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Antimicrobial activity and in vitro corneal epithelial toxicity of antimicrobial agents for gram-positive corneal
P E Cutarelli1, H M Lazarus, M R Jacobs
1Department of Ophthalmology, University Hospitals of Cleveland, OH 44106.
Abstract:
We assessed in vitro the antimicrobial activity of four agents (vancomycin, teicoplanin, mupirocin, and imipenem) which are effective against Gram-positive cocci causally associated with bacterial keratitis, as well as their corneal epithelial cytotoxicity. Minimal inhibitory concentrations inhibiting 90% of strains (MIC90s) against 10 strains each of methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis, penicillin-susceptible and -resistant Streptococcus pneumoniae, and viridans group streptococci were as follows: vancomycin (MIC90s 0.25-2 micrograms/ml), teicoplanin (MIC90s 0.25-4 micrograms/ml, mupirocin (MIC90s 0.12-4 micrograms/ml), and imipenem (MIC90s 0.008-0.25 micrograms/ml, except for methicillin-resistant staphylococci with MIC90 of 16 micrograms/ml). Cytotoxicity was assayed by uptake of 3H-thymidine by rabbit corneal epithelial cell cultures at drug concentrations of 12.5-100 mg/ml for vancomycin and teicoplanin, 1-8 mg/ml for mupirocin and 0.125-8 mg/ml for imipenem, with exposure times of 5, 30 and 60 min. Cytotoxicity was as follows: imipenem < mupirocin < vancomycin < or = teicoplanin. Resistance to methicillin-resistant S. aureus and S. epidermidis for imipenem and resistance to S. epidermidis and cytotoxicity for teicoplanin limit their consideration for suspected Gram-positive keratitis. On the other hand, vancomycin and mupirocin, because of their excellent therapeutic indices, should be considered for this indication.
Insights
Vancomycin and mupirocin show excellent therapeutic indices against Gram-positive bacteria causing keratitis, making them suitable for treatment. Imipenem and teicoplanin have limitations due to resistance and cytotoxicity, respectively.
Area of Science:
- Ophthalmology
- Microbiology
- Pharmacology
Background:
- Bacterial keratitis is a serious eye infection often caused by Gram-positive cocci.
- Effective antimicrobial agents are crucial for treating bacterial keratitis, but their corneal safety must also be considered.
Purpose of the Study:
- To evaluate the in vitro antimicrobial activity and corneal epithelial cytotoxicity of vancomycin, teicoplanin, mupirocin, and imipenem.
- To determine the suitability of these agents for treating bacterial keratitis.
Main Methods:
- Minimal inhibitory concentrations (MIC90s) were determined against various strains of Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pneumoniae.
- Corneal epithelial cytotoxicity was assessed using rabbit corneal epithelial cell cultures and measuring 3H-thymidine uptake at different drug concentrations and exposure times.
Main Results:
- Imipenem exhibited the lowest MIC90s overall, except against methicillin-resistant staphylococci. Vancomycin and teicoplanin showed good activity against most strains.
- Cytotoxicity varied, with imipenem being the least cytotoxic, followed by mupirocin, then vancomycin and teicoplanin.
- Imipenem resistance in resistant staphylococci and teicoplanin's cytotoxicity limited their use.
Conclusions:
- Vancomycin and mupirocin demonstrated favorable therapeutic indices, indicating their potential as effective treatments for bacterial keratitis.
- Imipenem and teicoplanin have drawbacks that may restrict their use in treating Gram-positive bacterial keratitis.