Gerald D. Cagle

Topical tobramycin and gentamicin sulfate in the treatment of ocular infections: multicenter study.

Tobramycin is an aminoglycoside antibiotic newly marketed for topical ophthalmic use. In a double-masked, multicenter study, tobramycin and gentamicin sulfate, the latter an established topical aminoglycoside, were evaluated in the treatment of patients with bacterial infections of the external eye. Efficacy was determined by resolution of signs and symptoms and the follow-up impression made by the physician. A quantitative, bacterial assay of the conjunctiva and skin-lash margin before and after treatment was used to determine the antimicrobial effectiveness of the two antibiotics. The results of the study, involving 511 patients, indicate that tobramycin is significantly more effective than gentamicin sulfate clinically, and the former exhibits a greater antibacterial efficacy, in the eye, against the combined conjunctival pathogens. On the conjunctiva, Staphylococcus aureus is significantly more susceptible to tobramycin than gentamicin sulfate. Although the solutions are equally safe, tobramycin ointment is associated with a significantly lower frequency of adverse reactions than gentamicin sulfate ointment. This may be due to the preservative used in gentamicin ophthalmic ointment, methyl and propyl paraben.

Anterior Juxtascleral Delivery of Anecortave Acetate in Eyes with Primary Open-Angle Glaucoma: A Pilot Investigation

PURPOSE To describe the intraocular pressure (IOP)-lowering effects in eyes with open-angle glaucoma (OAG) after treatment with an anterior juxtascleral depot of anecortave acetate. DESIGN Prospective, interventional case series. METHODS Seven eyes of six subjects with OAG, with uncontrolled IOP while being administered one or more topical medications, received 24 mg anecortave acetate delivered by anterior juxtascleral depot. IOP was assessed at baseline and regularly after treatment for up to 24 months. RESULTS Mean IOP before anecortave acetate treatment was 31.3 +/- 11.3 mm Hg and dropped by 9.5 +/- 4.5 mm Hg (32.7% +/- 16.8%) within one week after treatment. This IOP reduction was sustained through six months (8.4 +/- 5.4 mm Hg [29.6% +/- 12.4%]) and 12 months (9.5 +/- 5.7 mm Hg [34.0% +/- 15.9%]) after a single anecortave acetate treatment. The injection process was well tolerated, and no eyes experienced any injection-related or drug-related serious adverse events. CONCLUSIONS Both the anterior juxtascleral depot of a drug and anecortave acetate may be promising candidates for IOP reduction in eyes with OAG. Additional studies are required to establish better their efficacy and safety, optimal dosing frequency, mechanism of action, and potential additivity to other IOP-lowering therapies.

Ocular Bioavailability of Ciprofloxacin in Sustained Release Formulations

A novel sustained release delivery system of ciprofloxacin for the eye was developed. The system consists of a viscosity enhancer (carbopol gel or hydroxypropylmethylcellulose solution) plus a penetration enhancer (dodecylmaltoside) to overcome penetration barriers and loss due to wash-out and thus achieve the desired ciprofloxacin ocular absorption. The present studies were designed to assess the ocular penetration and bioavailability of ciprofloxacin in sustained release formulations. In vitro studies in rabbits indicated an approximate 10-fold increase in drug penetration through the rabbit cornea using the penetration enhancer, dodecylmaltoside. In vivo bioavailability studies demonstrate that these formulations provided a long drug duration in the cornea. After administration of a single topical dose of ciprofloxacin (0.3%/30 microL), corneal levels greater than the Minimum Inhibitory Concentration (MIC90) (0.5 microg/g) were observed through eight hours. These sustained release formulations delivered 10-fold more drug into the aqueous humor than the standard solution formulation. Maximum ciprofloxacin concentrations in the aqueous humor (0.5-0.7 microg/mL) were attained between one and two hours after dosing. Using these sustained release formulations, ciprofloxacin can penetrate to the anterior chamber of the eye in concentrations that are inhibitory for most gram-negative and gram-positive organisms. These topical ocular formulations have prophylactic utility for prevention of post-surgical infection, offering greater efficacy and safety than currently available treatments.

Tobramycin in external eye disease: a double-masked study vs. gentamicin.

A double-masked randomized study was conducted at four centers to compare the efficacy and safety of tobramycin and gentamicin ophthalmic ointment in the treatment of superficial external eye disease. Seventy-seven patients with blepharitis and/or conjunctivitis were evaluated for safety, and 56 of the 77 individuals also qualified for evaluation of drug efficacy. After a 10 day treatment regimen, 97% of the tobramycin treated patients and 91.3% of the gentamicin treated patients were clinically cured or improved. Antibacterial effectiveness studies in the conjunctiva showed that tobramycin eradicated or controlled 87.8% of the bacterial infections vs. 77.4% for gentamicin. There was also a 9.3% adverse reaction rate with tobramycin vs. 17.6% with gentamicin. Primary symptoms consisted of erythema, injection, discomfort and itching. All adverse reactions were mild and cleared upon discontinuation of the study drug. While the trends seem to favor tobramycin, no difference was statistically significant at the p less than or equal to 0.05 level. These results indicate that tobramycin is a clinically effective and safe topical antibiotic and that it is comparable to gentamicin for topical treatment of bacterial external eye infections. It also may be better tolerated than gentamicin.

A Clinical Comparison of Tobramycin and Gentamicin Sulfate in the Treatment of Ocular Infections

We evaluated the safety and efficacy of tobramycin and gentamicin sulfate ophthalmic solutions in the treatment of patients with bacterial infections of the conjunctivas. In this double-masked study involving 66 patients, the two aminoglycosides were found to be equally safe and effective, although the in vitro data suggested that tobramycin may be more efficacious against Pseudomonas infections. Staphylococcus aureus and S. epidermidis were the most frequent isolates from the infected eyes (59.8% and 20.6%, respectively).

BB-K 122: in vitro and in vivo activity against ocular pathogens.

BB-K 122 is a new aminoglycoside antibiotic and an analogue of amikacin. This study evaluated the in vitro and in vivo activity of BB-K 122 and gentamicin against important ocular pathogens. BB-K 122 and gentamicin demonstrated generally equivalent in vitro antibacterial activity, except that gentamicin was more active against Streptococcus sp. BB-K 122 showed significant in vitro activity against important ophthalmic pathogens, including Pseudomonas aeruginosa, Staphylococcus aureus, Acinetobacter calcoaceticus, and species of Klebsiella, Escherichia, Proteus, Haemophilus, and Moraxella. Solutions of BB-K 122 (1%) and gentamicin sulfate (0.3%) were compared in an experimentally induced rabbit keratoconjunctivitis model. Rabbit eyes infected with P. aeruginosa or S. pneumoniae were treated with one of the two antibiotic formulations and evaluated after 24 h. A topical formulation of 1% BB-K 122 was at least as effective as gentamicin sulfate (0.3%) solution against these infections.

Evaluation of BL-P1654: a semisynthetic penicillin as a topical ocular therapy.

BL-P1654 is a new semisynthetic penicillin that possesses broad spectrum antimicrobial activity against many gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa. An in vitro profile of BL-P1654 was established against strains of Staphylococcus aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa, three bacteria frequently associated with infections of the eye. The effectiveness of BL-P1654 in preventing the development of experimentally-induced keratitis by each of these bacteria was determined. The results of these experiments show BL-P1654 to be more effective than gentamicin and support further evaluation of the semisynthetic penicillin for ophthalmic indications.