant organisms such as Leuconostoc sp. While vancomycin resistance in E. faecium and E. faecalis was inducible, resistance in members of the genera Leuconostoc, Lactobacillus, and Pediococcus appeared to be expressed constitutively. Antibody to a vancomycin-induced membrane protein found in membranes of resistant enterococci did not detect a cross-reacting protein in other vancomycin-resistant species.
Insights
Rare vancomycin-resistant Gram-positive bacteria, including Leuconostoc and emerging Enterococcus strains, show varied resistance. Certain N-substituted vancomycin derivatives effectively combat these resistant bacteria, offering new therapeutic potential.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Vancomycin resistance in Gram-positive bacteria is uncommon but includes genera like Leuconostoc, Lactobacillus, Pediococcus, and emerging strains of Enterococcus faecium and Enterococcus faecalis.
- These resistant strains pose a significant challenge in clinical settings.
Purpose of the Study:
- To evaluate the activity of vancomycin, teicoplanin, and novel N-substituted vancomycin derivatives against vancomycin-resistant Gram-positive bacteria.
- To investigate the mechanisms and patterns of vancomycin resistance in different bacterial genera.
Main Methods:
- Antimicrobial susceptibility testing was performed using vancomycin, teicoplanin, and various vancomycin derivatives.
- Minimum inhibitory concentrations (MICs) were determined for vancomycin-resistant strains.
- Antibody-based assays were used to detect specific membrane proteins in resistant bacteria.
Main Results:
- Vancomycin-resistant Enterococcus faecium and Enterococcus faecalis exhibited cross-resistance to other glycopeptides.
- Several N-substituted vancomycin derivatives demonstrated potent activity against resistant enterococci, with MICs ranging from 2 to 32 µg/ml.
- These derivatives also showed activity against intrinsically vancomycin-resistant organisms like Leuconostoc species.
- Vancomycin resistance was inducible in enterococci but constitutive in Leuconostoc, Lactobacillus, and Pediococcus.
- No cross-reacting vancomycin-induced membrane protein was detected in non-enterococcal resistant species.
Conclusions:
- N-substituted vancomycin derivatives represent a promising therapeutic option for infections caused by vancomycin-resistant Gram-positive bacteria.
- Understanding the distinct mechanisms of vancomycin resistance (inducible vs. constitutive) is crucial for developing targeted treatment strategies.
- Further research into the specific resistance mechanisms and the development of novel agents is warranted.