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Comparative In Vitro Activity of New Lipoglycopeptides and Vancomycin Against Ocular Staphylococci and Their Toxicity
Camille André1,2, Mohammad Mirazul Islam1,3, Eleftherios Paschalis1,3
1Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA.
Purpose:
The purpose of this study was to assess the potential of new lipoglycopeptides as novel topical therapies for improved treatment of recalcitrant ocular infections. We evaluated the in vitro antimicrobial activity of oritavancin, dalbavancin, and telavancin compared with vancomycin (VAN) against a large collection of ocular staphylococcal isolates and their cytotoxicity on human corneal epithelial cells (HCECs).
Methods:
Antimicrobial susceptibility testing was performed by broth microdilution against 223 Staphylococcus spp. clinical isolates. Time-kill kinetics were determined for methicillin-resistant strains of Staphylococcus aureus (MRSA) (n = 2) and Staphylococcus epidermidis (MRSE) (n = 1). In vitro cytotoxicity assays were performed with AlamarBlue and live/dead staining on HCECs.
Results:
All new lipoglycopeptides showed strong in vitro potency against ocular staphylococci, including multidrug-resistant MRSA strains, with dalbavancin showing a slightly higher potency overall [minimum inhibitory concentration (MIC) 90 0.06 μg/mL] compared with telavancin and oritavancin (MIC 90 0.12 μg/mL), whereas VAN had the lowest potency (MIC 90 2 μg/mL). Oritavancin exerted rapid bactericidal activity within 1 h for MRSA and 2 h for MRSE. All other drugs were bactericidal within 24 h. At a concentration commonly used for topical preparations (25 mg/mL), cytotoxicity was observed for VAN after 5 min of incubation, whereas reduction in HCEC viability was not seen for telavancin and was less affected by oritavancin and dalbavancin. Cytotoxicity at 25 mg/mL was seen for all drugs at 30 and 60 min but was significantly reduced or undetected for lower concentrations.
Conclusions:
Our study demonstrates that new lipoglycopeptides have substantially better in vitro antimicrobial activity against ocular staphylococcal isolates compared with VAN, with a similar or improved toxicity profile on HCECs.
Insights
New lipoglycopeptides show potent antimicrobial activity against ocular staphylococci, including resistant strains. These novel topical therapies demonstrate improved efficacy and safety over vancomycin for treating eye infections.
Area of Science:
- Ophthalmology
- Infectious Diseases
- Pharmacology
Background:
- Recalcitrant ocular infections pose a significant treatment challenge.
- Staphylococcal species are common pathogens in ocular infections.
- Vancomycin is a standard treatment but can have limitations.
Purpose of the Study:
- To evaluate novel lipoglycopeptides (oritavancin, dalbavancin, telavancin) as topical treatments for ocular infections.
- To compare their in vitro antimicrobial activity against ocular staphylococcal isolates.
- To assess their cytotoxicity on human corneal epithelial cells (HCECs).
Main Methods:
- Broth microdilution and time-kill kinetics were used for antimicrobial susceptibility testing.
- Tested against 223 Staphylococcus spp. clinical isolates, including MRSA and MRSE.
- Cytotoxicity assays involved AlamarBlue and live/dead staining on HCECs.
Main Results:
- Lipoglycopeptides exhibited potent activity against ocular staphylococci (MIC90: 0.06-0.12 μg/mL), outperforming vancomycin (MIC90: 2 μg/mL).
- Oritavancin showed rapid bactericidal activity; all tested agents were bactericidal within 24 hours.
- At 25 mg/mL, vancomycin showed cytotoxicity, while lipoglycopeptides had less impact on HCEC viability, especially at lower concentrations.
Conclusions:
- New lipoglycopeptides possess superior in vitro antimicrobial activity against ocular staphylococcal isolates compared to vancomycin.
- These agents present a promising alternative with a favorable toxicity profile for topical ocular therapy.
- Further investigation into lipoglycopeptides could lead to improved treatments for resistant eye infections.
