Treatment Of Bacterial Keratitis Research Articles

Comparative Efficacy of Topical Moxifloxacin Versus Ciprofloxacin and Vancomycin in the Treatment of P. aeruginosa and Ciprofloxacin-Resistant MRSA Keratitis in Rabbits

To evaluate the in vivo efficacy of topical moxifloxacin 0.5% versus ciprofloxacin 0.3% in the treatment of Pseudomonas aeruginosa keratitis and topical moxifloxacin 0.5% versus vancomycin 50 mg/mL in the treatment of ciprofloxacin-resistant, methicillin-resistant Staphylococcus aureus (MRSA) keratitis in rabbits. Experimental bacterial keratitis was induced in rabbits by corneal intrastromal injection. Infection proceeded for 12 hours, after which topical antibiotics were applied hourly for 12 hours. Corneal homogenates were plated with serial dilutions for quantitative bacteriology. Both moxifloxacin and ciprofloxacin performed significantly better than control in the treatment of Pseudomonas aeruginosa keratitis (P=0.0046 and 0.0069, respectively); there were no significant differences between these 2 drugs in bactericidal activity (P=0.1120). Moxifloxacin performed significantly better than control in the treatment of ciprofloxacin-resistant MRSA (P=0.0321) keratitis, and vancomycin showed a trend toward statistical significance in performing better than control (P=0.0576); there were no significant differences between these 2 drugs in bactericidal activity (P=0.5205). Topical moxifloxacin 0.5% and ciprofloxacin 0.3% have similar efficacy in the treatment of Pseudomonas aeruginosa keratitis in rabbits. Topical moxifloxacin 0.5% and vancomycin 50 mg/mL have similar efficacy in the treatment of ciprofloxacin-resistant MRSA keratitis in rabbits. These results suggest a potential value for topical moxifloxacin as a broad-spectrum agent in the treatment of bacterial keratitis.

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 myoobacteria 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 90s) were reviewed and compared. Results: In the literature reviewed, the MIC 90 against M fortuitum was from 1 to 16 μg/mL for amikacin, from ≤2 to ≥8 μg/mL for clarithromycin, from 0.1 to 1 μg/mL for ciprofloxacin, from 0.5 to 3.13 μg/mL for ofloxacin, and ≤2 μg/mL for levofloxacin. The results were similar against M chelonae. The fourth-generation fluoroquinolones—gatifloxacin and moxifloxacin—had similar MIC 90s against M fortuitum (both, 0.2 to 1 μg/mL); however, moxifloxacin had greater activity than gatifloxacin against M chelonae (minimum inhibitory concentration range: moxifloxacin, ≤1 to 1.6 μg/mL; gatifloxacin, 3.2 to 6.25 μg/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 90s, 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.

Comparison of topical 0.3% ofloxacin with fortified tobramycin plus cefazolin in the treatment of bacterial keratitis

Ofloxacin is a broad spectrum fluoroquinolone antibiotic with good ocular penetration. We compared ofloxacin 3% solution with a combination of fortified tobramycin sulphate and cefazolin sodium solutions in the treatment of culture-proven bacterial keratitis. Thirty eyes with culture-proven bacterial corneal ulcers were enrolled in a prospective randomised, controlled, double-masked study for comparison. The ofloxacin drop and saline were decanted into two identical-looking bottles to the tobramycin and cefazolin. The cases were randomly allocated into treatment with 0.3% ofloxacin solution or a combination of fortified antibiotics (1.5% tobramycin and 10% cefazolin solutions; control group) along with supportive cycloplegic, vitamins and anti-glaucoma therapy. Student's t-test was used to compare the results. Staphylococcus aureus and coagulase-negative staphylococci were the two most common organisms isolated. Resolution of the ulcer was achieved in 93% and 87% of cases in the ofloxacin and control groups respectively. The mean time required for symptomatic relief was 7.8 +/- 1.54 days and for epithelial healing 15.0 +/- 3.86 days in ofloxacin group, compared with 8.33 +/- 1.54 days for symptomatic relief and 15.46 +/- 3.86 days for epithelial healing in the control group. Post-resolution best corrected visual acuity of 20/200 or better was achieved in all but one eye in both groups. Ofloxacin and combined fortified tobramycin and cefazolin topical drops were comparable for treating cases of bacterial corneal ulcer. However, considering its easy availability and cost-effectiveness, monotherapy with ofloxacin is preferred over the combined fortified tobramycin and cefazolin therapy.

Deposits of Topical Norfloxacin in the Treatment of Bacterial Keratitis

Fluoroquinolone solutions are widely used in therapy of bacterial keratitis. These drugs are safe, and their ocular side effects are mild and not serious in nature. The most frequent untoward effect associated with ciprofloxacin therapy has been a white crystalline deposit. This deposit has not been reported after using the other commercially available quinolones, ofloxacin and norfloxacin. We present three cases of norfloxacin deposits after treatment of bacterial keratitis. In the three cases, the norfloxacin was substituted for another antibiotic effective against the bacteria, and the precipitate spontaneously resolved in all cases within a few days with no untoward ocular effect. Crystalline corneal deposits can develop during topical norfloxacin therapy. The exact factors contributing to the formation are unknown, although the differences in the tear pH/solubility could be involved. Clinicians should be aware of this ocular side effect.

Fluoroquinolones in the Treatment of Bacterial Keratitis

We evaluated the potential role of three topical fluoroquinolones in the treatment of bacterial keratitis by means of a laboratory database. Antibiotic susceptibilities were determined for 153 isolates from patients with bacterial keratitis. Results were analyzed for each fluoroquinolone individually and in combination with cefazolin. Predicted susceptibility to each cefazolin-fluoroquinolone combination (98.7%) was superior to that for single-agent therapy with ofloxacin (88.2%), ciprofloxacin (82.3%), or norfloxacin (80.4%) (P = .0002). A cefazolin-fluoroquinolone combination (98.7%) was comparable to a cefazolin-gentamicin combination (97.4%). Combination therapy with cefazolin and a fluoroquinolone offers a reasonable alternative for the treatment of bacterial keratitis. Single-agent therapy with fluoroquinolones for vision-threatening bacterial keratitis is not advised.

Susceptibility of Corneal and Conjunctival Pathogens to Ciprofloxacin

Ciprofloxacin 0.3% ophthalmic solution has been shown to be effective in the treatment of bacterial keratitis and conjunctivitis, and many physicians use ciprofloxacin as sole therapy in these conditions. In this retrospective study, we found seven of 84 isolates from corneal and conjunctival cultures that were resistant to ciprofloxacin. All of the resistant organisms were gram positive. Six of the isolates (Staphylococcus aureus, Staphylococcus hominis, and four isolates of the Streptococcus viridans group) were from corneal cultures, and one (Staphylococcus aureus) was from a conjunctival culture. Yearly records of systemic isolates from 1988 to 1993 (n = 35,308) demonstrated a statistically significant decrease in susceptibility for several organisms that are common pathogens in the conjunctiva and cornea: Pseudomonas aeruginosa (95-90%, p = 0.001); Staphylococcus aureus (96-87%, p < 0.0001); Staphylococcus spp., coagulase negative (97-81%, p < 0.0001); Enterococcus spp. (92-79%, p < 0.0001); Acinetobacter anitratus (97-77%, p = 0.0006); and Enterobacter cloacae (100-96%, p = 0.03). Although the susceptibility of corneal and conjunctival isolates in this series remained relatively high (91.7%), a much larger series of systemic isolates that are common ocular pathogens revealed a statistically significant increase in resistance to ciprofloxacin over the preceding 5 years.

Pharmacokinetic considerations in the treatment of bacterial keratitis.

The eye is relatively impermeable to micro-organisms and other environmental elements. However, if corneal integrity is breached by trauma, a sight-threatening bacterial infection can result. Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus pneumoniae are the most common bacterial pathogens associated with infection of compromised corneas. Bacterial enzymes and toxins, as well as factors associated with the host immune response, can lead to tissue destruction during corneal infection. For successful therapy, an antibacterial agent must be active against the pathogen and must be able to overcome the permeability barrier of the cornea. Topical application of antibacterial agents adequately delivers drugs to the cornea and aqueous humour. However, drug concentrations at the site of infection are not always sufficient to rapidly kill infective organisms. Infections with antibiotic-resistant strains present an even greater therapeutic challenge. In addition, sterilisation of the cornea by antibacterial agents does not eliminate inflammation and corneal scarring that accompany infection. Steroidal and non-steroidal antiinflammatory agents limit corneal scarring during experimentally induced bacterial keratitis. However, although promising, concomitant use of these drugs with antibacterial agents remains controversial. Two ocular drug delivery systems that provide high and sustained concentrations of drug to ocular tissues are corneal collagen shields and transcorneal iontophoresis. The collagen shield, originally designed as a bandage lens, prolongs drug contact with the cornea. Chemotherapeutic studies of experimental bacterial keratitis demonstrate that shields hydrated with antibacterial agents reduce bacteria in the cornea as well as or better than frequent applications of fortified antibacterial drops. Transcorneal iontophoresis uses an electric current to drive charged drugs into the cornea. In experimentally induced bacterial keratitis, transcorneal iontophoresis of antibacterial agents is superior to topically administered ocular drops for reducing the numbers of bacteria in the cornea. Although both drug delivery systems appear to be well tolerated and nontoxic in animal models, clinical trials in patients are required to determine the usefulness of these drug delivery systems in clinical trials. Based on present experimental results, future therapy of bacterial keratitis will involve efficient drug delivery devices, the use of new antibacterial agents or combinations of presently available antibacterial agents, and careful use of adjuvant anti-inflammatory agents.

Use of Corticosteroids in Combination with Antimicrobial Drugs in the Treatment of Infectious Corneal Disease

AbstractThe use of corticosteroids in the management of infectious eye disease is controversial. In this study, the authors attempt to analyze the goals and risks of the use of corticosteroids in the treatment of various forms of infectious keratitis with reference to generally recognized principles for the treatment of infectious diseases. Existing clinical and research data are reviewed in this context to make appropriate recommendations for the use of corticosteroids in the treatment of bacterial, fungal, and acanthamebic keratitis. The authors conclude that corticosteroids are definitely contraindicated in the treatment of fungal keratitis, and relatively contraindicated in the treatment of Acanthamoeba keratitis. Topical corticosteroid therapy may have a role in the treatment of bacterial keratitis if appropriate guidelines are followed.

Experimental occular infections

Summary I have attempted in this overview to outline some experimental models of bacterial ocular infection. These models have been used to study the pathogenesis of ocular infections in particular and infectious diseases in general. They have also been useful in studying practical therapeutic issues such as the relative merits of topical and subconjunctival routes of treatment of bacterial keratitis and of intravitreal injections in the treatment of endophthalmitis.

Use of Collagen Corneal Shields in the Treatment of Bacterial Keratitis

We used an animal model of Pseudomonas keratitis to compare treatment by topical tobramycin with and without the presence of a commercially available collagen corneal shield. Pilot studies showed a significant, 30-fold increase in penetration of tobramycin into the anterior chamber in eyes with a collagen shield in place. Twenty albino rabbit eyes were inoculated with P. aeruginosa to produce stromal keratitis. After 12 hours of topical tobramycin dosing, eyes with a collagen corneal shield in place had a statistically significant (P < .01) decrease in colony forming unit counts in comparison to treated eyes without a shield and control eyes. We used an animal model of Pseudomonas keratitis to compare treatment by topical tobramycin with and without the presence of a commercially available collagen corneal shield. Pilot studies showed a significant, 30-fold increase in penetration of tobramycin into the anterior chamber in eyes with a collagen shield in place. Twenty albino rabbit eyes were inoculated with P. aeruginosa to produce stromal keratitis. After 12 hours of topical tobramycin dosing, eyes with a collagen corneal shield in place had a statistically significant (P < .01) decrease in colony forming unit counts in comparison to treated eyes without a shield and control eyes.

The Effect of Fortified Antibiotic Therapy on the Visual Outcome of Severe Bacterial Corneal Ulcers

Twenty-six patients with bacterial corneal ulcers measuring 4 mm or greater in the smallest diameter were evaluated retrospectively to determine the effect of different modes of antibiotic therapy on the ultimate visual result and medical treatment outcome. Eleven patients were treated only with topical commercially-supplied antibiotic solutions; 15 patients were treated with topical “fortified” antibiotics and/or subconjunctival antibiotic injections. No beneficial effect could be demonstrated in the group receiving the fortified antibiotics and subconjunctival injections. The use of subconjunctival antibiotic injections in the treatment of bacterial corneal ulceration is of questionable value. Although no increased benefit was found with the use of “fortified” antibiotic solutions, their probable enhanced antimicrobial effect and lack of increased epithelial toxicity justify their use in the treatment of bacterial keratitis