Treatment Of Ocular Infections Research Articles

Comparative Efficacy Of Topical Ciprofloxacin On Staphylococcus Aureus and Pseudomonas Aureginosa in vitro

Ciprofloxacinis often considered drug of first choice in the treatment of bacterial keratitis.Most of the ocular infections are caused by Staphylococcus aureus and Pseudomonas aeruginosa. This study set to compare the efficacy of ciprofloxacin on these two microorganisms in vitro. The “agar well diffusion” and the 10-fold serial dilution techniques were used respectively for the tests. Results of sensitivity test showed that P. aeruginosa aeruginosa had a higher meanzone of inhibition(4.72cm) than S. aureus (3.73cm), showingthat ciprofloxacin ismore efficacious against P. aeruginosathanagainst S. aureus. Ciprofloxacin is therefore recommended as drug of first choice in the treatment of ocular infections from Pseudomonas aeruginos.

Ophthalmic antimicrobial therapy in the horse

SummaryEffective antimicrobial therapy of infectious ocular disease in the horse may be difficult to achieve. This paper reviews the routes of delivery, the pharmacokinetics and the bioavailability of the various antimicrobial agents used in the treatment of ocular infection in the horse. The modes of action and the criteria for selection of the common antibacterial, antimycotic and antiviral drugs used are described.

Development of Effective Ocular Preparations of Antifungal Agents

In treating ophthalmic mycoses, the ultimate aim is to preserve vision, and this depends on rapid diagnosis and efficient antifungal therapy. Antifungal agents are used both for their superficial action as well as to treat infections of the internal eye. Their clinical efficacy would depend on the concentration achieved in ocular tissue, which, in turn, depends on the molecular mass, route of administration, duration of contact, and ability of the compound to penetrate the eye. Several of these agents have a high molecular mass exceeding 500 Da (such as amphotericin B, natamycin, and ketoconazole), resulting in their poor penetration (even if they are lipophilic in nature). In the present review, we present the physiochemical and pharmacokinetic profile and also the spectrum of antifungal activity of representative antifungal agents recommended for use in treatment of ocular infections. Suitable delivery systems, which can improve the effectiveness of these agents, are suggested as per the nature of each agent. These include liposomes/niosomes, lipid emulsions, nanoparticles including solid lipid nanoparticles, and use of cyclodextrin complexes. The advances made therein, followed by a critical appraisal and suggestions for achieving better therapy as per our expertise, are also included.

Anti-Inflammatory Effects of Besifloxacin, a Novel Fluoroquinolone, in Primary Human Corneal Epithelial Cells

Purpose: The aim of this study was to determine the anti-inflammatory effects of besifloxacin, a novel fluoroquinolone under clinical evaluation for the treatment of ophthalmic infections, in human corneal epithelial cells (HCEpiC). Methods: Cytokine expression in primary HCEpiC was stimulated by interleukin-1ß (IL-1ß), and Luminex technology was used to determine the effect of besifloxacin on IL-1ß-induced cytokine release. Effect of besifloxacin on nuclear factor kappa B (NFκB), and mitogen-activated protein kinase (MAPK) was assessed by measuring inhibitory kappa B protein (IκB) degradation, NFκB nuclear translocation, and MAPK phosphorylation by Western blotting. Moxifloxacin, a marketed fluoroquinolone, was used as the control. Anti-inflammatory efficacy of besifloxacin was also evaluated in rabbits infected with methicillin-resistant Staphylococcus aureus (MRSA). Results: Stimulation of HCEpiC with IL-1ß increased release of 12 of the 29 cytokines measured. Besifloxacin significantly inhibited IL-1ß-induced cytokine release in a dose-dependent manner, with a comparable (IL-8) or better (G-CSF, GM-CSF, IL-6, MCP-1, MIP-1ß, TGF-α, and TNF-α) efficacy compared to moxifloxacin. A significant inhibitory effect of besifloxacin was observed at 1 or 10 μg/ml. Besifloxacin inhibited IκB degradation, NFκB nuclear translocation, and activation of p38 and JNK MAPKs. Based on improvement of clinical score, besifloxacin showed statistically significant anti-inflammatory effect compared to saline treatment. Conclusions: Besifloxacin acts as an anti-inflammatory agent in corneal epithelial cells in vitro, by inhibiting the NFκB and MAPK pathways. Besifloxacin also exhibits anti-inflammatory efficacy in vivo. The anti-inflammatory attribute may enhance its efficacy in the treatment of ocular infections with an inflammatory component and warrants further investigation.

Ocular toxicity of fluoroquinolones

The ocular toxicity of fluoroquinolones and the risks of their use in the treatment of ocular infection were reviewed. Systematic identification, selection, review and synthesis of published English-language studies relating to fluoroquinolone use and safety in animals and humans was conducted. Although not free of complications, fluoroquinolones are generally safe when used to treat ocular infection. Ocular toxicity appears to be dose-dependent and results from class-effects and specific fluoroquinolone structures. Phototoxicity and neurotoxicity have been reported, and toxic effects on ocular collagen may be associated with Achilles tendinopathy. Corneal precipitation may provide an advantageous drug depot but delay healing and result in corneal perforation in approximately 10% of cases. Although human toxicity studies are limited, the current recommended dose for intracameral injection of ciprofloxacin is less than 25 microg. Intravitreal injections of ciprofloxacin 100 microg, ofloxacin 50 microg/mL, trovafloxacin 25 microg or less, moxifloxacin 160 microg/0.1 mL or less and pefloxacin 200 microg/0.1 mL are considered safe.

Twice a day ocular inserts of acyclovir by melt extrusion technique

Acyclovir, an antiviral is used in the treatment of ocular infections. Acyclovir is effective against human herpes viruses including Herpes simplex virus type 1 and 2, Varicella Zoster virus, Epstein-Barr virus and Cytomegalovirus. Acyclovir is available as a 3%w/w eye ointment to be applied 5 times a day in the eye. The present investigation was aimed at designing a twice a day ocular inserts of acyclovir by melt extrusion technique to improve patient compliance, using hydroxypropylcellulose as a thermoplastic polymer. Also, the developed formulation would overcome the greasy nature of the eye ointment. The developed inserts were stable, non-irritant and provided release of the drug over a period of 10 hours in vitro .

Rapid Species Determination of Nocardia Keratitis Using Pyrosequencing Technology

To describe a new technique, pyrosequencing, which allows for the rapid identification of Mycobacterium and Nocardia species. Interventional case report. The medical records of a patient presenting with an infectious keratitis were reviewed. A case of Nocardia abscessus/arthrititis/asiatica keratitis was diagnosed in a young individual with the aid of pyrosequencing technology. Based on presumed antibiotic sensitivities, therapy with topical trimethoprim-sulfamethoxazole eyedrops was initiated, and the infection was cleared rapidly with minimal residual scarring. Pyrosequencing may be a useful tool in aiding the rapid diagnosis and treatment of ocular infections caused by slow-growing pathogens.

SUSCEPTIBILITY TRENDS OF PSEUDOMONAS SPECIES FROM CORNEAL ULCERS

Purpose: To assess the changing trends in the antibiotic susceptibility of Pseudomonas spp. isolated from bacterial keratitis over a nine year period with special emphasis on fluoroquinolone susceptibilities. Methods: All corneal scraping cultures positive for Pseudomonas spp. (n=585) isolated from patients with bacterial keratitis at the Aravind Eye Hospital, Madurai from1995-2003 were evaluated. Cultures were performed in liquid and solid media and susceptibility testing was done against amikacin, gentamicin, tobramycin, ciprofloxacin and ofloxacin by Kirby-Bauer disc diffusion method. Results: The susceptibility of Pseudomonas spp. was over 90% from 1995-1998 to ciprofloxacin which decreased to 83% from 1999-2003. The total number of isolates resistant to ciprofloxacin was 51(9.4%). No statistically significant increase in the number of isolates resistant to ciprofloxacin was noted. Ofloxacin showed 54% susceptibility from 1995-1998 but increased to 64% from 1999-2003. Analysis of in vitro activity of amikacin reveals that there was 43% sensitivity from 1995-1998 but later it increased to 76% from 1999-2003. In case of gentamicin, the sensitivity decreased marginally from 80% to 70% through the years. Tobramycin showed 45% sensitivity from 1995-1998 but increased to 75% from 1999-2003. Conclusions: The fluoroquinolones remain a good choice in the treatment of ocular infections, with high susceptibility of Pseudomonas spp. Among the aminoglycosides, gentamicin was found to be highly effective against Pseudomonas corneal ulcers when compared to amikacin and tobramycin. The results show a need for continuous monitoring of bacterial resistance trends.

Susceptibility trends of Pseudomonas species from corneal ulcers

To assess the changing trends in the antibiotic susceptibility of Pseudomonas spp . isolated from bacterial keratitis over a nine year period with special emphasis on fluoroquinolone susceptibilities. All corneal scraping cultures positive for Pseudomonas spp. (n=585) isolated from patients with bacterial keratitis at the Aravind Eye Hospital, Madurai from 1995-2003 were evaluated. Cultures were performed in liquid and solid media and susceptibility testing was done against amikacin, gentamicin, tobramycin, ciprofloxacin and ofloxacin by Kirby-Bauer disc diffusion method. The susceptibility of Pseudomonas spp. was over 90% from 1995-1998 to ciprofloxacin which decreased to 83% from 1999-2003. The total number of isolates resistant to ciprofloxacin was 51 (9.4%). No statistically significant increase in the number of isolates resistant to ciprofloxacin was noted. Ofloxacin showed 54% susceptibility from 1995-1998 but increased to 64% from 1999-2003. Analysis of in vitro activity of amikacin reveals that there was 43% sensitivity from 1995-1998 but later it increased to 76% from 1999-2003. In case of gentamicin, the sensitivity decreased marginally from 80% to 70% through the years. Tobramycin showed 45% sensitivity from 1995-1998 but increased to 75% from 1999-2003. The fluoroquinolones remain a good choice in the treatment of ocular infections, with high susceptibility of Pseudomonas spp. Among the aminoglycosides, gentamicin was found to be highly effective against Pseudomonas corneal ulcers when compared to amikacin and tobramycin. The results show a need for continuous monitoring of bacterial resistance trends.

Shifting trends in in vitro antibiotic susceptibilities for common ocular isolates during a period of 15 years

Purpose To assess the in vitro susceptibility of the most common ocular bacterial isolates to several antibiotics and verify changing trends in the antibiotic susceptibility in a 15-year period. Design Experimental study. Methods All cultures positive for Staphylococcus aureus, coagulase-negative Staphylococcus (CNS), Streptococcus sp, and Pseudomonas sp in conjunctival (n = 4,585) and corneal (n = 3,779) samples from patients seen at the Federal University of São Paulo from 1985 to 2000 were evaluated. Cultures were performed in liquid and solid media, and susceptibility tests were done to amikacin, gentamicin, neomycin, tobramycin, ciprofloxacin, norfloxacin, ofloxacin, cephalothin, and chloramphenicol. Results Amikacin and neomycin showed an improvement of their sensitivity during the study period (88%–95% and 50%–85%, respectively) for corneal and conjunctival samples. Gentamicin and tobramycin revealed a decrease of sensitivity in time, from 95% to less than 80% in corneal and conjunctival samples. Ciprofloxacin, norfloxacin, and ofloxacin had good sensitivity to all evaluated bacteria, better in conjunctiva (95%) than in cornea (90%). Sensitivity of S. aureus to cephalothin decreased during the study but was still 98% for CNS. Chloramphenicol had good sensitivity to S. aureus (85% in corneal and 92%in conjunctival samples), CNS (87% and 88.5%), and Streptococcus sp (95% and 96%). Conclusions Gentamicin, tobramycin, and cephalothin decreased their in vitro susceptibility to all tested pathogens. The fluoroquinolones remained a good choice in the treatment of ocular infections, with high suscep-tibility to all pathogens tested. Chloramphenicol also revealed an increase in its susceptibility to all bacteria evaluated.

Fluconazole in Management of Ocular Infections due to Curvularia

The aim of this study was to determine the efficacy of fluconazole in treatment of ocular infections due to Curvularia fungus. Four patients who had proven infection of the ocular structures with Curvularia were treated with fluconazole orally and/or topically for 15 to 21 days. Success of therapy was determined by symptomatic improvement of the patient's ocular status and/or negative results on repeated culture in 2 cases. The therapeutic response was good in all patients.

Fluoroquinolones: place in ocular therapy.

The fluoroquinolones have become widely used antibacterial agents in the treatment of ocular infections, with topical, intravitreal and systemic routes of administration being used. In general, fluoroquinolones (such as ciprofloxacin, ofloxacin, lomefloxacin and norfloxacin) have good activity against gram-negative and gram-positive bacteria. Therapeutic concentrations are achieved in the cornea after topical administration so that the fluoroqinolones have largely replaced combination therapy for the treatment of bacterial keratitis. However, a second line agent is needed when resistance is likely, such as in disease caused by streptococcal species. Reversal of resistance to quinolones may not occur with withdrawal of the antibacterial. This stresses the importance of prudent prescribing to reduce the occurrence of resistance to quinolones. When used in therapeutic topical dosages, corneal toxicity does not occur. Similarly, retinal toxicity is not seen when fluoroquinolones are used at therapeutic dosages, systemically or topically. Corneal precipitation occurs, particularly with ciprofloxacin and to a lesser extent norfloxacin, but does not appear to interfere with healing. In the treatment of endophthalmitis there is reasonable penetration of systemic fluoroquinolones into the vitreous but sufficiently high concentrations to reach the minimum inhibitory concentration for 90% of isolates (MIC90) of all important micro-organisms may not be guaranteed. Systemic administration may be useful for prophylaxis after ocular trauma.

Alterations in ocular pathogen susceptibility to gentamicin and tobramycin

Purpose: To evaluate and compare the "in vitro" susceptibility of ocular bacterial isolates to aminoglycoside antibiotics (gentamicin and tobramycin) and to analyze the alteration in susceptibility after 14 years of introduction of tobramycin in Brazilian ophthalmic practice. Methods: The results of antibiotic susceptibility tests in a period of three years with 887 bacterial strains (Study "A") were retrospectively analyzed and then compared with the results obtained fourteen years ago with 124 microorganisms (Study "B"), when tobramycin was first tested in Brazil for isolated eye strains. In both studies, the data analyzed were from the files of the Ocular Microbiology Laboratory of the Federal University of São Paulo. Results: The "in vitro" effectiveness of both antibiotics regarding the total number of positive isolates was significantly higher for tobramycin in both studies. An increase in the Staphylococcus aureus strains resistant to tobramycin and only a decreasing trend in the number of microorganisms resistant to gentamicin was observed. With Pseudomonas sp, a strong tendency to the increase of susceptibility to gentamicin and to the appearance of strains resistant to tobramycin occurred. Conclusions: The introduction of tobramycin in the treatment of ocular infections and the possible decrease in number of gentamicin prescriptions during the last fourteen years might be the cause of modifications in the susceptibility observed in the total of positive isolates mainly Staphylococcus aureus and Pseudomonas sp. For the isolated microorganisms from the conjunctiva, the sensitivity to both antibiotics was equivalent.

Treatment of ocular infections with topical antibacterials.

Topically applied ophthalmic antibacterial preparations are widely used in the treatment of patients with superficial ocular infections. In addition, they are frequently used to augment treatment for intraocular infection administered systemically or via local instillation. Direct application delivers high concentrations of antimicrobial agents to the surface of the eye conveniently, quickly and with minimal systemic exposure to the agent. However, antibacterials are rapidly dissipated from the tear film and intraocular penetration of topical antibacterial agents is generally poor, necessitating intensive application for successful treatment of corneal infections. Therapeutic concentrations are rarely achieved at other sites in the eye. This article reviews what is known of the pharmacokinetics of topical ocular agents and how this information can be used to optimise ocular persistence and penetration and minimise systemic absorption of antibacterials. A review of the features of the most commonly employed topical antibacterials suggests that for the treatment of uncomplicated bacterial conjunctivitis there is little difference between the various agents in terms of clinical efficacy, although chloram-phenicol should be used with care because of its potential haematological toxicity. Carefully considered therapy is imperative for bacterial keratitis; fortified beta-lactam/aminoglycoside combinations are often used for these infections. The fluoroquinolones appear promising, but caution is necessary in treating keratitis of unknown aetiology with these agents alone because of inherent and emerging acquired resistance among Gram-positive bacteria.

Chloramphenicol 4. Responsible topical use in ophthalmology

Chloramphenicol has gained widespread use in the topical treatment of ocular infections. The rationale for this use was based on the ability of chloramphenicol to penetrate the cornea and enter the anterior segment, together with its broad spectrum of antimicrobial activity. However, routine use in corneal ulceration or keratitis is not desirable. Hypopyon, when present, is usually sterile. Concerns about human exposure to chloramphenicol and its recent prohibition of use in food-producing animals, raise the need to review its indications and discuss alternatives. The role of chloramphenicol in ocular therapeutics is examined in this article.

Antibacterial Agents in the Treatment of Ocular Infections

There are a number of barriers to the ocular transport of poorly lipid-soluble antibiotics such as beta-lactams and aminoglycosides. Knowledge of these barriers can help the physician in the choice of agent and the route of administration for specific ocular infections. Because of the corneal epithelial barrier, topically applied drugs should be administered frequently; "fortified" drops afford higher corneal concentrations than commercially available drops. Periocular injections may occasionally be of benefit in the treatment of refractory corneal ulcers. The mainstay of treatment of bacterial endophthalmitis should be intravitreal injection of antimicrobial agents; ancillary treatments include the periocular and systemic administration of antimicrobial agents, the systemic administration of probenecid, the administration of corticosteroids, and the use of vitrectomy.

Antibacterials in the treatment of ocular infections

ABSTRACTThis paper reviews the currently available antibiotics and antibacterial agents used in the treatment of ocular infections in small animals. The rationale behind the selection of a particular drug, the route of administration and the contraindications, are discussed.

Ophthalmic uptake of chloramphenicol from proprietary preparations using an in vitro method of evaluation

An in vitro method using ovine eyes was used to evaluate bioavailability of chloramphenicol from ophthalmic ointment and solution preparations. The results obtained were consistent with the findings of other studies using rabbit and human subjects verifying the usefulness of this in vitro technique. It was apparent that the ointment tested gave better ophthalmic levels of chloramphenicol than the solution and the former is therefore preferable in the treatment of ocular infections.

Antimicrobial drug delivery to the eye.

A major obstacle in the treatment of ocular infections is the difficulty in obtaining adequate antimicrobial drug concentration at the site of infection. This article reviews the pharmacokinetic principles of ophthalmic drug delivery as it pertains to antimicrobial therapy. The administration of antimicrobials by topical application, subconjunctival injection, intravitreal injection, vitreous replacement fluid, and systemic administration are addressed. Representative data on the intraocular penetration of antimicrobials as well as recommended doses of drugs for ocular infections are presented.

Intraocular penetration of rosoxacin in rabbits.

Rosoxacin, a new synthetic antimicrobial agent, has a wide spectrum of activity that may prove beneficial in the treatment of ocular infections. To determine the penetration of rosoxacin into ocular tissues and serum of the rabbit after topical, subconjunctival, and intravenous (IV) administration, rosoxacin levels were measured using a microbiological assay after enzymatic digestion of the ocular tissues. Quantities of rosoxacin that should prove to be of therapeutic value were detectable in the anterior segment of the eye after topical or subconjunctival administration. Subconjunctival administration also resulted in high levels in the retina and choroid area and in the optic nerve. Low levels were detected in the retina and choroid 15 minutes following IV injection; however, no detectable levels were found in the ocular tissues after this period.