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In vitro activity of GAR-936 against vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus
R Patel1, M S Rouse, K E Piper
1Division of Infectious Diseases and Infectious Diseases Research Laboratory, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA. patel.robin@mayo.edu
Abstract:
We report the activity of the new glycylcycline antimicrobial agent GAR-936 against 37 clinical isolates of vancomycin-resistant enterococci (including organisms carrying the vanA, vanB, vanC-1, and vanC-2/3 genes), 26 clinical isolates of methicillin-resistant S. aureus and 30 clinical isolates of high-level penicillin-resistant S. pneumoniae. All isolates of vancomycin-resistant enterococci, methicillin-resistant S. aureus, and penicillin-resistant S. pneumoniae were inhibited by < or = 1, < or = 2, or < or = 0.25 microg/ml of GAR-936, respectively. Time kill experiments using vancomycin-resistant enterococci did not demonstrate synergy or antagonism between 2 microg/ml of GAR-936 and 0.25 microg/ml of quinupristin/dalfopristin.
Insights
The novel glycylcycline antimicrobial GAR-936 effectively inhibits resistant bacteria, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. This new agent shows potent activity against challenging clinical isolates.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Emergence of antimicrobial resistance poses a significant global health threat.
- Vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and penicillin-resistant Streptococcus pneumoniae are key multidrug-resistant pathogens.
- Novel antimicrobial agents are urgently needed to combat these resistant infections.
Purpose of the Study:
- To evaluate the in vitro antimicrobial activity of the new glycylcycline agent GAR-936.
- To assess GAR-936 activity against a panel of clinically relevant resistant bacterial isolates.
- To investigate potential synergistic or antagonistic interactions between GAR-936 and quinupristin/dalfopristin.
Main Methods:
- Antimicrobial susceptibility testing (MIC determination) was performed on clinical isolates.
- Isolates included VRE (vanA, vanB, vanC-1, vanC-2/3 genes), MRSA, and high-level penicillin-resistant S. pneumoniae.
- Time-kill experiments were conducted to assess drug interactions.
Main Results:
- GAR-936 demonstrated potent activity against all tested isolates.
- Minimum inhibitory concentrations (MICs) were ≤1 µg/ml for VRE, ≤2 µg/ml for MRSA, and ≤0.25 µg/ml for resistant S. pneumoniae.
- Time-kill studies showed no synergy or antagonism between GAR-936 and quinupristin/dalfopristin against VRE.
Conclusions:
- GAR-936 exhibits broad-spectrum activity against important multidrug-resistant Gram-positive bacteria.
- The glycylcycline agent GAR-936 represents a promising therapeutic option for infections caused by VRE, MRSA, and resistant S. pneumoniae.
- GAR-936 does not appear to interact synergistically or antagonistically with quinupristin/dalfopristin in vitro.