besifloxacin and Corneal-Ulcer

Acute bacterial conjunctivitis is a common infection of the ocular surface. Increasing rates of bacterial resistance have prompted the development of new antibiotics with improved activity against the bacterial species most often found in this disease. Besifloxacin is the first topical chlorofluoroquinolone developed solely for ophthalmic use. Studies have attested to its in vitro potency against a broad range of bacteria, as well as its efficacy in clinical studies of bacterial conjunctivitis when dosed 2 or 3 times a day. This review provides an up-to-date summary of studies on causative pathogens in acute bacterial conjunctivitis; recent geographic trends in bacterial resistance among ocular pathogens, including that of methicillin-resistant Staphylococcus aureus; the efficacy of besifloxacin in preclinical and clinical studies; its safety; and the role of besifloxacin in combating resistant strains. Further, this review provides a brief update on bacterial keratitis, causative pathogens, the development of resistance among those pathogens, and the potential role of besifloxacin in the treatment of bacterial keratitis.

Topics: Anti-Bacterial Agents; Azepines; Bacteria; Conjunctivitis, Bacterial; Corneal Ulcer; Eye Infections, Bacterial; Fluoroquinolones; Humans; Topoisomerase II Inhibitors

To present the clinical outcome of 3 cases of ocular surface infections by Mycobacterium chelonae treated with besifloxacin (0.6%, Besivance; Bausch & Lomb, Tampa, FL).. In this retrospective review of a small case series, we reviewed the medical records of 3 clinical patients with M. chelonae infection involving the ocular surface. Besifloxacin was used as an adjunct in 2 cases of keratitis and as the principal therapeutic agent in a case of nodular conjunctivitis.. Two patients who presented with culture-proven M. chelonae keratitis initially had been treated with topical amikacin and oral clarithromycin for 6 months in the first case and for 2 months in the second without complete resolution. Topical besifloxacin was added as an adjunct therapy to amikacin with progressive weaning of clarithromycin. Both cases of keratitis eventually resolved without recurrence after discontinuation of topical amikacin and besifloxacin. A third patient presented with nodular conjunctival inflammation, which initially had been treated with topical ciprofloxacin and corticosteroids without improvement. One nodular lesion was excised and submitted for microbial culture, which revealed the growth of M. chelonae. Marked improvement of the conjunctivitis was noted after 3 weeks of treatment with topical besifloxacin. Complete resolution of the conjunctival nodules was achieved after 10 weeks of treatment with besifloxacin.. Topical besifloxacin seems to be a useful adjunct agent in the treatment of nontuberculous mycobacterial keratitis by M. chelonae and may be viable for use as a first-line agent in cases of nodular conjunctivitis by M. chelonae.

Topics: Administration, Topical; Aged; Amikacin; Anti-Bacterial Agents; Azepines; Clarithromycin; Corneal Ulcer; Drug Therapy, Combination; Eye Infections, Bacterial; Female; Fluoroquinolones; Humans; Middle Aged; Mycobacterium chelonae; Mycobacterium Infections, Nontuberculous; Ophthalmic Solutions; Retrospective Studies; Topoisomerase II Inhibitors; Visual Acuity

Determine the effectiveness of topical besifloxacin, gatifloxacin, and moxifloxacin in treating keratitis caused by 2 strains of Pseudomonas aeruginosa with different quinolone susceptibility profiles.. Minimal inhibitory concentrations (MICs) were determined for each fluoroquinolone. Sequence analysis was performed on the quinolone resistance determining regions of the ciprofloxacin/levofloxacin-resistant strain. Rabbit corneas were injected with 10 colony-forming units (CFU). After 16 hours, phosphate-buffered saline, besifloxacin (6 mg/mL), gatifloxacin (3 mg/mL), or moxifloxacin (5 mg/mL) was applied topically every 15 minutes for 5 doses, then every 30 minutes for 14 doses. Eyes were examined pre- and posttreatment. Corneas were harvested for bacterial quantitation.. MICs against the fully susceptible strain were 0.5, 0.25, and 0.5 μg/mL for besifloxacin, gatifloxacin, and moxifloxacin, respectively. The MICs against the ciprofloxacin/levofloxacin-resistant strain were 2, 16, and 32 μg/mL for besifloxacin, gatifloxacin, and moxifloxacin, respectively. Sequence analysis revealed amino acid mutations in all 4 fluoroquinolone target genes. None of the treatments had an effect on clinical severity of eyes infected with the fully susceptible strain (P > 0.05); however, all were effective at significantly reducing the bacterial CFU in the corneas (P < 0.05). For the ciprofloxacin/levofloxacin-resistant strain, clinical scores of besifloxacin-treated eyes were significantly lower than moxifloxacin-treated eyes (P < 0.037). The quantities of ciprofloxacin/levofloxacin-resistant bacteria recovered from corneas of all treatment groups were significantly lower than those recovered from phosphate-buffered saline-treated corneas (P < 0.05). Besifloxacin-treated eyes had significantly lower CFU recovered as compared with that of gatifloxacin- and moxifloxacin-treated eyes (P < 0.05).. These results support clinical investigation of the effectiveness of besifloxacin in treating Pseudomonas keratitis.

Topics: Administration, Topical; Animals; Anti-Bacterial Agents; Aza Compounds; Azepines; Colony Count, Microbial; Corneal Ulcer; Disease Models, Animal; Disease Susceptibility; DNA, Bacterial; Drug Resistance, Bacterial; Eye Infections, Bacterial; Female; Fluoroquinolones; Gatifloxacin; Male; Microbial Sensitivity Tests; Moxifloxacin; Polymerase Chain Reaction; Pseudomonas aeruginosa; Pseudomonas Infections; Quinolines; Rabbits; Sequence Analysis, DNA

To determine the effectiveness of topically applied besifloxacin, gatifloxacin, and moxifloxacin for the early treatment of experimental methicillin-resistant Staphylococcus aureus (MRSA) keratitis.. Ten hours post-MRSA infection, rabbit eyes were treated topically with 19 doses of phosphate-buffered saline (PBS), besifloxacin, gatifloxacin, or moxifloxacin. Slit-lamp examinations were performed before and after the inoculation. Corneas were harvested for bacterial quantitation and minimal inhibitory concentrations (MICs) were determined.. All 3 fluoroquinolones significantly lowered the clinical severity of the infection as compared to treatment with PBS (P < 0.05). However, the mean log(10) colony-forming unit (CFU) recovered from besifloxacin-treated corneas was significantly lower than all other treatment groups (P < 0.01). CFU recovered from corneas treated with moxifloxacin and PBS showed no significant difference (P = 0.12). Corneas treated with gatifloxacin had a significantly lower log(10) CFU recovered as compared to PBS-treated corneas (P < 0.01). The MICs for gatifloxacin and moxifloxacin were 8 microg/mL, whereas the MIC for besifloxacin was 1 microg/mL.. All 3 fluoroquinolones significantly lowered the clinical severity of the infection. Besifloxacin had an 8-fold lower MIC for MRSA than gatifloxacin and moxifloxacin, and was significantly more effective than gatifloxacin and moxifloxacin in reducing the number of MRSA in the rabbit cornea.

Topics: Administration, Topical; Animals; Anti-Bacterial Agents; Aza Compounds; Azepines; Colony Count, Microbial; Cornea; Corneal Ulcer; Disease Models, Animal; Eye Infections, Bacterial; Female; Fluoroquinolones; Gatifloxacin; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Moxifloxacin; Quinolines; Rabbits; Specific Pathogen-Free Organisms; Staphylococcal Infections; Treatment Outcome

The purpose of this study was to determine the effectiveness of topically applied besifloxacin (0.6%), gatifloxacin (0.3%), and moxifloxacin (0.5%) for the late treatment of experimental methicillin-resistant Staphylococcus aureus (MRSA) keratitis.. One hundred colony-forming units (CFUs) of bacteria were injected intrastromally into rabbit corneas. Sixteen hours after infection, one topical drop of phosphate-buffered saline, besifloxacin, gatifloxacin, or moxifloxacin was applied to each eye every 15 minutes for 5 doses and then every 30 minutes for 14 doses. Eyes were examined before and after treatment by slit lamp biomicroscopy. Corneas were harvested from treated and untreated rabbits for the quantitation of bacteria. Minimal inhibitory concentrations (MICs) were determined in vitro for each fluoroquinolone.. None of the treatments had an effect on clinical severity (P > 0.05). Although there were no differences in clinical severity between any groups after treatment, the mean log10 CFU of MRSA recovered from besifloxacin-treated corneas (5.111 +/- 0.251) was significantly lower than the CFU recovered from corneas treated with phosphate-buffered saline (7.006 +/- 0.144), gatifloxacin (7.108 +/- 0.346), and moxifloxacin (7.473 +/- 0.144; P < 0.001). CFU recovered from gatifloxacin- and moxifloxacin-treated corneas were not significantly different from phosphate-buffered saline-treated corneas (P = 1.000). The MICs against the MRSA strain were 8 microg/mL for both gatifloxacin and moxifloxacin, whereas the MIC for besifloxacin was 1 microg/mL.. Besifloxacin had an 8-fold lower MIC for MRSA than gatifloxacin and moxifloxacin and was significantly more effective than gatifloxacin and moxifloxacin in reducing the number of MRSA in the rabbit cornea 16 hours after infection.

Topics: Administration, Topical; Animals; Anti-Bacterial Agents; Aza Compounds; Azepines; Colony Count, Microbial; Corneal Ulcer; Disease Models, Animal; Eye Infections, Bacterial; Female; Fluoroquinolones; Gatifloxacin; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Moxifloxacin; Ophthalmic Solutions; Quinolines; Rabbits; Staphylococcal Infections; Treatment Outcome