A comparison of the fourth-generation fluoroquinolones gatifloxacin 0.3% and moxifloxacin 0.5% in terms of ocular tolerability

SUMMARY

Purpose: To compare the ocular tolerability of the commercially available ophthalmic solutions of the fourth-generation fluoroquinolones, gatifloxacin 0.3% (Zymart, Allergan, Inc., Irvine, CA) with benzalkonium chloride (BAK) and moxifloxacin 0.5% (Vigamoxt) without BAK.

Methods: A baseline evaluation was conducted on 30 healthy volunteers for conjunctival hyperemia, conjunctival vascularity, pupil size, and anterior chamber (AC) cell and flare. Pupils were measured under scotopic conditions with a Colvard pupillometer. Conjunctival hyperemia and vascularity, and AC reaction were measured on a Likert-like scale of 0-3. Subjects then received drops in both eyes from masked bottles of gatifloxacin ophthalmic solution 0.3% with BAK (in one eye determined randomly) and moxifloxacin ophthalmic solution 0.5% without BAK (in the contralateral eye) in a double-masked fashion. Subjects graded pain and ocular irritation in each eye on a scale of 1-10 after 5min with their eyes closed. The examination was then repeated.

Results: The average age of this study population was 34.4years. The groups of eyes receiving moxifloxacin 0.5% demonstrated an increase in mean conjunctival hyperemia (0.21 [range: 0-1] at baseline to 1.52 [range: 0-3] at 5min.)

that was significantly greater (p?=?0.0005) compared with that of the group receiving gatifloxacin 0.3% (0.22 [range: 0-1] at baseline to 0.45 [range: 0-2] at 5min). The group receiving moxifloxacin 0.5% showed an increase in conjunctival vascularity (0.55 [range: 0-1] at baseline to 1.61 [range: 0.5-3] at 5?min.) that was significantly greater (p?=?0.0005) compared with that of the group receiving gatifloxacin 0.3% (0.52 [range: 0-1] at baseline to 0.68 [range: 0-2] at 5?min.). Significantly less pain (1.2 vs. 3.2, p?=?0.001) and irritation (0.64 vs. 3.42, p?=?0.001) occurred with gatifloxacin 0.3% than with moxifloxacin 0.5%. Pupil size was significantly reduced (5.65mm-5.05mm) in eyes receiving moxifloxacin 0.5% (p?=?0.004) and no significant change occurred in pupil size (5.60mm-5.65mm) in eyes that received gatifloxacin 0.3% (p?=?0.878). No AC reaction was noted with either medication.

Conclusions: The group of eyes receiving gatifloxacin 0.3% with BAK demonstrated greater ocular tolerability in comparison to the group receiving moxifloxacin 0.5% without BAK. Moxifloxacin-induced pupillary miosis may be due to prostaglandin release in the anterior chamber. A limitation of this study is the relatively young age of the study population.     

Ocular penetration of moxifloxacin 0.5% and gatifloxacin 0.3% ophthalmic solutions into the aqueous humor following topical administration prior to routine cataract surgery

A prospective, double-masked, randomized, parallel-group study (n = 25) was conducted to examine the ocular penetration of moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution into the aqueous humor following topical administration prior to routine cataract surgery. One drop of antibiotic was instilled every 10 min for four doses beginning 1 h prior to surgery. Preliminary results showed aqueous humor concentrations for moxifloxacin that were significantly greater (p < 0.01) than those for gatifloxacin.     

Tolerability and safety of 0.1% diclofenac plus 0.3% tobramycin fixed-dose ophthalmic solution: a randomized, comparative, controlled study in healthy volunteers.

The purpose of this double-blind, observer-masked, randomized, crossover trial was to compare the tolerability and safety of a fixed-dose ophthalmic solution of 0.3% tobramycin plus 0.1% diclofenac versus Tobrex (tobramycin sulfate ophth) and Voltaren (diclofenac sodium). Control treatments included a saline solution and a control solution of 0.3% tobramycin prepared by Alcon Cusí. Ten healthy volunteers received three consecutive instillations of 1 drop of a given ophthalmic solution at 08:00, 11:00 and 14:00 h to the same eye; after a washout period of 18 h, the next ophthalmic solution was tested according to a randomized sequence. Occurrence, intensity, and duration of ocular irritation and conjunctival hyperemia at baseline and after the three instillations were recorded. Slit lamp biomicroscopy examination, measurement of intraocular pressure (IOP) changes, visual acuity, and examination of the fundus of the eye were performed after each third instillation by an ophthalmologist. Side effect incidence and patient and investigator opinions were also recorded. Results showed that Voltaren instillation induced statistically significant ocular irritation (p = 0.0077); the remaining ophthalmic solutions tested caused no ocular irritation (Physiological Saline Braun, p = 0.9808; Tobrex, p = 0.8826; control 0.3% tobramycin solution, p = 0.8327; and 0.1% diclofenac plus 0.3% tobramycin, p = 0.5399). None of the ophthalmic solutions tested caused severe conjunctival hyperemia. Analysis of the sum of conjunctival parameters of both eyes for all ophthalmic solutions studied showed no statistically significant differences (p = 0.4688). Moderate superficial punctate keratitis was observed after instillation of Voltaren and of 0.1% diclofenac plus 0.3% tobramycin (1 subject each) that spontaneously resolved within 2 days. Slit lamp biomicroscopy, visual acuity and IOP values showed no statistically significant changes. No systemic side effects related to the study treatments were recorded. In conclusion, the ophthalmic solution containing 0.1% diclofenac plus 0.3% tobramycin was well tolerated under the study conditions. Its tolerability was equivalent to that of Braun physiological saline, Tobrex and a control 0.3% tobramycin solution and was better than that of Voltaren.     

The effect of gatifloxacin 0.3% or moxifloxacin 0.5% on corneal healing,ocular tolerability and toxicity following pterygium surgery

Purpose: To compare the rate of corneal epithelial healing and ocular tolerability following pterygium surgery between gatifloxacin and moxifloxacin.

Methods: In this double masked, prospective, controlled study 40 patients were randomized to receive prophylactic topical gatifloxacin 0.3% or moxifloxacin 0.5% following pterygium surgery. Patients were examined on days 1, 3, 7 and 21 post-operatively or until complete corneal epithelial healing. The primary outcome measure was the area of corneal epithelial defect during the post-operative period. Patients graded post-operative ocular pain, foreign body sensation, tearing, general burning sensation and burning sensation post-antibiotic drops instillation on a scale of 1–5. Conjunctival hyperemia and superficial punctate keratopathy (SPK) were measured on a scale of 0–3.

Results: No significant differences between groups were found in terms of corneal epithelial defect percentage over time (p?=?0.989) and there was no significant difference between groups on each of the post-operative days. No significant differences were noted in terms of post-operative ocular pain, foreign body sensation, tearing, general burning sensation, burning sensation post-antibiotic drops instillation, conjunctival hyperemia and SPK.

Conclusions: Gatifloxacin and moxifloxacin showed equivalent results in terms of corneal epithelial healing and ocular tolerability following pterygium surgery. This study suggests that there was no apparent added epithelial toxicity due to the presence of benzalkonium chloride in the gatifloxacin preparation when compared to moxifloxacin.     

Ocular penetration of moxifloxacin 0.5% and gatifloxacin 0.3% ophthalmic solutions into the aqueous humor following topical administration prior to routine cataract surgery

ABSTRACT

A prospective, double-masked, randomized, parallel-group study (n = 25) was conducted to examine the ocular penetration of moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution into the aqueous humor following topical administration prior to routine cataract surgery. One drop of antibiotic was instilled every 10?min for four doses beginning 1?h prior to surgery. Preliminary results showed aqueous humor concentrations for moxifloxacin that were significantly greater (?p < 0.01) than those for gatifloxacin.     

A randomized, investigator- masked clinical trial comparing the efficacy and safety of gatifloxacin 0.3% administered BID versus QID for the treatment BID versus QID for the treatment of acute bacterial conjunctivitis of acute bacterial conjunctivitis

PURPOSE: To compare the efficacy and safety of To compare the efficacy and safety of gatifloxacin ophthalmic solution 0.3% (Zymar) administered BID versus QID in patients with acute bacterial conjunctivitis. METHODS: In a randomized, investigator-masked clinical trial, patients diagnosed with bacterial conjunctivitis (based on signs and symptoms) received gatifloxacin either BID or QID for 5 days. Visits were scheduled at day 0, day 3, and day 5. Conjunctival cultures were taken at each visit. The clinical cure rate at day 5 was determined for the entire patient population (primary endpoint). Additionally, clinical cure at day 5 was evaluated for a population of patients defined a priori (per protocol) as being culture positive at baseline and with no substantial protocol deviations. Safety was determined through recording of adverse events. Minimal inhibitory concentrations (MIC) and susceptibility of isolates to gatifloxacin were determined using a broth dilution method. RESULTS: Patient characteristics in both the BID and QID groups (N = 104) were similar in terms NN of baseline demographics and disposition. The clinical cure rate on day 5 in the entire, intentto-treat (ITT) population was 86.5% (45/52) in the gatifloxacin BID group and 71.2% (37/52) in the gatifloxacin QID group (95% CI: [-0.03, 30.80]; p = 0.096). In both treatment groups, 5/52 patients (9.6%) reported adverse events. The most common adverse event was conjunctivitis. No serious adverse events were reported. In the a priori-defined per-protocol (PP) population, the clinical cure rate on day 5 was 95.5% (21/22) in the gatifloxacin BID group and 85.7% (18/21) in the gatifloxacin QID group (95% CI: [-7.57, 21.05]; p = 0.294). At baseline, 96.1% (98/102) of the isolates were susceptible to gatifloxacin. The overall MIC(90) (mean +/- standard error of the mean) was 0.5 +/- 1.3 microg/mL. CONCLUSION: In this study, gatifloxacin 0.3% administered BID was as effective and as safe as gatifloxacin 0.3% administered QID for 5 days for the treatment of bacterial conjunctivitis.     

A randomized,investigator-masked clinical trial comparing the efficacy and safety of gatifloxacin 0.3% administered BID versus QID for the treatment of acute bacterial conjunctivitis

ABSTRACT

Purpose: To compare the efficacy and safety of gatifloxacin ophthalmic solution 0.3% (Zymar) administered BID versus QID in patients with acute bacterial conjunctivitis.

Methods: In a randomized, investigator-masked clinical trial, patients diagnosed with bacterial conjunctivitis (based on signs and symptoms) received gatifloxacin either BID or QID for 5?days. Visits were scheduled at day 0, day 3, and day 5. Conjunctival cultures were taken at each visit. The clinical cure rate at day 5 was determined for the entire patient population (primary endpoint). Additionally, clinical cure at day 5 was evaluated for a population of patients defined a priori (per protocol) as being culture positive at baseline and with no substantial protocol deviations. Safety was determined through recording of adverse events. Minimal inhibitory concentrations (MIC) and susceptibility of isolates to gatifloxacin were determined using a broth dilution method.

Results: Patient characteristics in both the BID and QID groups (N = 104) were similar in terms of baseline demographics and disposition. The clinical cure rate on day 5 in the entire, intent-to-treat (ITT) population was 86.5% (45/52) in the gatifloxacin BID group and 71.2% (37/52) in the gatifloxacin QID group (95% CI: [–0.03, 30.80]; p = 0.096). In both treatment groups, 5/52 patients (9.6%) reported adverse events. The most common adverse event was conjunctivitis. No serious adverse events were reported. In the a priori-defined per-protocol (PP) population, the clinical cure rate on day 5 was 95.5% (21/22) in the gatifloxacin BID group and 85.7% (18/21) in the gatifloxacin QID group (95% CI: [–7.57, 21.05]; p = 0.294). At baseline, 96.1% (98/102) of the isolates were susceptible to gatifloxacin. The overall MIC₉₀ (mean ± standard error of the mean) was 0.5 ± 1.3?µg/mL.

Conclusion: In this study, gatifloxacin 0.3% administered BID was as effective and as safe as gatifloxacin 0.3% administered QID for 5?days for the treatment of bacterial conjunctivitis.     

Comparative efficacy of olopatadine 0.1% ophthalmic solution versus levocabastine 0.05% ophthalmic suspension using the conjunctival allergen challenge model

OBJECTIVE: To compare the efficacy of olopatadine and levocabastine in reducing ocular allergic itching and vascular hyperemia (redness) induced by conjunctival allergen challenge. RESEARCH DESIGN AND METHODS: The study was a randomized, double-masked, contralateral study using the conjunctival allergen challenge (CAC) model. At Visit 1, subjects with a positive allergen skin test and a history of allergic conjunctivitis were administered increasing concentrations of allergen until at least a moderate grade 2 ocular itching and conjunctival redness response was obtained in both eyes. Allergic signs were graded on standardized 0-4 scales. Subjects who reacted positively were re-challenged at Visit 2 with the pre-determined concentration of allergen. Subjects who again responded with at least a grade 2 bilateral ocular itching and conjunctival redness score at Visit 2 were eligible for drug evaluation. At Visit 3, subjects received olopatadine in one eye and levocabastine in the contralateral eye according to a computer-generated randomization scheme generated prior to commencement of the study. Ocular discomfort was then graded in both eyes. Subjects were bilaterally challenged with the predetermined concentration of allergen 27 min after topical drug administration, such that the first post-challenge assessment was made 30 min post-drug instillation. Allergic signs and symptoms were evaluated at 3 min, 10 min, and 20 min postchallenge and safety and efficacy analyses were performed. RESULTS: Sixty-eight subjects received study drug and were included in the safety and efficacy analyses. Ocular itching scores for olopatadine were significantly lower than levocabastine at 3 min and 10 min post-challenge (p < 0.001). Ocular redness scores for olopatadine were significantly lower than levocabastine at all time points post-challenge (p < 0.0001). Of all subjects, 4.41% reported ocular discomfort in the olopatadine eye and 26.5% in the levocabastine treated eye. CONCLUSION: Olopatadine treated eyes had significantly less itching and redness than levocabastine treated eyes after conjunctival allergen challenge. Olopatadine was also associated with less discomfort upon instillation than levocabastine.     

Effects of gatifloxacin and levofloxacin on rates of hypoglycemia and hyperglycemia among elderly hospitalized patients

STUDY OBJECTIVES: To compare rates of hypoglycemia and hyperglycemia among elderly hospitalized patients with normal blood glucose concentrations at baseline who were receiving either gatifloxacin or levofloxacin, and to determine if appropriateness of their doses, according to their package inserts, was associated with hypoglycemia or hyperglycemia. DESIGN: Retrospective cohort study. SETTING: Integrated Veterans Administration (VA) health care system. PATIENTS: Nine hundred thirty-seven elderly (>or= 65 yrs) patients with documented blood glucose levels of 65-140 mg/dl before receiving a fluoroquinolone. MEASUREMENTS AND MAIN RESULTS: Between January 2003 and April 2004, 405 patients receiving levofloxacin met study criteria. In April 2004, gatifloxacin was substituted for levofloxacin on the formulary of this VA system. Thus, between April 2004 and December 2004, 532 patients received gatifloxacin. All blood glucose concentrations during hospitalization that were measured during fluoroquinolone therapy or within 72 hours of completion of therapy were reviewed. Demographic characteristics, comorbidities, insulin and oral hypoglycemic therapies, disease severity, blood glucose levels, and outcomes were recorded and compared between groups. The two groups were similar at baseline for all characteristics examined except previous hospitalization. In the logistic regression, gatifloxacin was independently associated with both hypoglycemia (adjusted odds ratio [AOR] 2.5, 95% confidence interval [CI] 1.2-5.7, p=0.04) and hyperglycemia (AOR 2.4, 95% CI 1.5-3.6, p<0.001). Improper dosage adjustment based on renal function was not associated with higher rates of hypoglycemia and hyperglycemia for either drug. Of the 532 patients receiving gatifloxacin, 465 (87.4%) received appropriate doses, yet gatifloxacin was associated with higher rates of hypoglycemia and hyperglycemia compared with patients receiving levofloxacin. CONCLUSIONS: Higher rates of both hypoglycemia and hyperglycemia were noted among elderly hospitalized patients who received gatifloxacin compared with those receiving levofloxacin, irrespective of dosing.     

Incidence of allergic reactions associated with antibacterial use in a large, managed care organisation.

BACKGROUND: Data on the incidence of serious allergic reactions to fluoroquinolone antibacterials are mainly derived from spontaneous reports that cannot be used to accurately estimate incidence. METHODS: This study estimated the drug-specific incidence of serious allergic reactions after fluoroquinolone, cephalosporin and phenoxymethylpenicillin potassium exposure, using claims for healthcare services with confirmation through medical record abstraction within a large health insurer database. Cohorts exposed to each antibacterial of interest (moxifloxacin, levofloxacin, ciprofloxacin, gatifloxacin, cephalosporins and penicillin) were identified, and followed for 14 days for anaphylaxis (9th revision of the International Classification of Diseases [ICD-9] code 995.0), other allergic drug reactions (ICD-9 995.2, 995.3) or cardiopulmonary resuscitation. RESULTS: The incidence per 10,000 first dispensings of any allergic diagnosis made in the hospital or emergency department was similar for moxifloxacin (4.3; 95% CI 3.5, 5.3), penicillin (4.7; 95% CI 3.8, 5.7) and ciprofloxacin (5.4; 95% CI 4.4, 6.5). The incidence for moxifloxacin was lower than that for levofloxacin (8.7; 95% CI 7.4, 10.0), gatifloxacin (6.7; 95% CI 5.6, 7.9) and the cephalosporins (7.5; 95% CI 6.3, 8.8). The incidence of anaphylaxis/anaphylactoid reactions after first dispensings was similar for the fluoroquinolones: 0.1 (95% CI 0.0, 0.3) for ciprofloxacin, 0.3 (95% CI 0.1, 0.5) for moxifloxacin, 0.3 (95% CI 0.1, 0.6) for gatifloxacin and 0.5 (95% CI 0.3, 0.9) for levofloxacin; and comparable with that of the cephalosporins (0.2; 95% CI 0.0, 0.4) and penicillin (0.1; 95% CI 0.0, 0.3). CONCLUSIONS: Anaphylactic reactions were rare and their incidence did not differ substantially among the drug groups studied. By determining the occurrence of reactions following defined exposures, these results provide a context for the interpretation of spontaneous reports of allergic reactions.     

Moxifloxacin 0.5% ophthalmic solution: in bacterial conjunctivitis

The fourth-generation 8-methoxyfluoroquinolone moxifloxacin is available as an 0.5% ophthalmic solution for use in the treatment of bacterial conjunctivitis. Moxifloxacin had good activity against various Gram-positive and -negative ocular isolates in vitro, and moxifloxacin 0.5% ophthalmic solution achieved good penetration into ocular tissues in healthy volunteers and patients undergoing ocular surgery. The efficacy of moxifloxacin 0.5% ophthalmic solution in the treatment of bacterial conjunctivitis has been shown in three randomized, double-blind, multicentre trials. In a trial in patients aged ≥1 year, the clinical success rate was significantly higher with moxifloxacin 0.5% ophthalmic solution than with placebo. In a trial in patients aged ≥12 years, moxifloxacin 0.5% ophthalmic solution was noninferior to levofloxacin 0.5% ophthalmic solution in terms of the clinical success rate. In a third trial, the clinical cure rate was significantly higher with moxifloxacin 0.5% ophthalmic solution than with trimethoprim 1.0%/polymixin B 10,000?IU/mL ophthalmic solution in paediatric patients aged ≤18 years. Moxifloxacin 0.5% ophthalmic solution was well tolerated in patients with bacterial conjunctivitis. Ocular adverse events (e.g. eye pain, eye irritation) were the most commonly reported treatment-related adverse events, with the majority being of mild severity.     

Clinical efficacy of olopatadine vs epinastine ophthalmic solution in the conjunctival allergen challenge model

BACKGROUND: Olopatadine hydrochloride 0.1% ophthalmic solution (Patanol) and epinastine hydrochloride 0.05% ophthalmic solution (Elestat) are two topical antiallergic agents. Olopatadine is indicated for the treatment of the signs and symptoms of allergic conjunctivitis that include itching, redness, tearing, lid swelling, and chemosis. Epinastine is indicated for the prevention of itching associated with allergic conjunctivitis. OBJECTIVE: This study compared the clinical efficacy of olopatadine and epinastine in the prevention of itching and conjunctival redness in the conjunctival allergen challenge (CAC) model. RESEARCH DESIGN AND METHODS: This was a prospective, randomized, double-masked, contralaterally-controlled, single center allergen challenge study. Ninety-six subjects with a history of allergic conjunctivitis were screened, and the 66 who responded to conjunctival allergen challenge at visits 1 and 2 were randomized into 1 of 3 treatment groups at visit 3 to receive one drop of study medication in each eye: (1) olopatadine in one eye and epinastine in the fellow eye, (2) olopatadine in one eye and placebo in the fellow eye, and (3) epinastine in one eye and placebo in the fellow eye. Five minutes after study drop instillation, subjects were bilaterally challenged with the allergen concentration that had elicited a positive conjunctival allergic response at Visits 1 and 2. Subjective itching assessments were given at 3 min, 5 min, and 7 min post challenge. Objective redness and chemosis assessments were made at 10 min, 15 min, and 20 min post challenge. Paired sample two-tailed t-tests were performed on the mean scores at each time point to assess statistical significance in the differences between treatments. MAIN OUTCOME MEASURES; RESULTS: Fifty-three subjects were randomized into the olopatadine/epinastine treatment group, the primary analysis group. Olopatadine treated eyes exhibited significantly lower mean itching and conjunctival redness scores than the contralateral epinastine treated eyes, -0.19 (p = 0.003) and -0.52 (p < 0.001), respectively. Olopatadine treated eyes also exhibited significantly less chemosis -0.24 (p < 0.001), ciliary redness -0.55 (p < 0.001), and episcleral redness -0.58 (p < 0.001) than epinastine treated eyes. CONCLUSION: Olopatadine is significantly more effective than epinastine in controlling itching, redness and chemosis associated with allergic conjunctivitis in the CAC model.     

Comparative efficacy of olopatadine 0.1% ophthalmic solution versus levocabastine 0.05% ophthalmic suspension using the conjunctival allergen challenge model

SUMMARY

Objective: To compare the efficacy of olopatadine and levocabastine in reducing ocular allergic itching and vascular hyperemia (redness) induced by conjunctival allergen challenge.

Research design and methods: The study was a randomized, double-masked, contralateral study using the conjunctival allergen challenge (CAC) model. At Visit 1, subjects with a positive allergen skin test and a history of allergic conjunctivitis were administered increasing concentrations of allergen until at least a moderate grade 2 ocular itching and conjunctival redness response was obtained in both eyes. Allergic signs were graded on standardized 0–4 scales. Subjects who reacted positively were re-challenged at Visit 2 with the pre-determined concentration of allergen. Subjects who again responded with at least a grade 2 bilateral ocular itching and conjunctival redness score at Visit 2 were eligible for drug evaluation. At Visit 3, subjects received olopatadine in one eye and levocabastine in the contralateral eye according to a computer-generated randomization scheme generated prior to commencement of the study. Ocular discomfort was then graded in both eyes. Subjects were bilaterally challenged with the predetermined concentration of allergen 27?min after topical drug administration, such that the first post-challenge assessment was made 30?min post-drug instillation. Allergic signs and symptoms were evaluated at 3?min, 10?min, and 20?min post-challenge and safety and efficacy analyses were performed.

Results: Sixty-eight subjects received study drug and were included in the safety and efficacy analyses. Ocular itching scores for olopatadine were significantly lower than levocabastine at 3?min and 10?min post-challenge (?p < 0.001). Ocular redness scores for olopatadine were significantly lower than levocabastine at all time points post-challenge (?p < 0.0001). Of all subjects, 4.41% reported ocular discomfort in the olopatadine eye and 26.5% in the levocabastine treated eye.

Conclusion: Olopatadine treated eyes had significantly less itching and redness than levocabastine treated eyes after conjunctival allergen challenge. Olopatadine was also associated with less discomfort upon instillation than levocabastine.     

The ocular penetration of levofloxacin 1.5% and gatifloxacin 0.3% ophthalmic solutions in subjects undergoing corneal transplant surgery

ABSTRACT

Objective: To compare corneal tissue and aqueous humor concentrations of levofloxacin 1.5% and gatifloxacin 0.3% ophthalmic solutions after topical dosing.

Research design and methods: This was a randomized, observer-masked, parallel-group, multicenter study. Fifty-nine subjects undergoing planned penetrating keratoplasty were randomly assigned to receive either levofloxacin 1.5% or gatifloxacin 0.3% as follows: one drop 15?min prior to surgery and a second drop 10?min before surgery. Corneal button and aqueous humor samples were collected during surgery and immediately stored at –70?°C. Levofloxacin and gatifloxacin concentrations were determined by high-pressure liquid chromatography and mass spectrometry.

Main outcome measures: Corneal tissue and aqueous humor concentrations of levofloxacin and gatifloxacin.

Results: Levofloxacin achieved statistically significantly higher concentrations in both corneal tissue and aqueous humor compared to gatifloxacin in patients undergoing penetrating keratoplasty. In corneal tissue the mean concentration of levofloxacin was 64.8 ± 123.4?µg/g vs. 7.0 ± 9.3?µg/g for gatifloxacin (p < 0.0001). Mean aqueous humor concentration of levofloxacin was 0.976 ± 2.215?µg/mL vs. 0.0523 ± 0.143?µg/mL for gatifloxacin (p = 0.0002).

Conclusions: The high concentrations of levofloxacin achievable in corneal tissue with topical dosing suggest that levofloxacin 1.5% should be a useful agent in the treatment of ocular bacterial infections. However, the corneal concentrations achieved in this study may not be representative of concentrations in patients using less frequent dosing.     

A retrospective, comparative evaluation of dysglycemias in hospitalized patients receiving gatifloxacin, levofloxacin, ciprofloxacin, or ceftriaxone

STUDY OBJECTIVES: To compare rates of blood glucose abnormalities in hospitalized patients receiving fluoroquinolones or ceftriaxone, and to describe the characteristics of patients who develop blood glucose abnormalities while receiving these agents. DESIGN: Retrospective chart review. SETTING: Two community-based hospitals in the Houston, Texas, region. PATIENTS: Seventeen thousand one hundred eight patients who received fluoroquinolones or ceftriaxone; of those, 101 received levofloxacin, gatifloxacin, or ceftriaxone and also had serum glucose concentrations above 200 or below 50 mg/dl within 72 hours of receiving the drug. MEASUREMENTS AND MAIN RESULTS: Baseline demographics of patients with glucose abnormalities while receiving gatifloxacin, levofloxacin, or ceftriaxone were similar. Mean +/- SD patient age, weight, and estimated creatinine clearance were 67 +/- 17 years, 79 +/- 21 kg, and 52 +/- 32 ml/minute, respectively. Dysglycemia rates relative to treatment were as follows: gatifloxacin 76 (1.01%) of 7540 patients, levofloxacin 11 (0.93%) of 1179, ceftriaxone 14 (0.18%) of 7844, ciprofloxacin 0 (0%) of 545, and any fluoroquinolone 87 (0.94%) of 9264. Dysglycemia was more likely to occur in patients receiving any fluoroquinolone than in those receiving ceftriaxone (relative risk [RR] 3.32, 95% confidence interval (CI) 2.31-4.78, p < 0.05). The rate of dysglycemia did not differ with gatifloxacin and levofloxacin (RR 1.07, 95% CI 0.62-1.86, p = 0.8). Of the 101 patients with dysglycemias, hypoglycemia occurred in nine (9%) and hyperglycemia in 92 (91%). In a multivariate analysis of patients receiving fluoroquinolones, only concomitant sulfonylurea therapy was identified as an independent risk factor for development of hypoglycemia compared with patients who experienced hyperglycemia. CONCLUSION: In the 17,108 patients receiving a fluoroquinolone or ceftriaxone, the rate of dysglycemia was greater in those receiving levofloxacin or gatifloxacin than in those receiving ceftriaxone. However, no difference was noted in the rate of glucose abnormalities with levofloxacin versus gatifloxacin. Clinicians should be aware of dysglycemic events that may occur in patients receiving fluoroquinolones, especially in those with diabetes mellitus or those receiving sulfonylureas.     

Intraocular pressure lowering effect of brinzolamide 1.0% as adjunctive therapy to latanoprost 0.005% in patients with open angle glaucoma or ocular hypertension: an uncontrolled, open-label study

PURPOSE: A prospective study was conducted to evaluate the intraocular pressure (IOP) lowering effect of brinzolamide 1.0% ophthalmic suspension as an adjunctive therapy with latanoprost 0.005% ophthalmic solution in patients with open angle glaucoma or ocular hypertension. PATIENTS AND METHODS: Fourteen patients with open angle glaucoma (OAG) or ocular hypertension (OH) who had been using latanoprost 0.005% for more than 6 months were initiated on adjunctive brinzolamide therapy. The IOP values at 1 month, 2 months, and 3 months were compared with those measured immediately before adding brinzolamide to the regimen (baseline). The incidence of adverse events such as conjunctival hyperemia and corneal epithelial defect were also examined. RESULTS: The baseline IOP was 21.1 +/- 4.8 mmHg (mean +/- standard deviation). After 1 month, 2 months, and 3 months of therapy IOP was 16.9 +/- 4.5 mmHg, 16.6 +/- 4.0 mmHg, and 15.9 +/- 3.1 mmHg, respectively, showing significant reductions in IOP at all the measuring time-points during the study compared with the baseline value (p < 0.01). Conjunctival hyperemia developed in one patient after 1 month and in another after 2 months; however, both were mild, and therapy was continued. Corneal epithelium defect was observed in 3 patients. One of them had mild defect before brinzolamide was added to the regimen. Increase of eye discharge was seen in one patient. No serious side effects were otherwise observed. CONCLUSION: The addition of brinzolamide to a latanoprost 0.005% regimen may further lower intraocular pressure in patients with open angle glaucoma or ocular hypertension.     

Comparison of minimal inhibitory and mutant prevention drug concentrations of 4 fluoroquinolones against clinical isolates of methicillin-susceptible and -resistant Staphylococcus aureus

Staphylococcus aureus remains an important human pathogen affecting both outpatients and those hospitalized. Increasing antimicrobial resistance is global but prevalence rates are variable for different geographical areas. Fluoroquinolones have been used to treat S. aureus infections and the newer quinolones have enhanced in vitro activity against this organism. The mutant prevention concentration (MPC) defines the antimicrobial drug concentration threshold that would require an organism to simultaneously possess two mutations for growth in the presence of the drug. We tested clinical isolates of methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) S. aureus by minimum inhibitory concentration (MIC) and MPC against gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin. For MSSA strains, the rank order of potency based on MIC(90) values were gemifloxacin (0.063 mg/l) = moxifloxacin (0.063 mg/l) > gatifloxacin (0.05 mg/l) = levofloxacin (0.25 mg/l) and by MPC values moxifloxacin (0.25 mg/l) > gemifloxacin (0.5 mg/l) > gatifloxacin (1 mg/l) = levofloxacin (1mg/l). For 87% of the isolates the MPC value was 0.5 mg/l for gatifloxacin. The rank order of potency based on the time the serum drug concentration exceeded the MPC(90), was as follows: moxifloxacin (>24 h) > levofloxacin (>18 h) > gatifloxacin (12 h) > gemifloxacin (9 h). Serum drug concentration remained in excess of the MPC(87) for 24 h for gatifloxacin. Both MIC(90) and MPC(90) values were higher against MRSA strains and the time above the MPC(90) was significantly shorter for all agents.     

不同材质滤膜对于加替沙星滴眼液中抑菌剂的吸附性研究

目的：考察加替沙星滴眼液除菌过滤时不同材质滤膜对于苯扎氯铵的吸附性;建立高效液相色谱法测定加替沙星滴眼液中苯扎氯铵的含量。方法：采用材质为聚醚砜（PES）、聚偏二氟乙烯（PVDF）的滤膜过滤加替沙星滴眼液后,收集滤液,于100,500,1 000,1 500,2 000 mL时取样,测定过滤后苯扎氯铵的含量;以水（用1 mol·L^-1高氯酸调pH至2.2±0.05）-乙腈-异丙醇（58：33：9）为流动相等度洗脱;流速1.0 mL·min^-1;柱温40℃;检测波长214 nm。结果：材质为聚偏二氟乙烯（PVDF）的滤膜对于苯扎氯铵有6.3%的吸附,而材质聚醚砜（PES）对于苯扎氯铵无吸附性;苯扎氯铵在11.1~111 μg·mL^-1（222~2 220 ng）浓度范围内呈良好的线性,线性方程为y=22 162x-15 620（r=0.999 9）,平均回收率为100.58%、RSD=0.60%（n=9）,准确度较好。结论：对于加替沙星滴眼液的生产,采用材质为聚醚砜（PES）的滤膜对其中抑菌剂苯扎氯铵无吸附;建立了HPLC法测定加替沙星滴眼液中苯扎氯铵的方法,操作简便,灵敏度高,重复性好,可快速准确用于加替沙星滴眼液中苯扎氯铵含量分析。