Barry A. Schlech

Biocide uptake in contact lenses and loss of fungicidal activity during storage of contact lenses.

Purpose. With recent outbreaks of Fusarium keratitis related to contact lens wear, studies were conducted to determine the biocide uptake during lens storage, and the resulting effect on antifungal activity of related products. Methods. ACUVUE 2 (etafilcon A) soft, hydrophilic contact lenses (group IV) were soaked from 1 hour to 7 days in OPTI-FREE Express and OPTI-FREE RepleniSH multipurpose disinfecting solutions with POLYQUAD (polyquaternium-1) and ALDOX (myristamidopropyl dimethylamine) biocides and multipurpose solutions, Bausch & Lomb ReNu with MoistureLoc (Alexidine), ReNu MultiPlus (polyhexamethylene biguanide [PHMB]), and AMO Complete MoisturePLUS (PHMB). Storage solutions were tested to evaluate the effect of preservative uptake on the residual biocide activity against Fusarium solani. Results. Approximately 30% to 60% of the PHMB and Alexidine were depleted by 6 hours, with comparable loss of antimicrobial activity. Decreasing activity was noted with corresponding decreases in active concentration throughout the course of the evaluation. The POLYQUAD systems retained nearly 100% of the biocide and fungicidal activity and maintained their concentration in the solution. Conclusions. OPTI-FREE Express and OPTI-FREE RepleniSH multipurpose disinfecting solutions maintained fungicidal efficacy after storage of lenses. The Alexidine- and PHMB-based multipurpose solutions tested showed significant uptake of preservative into group IV lenses, resulting in a decrease in the residual activity of the storage solution. The POLYQUAD systems showed a low uptake of biocide and maintained fungicidal efficacy against F. solani.

Topical antibacterial therapy for mycobacterial keratitis: Potential for surgical prophylaxis and treatment

BACKGROUND Mycobacterium chelonae and Mycobacterium fortuitum are the 2 most commonly implicated species of nontuberculous mycobacteria in cases of bacterial keratitis. OBJECTIVES This article summarizes available data on the in vitro antibacterial activity against M chelonae or M fortuitum of 2 agents-amikacin and clarithromycin-that have been used in the treatment of bacterial keratitis. In addition, the article reviews the in vitro activity of 5 commercially available topical ocular fluoro-quinolones (in order of availability, ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin) that may have potential in the surgical prophylaxis and treatment of keratitis caused by M chelonae or M fortuitum. METHODS A search of the English-language literature indexed on the MEDLINE, Life Sciences, EMBASE, BIOSIS, and Pharmaprojects databases from 1966 to October 7, 2003, was conducted using the terms Mycobacterium chelonae, Mycobacterium fortuitum, bacterial keratitis, topical antibiotic therapy, ocular infection-mycobacteria, and LASIK infections. Data on the minimum concentrations at which 90% of isolates were inhibited (MIC(90)s) were reviewed and compared. RESULTS In the literature reviewed, the MIC(90) against M fortuitum was from 1 to 16 microg/mL for amikacin, from </=2 to >/=8 microg/mL for clarithromycin, from 0.1 to 1 microg/mL for ciprofloxacin, from 0.5 to 3.13 microg/mL for ofloxacin, and </=2 microg/mL for levofloxacin. The results were similar against M chelonae. The fourth-generation fluoroquinolones-gatifloxacin and moxifloxacin-had similar MIC(90)s against M fortuitum (both, 0.2 to 1 microg/mL); however, moxifloxacin had greater activity than gatifloxacin against M chelonae (minimum inhibitory concentration range: moxifloxacin, </=1 to 1.6 microg/mL; gatifloxacin, 3.2 to 6.25 microg/mL). CONCLUSIONS Topical fluoroquinolones may be beneficial for ocular surgical prophylaxis and for the treatment of keratitis caused by M chelonae or M fortuitum. Based on their reported MIC(90)s, none of the antibacterials reviewed had greater in vitro activity than moxifloxacin. In addition, moxifloxacin had greater in vitro activity than gatifloxacin against M chelonae, one of the predominant nontuberculous mycobacterial species involved in bacterial keratitis. Pending the conduct of controlled clinical studies, these findings suggest that moxifloxacin may have utility in the prevention and treatment of atypical mycobacterial keratitis.

Anatomy of a regimen: consideration of multipurpose solutions during non-compliant use

Consumers are often non-compliant with instructions for contact lens care products. This study explores the antimicrobial capacity of multipurpose solutions using variable use conditions. Opti-Free Express (Alcon) Multi-Purpose Disinfecting Solution with Polyquad (Alcon) and Aldox (Alcon) antimicrobial system and products containing PHMB (ReNu MultiPlus, Solo-care, and Complete multipurpose solutions) were evaluated. Products were challenged with Fusarium solani, Candida albicans, Serratia marcescens, Pseudomonas aeruginosa, and Staphylococcus aureus. The antimicrobial activity and effectiveness of regimen steps, rinse volume, stored lenses and organic soil were evaluated. The results show that products using similar regimens can show different disinfection abilities. Opti-Free Express Multi-Purpose Disinfecting Solution retained effectiveness using variable and non-compliant conditions.

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.

Efficacy of Myristamidopropyl Dimethylamine (Aldox®) Against Corneal Isolates of Acanthamoeba spp.

Amebic keratitis (AK) is a sight-threatening infection caused by the free-living ameba, Acanthamoeba. It can result from corneal trauma but by far the greatest number of cases of AK has been associated with the use of extended-wear soft contact lenses [S]. To date, approximately 3,000 cases have been reported or described in the literature. Among contact lens wearers, a source of infection is the use of ophthalmic saline solutions prepared from non-sterile tap or distilled waters, in which amebae are present either as trophozoites or cysts. Another source is bacterial films that develop in the lens case as a result of poor hygiene, which can provide a food supply for amebae and an opportunity for their attachment to the stored contact lens and, ultimately, the corneal surface. Chlorhexidene gluconate, polyhexamethylene biguanide, and propamidine isethionate used in therapy for AK have greatly improved chances of recovery following infection [7]. However, there are strains of Acanthamoeba isolated from keratitis victims that have shown resistance to these drugs, and there is interest in finding new drugs for controlling infection. We have tested myristamidopropyl dimethylamine (MAPD), present as AldoxB (at a concentration of 5 pg/ml) in Opti-Free Express Disinfecting Solution for contact lens care [51 for its potential as a drug in treatment of Acanthamoeba keratitis. MAPD is an amidoarnine compound that shows activity against Acanthamoeba as well as a variety of other causal agents of microbial keratitis [1,31.

Efficacy of topical chloramphenicol and tobramycin ophthalmic solutions in preventing severe Staphylococcus aureus keratitis in rabbits: Current Eye Research

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)

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 Tobrexh Ophthalmic Solution were tested for effectiveness in a Staphylococcus aureus rabbit keratitis model. Anesthetized rabbit3 were each infected intracorneally with 10 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 ocdlar parameters were selected, based on previous Stepwise Oiscriminant Compliter 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. This dork has shown that: first, tobramycin is about

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.