Abstract
Purpose: :
To compare the bactericidal effectiveness of Tobradex ophthalmic suspension to a new formulation containing half the concentration of dexamethasone enhanced with novel suspension technology using rabbit models of Staphylococcus aureus and Pseudomonas aeruginosa keratitis.
Methods: :
Eyes were intrastromally injected with 100 colony forming units (CFU) of methicillin-sensitive S. aureus (MSSA; 8325-4) or methicillin-resistant S. aureus (MRSA; strain 70490) or 1000 CFU P. aeruginosa (27853). S. aureus infected eyes were treated every hour from 10 to 15 hours postinfection (PI) with a single drop of formulation. Eyes infected with Pseudomonas were treated at 16 hours PI with a single drop every 15 minutes for one hour and then every hour from 17 to 22 hours PI. Tested were untreated eyes (n = 12 per strain) and eyes treated with dexamethasone (0.1%, Maxidex; n = 6 per strain), tobramycin (0.3%, Tobrex; n = 6 per strain), the standard combination of tobramycin (0.3%) and dexamethasone (0.1%) (Tobradex, n = 6 per strain) or a new formulation of tobramycin (0.3%) and dexamethasone (0.05%) with pharmaceutical-grade xanthan gum (Tobradex ST; n = 6 per strain). Corneas were cultured 1 hour after the last treatment to determine the log CFU ± SEM per cornea.
Results: :
Corneas in untreated eyes infected with MSSA or MRSA at 16 hours PI had 6.73 ± 0.1 and 6.95 ± 0.08 logs of bacteria, respectively; for P. aeruginosa, 7.55 ± 0.09 logs of bacteria were present at 23 hours PI. All eyes treated with Maxidex had no significant reduction in CFU as compared to the untreated control (P ≥ 0.15). Eyes treated with Tobrex had a significant reduction in CFU in MSSA-infected or MRSA-infected corneas (P = 0.002 and 0.04, respectively). Tobrex did not significantly reduce the CFU of P. aeruginosa (P = 0.09). Tobradex formulation significantly reduced the CFU in either Staphylococcus model (P ≤ 0.008), but not in the Pseudomonas model (P = 0.07). The Tobradex ST formulation in both Staphylococcus models significantly reduced the CFU per cornea relative to untreated eyes (P ≤ 0.003) and relative to eyes treated with the Tobradex formulation (P ≤ 0.01). The Tobradex ST in the Pseudomonas model also caused a significant reduction in CFU as compared to untreated controls (P = 0.007) and to eyes treated with the Tobradex formulation (P = 0.03).
Conclusions: :
The Tobradex ST formulation is effective for S. aureus and P. aeruginosa keratitis in a rabbit model.
Keywords: keratitis • Staphylococcus • pseudomonas