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.

Evaluation of the preserving efficacy of lubricant eye drops with a novel preservative system.

Products provided in multidose containers must be adequately preserved in order to prevent contamination during repeated use. The aim of this study was to evaluate the ability of a lubricant eye drop formulation without traditional preservatives to control and prevent contamination under extreme microbial conditions. Bottles of a new lubricant eye drop with a novel preservative system (SYSTANE FREE Lubricant Eye Drops, Alcon Laboratories, Inc., Fort Worth, TX) were stored at elevated (40 degrees C) and room temperature (25 degrees C) for up to 1 year. The formulation was inoculated with microorganisms to contain high levels (approximately 1x10(6) colony forming units [cfu]/mL) of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, and Aspergillus niger. The inoculated samples were stored at 20-25 degrees C during testing. Three types of tests were conducted: (1) tests with 1 inoculation, (2) tests with 2 inoculations over 28-day test periods, and (3) tests with 6 inoculations over a 6-month test period. Additionally, a comparison of the preservative efficacy of the SYSTANE FREE formulation to marketed products, including sodium perborate, stabilized oxychloro complex, and polyhexamethylene biguanide eye drops, was performed. In all studies, the number of survivors was determined using standard microbiological dilution pour-plate techniques. The results consistently showed that the SYSTANE FREE formulation meets preservative efficacy standards equally well, or better, than, marketed eye drop products. Even with multiple inoculations, the formulation repeatedly showed no recovery of the organisms. Though the SYSTANE FREE formulation contains no traditional preservatives, its unique blend of ions and buffers was capable of preventing contamination of the contents even after exposure to extreme conditions.

Ocular pharmacokinetics of moxifloxacin after topical treatment of animals and humans.

The ocular penetration and pharmacokinetics of moxifloxacin in comparison to other fluoroquinolones (ofloxacin, ciprofloxacin, gatifloxacin, norfloxacin, levofloxacin, and lomefloxacin) have been determined by in vitro and ex vivo techniques, as well as in animal and human studies. This article reviews the original pharmacokinetics work performed by Alcon and other studies reported in the ocular fluoroquinolone literature. The results consistently demonstrate higher maximum concentrations for moxifloxacin relative to the other fluoroquinolones in ocular tissues with levels well above its minimum inhibitory concentrations for relevant ocular pathogens. This superior performance is due to the unique structure of moxifloxacin that combines high lipophilicity for enhanced corneal penetration with high aqueous solubility at physiological pH. The latter property creates a high concentration gradient at the tear film/corneal epithelial interface providing a driving force for better ocular penetration for moxifloxacin. In addition, the higher concentration of moxifloxacin in VIGAMOX (i.e., 0.5% vs. 0.3%) allows more antibiotic to be available to ocular tissues. It is clear from the array of studies summarized in this report that moxifloxacin penetrates ocular tissues better (two- to three-fold) than gatifloxacin, ciprofloxacin, ofloxacin, or levofloxacin. This consistent, enhanced penetration of topical moxifloxacin offers powerful advantages for ophthalmic therapy.

In vitro and in vivo potency of moxifloxacin and moxifloxacin ophthalmic solution 0.5%, a new topical fluoroquinolone.

Fluoroquinolones are a class of synthetic antibacterial agents that were approved for ocular therapy in 1991 and have become popular therapy for the treatment and prevention of various ocular infections. These agents are synthetic, broad-spectrum, rapidly bactericidal, and have good penetration into ocular tissues. Their main mechanism of action is the inhibition of bacterial enzymes needed for bacterial DNA synthesis. However, antibiotic resistance occurred swiftly to the earlier fluoroquinolones and better fluoroquinolones were needed. The fourth-generation fluoroquinolones, such as moxifloxacin and gatifloxacin, have enhanced activity against gram-positive bacteria while retaining potent activity against most gram-negative bacteria. These fourth-generation fluoroquinolones have improved penetration into the anterior chamber and have also demonstrated increased in vivo efficacy in several animal models of ocular infections. In addition, topical ophthalmic antibiotic products can deliver antibiotic concentrations directly to the eye that are thousands of times higher than their MICs. This article reviews published data describing the in vitro potency of moxifloxacin and its in vivo activity for treating and preventing experimental ocular infections.

Future of ophthalmic anti-infective therapy and the role of moxifloxacin ophthalmic solution 0.5% (VIGAMOX).

The vintage antibiotics that were available in the 1950s-1980s were sometimes toxic, had limited spectra, and were bacteriostatic agents, and they have been replaced by significantly broader-spectrum therapies. We ask more of our future antibiotic products for ophthalmology: they must be 1) broad spectrum, 2) convenient to use, 3) useful prophylactically, 4) effective therapeutically, 5) benzalkonium chloride-free, 6) comfortable, and 7) nontoxic. The emergence of antibiotic resistance has focused us on more potent agents effective against resistant strains of bacteria. Fluoroquinolones have become a dominant family of ophthalmic antibiotics. But even the older fluoroquinolones (e.g., ofloxacin, ciprofloxacin) have lost much of their effectiveness against some important ocular isolates. Considering all of the characteristics for an ideal ophthalmic antibiotic product available today, moxifloxacin ophthalmic solution 0.5% represents a primary antibiotic product of choice for treating and preventing ophthalmic infections.

Overview of the potency of moxifloxacin ophthalmic solution 0.5% (VIGAMOX).

Antibiotics have been the mainstay of therapy for infectious diseases since their origins in the 1940s. As microorganisms changed and resistance developed, more advanced antibiotics were ultimately needed to provide adequate coverage and spectrum. By selecting optimal antibiotics and dosing regimens, clinicians can avoid treatment failures and adverse events and can help prevent the emergence of further antibiotic resistance. The fourth-generation ophthalmic fluoroquinolones include moxifloxacin (VIGAMOX, Alcon Laboratories, Inc., Fort Worth, TX) and gatifloxacin (Zymar, Allergan, Irvine, CA), and they are now approved for the treatment of bacterial conjunctivitis. This review highlights four scientific methods that compare and rank antibiotic potencies and predict their clinical efficacy and their propensity to develop resistance: 1) in vitro assay for minimum inhibitory concentrations, 2) in vivo models for pharmacokinetic and pharamacodynamic properties, 3) therapeutic index or inhibitory quotient, and 4) in vitro assay for mutant prevention concentration. The fourth-generation ophthalmic fluoroquinolones perform well in these assays. Both antibiotics have better in vitro activity against gram-positive bacteria than ciprofloxacin or ofloxacin. Moxifloxacin penetrates better into ocular tissues than gatifloxacin and older fluoroquinolones; in vitro activity of moxifloxacin and gatifloxacin against gram-negative bacteria is similar to that of older fluoroquinolones. Moxifloxacin also has better mutant prevention characteristics than other fluoroquinolones. These findings support the use of the newer fluoroquinolones for the prevention and treatment of serious ophthalmic infections (e.g., keratitis, endophthalmitis) caused by susceptible bacteria.

Amoebicidal activity of multipurpose contact lens solutions.

PURPOSE: To compare the amoebicidal activity of two commercially available multipurpose contact lens care systems, by using cyst and trophozoite growth of two strains each of Acanthamoeba castellanii and Acanthamoeba polyphaga. METHODS: Trophozoites and cysts of Acanthamoeba species, isolated from corneal ulcers and an ATCC strain, were exposed to two commonly used multipurpose solutions and a saline control for 4 or 6 hours at ambient temperature. After neutralization of the disinfecting solution, track forming units were enumerated on Escherichia coli-seeded nutrient agar plates. RESULTS: There were significant differences (P<0.01) between solutions, strains, and cysts or trophozoites, but not between the different periods. Solution 2, containing polyquaternium-1 and myristamidopropyl dimethylamine (among other ingredients), gave greater mean log reductions than did solution 1, containing polyaminopropyl biguanide and poloxamine (among other ingredients). Both solutions generally reduced more trophozoites than cysts. CONCLUSIONS: The multipurpose solution containing polyquaternium-1 and myristamidopropyl dimethylamine reduced more cysts and trophozoites than did the alternative solution tested. Because there were differences in the effect of the multipurpose solutions on strains, it is recommended that more than one strain or species of Acanthamoeba be tested to determine efficacy of disinfecting solutions. The lack of difference between disinfection times may indicate that 4 hours could be considered as an adequate disinfecting time to ensure sufficient kill of Acanthamoeba species.

Clinical and epidemiological advantages of culturing bacterial keratitis.

PURPOSE: To examine how the corneal culture result is associated with the antibacterial treatment response rate of ulcerative keratitis in a prospective cohort study and to determine whether culture confirmation affects the relative treatment effect in randomized clinical trials of bacterial keratitis. METHODS: The influence of a positive bacterial culture on the rates of antibacterial improvement and cure was estimated by proportional hazards regression among 608 patients with ulcerative keratitis treated with topical ciprofloxacin monotherapy. The interaction of culture confirmation on the relative cure rates of 735 patients enrolled in 4 clinical trials comparing fluoroquinolone monotherapy to combined cephalosporin and aminoglycoside therapy was evaluated by metaregression. RESULTS: In a prospective cohort study, bacterial keratitis that was culture positive and longer than 4 mm had a 37% (95% confidence interval, 20%, 51%) slower improvement rate and a 56% (95% confidence interval, 41%, 67%) slower cure rate during ciprofloxacin therapy. Among randomized clinical trials, the culture result did not modify the relative effect of treatments having similar 1-week cure rates. CONCLUSIONS: Culture confirmation affects the antibacterial therapeutic response rate of ulcerative keratitis and, while not modifying the comparative effect of equivalent antibacterial treatments, facilitates generalizability of clinical trials of bacterial keratitis.

Contribution of regimen steps to disinfection of hydrophilic contact lenses.

The effect of regimen steps on overall performance of contact lens disinfection processes was evaluated. Hydrophilic lenses were inoculated with Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens, Candida albicans, or Fusarium solani. Contributions of regimen steps and rinse volumes to disinfection abilities of OPTI-FREE EXPRESS, Solo-care Plus (Ciba Vision), Complete (Allergan), and ReNu MultiPlus (Bausch & Lomb) multi-purpose solutions were examined. Numbers of surviving microorganisms were determined. Results showed that the number and timing of regimen steps was directly related to performance of products. OPTI-FREE EXPRESS solution showed fewer survivors than did other products. Minimizing regimen steps could adversely affect product efficacy.

Influence of fluoroquinolone susceptibility on the therapeutic response of fluoroquinolone-treated bacterial keratitis.

OBJECTIVE: To estimate how a corneal isolate's minimal inhibitory concentration for a fluoroquinolone agent affects the rate of clinical response of bacterial keratitis to fluoroquinolone therapy. DESIGN: Prospective cohort study. METHODS: Six hundred sixty-three individuals with suspected bacterial keratitis underwent diagnostic corneal scraping and were treated with topical 0.3% ciprofloxacin solution or ointment. Of 407 patients with culture-confirmed bacterial keratitis, improvement and cure rates with ciprofloxacin monotherapy were estimated for 391 who had in vitro ciprofloxacin susceptibility of the principal corneal isolate. MAIN OUTCOME MEASURES: Slitlamp biomicroscopic assessment for clinical improvement of corneal inflammation and for clinical cure with complete reepithelialization. RESULTS: Adjusted rates of improvement and of cure were reduced, respectively, by 43% (95% confidence limits, 8%, 64%) and by 29% (95% confidence limits, 0%, 49%) among corneal infections having a ciprofloxacin minimal inhibitory concentration above 1.0 micro g/mL compared with those with more sensitive isolates. CONCLUSIONS: Corneal infection by relatively ciprofloxacin-resistant bacteria responds more slowly to ciprofloxacin therapy. Antibacterial susceptibility testing of corneal cultures may predict the fluoroquinolone therapeutic response rate of bacterial 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.

Review of standard for evaluating the effectiveness of contact lens disinfectants.

A new standard has been developed by the International Organization for Standardization (ISO) for evaluating contact lens disinfectants. This paper reviews the ISO 14729 standard and applies it to marketed products. The historical significance, justifications, scope, interpretations, application, and worthiness are discussed. The standard provides a more consistent procedure and a higher standard for contact lens disinfectants. As a result, more effective contact lens disinfectants have been marketed.