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.

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 >or= 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 or= 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.

Methods used to evaluate the effectiveness of contact lens care solutions and other compounds against Acanthamoeba: a review of the literature.

PURPOSE: The purpose of this paper is to review the literature concerning the methods used to evaluate contact lens care solutions against Acanthamoeba. Acanthamoeba keratitis is a potential threat, with 85% of the cases being reported in contact lens wearers. METHODS: Several studies from the published literature that evaluated contact lens disinfectants were reviewed. The variables included test organism, strain and morphology, growth conditions, inoculum preparation, inoculation method, test solutions and concentration, contact time, neutralization, recovery, quantitation method, and viability determination of survivors. The methods used to test Acanthamoeba against the disinfectants were compared and contrasted. RESULTS: After a thorough review of methods used to test Acanthamoeba, it was found that there is great variability in the methods used to evaluate contact lens disinfectants. The majority of the studies used A.castellanii and A.polyphaga cysts grown axenically in PYG medium containing cations at about 30 degrees C and the inoculum contained about 1.0 x 10(5) cells/mL. Inactivation media or centrifugation of cells was used to neutralize test samples. Quantitation was performed in most studies and viability was checked in all studies. The disinfectants tested most often were PHMB, hydrogen peroxide, thimerosal, and chlorhexidine. CONCLUSIONS: After reviewing the studies presented here it can be concluded that an effective method for testing Acanthamoeba against contact lens disinfectants would include A.castellanii or A.polyphaga grown axenically in PYG containing cations and a concentration of organisms high enough to adequately measure kill, a neutralization step, recovery and quantitation of organisms followed by a viability check of survivors.

Antimicrobial comparison of a new multi-purpose disinfecting solution to a 3% hydrogen peroxide system.

PURPOSE: We compared the antimicrobial activity of a new multi-purpose disinfection solution (OPTI-FREE EXPRESS with ALDOX) to a 3% hydrogen peroxide disinfecting system. The antimicrobial ingredients in the new solution are polyquaternium-1 and myristamidopropyl dimethylamine. METHODS: The solutions were tested for antimicrobial activity against Staphylococcus sp.., Pseudomonas aeruginosa, Serratia marcescens, Candida albicans, Fusarium solani, and two Acanthamoeba species and were evaluated according to the primary criteria of the FDA and ISO contact lens disinfection procedures. RESULTS AND CONCLUSIONS: OPTI-FREE EXPRESS with ALDOX (EXPRESS MPDS) Multi-Purpose Disinfecting Solution provided a multiple spectrum of antimicrobial activity and met the FDA and ISO primary Stand Alone Test criteria for disinfection of contact lenses. EXPRESS MPDS showed disinfection activity in the range of a 3% hydrogen peroxide system. Unlike the 3% hydrogen peroxide system, it retarded contamination during storage.

A comparative study of the microbiologic effectiveness of chemical disinfectants and peroxide-neutralizer systems.

We evaluated the antimicrobial activity of chemical and hydrogen peroxide-neutralizer contact lens disinfection systems. The acute activity, storage, and recontamination potential of the two disinfection methods were compared by challenging the disinfectants with Staphylococcus spp., Pseudomonas aeruginosa, Serratia marcescens, Candida spp., and Aspergillus fumigatus. Chemical disinfectants preserved with polyquaternium-1 and polyhexamethylene biguanide and hydrogen peroxide-neutralizer systems with no additional preservatives were tested. Additionally, lens cases from patients using both systems were evaluated. Lens cases from patients using peroxide-neutralizer systems tended toward heavier contamination (31.8%) than the cases disinfected with a chemical system (20.3%, P = 0.16). The laboratory results showed that the differences in activity of chemical and peroxide-neutralizer systems was not statistically significant at the disinfection times against Staphylococcus epidermidis, S. marcescens, Candida parapsilosis, and A. fumigatus (P = 0.1037 to P = 0.5412). A statistical difference was shown against C. albicans (P = 0.0176) in favor of the peroxide-neutralizer systems. The reverse was true during storage. Although the chemical disinfectants maintained the population of microorganisms, the bacteria and yeast increased to over 10(7) CFU/mL in neutralized peroxide systems. Overall, the results emphasize the importance of contact lens products containing preservatives for lasting protection from microorganisms.

Efficacy of topical chloramphenicol and tobramycin ophthalmic solutions in preventing severe Staphylococcus aureus keratitis in rabbits.

Various marketed chloramphenicol ophthalmic solutions were compared and various dilutions of Tobrex Ophthalmic Solution were tested for effectiveness in a Staphylococcus aureus rabbit keratitis model. Anesthetized rabbits were each infected intracorneally with 10(4) Staphylococcus aureus ATCC 29737 cells. Treatment groups consisted of five or six rabbits (10 or 12 eyes) per group. One group of rabbits was infected but not treated (Positive Control Group). Topical dosing of commercially available ophthalmic solutions was accomplished by depositing 0.1 mL of a color-coded test solution into the lower cul-de-sac of each eye. Dosing begin one hour after the mid-infection time and continued for a total of nine hourly treatments. Twenty-four hours after infection the rabbit eyes were graded (masked) using standard slit-lamp scoring procedures. The slit-lamp scores for five of eight ocular parameters were used to calculate an eye score value for each rabbit eye. The five ocular parameters were selected, based on previous Stepwise Discriminant Computer Analysis of over 300 rabbit eyes infected with Staphylococcus aureus ATCC 29737 and treated with various antibiotics. The eye score values for each group were averaged and the treatments were compared for significant differences in efficacy using the nonparametric, Wilcoxon-Mann-Whitney Rank Sum Test.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

Effectiveness of neomycin and polymyxin ointments: prevention of Staphylococcus Aureus keratitis in rabbits.

Combinations of neomycin sulfate and polymyxin B sulfate are commonly used in ophthalmic ointments for the treatment or the prevention of bacterial keratoconjunctivitis. In this study we evaluated the effectiveness of various ointments containing these two antibiotics, alone and in combination, in preventing Staphylococcus aureus keratitis in rabbits. Rabbit eyes were infected by intracorneal inoculation, treated topically with ointment and graded by gross observation 24 hours after inoculation. Treatment with ointments containing neomycin alone offered significant protection against these corneal infections. The polymyxin B ointments, as well as the vehicle controls, were ineffective in preventing S aureus infections in the rabbit eyes. However, by far, the most effective ointment formulations tested were the combination ointments and specifically those containing 1.75-3.50 mg neomycin and 3,000-6,000 units polymycin B per gram of ointment.

Effect of three proteinaceous foreign materials on infected and subinfected wound models.

A model was devised to determine the effects of several foreign bodies (microcrystalline collagen hemostat (MCCH), blood clot, catgut suture) on S. aureus wound contamination and wound infection. In a subinfected wound model, MCCH, when compared with the other foreign bodies, showed an increase in the number of wounds classified as "contaminated," but 84 percent of these wounds yielded bacterial counts below the level accepted for biologically significant wound infection (10 to the 5th power bacteria per gram tissue). The number of "infected" wounds was not significantly greater than the number found in the uninoculated control group. In the infected wound model, all groups of inoculated animals showed significant infections. The severity of the wound infection was unaffected by the presence of catgut suture, clotted blood, or MCCH. Higher levels were not seen for the MCCH animals than for the inoculated control animals. We did not see in these experimental wound studies with MCCH a significant aggravation of wound contamination or wound infection during the 48 hour period following inoculation with varying dose levels of S. aureus. Further studies would be necessary to determine the possible bacteriological response after 48 hours.

Phospholipids of Azotobacter vinelandii.

Analyses of resting cells of Azotobacter vinelandii revealed that numerous phospholipids were present that did not concentrate in the membranous R(3) fraction which carried out electron transport function.