Antimicrobial activity and in vitro corneal epithelial toxicity of antimicrobial agents for gram-positive corneal pathogens.
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.
Cutarelli
P E
PE
Department of Ophthalmology, University Hospitals of Cleveland, OH 44106.
Lazarus
H M
HM
Jacobs
M R
MR
Lass
J H
JH
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003315:Cornea / Q000187:drug effects* / Q000382:microbiology; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects; D007769:Lactams; D008826:Microbial Sensitivity Tests; D010455:Peptides; D011817:Rabbits; D013210:Staphylococcus / Q000187:drug effects*; D013936:Thymidine
D000900:Anti-Bacterial Agents; D007769:Lactams; D010455:Peptides; D004247:DNA; D013936:Thymidine