Judy M. Moreau

Immunization with alpha-toxin toxoid protects the cornea against tissue damage during experimental Staphylococcus aureus keratitis.

ABSTRACT Alpha-toxin is a major virulence factor in Staphylococcus aureus keratitis. Active or passive immunization with alpha-toxin toxoid could protect against corneal damage. Results show that either form of immunization did not kill bacteria but did significantly protect against corneal pathology, especially epithelial erosion.

Effectiveness of mupirocin and polymyxin B in experimental Staphylococcus aureus, Pseudomonas aeruginosa, and Serratia marcescens keratitis.

Purpose. The purpose of this study was to determine the effectiveness of mupirocin and polymyxin B, alone and in combination, in vitro and in vivo using rabbit models of Staphylococcus aureus, Pseudomonas aeruginosa, and Serratia marcescens keratitis. Methods. Rabbit eyes were intrastromally injected with 1,000 colony-forming units (CFUs) of P. aeruginosa or S. marcescens or 100 CFUs of S. aureus. Rabbits were then treated with 2.7 mg/mL mupirocin, 10,000 U/mL polymyxin B, a mupirocin:polymyxin B combination, or 0.3% ciprofloxacin. Vehicle and untreated controls were also included. Treatment schedules depended on the strain injected. The number of CFUs was determined for all eyes after treatment. Results. The mupirocin:polymyxin B combination was effective for all three genera both in vitro and in vivo. For S. aureus keratitis, the mupirocin:polymyxin B combination was more effective than either drug alone and significantly reduced the log number of bacteria in the cornea by more than 3 logs compared with the vehicle or untreated controls (p ≤ 0.0016). For P. aeruginosa, the mupirocin:polymyxin B combination treatment significantly reduced the number of CFUs per cornea relative to the individual drugs, vehicle, or untreated controls (p ≤ 0.016). For S. marcescens, the mupirocin:polymyxin B combination therapy significantly reduced the number of bacteria in rabbit corneas relative to the individual drugs, vehicle, or untreated groups (p ≤ 0.0001). Therapy with the mupirocin:polymyxin B combination was equivalent to ciprofloxacin therapy (p = 0.80). Conclusion. The mupirocin:polymyxin B combination was effective in treating experimental S. aureus, P. aeruginosa, and S. marcescens keratitis.

Effectiveness of ciprofloxacin-polystyrene sulfonate (PSS), ciprofloxacin and ofloxacin in a Staphylococcus keratitis model

PURPOSE Staphylococcus aureus causes severe corneal infections that often result in corneal scarring and blindness. Presently, therapy often involves the use of a fluoroquinolone antibiotic. This study, employing an experimental rabbit model of Staphylococcus keratitis, compared the effectiveness of two commonly prescribed formulations of fluoroquinolones to an experimental formulation, ciprofloxacin with polystyrene sulfonate (ciprofloxacin-PSS). The ciprofloxacin-PSS formulation uses an ion exchange resin to aid in the delivery of drug to the cornea. METHODS Early (4-9 h postinfection, PI) and late (10-15 h PI) therapies were studied, employing 5 groups: ciprofloxacin-PSS, ciprofloxacin, ofloxacin, PSS vehicle. and untreated. Dosing regimens were: every 30 min, 60 min, or a single drop applied at 9 h PI. Eyes were observed by slit lamp examination (SLE) and bacterial colony forming units (CFU) per cornea were determined. RESULTS Early phase therapy with ciprofloxacin-PSS, ciprofloxacin, or ofloxacin administered every 30 or 60 min were equally effective (P > or = 0.2880), decreasing CFU per cornea by >5 log. Ciprofloxacin was significantly more active than ciprofloxacin-PSS or ofloxacin (P < or = 0.0410) when applied as a single drop. Late therapy with ciprofloxacin-PSS, ciprofloxacin, or ofloxacin administered every 30 or 60 min resulted in >3 log decrease in CFU per cornea relative to controls (P < or = 0.0001). CONCLUSIONS Topical treatment of experimental Staphylococcus keratitis with ciprofloxacin-PSS, ciprofloxacin, or ofloxacin was effective. The effectiveness of ciprofloxacin-PSS suggests that improved drug delivery systems employing an ion exchange resin could be useful in an ocular fluoroquinolone formulation.

Effectiveness of ciprofloxacin and ofloxacin in a prophylaxis model of Staphylococcus keratitis.

Purpose. To determine the effectiveness of prophylactic fluoroquinolone treatment against staphylococci in a rabbit keratitis model. Methods. Prophylactic ciprofloxacin or ofloxacin was applied as one topical drop 15 minutes before infection or as one drop at three time points (19, 17, and 15 minutes) before infection. In a second experiment, rabbits were treated with two, three, or four drops of ciprofloxacin 1 hour before infection. Approximately 250 colony-forming units (CFUs) of Staphylococcus aureus were injected intrastromally, and CFUs were determined 5 hours after infection. Results. The CFUs per cornea in all treatment groups were significantly less than the 5.6 ± 0.11 log CFUs per cornea in the untreated group (p ≤ 0.0001). Rabbit eyes treated 15 minutes before infection with Ciloxan or Ocuflox had 0.96 ± 0.48 log CFUs per cornea (three of six sterile corneas) or 1.26 ± 0.31 log CFUs per cornea (one of six sterile corneas), respectively (p = 0.5226). Eyes treated with Ciloxan 19, 17, and 15 minutes before infection had 0.0 ± 0.0 log CFUs per cornea, and all eyes were sterile, whereas eyes treated with Ocuflox had 0.98 ± 0.48 log CFUs per cornea and two of six eyes sterile (p = 0.0435). Eyes treated 1 hour before infection with two, three, or four drops of Ciloxan had 2.61 ± 0.69 log CFUs, 1.23 ± 0.32 log CFUs, or 0.85 ± 0.28 log CFUs per cornea, respectively, which was significantly less than untreated eyes (p ≤ 0.0001). Conclusions. Multiple topical drops of a fluoroquinolone administered prophylactically were effective for subsequent staphylococcal ocular infection.

The effectiveness of tobramycin and Ocuflox® in a prophylaxis model of Staphylococcus keratitis

Purpose. To determine the effectiveness of prophylactic antibiotic treatment prior to intra-corneal infection with Staphylococcus aureus. Methods. One topical drop of Tobrex ® (0.3% tobramycin), tobramycin (0.3%) in the Tobrex ® vehicle with 0.05% dodecyl maltoside (DDM)/4.0% hydroxypropylmethycellulose (HPMC), Ocuflox ® (0.3% ofloxacin) or DDM/HPMC vehicle were applied to rabbit eyes at one or five hours prior to injection of bacteria. Approximately 500 colony-forming units (CFU) of S. aureus strain 8325-4 were injected into the corneal stroma. Rabbits were sacrificed five hours after infection and corneal homogenates were cultured to determine the number of colony forming units (CFU) per cornea. Results. Rabbits treated at five hours prior to infection with tobramycin-DDM/HPMC reduced the bacterial load by approximately 2.4 log CFU/cornea as compared to the untreated control (3.47 ± 0.98 vs. 5.71 ± 0.14 log CFU/cornea, respectively; P = 0.0010); however, Ocuflox ®, Tobrex ®, or DDM/HPMC vehicle did not significantly reduce the log CFU (P = 0.4837). Rabbits treated at 1 hour prior to infection with Ocuflox ® or tobramycin-DDM/HPMC had significantly reduced CFU/cornea (1.31 ± 0.86 and 0.48 ± 0.31 log CFU/cornea, respectively) as compared to the untreated group (5.71 ± 0.14 log CFU/cornea; P = 0.0001). Neither Tobrex ® nor the DDM/HPMC vehicle significantly reduced the CFU/cornea compared to the untreated group (P = 0.2312). Conclusions. This pre-treatment model of Staphylococcus keratitis quantitatively measured the prophylactic effectiveness of topical antibiotic formulations. An important finding was that a tobramycin-DDM/HPMC formulation was highly effective as a prophylactic medication.